Torill Ueland

• Blakstad, Eirik Gustav; Bakke, Laura Anne Wortinger; Jørgensen, Kjetil Nordbø; Nerland, Stener; Barth, Claudia & Andreou, Dimitrios [Show all 10 contributors for this article] (2026). Structural brain alterations of the subcortical limbic system in schizophrenia and bipolar disorders. Schizophrenia Research. ISSN 0920-9964. 296, p. 91–101. doi: 10.1016/j.schres.2026.07.007. Full text in Research Archive
• Busch, Cecilie; Ueland, Torill; Høegh, Margrethe Collier; Simonsen, Carmen; Aminoff, Sofie R. & Barrett, Elizabeth Ann [Show all 11 contributors for this article] (2026). Wish list from people with lived experience of bipolar disorder - for clinicians and researchers. Journal of Affective Disorders Reports. 25, p. 101114–101114. doi: 10.1016/j.jadr.2026.101114. Full text in Research Archive
• Gjerdalen, Oda Skancke; Aas, Erlend Marius; Lystad, June Ullevoldsæter; Ueland, Torill; Arnevik, Espen Ajo & Falkum, Erik [Show all 12 contributors for this article] (2026). A comparison of characteristics of individuals with psychosis and substance use disorders seeking vocational rehabilitation. Nordic Journal of Psychiatry. ISSN 0803-9488. 80(3), p. 177–181. doi: 10.1080/08039488.2026.2625696. Full text in Research Archive
• Calkova, Tereza; Vaskinn, Anja; Mørch-Johnsen, Lynn Egeland; Smelror, Runar; Jørgensen, Kjetil Nordbø & Wortinger, Laura Anne [Show all 18 contributors for this article] (2025). Early versus adult onset of schizophrenia: an examination of premorbid and current IQ. Schizophrenia Research: Cognition. 43, p. 100397–100397. doi: 10.1016/j.scog.2025.100397. Full text in Research Archive Show summary

  Background Cognitive deficits are core findings in schizophrenia, but whether the severity of impairments is related to the age of onset remains unclear. We hypothesized that early onset schizophrenia (EOS; onset before age 19) is associated with lower IQ compared to adult-onset schizophrenia (AOS; onset from age 19). Methods We included 99 adult patients with EOS (age of onset: 15.3 ± 2.8 years), 282 adult patients with AOS (age of onset: 26.5 ± 7.4 years), and 863 adult healthy controls (HC). We assessed current IQ with Wechsler Abbreviated Scale of Intelligence (WASI) and estimated premorbid IQ with National Adult Reading Test (NART). Results Both patient groups had lower current IQ than HC ( p < 0.001). Full-scale ( p = 0.004), performance ( p = 0.003) and verbal ( p = 0.011) current IQ were significantly lower in EOS than in AOS, with 5 IQ units difference for all three measures. EOS and AOS did not differ in premorbid IQ, but EOS showed a steeper IQ decline from premorbid levels than AOS (11.4 vs. 8 IQ units, respectively, p = 0.013). Conclusion EOS had lower current IQ than AOS, but did not differ in premorbid IQ, suggesting a larger decline from premorbid IQ levels. This could imply different neurodevelopmental processes underlying cognitive dysfunction related to age of onset in schizophrenia, underscoring the necessity for further inquiry into the mechanisms driving this decline and strategies for its prevention.

• Øie, Merete Glenne; Fernando, Barbosa,; Sandra, Lettner,; Gus, Baker,; Cedric, Duarte, & Hessen, Erik [Show all 7 contributors for this article] (2025). Why clinical neuropsychology matters in schizophrenia care. Frontiers in Psychology. 16, p. 1–12. doi: 10.3389/fpsyg.2025.1713751. Full text in Research Archive Show summary

  Cognitive impairments in schizophrenia are widespread, persistent throughout the illness course, and significantly impact quality of life and functional outcomes. Integrating neuropsychological evaluations into routine clinical care is essential for early identification of cognitive impairments. This approach facilitates the implementation of personalized treatment strategies, including tailored neuropsychological rehabilitation, to promote functional recovery. Although recommended by national and international guidelines, many individuals with schizophrenia do not receive neuropsychological assessment. This article emphasizes the integral role of clinical neuropsychology in schizophrenia care, focusing on six key areas: (1) cognitive domains to assess; (2) addressing subjective cognitive complaints; (3) the impact of symptoms, medication, and substance use on cognitive function; (4) test administration and evaluation procedures; (5) the utilization of neuropsychological results and feedback; and (6) the design and implementation of individualized neuropsychological rehabilitation.

• Ormerod, Monica Bettina E. Greenwood; Sheikh, Mashhood Ahmed; Ueland, Thor; Hjell, Gabriela; Rødevand, Linn & Sæther, Linn Sofie [Show all 15 contributors for this article] (2025). Minor immunomodulatory effects of psychotropics suggested in severe mental disorders: Associations of antipsychotics with beta defensin 2, antidepressants with C-reactive protein, and mood stabilizers with soluble interleukin 2 receptor. European psychiatry. ISSN 0924-9338. 68(1). doi: 10.1192/j.eurpsy.2025.10104. Full text in Research Archive Show summary

  Background: Immunomodulatory effects of psychotropic agents used to treat severe mental disorders (SMDs) have been suggested. We investigated associations between immune marker levels and antipsychotic- (AP), antidepressant- (AD), and mood stabilizing agents (MS) use in SMDs. Methods: We included 1215 participants with SMDs (777 with schizophrenia spectrum disorders and 438 with bipolar disorders). Circulating levels of 45 immune markers were determined by enzyme-immunoassay or immunoturbidimetry and analyzed for associations with use, doses, and serum concentrations of AP, AD, and MS. Extensive adjustments for potential confounders were performed. Immune marker levels of 1008 healthy controls served as a reference. Results: AP use was significantly associated with higher plasma levels of beta defensin 2 (BD-2) ( β  = 0.094, p  = 0.8E-4), AD use with higher serum levels of CRP ( β  = 0.072, p  = 0.8E-3), and MS use with higher plasma levels of soluble interleukin 2 receptor (sIL-2R) ( β  = 0.063, p  = 0.9E-4). These findings were paralleled by positive associations with psychotropic agent dose and serum concentrations: AP dose was associated with BD-2 levels ( β  = 0.045, p  = 2.3E-4), AD dose with CRP levels ( β  = 0.039, p  = 0.001), MS dose with sIL-2R levels ( β  = 0.048, p  = 0.001), and serum concentration of AD was nominally positively associated with CRP ( β  = 0.072, p  = 0.002). Conclusions: The findings suggest that AP and MS use affect pathways involved in immune homeostasis and inflammatory regulation in individuals with SMDs, while AD use augments low-grade systemic inflammation reflected by CRP.

• Lunding, Synve Hoffart; Kreis, Isabel; Rødevand, Linn; Aas, Monica; Werner, Maren Caroline Frogner & Johansen, Ingrid Torp [Show all 16 contributors for this article] (2025). Self-harming behavior linked to earlier onset of cardiovascular disease in severe mental disorders. European psychiatry. ISSN 0924-9338. 68(1). doi: 10.1192/j.eurpsy.2025.10106. Full text in Research Archive Show summary

  Background People with severe mental disorders (SMDs) have about 15 years shorter life expectancy than the general population. Cardiovascular disease (CVD) is among the leading causes of premature mortality and shares genetic underpinnings with SMDs. We investigated the link between clinical traits in SMDs and time to the first CVD diagnosis. Methods The study included 1,627 well-characterized participants with schizophrenia spectrum (SCZ, N  = 998) and bipolar spectrum disorders (BDs, N  = 629), and a reference group of 1,201 healthy controls. CVD diagnoses were obtained from two Norwegian national registries (covering both primary and specialist health care) for the period of 2006–2020. Applying Cox proportional hazard models, we investigated associations between SMD clinical traits and time to first CVD diagnosis in SMD participants, adjusting for age, sex, diagnosis, and tobacco use. Results Among individuals with SMD, recurring self-harming behavior (SHB) was associated with a shorter time to first CVD diagnosis ( p  = .029) relative to those without SHB. In the subgroup with SHB and a history of attempted suicide(s), more suicide attempts were associated with shorter time to first CVD diagnosis ( p  = .041). Significant associations of time to first CVD diagnosis with age at SMD onset and comorbid substance use disorder were not demonstrated. Conclusions SHB and a history of suicide attempts in individuals with SMD seem to be associated with earlier CVD onset, and may improve the prediction of CVD, in addition to standard cardiovascular risk factors.

• Grimstad, Kristoffer; Sørensen, Håkon; Vaskinn, Anja; Mohn, Hanne Christine; Glastad, Stine Holmstul & Andreassen, Ole [Show all 11 contributors for this article] (2025). Subjective cognition in schizophrenia and bipolar disorder: Investigation of group differences and associations with objective cognition and clinical characteristics using a novel measure of subjective cognition. Schizophrenia Research: Cognition. 40. doi: 10.1016/j.scog.2025.100345. Full text in Research Archive
• Ormerod, Monica Bettina E. Greenwood; Ueland, Thor; Aas, Monica; Hjell, Gabriela; Rødevand, Linn & Sæther, Linn Sofie [Show all 16 contributors for this article] (2025). Limited evidence of association between dysregulated immune marker levels and telomere length in severe mental disorders. Acta Neuropsychiatrica. ISSN 0924-2708. 37. doi: 10.1017/neu.2024.62. Full text in Research Archive Show summary

  Objective: Accelerated ageing indexed by telomere attrition is suggested in schizophrenia spectrum- (SCZ) and bipolar disorders (BD). While inflammation may promote telomere shortening, few studies have investigated the association between telomere length (TL) and markers of immune activation and inflammation in severe mental disorders. Methods: Leucocyte TL defined as telomere template/amount of single-copy gene template (T/S ratio), was determined in participants with SCZ (N = 301) or BD (N = 211) and a healthy control group (HC, N = 378). TL was analysed with linear regressions for associations with levels of 12 immune markers linked to SCZ or BD. Adjustments were made for a broad range of potential confounding variables. TL was measured by quantitative polymerase chain reaction (qPCR) and the immune markers were measured by enzyme immunoassays. Results: A positive association between levels of soluble tumour necrosis factor receptor 1A (sTNF-R1) and TL in SCZ (β = 0.191, p = 0.012) was observed. Plasma levels of the other immune markers were not significantly associated with TL in the BD, SCZ or HC groups. Conclusion: There was limited evidence of association between immune markers and TL in SCZ and BD. The results provide little support for involvement of immune dysregulation, as reflected by current systemic markers, in telomere attrition-related accelerated ageing in severe mental disorders.

• Marquand, Andre F.; Bučková, Barbora Rehák; Cattaranusi, Giulia; Flaaten, Camilla Bärthel; Busch, Cecilie & Lemvigh, Cecilie K. [Show all 15 contributors for this article] (2025). Learning Latent Profiles via Cognitive Growth Charting in Psychosis: Design and Rationale for the PRECOGNITION Project. Schizophrenia Bulletin Open. 6(1). doi: 10.1093/schizbullopen/sgaf007. Full text in Research Archive
• Åsbø, Gina; Haavind, Hanne; Kruse, Sindre Hembre; Wold, Kristin Fjelnseth; Hegelstad, Wenche & Romm, Kristin Lie [Show all 10 contributors for this article] (2025). “Why shouldn’t I expect a lot from life?” – a qualitative study of what facilitates long-term recovery in first-episode psychosis. BMC Psychiatry. 25. doi: 10.1186/s12888-025-06681-y. Full text in Research Archive Show summary

  Background Qualitative research frequently characterises recovery, but more knowledge on subjective experiences of facilitators of long-term recovery in psychosis is needed. This interview study aimed to explore what people with first-episode psychosis (FEP) highlight as important for their long-term recovery. Methods Interviews with 20 individuals in recovery (personal and/or clinical) participating in two follow-up studies, 10 and 20-years after treatment start for a first episode schizophrenia or bipolar spectrum disorder. Interviews were thematically analysed by a research team that included a peer researcher. Results The analysis generated that personal resources and agency were experienced as the overarching facilitators of recovery, with five themes: (1) Doing recovery in everyday life, involving agency in daily life; (2) Re-evaluating risk, involving re-evaluating limitations and stress reduction; (3) Becoming a caregiver, involving development from being cared for to taking care of others; (4) Negotiating normality, involving identity and social inclusion; (5) Owning and sharing your story, involving accepting lived experience and overcoming stigma. Discussion All participants described themselves as the main facilitators of their own recovery, and treatment as secondary to their efforts. Gradually testing limitations and taking risks, providing social support to others, as well as owning and sharing your story were crucial for promoting long-term recovery in FEP. Clinical implications include supporting service users’ agency with strength- based interventions and shared-decision making, as well as refining psychoeducation on stress reduction in a long-term perspective.

• Kim, Milin; Sharma, Nitin; Leonardsen, Esten Høyland; Rutherford, Saige; Selbæk, Geir & Persson, Karin Ester Torun [Show all 19 contributors for this article] (2025). Predicting Mental and Neurological Illnesses Based on Cerebellar Normative Features. Biological Psychiatry: Global Open Science. 5(5), p. 1–11. doi: 10.1016/j.bpsgos.2025.100541. Full text in Research Archive
• Gjerdalen, Oda Skancke; Zucknick, Manuela; Westlie, Ingvild Tvedt; Bull, Helen; Evensen, Stig & Falkum, Erik [Show all 17 contributors for this article] (2025). An exploratory study of the relevance of therapy format and therapist’ training in individual cognitive behavioral therapy for psychosis. Frontiers in Psychiatry. 16. doi: 10.3389/fpsyt.2025.1527549. Full text in Research Archive Show summary

  Introduction: Cognitive Behavioral Therapy for psychosis (CBTp) is an evidence-based intervention that can be delivered in various formats, including as part of vocational rehabilitation. However, due to scarcity of resources, CBTp is currently accessible to only a minority of individuals with psychosis. This secondary analysis aims to explore potential differences in clinical outcomes between distinct CBTp formats and to examine whether therapist training influences treatment effect. Exploring these aspects is of importance, as they may influence the scalability and accessibility of CBTp in routine care. Material and methods: Data in this study is sourced from two independent projects; KATOslo and JUMP, comprising a total of 200 participants with broad schizophrenia-spectrum disorders. The current study compares CBTp delivered as either symptom-focused individual therapy (KATOslo) or as an add-on to a vocational rehabilitation (VR) program (JUMP), with two reference groups; VR combined with cognitive remediation (JUMP) and treatment as usual (KATOslo). Using a series of mixed effects models for repeated measurements, we examined differences between the groups in terms of general functioning and psychiatric symptom severity. Emphasis was placed on potential differences between the two groups receiving CBTp, considering both average differences across assessment points and trajectories over time. Results: In line with expectations, all groups demonstrated overall improvements in functioning and symptom levels. After adjusting for relevant confounders, no statistically significant differences were found between the two groups receiving CBTp following treatment initiation. Conclusions: These findings suggest that CBTp may be effective across different delivery formats and levels of therapist training in terms of similar, positive clinical outcomes for this patient group. This has potential implications for service design and broader implementation of CBTp in real-world settings.

• Inova, Amina; Birkenæs, Viktoria; Quintana, Daniel; Ormerod, Monica Bettina E. Greenwood; Ueland, Torill & Ueland, Thor [Show all 10 contributors for this article] (2024). Cortisol and C-reactive protein (CRP) regulation in severe mental disorders. Psychoneuroendocrinology. ISSN 0306-4530. 172. doi: 10.1016/j.psyneuen.2024.107272. Full text in Research Archive Show summary

  Background People with schizophrenia (SZ) and bipolar disorder (BD) show abnormalities in the biological stress system and low-grade inflammation. However, whether the hypothalamic-pituitary-adrenal (HPA) axis-immune regulation is disrupted in SZ and BD, is yet to be determined. Methods Cortisol and C-reactive protein (CRP) were measured in blood samples collected at or before 10 am in participants with SZ (N = 257), BD (N = 153), and healthy controls (N = 40). Cortisol/CRP ratio was calculated as an indicator of the balance between HPA axis activity and inflammatory activity, called HPA axis-immune regulation. Global functioning and symptom levels were obtained using the Global Assessment of Functioning (GAF) Scale and Positive and Negative Syndrome Scale (PANSS). Standardized neuropsychological tests were used to assess cognitive function. All analyses were adjusted for demographic variables (age and sex) and the time of blood sampling. Results Participants with a SZ or BD diagnosis had lower cortisol/CRP ratios (F=5.93, p = 0.003) compared to healthy controls. The difference was no longer statistically significant (p > 0.1) when BMI was added as a covariate to the model. Within patients, those on psychotropic treatment (n = 337) had lower cortisol/CRP ratio than those not taking psychotropic agents (n = 59) (F=4.72, p = 0.03). Compared to HC, only patients on regular psychotropic agents had lower cortisol/CRP ratio (p = 0.02). Within the SZ group, lower cortisol/CRP ratio was associated with having poorer general functioning as measured by GAF (ß=-0.18, p = 0.01), and more severe negative and general symptomatology as measured by PANSS (ß=0.19, p = 0.007 and ß=0.18, p = 0.01, respectively). In SZ, lower cortisol/CRP ratio was also associated with poorer verbal memory, learning, and processing speed (ß=-0.20 p = 0.007, ß=-0.19 p = 0.01, ß=-0.25, p > 0.001, respectively). No associations were observed between cortisol/CRP ratio and clinical and cognitive functioning in the BD group. Conclusion These findings may indicate HPA axis-immune dysregulation in SZ. Our study further indicates that disrupted HPA axis-immune regulation in people with SZ and BD is associated with psychotropic treatment and fat mass, highlighting the clinical importance of weight control and regular psychotropic treatment follow-ups within this group.

• Simonsen, Carmen; Åsbø, Gina; Slade, Michael; Wold, Kristin Fjelnseth; Widing, Line Hustad & Flaaten, Camilla Bärthel [Show all 13 contributors for this article] (2024). A good life with psychosis: Rate of positive outcomes in first-episode psychosis at 10-year follow-up. Psychological Medicine. ISSN 0033-2917. 54(9), p. 2112–2121. doi: 10.1017/S0033291724000205. Full text in Research Archive Show summary

  Background More knowledge about positive outcomes for people with first-episode psychosis (FEP) is needed. An FEP 10-year follow-up study investigated the rate of personal recovery, emotional wellbeing, and clinical recovery in the total sample and between psychotic bipolar spectrum disorders (BD) and schizophrenia spectrum disorders (SZ); and how these positive outcomes overlap. Methods FEP participants (n = 128) were re-assessed with structured clinical interviews at 10-year follow-up. Personal recovery was self-rated with the Questionnaire about the Process of Recovery-15-item scale (total score ⩾45). Emotional wellbeing was self-rated with the Life Satisfaction Scale (score ⩾5) and the Temporal Experience of Pleasure Scale (total score ⩾72). Clinical recovery was clinician-rated symptom-remission and adequate functioning (duration minimum 1 year). Results In FEP, rates of personal recovery (50.8%), life satisfaction (60.9%), and pleasure (57.5%) were higher than clinical recovery (33.6%). Despite lower rates of clinical recovery in SZ compared to BD, they had equal rates of personal recovery and emotional wellbeing. Personal recovery overlapped more with emotional wellbeing than with clinical recovery (χ2). Each participant was assigned to one of eight possible outcome groups depending on the combination of positive outcomes fulfilled. The eight groups collapsed into three equal-sized main outcome groups: 33.6% clinical recovery with personal recovery and/or emotional wellbeing; 34.4% personal recovery and/or emotional wellbeing only; and 32.0% none. Conclusions In FEP, 68% had minimum one positive outcome after 10 years, suggesting a good life with psychosis. This knowledge must be shared to instill hope and underlines that subjective and objective positive outcomes must be assessed and targeted in treatment.

• Berthet, Pierre; Haatveit, Beathe; Kjelkenes, Rikka; Worker, Amanda; Kia, Seyed Mostafa & Wolfers, Thomas [Show all 21 contributors for this article] (2024). A 10-Year Longitudinal Study of Brain Cortical Thickness in People with First-Episode Psychosis Using Normative Models. Schizophrenia Bulletin. ISSN 0586-7614. 51(1), p. 95–107. doi: 10.1093/schbul/sbae107. Full text in Research Archive Show summary

  Background Clinical forecasting models have potential to optimize treatment and improve outcomes in psychosis, but predicting long-term outcomes is challenging and long-term follow-up data are scarce. In this 10-year longitudinal study, we aimed to characterize the temporal evolution of cortical correlates of psychosis and their associations with symptoms. Design Structural magnetic resonance imaging (MRI) from people with first-episode psychosis and controls (n = 79 and 218) were obtained at enrollment, after 12 months (n = 67 and 197), and 10 years (n = 23 and 77), within the Thematically Organized Psychosis (TOP) study. Normative models for cortical thickness estimated on public MRI datasets (n = 42 983) were applied to TOP data to obtain deviation scores for each region and timepoint. Positive and Negative Syndrome Scale (PANSS) scores were acquired at each timepoint along with registry data. Linear mixed effects models assessed effects of diagnosis, time, and their interactions on cortical deviations plus associations with symptoms. Results LMEs revealed conditional main effects of diagnosis and time × diagnosis interactions in a distributed cortical network, where negative deviations in patients attenuate over time. In patients, symptoms also attenuate over time. LMEs revealed effects of anterior cingulate on PANSS total, and insular and orbitofrontal regions on PANSS negative scores. Conclusions This long-term longitudinal study revealed a distributed pattern of cortical differences which attenuated over time together with a reduction in symptoms. These findings are not in line with a simple neurodegenerative account of schizophrenia, and deviations from normative models offer a promising avenue to develop biomarkers to track clinical trajectories over time.

• Mlakar, Vid; Akkouh, Ibrahim Ahmed; Halff, Els F.; Srivastava, Deepak P.; Birkenæs, Viktoria & Ueland, Torill [Show all 12 contributors for this article] (2024). Telomere biology and its maintenance in schizophrenia spectrum disorders: Exploring links to cognition. Schizophrenia Research. ISSN 0920-9964. 272, p. 89–95. doi: 10.1016/j.schres.2024.08.011. Full text in Research Archive Show summary

  Objective Contemporary research suggests reduced telomere length in schizophrenia spectrum disorders (SZ) compared to age-adjusted non-affected individuals. However, the role of telomere maintenance and telomere repair in SZ is poorly understood as well as the involvement of telomere biology in cognitive abnormalities in SZ. Methods The study consisted of 758 participants (SZ [n = 357] and healthy controls, HC [n = 401]) collected as part of the Norwegian TOP study. Participants were assessed with standardized neuropsychological tests measuring five cognitive domains. Leucocyte telomere length (TL) was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio), used to estimate the mean telomere length. Telomerase activity was assessed by the expression levels of the Telomerase Reverse Transcriptase (TERT) and Telomerase RNA Component (TERC) genes. To assess telomere maintenance and telomere repair we calculated the telomerase expression to TL ratio (TERT/TL and TERC/TL respectively). Results Patients had reduced TERT (F = 5.03, p = 0.03), but not TERC expression (F = 1.04, p = 0.31), and higher TERT/TL (F = 6.68, p = 0.01) and TERC/TL (F = 6.71, p = 0.01), adjusted for age, sex, and ethnicity. No statistically significant association was observed between any of the telomere biology markers and the cognitive domains (p > 0.05). Conclusion Our study shows changes in TERT expression and telomere maintenance and telomere repair in SZ compared HC. However, the role of telomere biology in the mechanism underlying cognitive impairment in psychosis seems limited.

• Kreis, Isabel; Wold, Kristin Fjelnseth; Åsbø, Gina; Simonsen, Carmen; Flaaten, Camilla Bärthel & Engen, Magnus Johan [Show all 10 contributors for this article] (2024). The relationship between visual hallucinations, functioning, and suicidality over the course of illness: a 10-year follow-up study in first-episode psychosis. Schizophrenia. 10(1). doi: 10.1038/s41537-024-00450-8. Full text in Research Archive Show summary

  Visual hallucinations in psychosis are under-researched despite associations with increased illness severity, functional impairments, and suicidality in the few existing studies. Further, there are no long-term longitudinal studies, making it impossible to conclude if these associations are state or trait phenomena. In the current prospective longitudinal study, 184 individuals with first-episode psychosis were assessed with semi-structured clinical interviews and self-report questionnaires at baseline and 10-year follow-up. Participants were grouped based on lifetime experience of visual hallucinations: before or at baseline (VH+/+), first during follow-up (VH−/+), or never (VH−/−). Associations with functioning, suicide attempts, childhood trauma and other markers of illness severity were tested using multinomial logistic regression analysis. At baseline, the VH+/+ group (37.5%), but not VH−/+ (12.5%), had poorer functioning, higher symptom severity, a lower age at onset, and included more individuals with a history of multiple suicide attempts than the VH−/− group (50%). At follow-up, the VH−/+ group, but not VH+/+, had poorer functioning and higher symptom severity than the VH−/− group. However, the number of participants who committed multiple suicide attempts during the follow-up period was again significantly higher in the VH+/+ group. There was no association with childhood trauma. Hence, visual hallucinations are associated with impaired functioning and higher symptom severity, but only in the short-term. However, visual hallucinations that arise early in the course of illness are a risk indicator for repeated suicide attempts throughout the illness course. These findings highlight the relevance of assessing visual hallucinations and monitoring their development over time.

• Szabo, Attila; O'Connell, Kevin Sean; Akkouh, Ibrahim Ahmed; Ueland, Thor; Sønderby, Ida Elken & Hope, Sigrun [Show all 16 contributors for this article] (2024). Elevated levels of peripheral and central nervous system immune markers reflect innate immune dysregulation in autism spectrum disorder. Psychiatry Research. ISSN 0165-1781. 342. doi: 10.1016/j.psychres.2024.116245. Full text in Research Archive Show summary

  Background Evidence suggests dysregulated immune functions in the pathophysiology of Autism spectrum disorder (ASD), although specific immune mechanisms are yet to be identified. Methods We assessed circulating levels of 25 immune/neuroinflammatory markers in a large ASD sample (n = 151) and matched controls (n = 72) using linear models. In addition, we performed global brain transcriptomics analyses of relevant immune-related genes. We also assessed the expression and function of factors and pathway elements of the inflammasome system in peripheral blood mononuclear cells (PBMC) isolated from ASD and controls using in vitro methods. Results We found higher circulating levels of IL-18 and adhesion factors (ICAM-1, MADCAM1) in individuals with ASD relative to controls. Consistent with this, brain levels of ICAM1 mRNA were also higher in ASD compared to controls. Furthermore, we found higher expression/activity of Caspase-1 and the inflammasome sensor NLRP3 in PBMCs in ASD, both at baseline and following inflammatory challenge. This corresponded with higher levels of secreted IL-18, IL-1β, and IL-8, as well as increased expression of adhesion factors following inflammasome activation in ASD PBMC cultures. Inhibition of the NLRP3-inflammasome rescued the observed immune phenotype in ASD in vitro. Conclusion Our results suggest a role for inflammasome dysregulation in ASD pathophysiology.

• Åsbø, Gina; Haavind, Hanne; Kruse, Sindre Hembre; Wold, Kristin Fjelnseth; Hegelstad, Wenche & Romm, Kristin Lie [Show all 10 contributors for this article] (2024). Taking what you get or Getting what you Need: A Qualitative Study on Experiences with Mental Health and Welfare Services in Long-Term Recovery in First-Episode Psychosis. Community mental health journal. ISSN 0010-3853. 24. doi: 10.1007/s10597-024-01356-6. Full text in Research Archive Show summary

  How people in long-term recovery (clinical and personal) in first-episode psychosis (schizophrenia and bipolar spectrum disorders) experience the mental health and welfare services they interact with is not frequently studied but has significant implications. We therefore aimed to explore which aspects of these services people with FEP evaluate as important for their long-term recovery. Twenty participants in clinical and/or personal recovery from two Norwegian long-term follow-up studies after FEP (TOP 10-year and TIPS 20-year) were sampled for this interview-based qualitative study. The research-team included service user experience. A deductive analysis based on personal accounts of recovery generated five service aspects. Few specific types of interventions were reported to promote recovery although medications, psychotherapy and employment support were mentioned. Participants valued services based in collaboration and that focused on their resources rather than limitations. The importance of long-term follow-up with a consistent aim was highlighted, as was the inclusion of caregivers and peers. Welfare services contributed to recovery by supporting basic needs and safety, but some experienced social exclusion when not participating in the labor market. This study is unique in exploring the role of services, including welfare, in long-term FEP recovery from service user perspectives. Participants evaluated that services played a more indirect role in long-term recovery by supporting their personal resources, although what they needed from services had frequently not been offered. Their expertise by experience contributes valuable knowledge. Better service coordination and consistent implementation of this knowledge are crucial to support recovery in FEP.

• Sæther, Linn Sofie; Szabo, Attila; Akkouh, Ibrahim Ahmed; Haatveit, Beathe; Mohn, Christine & Vaskinn, Anja [Show all 14 contributors for this article] (2024). Cognitive and inflammatory heterogeneity in severe mental illness: Translating findings from blood to brain. Brain, Behavior, and Immunity. ISSN 0889-1591. 118, p. 287–299. doi: 10.1016/j.bbi.2024.03.014. Full text in Research Archive Show summary

  Recent findings link cognitive impairment and inflammatory-immune dysregulation in schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, heterogeneity and translation between the periphery and central (blood-to-brain) mechanisms remains a challenge. Starting with a large SZ, BD and healthy control cohort (n = 1235), we aimed to i) identify candidate peripheral markers (n = 25) associated with cognitive domains (n = 9) and elucidate heterogenous immune-cognitive patterns, ii) evaluate the regulation of candidate markers using human induced pluripotent stem cell (iPSC)-derived astrocytes and neural progenitor cells (n = 10), and iii) evaluate candidate marker messenger RNA expression in leukocytes using microarray in available data from a subsample of the main cohort (n = 776), and in available RNA-sequencing deconvolution analysis of postmortem brain samples (n = 474) from the CommonMind Consortium (CMC). We identified transdiagnostic subgroups based on covariance between cognitive domains (measures of speed and verbal learning) and peripheral markers reflecting inflammatory response (CRP, sTNFR1, YKL-40), innate immune activation (MIF) and extracellular matrix remodelling (YKL-40, CatS). Of the candidate markers there was considerable variance in secretion of YKL-40 in iPSC-derived astrocytes and neural progenitor cells in SZ compared to HC. Further, we provide evidence of dysregulated RNA expression of genes encoding YKL-40 and related signalling pathways in a high neuroinflammatory subgroup in the postmortem brain samples. Our findings suggest a relationship between peripheral inflammatory-immune activity and cognitive impairment, and highlight YKL-40 as a potential marker of cognitive functioning in a subgroup of individuals with severe mental illness.

• Schjøtt-Pedersen, Olivia; Bull, Helen; Falkum, Erik; Ueland, Torill; Gjerdalen, Oda Skancke & Haaland, Vegard Øksendal [Show all 8 contributors for this article] (2024). Measuring the concurrent validity of the norwegian versions of the psychotic symptom rating scales (PSYRATS) and the positive scale from the positive and negative syndrome scale (PANSS). Nordic Journal of Psychiatry. ISSN 0803-9488. doi: 10.1080/08039488.2024.2367638. Full text in Research Archive Show summary

  Purpose: The Positive and Negative Syndrome Scale (PANSS) is one of the most commonly used assessment tools for measuring psychotic symptoms. The Psychotic Symptom Rating Scales (PSYRATS) is another instrument created specifically to assess delusions and auditory hallucinations. However, research on the concurrent validity of PSYRATS with PANSS is limited. There are also inconsistent findings regarding the association between the PSYRATS scales and the PANSS positive scale. The present study aims to add to the understanding of the concurrent validity of these measures, while also incorporating a broader measure of psychiatric symptoms (the symptom scale from the Global Assessment of Functioning Scale – split version, GAF-S). Materials and Methods: Spearman’s Rank Order Correlations (rho) were calculated for scores from the PANSS positive scale, PSYRATS and GAF-S in a sample of 148 participants with psychotic disorders at three time points. Results: The findings indicate concurrent validity between PSYRATS and PANSS, while the PSYRATS scales were not consistently correlated with GAF-S. Conclusions: PSYRATS may be a valid assessment tool for evaluating psychotic symptoms. The utility of PSYRATS in research and clinical practice should be investigated further.

• Kim, Milin; Leonardsen, Esten Høyland; Rutherford, Saige; Selbæk, Geir; Persson, Karin Ester Torun & Steen, Nils Eiel [Show all 15 contributors for this article] (2024). Mapping cerebellar anatomical heterogeneity in mental and neurological illnesses. Nature Mental Health. 2(10), p. 1196–1207. doi: 10.1038/s44220-024-00297-z. Full text in Research Archive Show summary

  The cerebellum is linked to motor coordination, cognitive and affective processing, in addition to a wide range of clinical illnesses. To enable robust quantification of individual cerebellar anatomy relative to population norms, we mapped the normative development and aging of the cerebellum across the lifespan using brain scans of >54,000 participants. We estimated normative models at voxel-wise spatial precision, enabling integration with cerebellar atlases. Applying the normative models in independent samples revealed substantial heterogeneity within five clinical illnesses: autism spectrum disorder, mild cognitive impairment, Alzheimer disease, bipolar disorder, and schizophrenia. Notably, individuals with autism spectrum disorder and mild cognitive impairment exhibited increased positive and negative extreme deviations in cerebellar anatomy, while those with schizophrenia and Alzheimer disease showed predominantly negative deviations. Finally, extreme deviations were associated with cognitive scores. Ou

• Kreis, Isabel; Lagerberg, Trine Vik; Wold, Kristin Fjelnseth; Åsbø, Gina; Simonsen, Carmen & Flaaten, Camilla Bärthel [Show all 11 contributors for this article] (2024). Behind the heterogeneity in the long-term course of first-episode psychosis: Different psychotic symptom trajectories are associated with different patterns of cannabis and stimulant use. Schizophrenia Research. ISSN 0920-9964. 271, p. 91–99. doi: 10.1016/j.schres.2024.07.006. Full text in Research Archive Show summary

  Background Data-driven classification of long-term psychotic symptom trajectories and identification of associated risk factors could assist treatment planning and improve long-term outcomes in psychosis. However, few studies have used this approach, and knowledge about underlying mechanisms is limited. Here, we identify long-term psychotic symptom trajectories and investigate the role of illness-concurrent cannabis and stimulant use. Methods 192 participants with first-episode psychosis were followed up after 10 years. Psychotic symptom trajectories were estimated using growth mixture modeling and tested for associations with baseline characteristics and cannabis and stimulant use during the follow-up (FU) period. Results Four trajectories emerged: (1) Stable Psychotic Remission (54.2 %), (2) Delayed Psychotic Remission (15.6 %), (3) Psychotic Relapse (7.8 %), (4) Persistent Psychotic Symptoms (22.4 %). At baseline, all unfavorable trajectories (2–4) were characterized by more schizophrenia diagnoses, higher symptom severity, and longer duration of untreated psychosis. Compared to the Stable Psychotic Remission trajectory, unstable trajectories (2,3) showed distinct associations with cannabis/stimulant use during the FU-period, with dose-dependent effects for cannabis but not stimulants (Delayed Psychotic Remission: higher rates of frequent cannabis and stimulant use during the first 5 FU-years; Psychotic Relapse: higher rates of sporadic stimulant use throughout the entire FU-period). The Persistent Psychosis trajectory was less clearly linked to substance use during the FU-period. Conclusions The risk for an adverse long-term course could be mitigated by treatment of substance use, where particular attention should be devoted to preventing the use of stimulants while the use reduction of cannabis may already yield positive effects.

• Vaskinn, Anja; Ueland, Torill; Melle, Ingrid & Sundet, Kjetil Søren (2024). Sex differences in social cognition among individuals with schizophrenia and in healthy control participants: a secondary analysis of published data. Archives of Women's Mental Health. ISSN 1434-1816. doi: 10.1007/s00737-024-01422-8. Full text in Research Archive Show summary

  Purpose Sex differences are present among individuals experiencing schizophrenia. Whether these differences extend to social cognition is unclear. In this study, we investigated sex differences in emotion perception, social perception and theory of mind (ToM). Methods We examined sex differences between males and females with schizophrenia on five social cognitive tests. Healthy male and female control participants were included to examine if any sex difference was illness-specific. Emotion perception was measured with Pictures of Facial Affect (PFA) and Emotion in Biological Motion (EmoBio); social perception with the Relationships Across Domains Test (RAD); and ToM with the Movie for the Assessment of Social Cognition (MASC) and Hinting Task. Results Two-way analyses of variance revealed overall group differences for all tests, with healthy controls outperforming individuals with schizophrenia. Significant sex effects were present for PFA and Hinting Task. There were no significant interaction effects. Within-group independent samples t-tests yielded one significant sex difference, i.e., among healthy controls for PFA. Conclusions Females had better facial emotion perception than males. This sex difference was statistically significant among healthy controls and medium-large among individuals experiencing schizophrenia. There were no significant sex differences for other social cognitive domains. The study did not find evidence for a general female advantage in social cognition.

• Karadag, Naz; Hagen, Espen; Shadrin, Alexey; Meer, Dennis van der; O'Connell, Kevin Sean & Rahman, Mohammad Zillur [Show all 19 contributors for this article] (2024). Unraveling the shared genetics of common epilepsies and general cognitive ability. Seizure. ISSN 1059-1311. 122, p. 105–112. doi: 10.1016/j.seizure.2024.09.016. Full text in Research Archive Show summary

  Purpose Cognitive impairment is prevalent among individuals with epilepsy, and increasing evidence indicates that genetic factors can underlie this relationship. However, the extent to which epilepsy subtypes differ in their genetic relationship with cognitive function, and information about the specific genetic variants involved remain largely unknown. Methods We investigated the genetic relationship between epilepsies and general cognitive ability (COG) using complementary statistical tools, including linkage disequilibrium score (LDSC) regression, MiXeR and conjunctional false discovery rate (conjFDR). We analyzed genome-wide association study data on COG (n = 269,867) and common epilepsies (n = 27,559 cases, 42,436 controls), including the broad phenotypes ‘all epilepsy’, focal epilepsies and genetic generalized epilepsies (GGE), as well as specific subtypes. We functionally annotated the identified loci using several biological resources and validated the results in independent samples. Results Using MiXeR, COG (11.2k variants) was estimated to be almost four times more polygenic than ‘all epilepsy’, GGE, juvenile myoclonic epilepsy (JME), and childhood absence epilepsy (CAE) (2.5k – 2.9k variants). The other epilepsy phenotypes were insufficiently powered for MiXeR analysis. We quantified extensive genetic overlap between COG and epilepsy types, but with varying negative genetic correlations (-0.23 to -0.04). COG was estimated to share 2.9k variants with both GGE and ‘all epilepsy’, and 2.3k variants with both JME and CAE. Using conjFDR, we identified 66 distinct loci shared between COG and epilepsies, including novel associations for GGE (27), ‘all epilepsy’ (5), JME (5) and CAE (5). The implicated genes were significantly expressed in multiple brain regions. The results were validated in independent samples (COG: p = 3.62 × 10–7; ‘all epilepsy’: p = 2.58 × 10–3). Conclusion Our study further dissects the substantial genetic basis shared between epilepsies and COG and identifies novel shared loci. An improved understanding of the genetic relationship between epilepsies and COG may lead to the development of novel comorbidity-targeted epilepsy treatments.

• Wold, Kristin Fjelnseth; Kreis, Isabel; Åsbø, Gina; Flaaten, Camilla Bärthel; Widing, Line Hustad & Engen, Magnus Johan [Show all 11 contributors for this article] (2024). Long-term clinical recovery and treatment resistance in first-episode psychosis: a 10-year follow-up study. Schizophrenia. 10(1). doi: 10.1038/s41537-024-00489-7. Full text in Research Archive Show summary

  Illness trajectories in people with first-episode psychosis (FEP) vary significantly over time. Identifying early-course parameters predicting outcomes is essential, but long-term data still needs to be provided. We conducted a 10-year follow-up study of a comprehensive first-episode psychosis (FEP) cohort investigating the prevalence of clinical recovery (CR) and treatment resistance (TR) after ten years, as well as clinical, demographic, and pre-illness predictors of long-term outcomes. 102 participants with FEP DSM-IV Schizophrenia spectrum disorders were recruited within their first year of treatment. The Treatment Response and Resistance in Psychosis Working Group (TRRIP) and the Remission in Schizophrenia Working Group (RSWG) criteria were used to define TR and CR, respectively. At 10-year follow-up, 29 (29%) of the participants were classified as in CR, while 32 (31%) were classified as TR. We also identified a larger middle group (n = 41, 40%) consisting of participants in partial recovery. 7% of all participants had tried Clozapine at the 10-year follow-up. Logistic regression analyses identified insidious onset (OR = 4.16) and baseline disorganized symptoms (OR = 2.96) as significantly associated with an increased risk of developing TR. Good premorbid academic adjustment (OR = 1.60) and acute onset (OR = 3.40) were associated with an increased chance of CR. We identified three long-term outcome groups by using recent consensus definitions. We also identified the potential importance of assessing baseline disorganized symptoms and monitoring patients with insidious onset more closely. Further, the findings suggest that clinicians should pay close attention to early-course parameters and provide adequate treatment to improve long-term outcomes of FEP.

• Mohn, Christine; Ueland, Torill; Haatveit, Beathe; Sæther, Linn Sofie; Lagerberg, Trine Vik & Andreassen, Ole A. [Show all 8 contributors for this article] (2024). Neurocognitive function and delusion severity in schizophrenia spectrum disorders. Schizophrenia Research. ISSN 0920-9964. 270, p. 172–177. doi: 10.1016/j.schres.2024.06.028. Full text in Research Archive
• Schjøtt-Pedersen, Olivia; Bull, Helen; Falkum, Erik; Ueland, Torill; Gjerdalen, Oda Skancke & Haaland, Vegard Øksendal [Show all 8 contributors for this article] (2024). Exploring the Benefits of Vocational Activity for People with Schizophrenia Spectrum Disorder in Norway. Journal of Psychosocial Rehabilitation and Mental Health. ISSN 2198-9834. doi: 10.1007/s40737-024-00389-0. Full text in Research Archive Show summary

  Vocational activity holds many benefits for people with severe mental illness. The purpose of the present study is to explore potential benefits of vocational activity on self-esteem and benefits as described by employment specialists. Data from 148 adults with schizophrenia spectrum disorders participating in a comprehensive vocational rehabilitation program was collected as part of the Job Management Program (JUMP) study. Assessments were conducted at inclusion, post intervention (10 months) and 2 years after inclusion. Multiple regressions and mixed between-within subjects analysis of variance were applied to assess potential effects of vocational activity on self-esteem as measured by the Rosenberg Self-Esteem Scale. One hundred and twentyone reports submitted by the employment specialists post intervention were assessed through a qualitative approach based on thematic analysis. Statistical analyses indicate that vocational activity might be beneficial for self-esteem. Qualitative analysis indicate that vocational activity may provide opportunities for experiencing capability, achievement, and positive social interaction, and be beneficial for well-being, self-confidence, and self-esteem. Vocational activity may be beneficial for well-being and self-esteem among people with schizophrenia spectrum disorders. Statistical analysis indicate that vocational activity may have a positive effect on self-esteem, and there was a non-significant trend indicating that competitive employment may be particularly favourable. However, more research is needed regarding potential differences in effect between types of vocational activity.

• Sæther, Linn Sofie; Ueland, Thor; Haatveit, Beathe; Vaskinn, Anja; Flaaten, Camilla Bärthel & Mohn, Hanne Christine [Show all 12 contributors for this article] (2024). Longitudinal course of inflammatory-cognitive subgroups across first treatment severe mental illness and healthy controls. Psychological Medicine. ISSN 0033-2917. 54, p. 3519–3529. doi: 10.1017/S003329172400206X. Full text in Research Archive Show summary

  Background - While inflammation is associated with cognitive impairment in severe mental illnesses (SMI), there is substantial heterogeneity and evidence of transdiagnostic subgroups across schizophrenia (SZ) and bipolar (BD) spectrum disorders. There is however, limited knowledge about the longitudinal course of this relationship.<p> <p>Methods - Systemic inflammation (C-Reactive Protein, CRP) and cognition (nine cognitive domains) was measured from baseline to 1 year follow-up in first treatment SZ and BD (n = 221), and healthy controls (HC, n = 220). Linear mixed models were used to evaluate longitudinal changes separately in CRP and cognitive domains specific to diagnostic status (SZ, BD, HC). Hierarchical clustering was applied on the entire sample to investigate the longitudinal course of transdiagnostic inflammatory-cognitive subgroups.<p> <p>Results - There were no case-control differences or change in CRP from baseline to follow-up. We confirm previous observations of case-control differences in cognition at both time-points and domain specific stability/improvement over time regardless of diagnostic status. We identified transdiagnostic inflammatory-cognitive subgroups at baseline with differing demographics and clinical severity. Despite improvement in cognition, symptoms and functioning, the higher inflammation – lower cognition subgroup (75% SZ; 48% BD; 38% HC) had sustained inflammation and lower cognition, more symptoms, and lower functioning (SMI only) at follow-up. This was in comparison to a lower inflammation – higher cognition subgroup (25% SZ, 52% BD, 62% HC), where SMI participants showed cognitive functioning at HC level with a positive clinical course.<p> <p>Conclusions - Our findings support heterogenous and transdiagnostic inflammatory-cognitive subgroups that are stable over time, and may benefit from targeted interventions.

• Wootton, Olivia; Shadrin, Alexey; Bjella, Thomas; Smeland, Olav Bjerkehagen; Meer, Dennis van der & Frei, Oleksandr [Show all 11 contributors for this article] (2024). Genomic insights into the shared and distinct genetic architecture of cognitive function and schizophrenia. Scientific Reports. 14(1). doi: 10.1038/s41598-024-66085-y. Full text in Research Archive Show summary

  Cognitive impairment is a major determinant of functional outcomes in schizophrenia, however, understanding of the biological mechanisms underpinning cognitive dysfunction in the disorder remains incomplete. Here, we apply Genomic Structural Equation Modelling to identify latent cognitive factors capturing genetic liabilities to 12 cognitive traits measured in the UK Biobank. We identified three broad factors that underly the genetic correlations between the cognitive tests. We explore the overlap between latent cognitive factors, schizophrenia, and schizophrenia symptom dimensions using a complementary set of statistical approaches, applied to data from the latest schizophrenia genome-wide association study (Ncase = 53,386, Ncontrol = 77,258) and the Thematically Organised Psychosis study (Ncase = 306, Ncontrol = 1060). Global genetic correlations showed a significant moderate negative genetic correlation between each cognitive factor and schizophrenia. Local genetic correlations implicated unique genomic regions underlying the overlap between schizophrenia and each cognitive factor. We found substantial polygenic overlap between each cognitive factor and schizophrenia and biological annotation of the shared loci implicated gene-sets related to neurodevelopment and neuronal function. Lastly, we show that the common genetic determinants of the latent cognitive factors are not predictive of schizophrenia symptoms in the Norwegian Thematically Organized Psychosis cohort. Overall, these findings inform our understanding of cognitive function in schizophrenia by demonstrating important differences in the shared genetic architecture of schizophrenia and cognitive abilities.

• Ihler, Henrik Myhre; Lyngstad, Siv Hege; Gardsjord, Erlend Strand; Widing, Line Hustad; Flaaten, Camilla Bärthel & Åsbø, Gina [Show all 13 contributors for this article] (2023). The trajectory of two negative symptom dimensions in first-episode psychosis and the role of cannabis use: A 10-year follow-up study. Schizophrenia Research. ISSN 0920-9964. 252, p. 317–325. doi: 10.1016/j.schres.2023.01.024. Full text in Research Archive Show summary

  Objective To investigate the trajectories of diminished expression and apathy over 10 years. Further, to explore the effects of baseline- and persistent cannabis use on the development of diminished expression and apathy during follow-up, while controlling other potential sources and predictors of secondary negative symptoms. Methods 351 participants with a first episode of non-affective psychosis were examined at baseline and invited to follow-up at one year and 10 years. The trajectories of diminished expression and apathy were investigated using linear mixed models. Subsequently, cannabis use and other potential predictors and sources of secondary negative symptoms were added to the model to investigate the respective impact on their trajectories. Results The severity of both diminished expression and apathy decreased during the follow-up period after the first episode of psychosis, with the most improvement observed from baseline to 1-year follow-up. Cannabis use at baseline was associated with a long-lasting higher symptom load for diminished expression, but not apathy. Introducing persistent cannabis use to the model further strengthened the association with diminished expression. Conclusion Both cannabis use at baseline and persistent cannabis use after a first episode of psychosis were associated with more severe symptoms of diminished expression. Our results imply a causal relationship between cannabis use and diminished expression and suggest that measures to reduce cannabis use both before and after psychosis onset may reduce expressive negative symptoms.

• Widing, Line Hustad; Simonsen, Carmen; Bjella, Thomas; Engen, Magnus Johan; Flaaten, Camilla Bärthel & Gardsjord, Erlend Strand [Show all 15 contributors for this article] (2023). Long-term Outcomes of People With DSM Psychotic Disorder NOS. Schizophrenia Bulletin Open. 4(1). doi: 10.1093/schizbullopen/sgad005. Full text in Research Archive Show summary

  Introduction: The Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnostic category “Psychotic disorder not otherwise specified” (PNOS) is seldom investigated, and we lack knowledge about longterm outcomes. We examined long-term symptom severity, global functioning, remission/recovery rates, and diagnostic stability after the first treatment for PNOS. Methods: Participants with first-treatment PNOS (n = 32) were reassessed with structured interviews after 7 to 10 years. The sample also included narrow schizophrenia spectrum disorders (SSD, n = 94) and psychotic bipolar disorders (PBD, n = 54). Symptomatic remission was defined based on the Remission in Schizophrenia Working Group criteria. Clinical recovery was defined as meeting the criteria for symptomatic remission and having adequate functioning for the last 12 months. Results: Participants with baseline PNOS or PBD had lower symptom severity and better global functioning at follow-up than those with SSD. More participants with PNOS and PBD were in symptomatic remission and clinical recovery compared to participants with SSD. Seventeen (53%) PNOS participants retained the diagnosis, while 15 participants were diagnosed with either SSD (22%), affective disorders (19%), or substanceinduced psychotic disorders (6%). Those rediagnosed with SSD did not differ from the other PNOS participants regarding baseline clinical characteristics. Conclusions: Long-term outcomes are more favorable in PNOS and PBD than in SSD. Our findings confirm diagnostic instability but also stability for a subgroup of participants with PNOS. However, it is challenging to predict diagnostic outcomes of PNOS based on clinical characteristics at first treatment.

• Barth, Claudia; Nerland, Stener; Jørgensen, Kjetil Nordbø; Haatveit, Beathe; Bakke, Laura Anne Wortinger & Melle, Ingrid [Show all 10 contributors for this article] (2023). Altered Sex Differences in Hippocampal Subfield Volumes in Schizophrenia. Schizophrenia Bulletin. ISSN 0586-7614. 50(1), p. 107–119. doi: 10.1093/schbul/sbad091. Full text in Research Archive Show summary

  Background and hypothesis: The hippocampus is a heterogenous brain structure that differs between the sexes and has been implicated in the pathophysiology of psychiatric illnesses. Here, we explored sex and diagnostic group differences in hippocampal subfield volumes, in individuals with schizophrenia spectrum disorder (SZ), bipolar disorders (BD), and healthy controls (CTL). Study design: One thousand and five hundred and twenty-one participants underwent T1-weighted magnetic resonance imaging (SZ, n = 452, mean age 30.7 ± 9.2 [SD] years, males 59.1%; BD, n = 316, 33.7 ± 11.4, 41.5%; CTL, n = 753, 34.1 ± 9.1, 55.6%). Total hippocampal, subfield, and intracranial volumes were estimated with Freesurfer (v6.0.0). Analysis of covariance and multiple regression models were fitted to examine sex-by-diagnostic (sub)group interactions in volume. In SZ and BD, separately, associations between volumes and clinical as well as cognitive measures were examined between the sexes using regression models. Study results: Significant sex-by-group interactions were found for the total hippocampus, dentate gyrus, molecular layer, presubiculum, fimbria, hippocampal-amygdaloid transition area, and CA4, indicating a larger volumetric deficit in male patients relative to female patients when compared with same-sex CTL. Subgroup analyses revealed that this interaction was driven by males with schizophrenia. Effect sizes were overall small (partial η < 0.02). We found no significant sex differences in the associations between hippocampal volumes and clinical or cognitive measures in SZ and BD. Conclusions: Using a well-powered sample, our findings indicate that the pattern of morphological sex differences in hippocampal subfields is altered in individuals with schizophrenia relative to CTL, due to higher volumetric deficits in males.

• Lunding, Synve Hoffart; Ueland, Torill; Aas, Monica; Høegh, Margrethe Collier; Werner, Maren Caroline Frogner & Rødevand, Linn [Show all 16 contributors for this article] (2023). Tobacco smoking related to childhood trauma mediated by cognitive control and impulsiveness in severe mental disorders. Schizophrenia Research. ISSN 0920-9964. 261, p. 236–244. doi: 10.1016/j.schres.2023.09.041. Full text in Research Archive Show summary

  Background People with severe mental disorders (SMDs) show an increased prevalence of tobacco smoking compared to the general population. Tobacco smoking and other adult adverse health behaviors have been associated with traumatic experiences in childhood. In the present study we investigated the relationship between childhood trauma and tobacco smoking in people with SMDs, including the possible mediating role of cognitive- and personality characteristics, i.e. cognitive control, impulsiveness, affective lability and self-esteem. Methods Enrolled in the study were 871 participants with schizophrenia (SCZ, N = 484) and bipolar (BD, N = 387) spectrum disorders. We assessed tobacco smoking behavior (yes/no and amount), and history of childhood trauma with the Childhood Trauma Questionnaire. Data on cognitive control, impulsiveness, affective lability, and self-esteem were available in subsamples. We performed linear and logistic regressions, and conducted mediation analyses in PROCESS. All analyses were as standard adjusted for age, sex, and diagnostic group. Results Experience of one or more subtypes of childhood trauma was significantly associated with smoking tobacco in SMDs (p = 0.002). There were no significant associations between childhood trauma and amount of tobacco smoking. Cognitive control and impulsiveness were significant mediators between childhood trauma and tobacco smoking. Conclusions These findings indicate the experience of childhood trauma as a predisposing factor for tobacco smoking in SMDs. Cognitive control and impulsiveness were suggested as mediating mechanisms, indicating the importance of considering inhibition related self-regulatory aspects in efforts to improve health behavior in individuals with SMDs and childhood trauma.

• Løchen, Aili Røtterud; Kolskår, Knut-Kristian; Lange, Ann-Marie Glasø de; Sneve, Markus Handal; Haatveit, Beathe & Lagerberg, Trine Vik [Show all 11 contributors for this article] (2023). Visual processing deficits in patients with schizophrenia spectrum and bipolar disorders and associations with psychotic symptoms, and intellectual abilities. Heliyon. 9(2). doi: 10.1016/j.heliyon.2023.e13354. Full text in Research Archive Show summary

  Abstract Objective Low-level sensory disruption is hypothesized as a precursor to clinical and cognitive symptoms in severe mental disorders. We compared visual discrimination performance in patients with schizophrenia spectrum disorder or bipolar disorder with healthy controls, and investigated associations with clinical symptoms and IQ. Methods Patients with schizophrenia spectrum disorder (n = 32), bipolar disorder (n = 55) and healthy controls (n = 152) completed a computerized visual discrimination task. Participants responded whether the latter of two consecutive grids had higher or lower spatial frequency, and discrimination thresholds were estimated using an adaptive maximum likelihood procedure. Case-control differences in threshold were assessed using linear regression, F-test and post-hoc pair-wise comparisons. Linear models were used to test for associations between visual discrimination threshold and psychotic symptoms derived from the PANSS and IQ assessed using the Matrix Reasoning and Vocabulary subtests from the Wechsler Abbreviated Scale of Intelligence (WASI). Results Robust regression revealed a significant main effect of diagnosis on discrimination threshold (robust F = 6.76, p = .001). Post-hoc comparisons revealed that patients with a schizophrenia spectrum disorder (mean = 14%, SD = 0.08) had higher thresholds compared to healthy controls (mean = 10.8%, SD = 0.07, β = 0.35, t = 3.4, p = .002), as did patients with bipolar disorder (12.23%, SD = 0.07, β = 0.21, t = 2.42, p = .04). There was no significant difference between bipolar disorder and schizophrenia (β = −0.14, t = −1.2, p = .45). Linear models revealed negative associations between IQ and threshold across all participants when controlling for diagnostic group (β = −0.3, t = −3.43, p = .0007). This association was found within healthy controls (t = −3.72, p = .0003) and patients with bipolar disorder (t = −2.53, p = .015), and no significant group by IQ interaction on threshold (F = 0.044, p = .97). There were no significant associations between PANSS domain scores and discrimination threshold. Conclusion Patients with schizophrenia spectrum or bipolar disorders exhibited higher visual discrimination thresholds than healthy controls, supporting early visual deficits among patients with severe mental illness. Discrimination threshold was negatively associated with IQ among healthy controls and bipolar disorder patients. These findings elucidate perception-related disease mechanisms in severe mental illness, which warrants replication in independent samples.

• Hindley, Guy Frederick Lanyon; Shadrin, Alexey; Meer, Dennis van der; Parker, Nadine; Cheng, Weiqiu & O'Connell, Kevin Sean [Show all 23 contributors for this article] (2023). Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy. Nature Human Behaviour. 7, p. 1584–1600. doi: 10.1038/s41562-023-01630-9. Full text in Research Archive
• Mlakar, Vid; Birkenæs, Viktoria; Elvsåshagen, Torbjørn; Ormerod, Monica Bettina E. Greenwood; Quintana, Daniel & Ueland, Torill [Show all 13 contributors for this article] (2023). Telomere length and verbal learning in bipolar disorders. Journal of Affective Disorders. ISSN 0165-0327. 339, p. 555–560. doi: 10.1016/j.jad.2023.07.087. Full text in Research Archive Show summary

  Introduction: Recent studies indicate accelerated ageing processes, shorter telomere length and poorer cognitive functioning in patients with bipolar disorder. The neurobiology underlying cognitive function in bipolar disorder is yet to be established. We anticipated that accelerated ageing as indicated by shortened telomere length, would be associated with reduced cognitive performance in bipolar disorder, particularly for ageing sensitive functions such as memory and learning. Methods: The study consisted of 647 participants (bipolar disorder [n =246] and healthy controls [n =401]). All participants underwent a standardized neuropsychological test battery, including working memory, executive functioning, processing speed, verbal learning, and verbal memory. Leucocyte telomere length was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio). The T/S ratio was used as an estimate of the mean telomere length of each participant. All analyses were adjusted for medication, Daily Defined Dose (DDD), chronological age, sex, and ethnicity. Results: Patients had shorter telomere lengths than healthy controls (Cohen’s d =0.11, p =0.01). Within patients’ , a positive association was observed for verbal learning and telomere length (β =0.14, p =0.025), along with a trend for verbal memory and telomere length (β =0.11, p =0.07). No other associations were observed for telomere length and cognitive functioning in the patient or the control group (p > 0.1). Conclusion: Our study may suggest poorer brain health in bipolar disorder as indexed by shorter telomere length and reduced learning correlates. However, the role of telomere length on cognitive functioning in bipolar disorder seems limited.

• Haatveit, Beathe; Westlye, Lars Tjelta; Vaskinn, Anja; Flaaten, Camilla Bärthel; Mohn, Hanne Christine & Bjella, Thomas [Show all 12 contributors for this article] (2023). Intra- and inter-individual cognitive variability in schizophrenia and bipolar spectrum disorder: an investigation across multiple cognitive domains. Schizophrenia. 9(1). doi: 10.1038/s41537-023-00414-4. Full text in Research Archive Show summary

  There is substantial cognitive heterogeneity among patients with schizophrenia (SZ) and bipolar disorders (BD). More knowledge about the magnitude and clinical correlates of performance variability could improve our understanding of cognitive impairments. Using double generalized linear models (DGLMs) we investigated cognitive mean and variability differences between patients with SZ (n = 905) and BD spectrum disorders (n = 522), and healthy controls (HC, n = 1170) on twenty-two variables. The analysis revealed significant case-control differences on 90% of the variables. Compared to HC, patients showed larger intra-individual (within subject) variability across tests and larger inter-individual (between subject) variability in measures of fine-motor speed, mental processing speed, and inhibitory control (SZ and BD), and in verbal learning and memory and intellectual functioning (SZ). In SZ, we found that lager intra -and inter (on inhibitory control and speed functions) individual variability, was associated with lower functioning and more negative symptoms. Inter-individual variability on single measures of memory and intellectual function was additionally associated with disorganized and positive symptoms, and use of antidepressants. In BD, there were no within-subject associations with symptom severity. However, greater inter-individual variability (primarily on inhibitory control and speeded functions) was associated with lower functioning, more negative -and disorganized symptoms, earlier age at onset, longer duration of illness, and increased medication use. These results highlight larger individual differences in patients compared to controls on various cognitive domains. Further investigations of the causes and correlates of individual differences in cognitive function are warranted.

• Wold, Kristin Fjelnseth; Ottesen, Akiah; Flaaten, Camilla Bärthel; Johnsen, Erik; Lagerberg, Trine Vik & Romm, Kristin Lie [Show all 11 contributors for this article] (2023). Early identification of treatment non-response in first-episode psychosis. European psychiatry. ISSN 0924-9338. 66(1). doi: 10.1192/j.eurpsy.2023.15. Full text in Research Archive Show summary

  Background Approximately one-third of patients with psychotic disorders does not respond to standard antipsychotic treatments. Consensus criteria for treatment resistance (TR) may aid the identification of non-response and subsequent tailoring of treatments. Since consensus criteria require stability of clinical status, they are challenging to apply in first-episode psychosis (FEP). This study aims to investigate (a) if an adaptation of consensus criteria can be used to identify FEP patients with early signs of TR (no early clinical recovery—no-ECR) after 1 year in treatment and (b) to what extent differences in antipsychotic treatments differentiate between outcome groups. Methods Participants with FEP DSM-IV schizophrenia spectrum disorders were recruited during their first treatment. A total of 207 participated in the 1-year follow-up. Remission and recovery definitions were based on adaptations of the “Remission in Schizophrenia Working Group” criteria and TR on adaptations of the “Treatment Response and Resistance in Psychosis” (TRRIP) working group criteria. Results 97 participants (47%) could be classified as no-ECR, 61 (30%) as ECR, and 49 (23%) as with partial ECR (P-ECR). Statistically significant baseline predictors of no-ECR matched previously identified predictors of long-term TR. Only 35 no-ECR participants had two adequate treatment trials and met the full TRRIP criteria. 21 no-ECR participants were using the same medication over the follow-up year despite the lack of significant effects. Conclusion The difference in the percentage of FEP participants classified as no-ECR versus TR indicates that we may underestimate the prevalence of early TR when using consensus criteria.

• Flaaten, Camilla Bärthel; Melle, Ingrid; Bjella, Thomas; Engen, Magnus Johan; Åsbø, Gina & Wold, Kristin Fjelnseth [Show all 13 contributors for this article] (2023). Long-term course of cognitive functioning in bipolar disorder: A ten-year follow-up study. Bipolar Disorders. ISSN 1398-5647. doi: 10.1111/bdi.13364. Full text in Research Archive Show summary

  Abstract Introduction Cognitive impairments are common in bipolar disorder (BD), but the long‐term course remains understudied. Longitudinal data on cognitive functioning from the start of the first treatment could help clarify pathophysiological processes that shape the illness outcome. We here aim to investigate the 10‐year cognitive course in BD compared to healthy controls (HC) and the effects of clinical symptoms on cognitive trajectories. Methods Fifty‐six BD participants recruited within their first year of treatment and 108 HC completed clinical and cognitive assessments at baseline and 10‐year follow‐up. We derived eight cognitive domain scores and a cognitive composite score, which were further investigated using linear mixed model analyses. Correlation analyses were used to assess associations between the composite score and depressive, manic and psychotic symptoms. Results BD participants performed poorer than HCs in all domains except mental speed and verbal fluency. Verbal learning and memory, verbal fluency and the composite score improved over time in both BD participants and HC, while short‐term memory, mental speed, psychomotor speed and working memory were stable. We found no significant correlations between cognition and symptom level at either time point in BD participants. Conclusions We found evidence of long‐term cognitive stability or improvement in BD participants from first treatment to 10‐year follow‐up. Though the BD group was impaired in all domains except mental speed and verbal fluency, the change in cognitive functioning was parallel to that of HCs. These findings are not consistent with the notion of neuroprogression in BD.

• Sahl, André C.; Rognlien, Henning F.; Andreassen, Ole; Melle, Ingrid; Ueland, Torill & Vaskinn, Anja (2022). Theory of mind in schizophrenia: a comparison of subgroups with low and high IQ. Nordic Journal of Psychiatry. ISSN 0803-9488. doi: 10.1080/08039488.2022.2106512. Full text in Research Archive Show summary

  Background: Social cognitive impairment is common in schizophrenia, but it is unclear if it is present in individuals with high IQ. This study compared theory of mind (ToM) in schizophrenia participants with low or high IQ to healthy controls. Methods: One hundred and nineteen participants (71 healthy controls, 17 high IQ (IQ ≥115), and 31 low IQ (IQ ≤95) schizophrenia participants) were assessed with the Movie for the Assessment of Social Cognition, providing scores for total, cognitive, and affective ToM, along with overmentalizing, undermentalizing, and no-mentalizing errors. IQ was measured with Wechsler Abbreviated Scale of Intelligence; clinical symptoms with the Positive and Negative Syndrome Scale. Results: Healthy controls performed better than the low IQ schizophrenia group for all ToM scores, and better than the high IQ schizophrenia group for the total score and under- and no-mentalizing errors. The high IQ group made fewer overmentalizing errors and had better total and cognitive ToM than the low IQ group. Their number of overmentalizing errors was indistinguishable from healthy controls. Conclusion: Global ToM impairment was present in the low IQ schizophrenia group. Overmentalizing was not present in the high IQ group and appears related to lower IQ. Intact higher-level reasoning may prevent the high IQ group from making overmentalizing errors, through self-monitoring or inhibition. We propose that high IQ patients are chiefly impaired in lower-level ToM, whereas low IQ patients also have impaired higher-level ToM. Conceivably, this specific impairment could help explain the lower functioning reported in persons with intact IQ.

• Sæther, Linn Sofie; Ueland, Thor; Haatveit, Beathe; Maglanoc, Luigi; Szabo, Attila & Djurovic, Srdjan [Show all 15 contributors for this article] (2022). Inflammation and cognition in severe mental illness: patterns of covariation and subgroups. Molecular Psychiatry. ISSN 1359-4184. 8, p. 1284–1292. doi: 10.1038/s41380-022-01924-w. Full text in Research Archive Show summary

  A potential relationship between dysregulation of immune/inflammatory pathways and cognitive impairment has been suggested in severe mental illnesses (SMI), such as schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, multivariate relationships between peripheral inflammatory/immune-related markers and cognitive domains are unclear, and many studies do not account for inter-individual variance in both cognitive functioning and inflammatory/immune status. This study aimed to investigate covariance patterns between inflammatory/immune-related markers and cognitive domains and further elucidate heterogeneity in a large SMI and healthy control (HC) cohort (SZ = 343, BD = 289, HC = 770). We applied canonical correlation analysis (CCA) to identify modes of maximum covariation between a comprehensive selection of cognitive domains and inflammatory/immune markers. We found that poor verbal learning and psychomotor processing speed was associated with higher levels of interleukin-18 system cytokines and beta defensin 2, reflecting enhanced activation of innate immunity, a pattern augmented in SMI compared to HC. Applying hierarchical clustering on covariance patterns identified by the CCA revealed a high cognition—low immune dysregulation subgroup with predominantly HC (24% SZ, 45% BD, 74% HC) and a low cognition—high immune dysregulation subgroup predominantly consisting of SMI patients (76% SZ, 55% BD, 26% HC). These subgroups differed in IQ, years of education, age, CRP, BMI (all groups), level of functioning, symptoms and defined daily dose (DDD) of antipsychotics (SMI cohort). Our findings suggest a link between cognitive impairment and innate immune dysregulation in a subset of individuals with severe mental illness.

• Burdick, Katherine E.; Millett, Caitlin E.; Yocum, Anastasia K.; Altimus, Cara M.; Andreassen, Ole & Aubin, Valerie [Show all 50 contributors for this article] (2022). Predictors of functional impairment in bipolar disorder: Results from 13 cohorts from seven countries by the global bipolar cohort collaborative. Bipolar Disorders. ISSN 1398-5647. p. 1–11. doi: 10.1111/bdi.13208. Full text in Research Archive Show summary

  Objectives Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD. Methods Thirteen cohorts from 7 countries included n = 5882 individuals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived “higher versus lower function” as the dependent variable and selected clinical and demographic variables as predictors. Results We found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning. Conclusions The bipolar clinical research community is poised to work together to characterize the multi-dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large-scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every individual with this illness.

• Flaaten, Camilla Bärthel; Melle, Ingrid; Gardsjord, Erlend Strand; Bjella, Thomas; Engen, Magnus Johan & Vaskinn, Anja [Show all 13 contributors for this article] (2022). Course of intellectual functioning in schizophrenia and bipolar disorder: A 10-year follow-up study. Psychological Medicine. ISSN 0033-2917. p. 1–9. doi: 10.1017/S0033291721004645. Full text in Research Archive Show summary

  Background Intellectual functioning (IQ) is lower in schizophrenia patients compared to healthy controls, with bipolar patients intermediate between the two. Declines in IQ mark the onset of schizophrenia, while stability is generally found post-onset. There are to date few studies on long-term IQ development in bipolar disorder. This study presents 10-year follow-up data on IQ, including premorbid IQ estimates, to track the developmental course from pre-onset levels to long-term outcomes in both patient groups compared to healthy controls. Methods We included 139 participants with schizophrenia, 76 with bipolar disorder and 125 healthy controls. Mixed model analyses were used to estimate developmental slopes for IQ scores from estimated premorbid level (NART IQ) through baseline (WASI IQ) measured within 12 months post-onset, to 10-year follow-up (WASI IQ), with pairwise group comparisons. The best fit was found using a model with a breakpoint at baseline assessment. Results Only the schizophrenia group had significant declines from estimated premorbid to baseline IQ levels compared to controls. When comparing patient groups, schizophrenia patients had steeper declines than the bipolar group. Increases in IQ were found in all groups over the follow-up period. Conclusions Trajectories of IQ from premorbid level to 10-year follow-up indicated declines from estimated premorbid level to illness onset in both patient groups, followed by increases during the follow-up period. Schizophrenia patients had a steeper decline than bipolar patients. During follow-up, increases indicate developmental improvement for both patient groups, but with a maintained lag compared to healthy controls due to lower premorbid levels.

• Andreou, Dimitrios; Jørgensen, Kjetil Nordbø; Nerland, Stener; Ueland, Torill; Vaskinn, Anja & Haukvik, Unn Kristin Hansen [Show all 9 contributors for this article] (2022). Herpes simplex virus 1 infection on grey matter and general intelligence in severe mental illness. Translational Psychiatry. 12(1). doi: 10.1038/s41398-022-02044-3. Full text in Research Archive Show summary

  Abstract Schizophrenia and bipolar disorder are severe mental illnesses (SMI) linked to both genetic and environmental factors. Herpes simplex virus 1 (HSV1) is a common neurotropic pathogen which after the primary infection establishes latency with periodic reactivations. We hypothesized that the latent HSV1 infection is associated with brain structural abnormalities and cognitive impairment, especially in SMI. We included 420 adult patients with SMI (schizophrenia or bipolar spectrum) and 481 healthy controls. Circulating HSV1 immunoglobulin G concentrations were measured with immunoassays. We measured the total grey matter volume (TGMV), cortical, subcortical, cerebellar and regional cortical volumes based on T1-weighted MRI scans processed in FreeSurfer v6.0.0. Intelligence quotient (IQ) was assessed with the Wechsler Abbreviated Scale of Intelligence. Seropositive patients had significantly smaller TGMV than seronegative patients (642 cm 3 and 654 cm 3 , respectively; p  = 0.019) and lower IQ (104 and 107, respectively; p  = 0.018). No TGMV or IQ differences were found between seropositive and seronegative healthy controls. Post-hoc analysis showed that (a) in both schizophrenia and bipolar spectrum, seropositive patients had similarly smaller TGMV than seronegative patients, whereas the HSV1-IQ association was driven by the schizophrenia spectrum group, and (b) among all patients, seropositivity was associated with smaller total cortical ( p  = 0.016), but not subcortical or cerebellar grey matter volumes, and with smaller left caudal middle frontal, precentral, lingual, middle temporal and banks of superior temporal sulcus regional cortical grey matter volumes. The results of this cross-sectional study indicate that HSV1 may be an environmental factor associated with brain structural abnormalities and cognitive impairment in SMI.

• Gjerdalen, Oda Skancke; Lystad, June Ullevoldsæter; Bull, Helen; Ringen, Petter Andreas; Røssberg, Jan Ivar & Martinsen, Egil Wilhelm [Show all 9 contributors for this article] (2022). Vocational rehabilitation augmented with cognitive behavioral therapy or cognitive remediation for individuals with schizophrenia: a 5-year follow-up study. Nordic Journal of Psychiatry. ISSN 0803-9488. 77(1), p. 23–30. doi: 10.1080/08039488.2022.2042598. Full text in Research Archive Show summary

  Introduction: Although employment is an important part of recovery for individuals with schizophrenia spectrum disorders, the employment rate for this group remains low. Increasing evidence supports the use of augmented vocational rehabilitation (VR) programs to improve occupational outcome. The aim of this study is to explore 5-year follow-up registry data from the JUMP study, a VR program for individuals with schizophrenia spectrum disorders, specifically with regard to competitive employment outcome and predictors of competitive employment. The VR was augmented with either cognitive remediation (CR) or elements from cognitive behavior therapy (CBT). Methods: One hundred and forty eight participants with schizophrenia spectrum disorders from six Norwegian counties received 10 months VR augmented with either CR (n ¼ 64) or CBT (n ¼ 84). Both competitive and sheltered workplaces were used. Assessments were conducted at baseline, at post intervention and at 2-year follow-up. Data on employment status at 5-year follow-up was obtained by registry. Results: At 5-year follow-up 55.4% were engaged in working activity, of which 22.3% had obtained competitive employment. A further 18.2% had work placements in competitive workplaces. Number of received intervention hours and competitive employment at 2-year follow-up emerged as significant predictors of competitive employment. IQ and intervention type in marginal favor of CBT were predictors on trend level. Conclusion: To the best of our knowledge, this is the first study investigating competitive employment at 5-year follow-up for individuals with schizophrenia spectrum disorders. The results add to existing evidence that competitive employment is attainable for this group.

• Haugen, Ingvild; Ueland, Torill; Stubberud, Jan Egil; Brunborg, Cathrine; Wykes, Til & Øie, Merete Glenne [Show all 7 contributors for this article] (2022). Moderators of metacognitive strategy training for executive functioning in early schizophrenia and psychosis risk. Schizophrenia Research: Cognition. 31. doi: 10.1016/j.scog.2022.100275. Full text in Research Archive Show summary

  Goal Management Training (GMT) improved self-reported executive functioning in a recent randomized, controlled trial in early intervention for psychosis participants. Little is known about the mechanism for this benefit, so this study investigates objectively measured executive function, the difference between subjective and objective executive function, independent living and employment status as potential moderators of efficacy of GMT. Baseline scores from 81 participants (GMT n = 39 vs Treatment-as-usual; TAU n = 42) were analyzed in a linear mixed model analysis for repeated measures as predictors of improvement on the self-reported Behavior Rating Inventory of Executive Function–Adult version (BRIEF-A) immediately and 30 weeks after GMT. Potential moderators were scores from objective measures of executive functioning, discrepancy between subjective and objective measures, independent living and employment status. Discrepancy was assessed by comparing four clusters of participants with differing patterns of scores. The effect of GMT remained significant regardless of initial objective executive functioning at baseline. Those with higher subjective complaints at baseline in two clusters with (i) both objective and subjective executive dysfunction, and (ii) mostly subjective executive dysfunction experienced greater change after treatment. Living arrangements or participation in education or work did not significantly moderate the effects of GMT. Poor performance on neuropsychological tasks is not an obstacle to making use of GMT, but further knowledge is needed about the benefits of strategy training for individuals with a combination of poor performance with few subjective complaints.

• Flaaten, Camilla Bärthel; Melle, Ingrid; Bjella, Thomas; Engen, Magnus Johan; Åsbø, Gina & Wold, Kristin Fjelnseth [Show all 14 contributors for this article] (2022). Domain-specific cognitive course in schizophrenia: Group- and individual-level changes over 10 years. Schizophrenia Research: Cognition. 30, p. 1–8. doi: 10.1016/j.scog.2022.100263. Full text in Research Archive Show summary

  Cognitive impairments in schizophrenia are well-documented, present across several cognitive domains and found to be relatively stable over time. However, there is a high degree of heterogeneity and indications of domain-specific developmental courses. The present study investigated the 10-year cognitive course in participants with first-episode schizophrenia (FES) and healthy controls on eight cognitive domains and a composite score, looking at group- and individual-level changes. A total of 75 FES participants and 91 healthy controls underwent cognitive assessment at baseline and follow-up. Linear mixed models were used for group-level analyses and reliable change index (RCI) analyses were used to investigate individual change. The prevalence of clinically significant impairment was explored at both time points, using a cut-off of < −1.5 SD, with significant cognitive impairment defined as impairment on ≥2 domains. Group-level analyses found main effects of group and time, and time by group interactions. Memory, psychomotor processing speed and verbal fluency improved, while learning, mental processing speed and working memory were stable in both groups. FES participants showed deteriorations in attention and cognitive control. Individual-level analyses mainly indicated stability in both FES and controls, except for a higher prevalence of decline in cognitive control in FES. At baseline, 68.8 % of FES participants had clinically significant impairment, compared to 62.3 % at follow-up. We mainly found long-term stability and modest increases in cognition over time in FES, as well as a high degree of within-group heterogeneity. We also found indications of deterioration in participants with worse cognitive performance at baseline.

• Ormerod, Monica Bettina E. Greenwood; Ueland, Thor; Werner, Maren Caroline Frogner; Hjell, Gabriela; Rødevand, Linn Nilsen & Sæther, Linn Sofie [Show all 14 contributors for this article] (2022). Composite immune marker scores associated with severe mental disorders and illness course. Brain, Behavior, and Immunity - Health (BBI - Health). 24. doi: 10.1016/j.bbih.2022.100483. Full text in Research Archive Show summary

  Background Low-grade inflammation has been implicated in the pathophysiology of severe mental disorders (SMDs) and a link between immune activation and clinical characteristics is suggested. However, few studies have investigated how patterns across immune markers are related to diagnosis and illness course. Methods A total of 948 participants with a diagnosis of schizophrenia (SCZ, N = 602) or bipolar (BD, N = 346) spectrum disorder, and 814 healthy controls (HC) were included. Twenty-five immune markers comprising cell adhesion molecules (CAMs), interleukin (IL)-18-system factors, defensins, chemokines and other markers, related to neuroinflammation, blood-brain barrier (BBB) function, inflammasome activation and immune cell orchestration were analyzed. Eight immune principal component (PC) scores were constructed by PC Analysis (PCA) and applied in general linear models with diagnosis and illness course characteristics. Results Three PC scores were significantly associated with a SCZ and/or BD diagnosis (HC reference), with largest, however small, effect sizes of scores based on CAMs, BBB markers and defensins (p < 0.001, partial η2 = 0.02–0.03). Number of psychotic episodes per year in SCZ was associated with a PC score based on IL-18 system markers and the potential neuroprotective cytokine A proliferation-inducing ligand (p = 0.006, partial η2 = 0.071). Conclusion Analyses of composite immune markers scores identified specific patterns suggesting CAMs-mediated BBB dysregulation pathways associated with SMDs and interrelated pro-inflammatory and neuronal integrity processes associated with severity of illness course. This suggests a complex pattern of immune pathways involved in SMDs and SCZ illness course.

• Aas, Monica; Ueland, Torill; Lagerberg, Trine Vik; Melle, Ingrid; Aminoff, Sofie Ragnhild & Høegh, Margrethe Collier [Show all 10 contributors for this article] (2022). Retrospectively assessed childhood trauma experiences are associated with illness severity in mental disorders adjusted for symptom state. Psychiatry Research. ISSN 0165-1781. 320. doi: 10.1016/j.psychres.2022.115045. Full text in Research Archive Show summary

  Converging evidence suggests that childhood trauma is a causal factor in schizophrenia (SZ) and in bipolar disorders (BD). Here, we investigated whether retrospective reports are associated with severity of illness, independent of current symptom state in a large sample of participants with SZ or BD. We included 1260 individuals (SZ [n = 461], BD [n = 352]), and healthy controls; HC [n = 447]) recruited from the same catchment area. A history of childhood trauma was obtained with the Childhood Trauma Questionnaire (CTQ). Diagnosis and episodes were obtained with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Clinical symptoms (state) were assessed with the Positive and Negative Syndrome scale (PANSS), the Calgary Depression Scale (CDSS). Trait related illness characteristics were assessed with age at illness onset, number of episodes, and lifetime suicide attempts. Patients who reported multiple types of childhood trauma experiences had significantly more severe illness course including an earlier illness onset, more mood episodes, and increased risk of at least one suicide attempt, also after adjusting for current symptom state. Retrospective assessed childhood trauma experiences are associated with illness severity in mental disorders adjusted for symptom state. Our results strengthen the role of childhood trauma in development of psychopathology.

• Widing, Line Hustad; Simonsen, Carmen Elisabeth; Flaaten, Camilla Bärthel; Haatveit, Beathe; Vik, Ruth Kristine & Wold, Kristin Fjelnseth [Show all 9 contributors for this article] (2022). Premorbid characteristics of patients with DSM-IV psychotic disorders. Comprehensive Psychiatry. ISSN 0010-440X. 115, p. 1–7. doi: 10.1016/j.comppsych.2022.152310. Full text in Research Archive Show summary

  Introduction Psychotic disorder not otherwise specified (PNOS) is considered part of the psychosis spectrum, together with schizophrenia spectrum disorders (SSD) and psychotic bipolar spectrum disorders (PBD). The atypical clinical presentations of PNOS conditions may lead to uncertainty regarding treatment choices and expected outcomes. PNOS is understudied, and little is known about patients' premorbid characteristics including premorbid adjustment, prevalence of early cannabis use and childhood trauma. Knowledge about early illness phases can increase our understanding of this diagnostic group. Methods We included 1099 participants from the Norwegian TOP-study; 688 with narrow SSD diagnoses (schizophrenia, schizoaffective disorder, schizophreniform disorder), 274 with PBD (psychotic bipolar 1 and bipolar NOS) and 137 with PNOS diagnosed with the SCID-I for DSM-IV. Participants were assessed with the Premorbid Adjustment Scale (PAS) divided into the areas of premorbid academic and social functioning. We obtained information on age at first exposure to cannabis and use of cannabis before the age of 16. The participants also provided information regarding early traumatic experiences using the Childhood Trauma Questionnaire (CTQ). Results Participants with PNOS and SSD had poorer premorbid academic functioning than those with PBD (F2, 1029 = 7.81, p < 0.001, pη2 = 0.015). Premorbid social adjustment was significantly worse in the SSD group compared to the PBD group (F2, 1024 = 3.10, p = 0.045, pη2 = 0.006), with PNOS in the middle position. Significantly more of the participants with PNOS (17.5%) and SSD (11.5%) used cannabis before the age of 16 compared with PBD (5.3%, Wald χ2 = 6.86, p = 0.03). There were no significant differences between the three groups regarding mean CTQ scores or in the proportion of participants who had experienced at least one type of childhood adversity. Conclusions Participants with PNOS appear as more similar to participants with SSD than to those with PBD regarding early premorbid adjustment and early cannabis use. The results indicate that many conditions classified as PNOS have functional impairments and problematic substance use from an early age. The prevalence of childhood adversities are high in all three groups.

• Bjella, Thomas; Høegh, Margrethe Collier; Olsen, Stine Holmstul; Aminoff, Sofie Ragnhild; Barrett, Elizabeth Ann & Ueland, Torill [Show all 14 contributors for this article] (2022). Developing "MinDag" - an app to capture symptom variation and illness mechanisms in bipolar disorder. Frontiers in Medical Technology. 4. doi: 10.3389/fmedt.2022.910533. Full text in Research Archive Show summary

  Introduction: The illness course of bipolar disorder (BD) is highly heterogeneous with substantial variation between individuals with the same BD subtype and within individuals over time. This heterogeneity is not well-delineated and hampers the development of more targeted treatment. Furthermore, although lifestyle-related behaviors are believed to play a role in the illness course, such mechanisms are poorly understood. To address some of these knowledge gaps, we aimed to develop an app for collection of multi-dimensional longitudinal data on BD-relevant symptoms and lifestyle-related behaviors. Methods: An app named MinDag was developed at the Norwegian Center for Mental Disorders Research in Oslo, Norway. The app was designed to tap into selected areas: mood, sleep, functioning/activities (social, occupational, physical exercise, leisure), substance use, emotional reactivity, and psychotic experiences. Ethical, security and usability issues were highly prioritized throughout the development and for the final app solution. We conducted beta- and pilot testing to eliminate technical problems and enhance usability and acceptability. Results: The final version of MinDag comprises six modules; three which are presented for the user once daily (the Sleep module in the morning and the Mood and Functoning/Activities modules in the evening) and three which are presented once weekly (Substance Use, Emotional Reactivity, and Psychotic Experiences modules). In general, MinDag was well received in both in the beta-testing and the pilot study, and the participants provided valuable feedback that was taken into account in the final development. MinDag is now in use as part of the research protocol at the NORMENT center and in a specialized treatment unit for BD at Oslo University Hospital in Norway. Discussion: We believe that MinDag will generate unique longitudinal data well suited for capturing the heterogeneity of BD and clarifying important unresolved issues such as how life-style related behavior may influence BD symptoms. Also, the experiences and knowledge derived from the development of MinDag may contribute to improving the security, acceptability, and benefit of digital tools in mental health.

• Mørch-Johnsen, Lynn Egeland; Smelror, Runar; Andreou, Dimitrios; Barth, Claudia; Johannessen, Cecilie Haggag & Wedervang-Resell, Kirsten [Show all 15 contributors for this article] (2022). Negative Symptom Domains Are Associated With Verbal Learning in Adolescents With Early Onset Psychosis. Frontiers in Psychiatry. 12. doi: 10.3389/fpsyt.2021.825681. Full text in Research Archive Show summary

  Background: Early-onset psychosis (EOP) is among the leading causes of disease burden in adolescents. Negative symptoms and cognitive deficits predicts poorer functional outcome. A better understanding of the association between negative symptoms and cognitive impairment may inform theories on underlying mechanisms and elucidate targets for development of new treatments. Two domains of negative symptoms have been described in adult patients with schizophrenia: apathy and diminished expression , however, the factorial structure of negative symptoms has not been investigated in EOP. We aimed to explore the factorial structure of negative symptoms and investigate associations between cognitive performance and negative symptom domains in adolescents with EOP. We hypothesized that (1) two negative symptom factors would be identifiable, and that (2) diminished expression would be more strongly associated with cognitive performance, similar to adult psychosis patients. Methods: Adolescent patients with non-affective EOP ( n = 169) were included from three cohorts: Youth-TOP, Norway ( n = 45), Early-Onset Study, Norway ( n = 27) and Adolescent Schizophrenia Study, Mexico ( n = 97). An exploratory factor analysis was performed to investigate the underlying structure of negative symptoms (measured with the Positive and Negative Syndrome Scale (PANSS)). Factor-models were further assessed using confirmatory factor analyses. Associations between negative symptom domains and six cognitive domains were assessed using multiple linear regression models controlling for age, sex and cohort. The neurocognitive domains from the MATRICS Consensus Cognitive Battery included: speed of processing, attention, working memory, verbal learning, visual learning, and reasoning and problem solving. Results: The exploratory factor analysis of PANSS negative symptoms suggested retaining only a single factor, but a forced two factor solution corroborated previously described factors of apathy and diminished expression in adult-onset schizophrenia. Results from confirmatory factor analysis indicated a better fit for the two-factor model than for the one-factor model. For both negative symptom domains, negative symptom scores were inversely associated with verbal learning scores. Conclusion: The results support the presence of two domains of negative symptoms in EOP; apathy and diminished expression. Future studies on negative symptoms in EOP should examine putative differential effects of these symptom domains. For both domains, negative symptom scores were significantly inversely associated with verbal learning.

• Åsbø, Gina; Ueland, Torill; Haatveit, Beathe; Bjella, Thomas; Flaaten, Camilla Bärthel & Wold, Kristin Fjelnseth [Show all 13 contributors for this article] (2022). The Time is Ripe for a Consensus Definition of Clinical Recovery in First-episode Psychosis: Suggestions Based on a 10-Year Follow-up Study. Schizophrenia Bulletin. ISSN 0586-7614. 48(4), p. 839–849. doi: 10.1093/schbul/sbac035. Full text in Research Archive Show summary

  Abstract Objectives A consensus definition of clinical recovery in first-episode psychosis (FEP) is required to improve knowledge about recovery rates in this population. To propose criteria for a future consensus definition, this study aims to investigate rates of clinical recovery when using a standard definition (full psychotic symptom remission and adequate functioning for minimum one year) across both affective and nonaffective FEP groups (bipolar spectrum and schizophrenia spectrum disorders). Second, we aim to explore changes in rates when altering the standard definition criteria. Third, to examine the extent to which healthy controls meet the functioning criteria. Study design In total, 142 FEP participants and 117 healthy controls preselected with strict criteria, were re-assessed with structured clinical interviews at 10-year follow-up. Study results A total of 31.7% were in clinical recovery according to the standard definition, with significantly higher recovery rates in bipolar (50.0%) than in schizophrenia spectrum disorders (22.9%). Both groups’ recovery rates decreased equally when extending duration and adding affective symptom remission criteria and increased with looser functioning criteria. In healthy controls, 18.8% did not meet the standard criteria for adequate functioning, decreasing to 4.3% with looser criteria. Conclusions Findings suggest that clinical recovery is common in FEP, although more in bipolar than in schizophrenia spectrum disorders, also when altering the recovery criteria. We call for a future consensus definition of clinical recovery for FEP, and suggest it should include affective symptom remission and more reasonable criteria for functioning that are more in line with the general population.

• Engen, Magnus Johan; Vaskinn, Anja; Melle, Ingrid; Færden, Ann; Lyngstad, Siv Hege & Flaaten, Camilla Bärthel [Show all 12 contributors for this article] (2022). Cognitive and Global Functioning in Patients With First-Episode Psychosis Stratified by Level of Negative Symptoms. A 10-Year Follow-Up Study. Frontiers in Psychiatry. 13:841057, p. 1–13. doi: 10.3389/fpsyt.2022.841057. Full text in Research Archive Show summary

  Negative and cognitive symptoms are core features of schizophrenia that are correlated in cross-sectional designs. To further explore the relationship between these critical symptom dimensions we use a method for stratifying participants based on level and persistence of negative symptoms from absent to sustained levels over a 10-year follow-up period. We investigate associations with cognitive performance and level of global functioning. First-episode psychosis (FEP) participants ( n = 102) and healthy controls ( n = 116) were assessed at baseline and follow-up. A cognitive battery consisting of 14 tests derived into four domains and a composite score were used in the analyses. FEP participants were stratified based on negative symptom items from the Positive and Negative Syndrome Scale (PANSS-R) into four groups with either no, mild, transitory or sustained symptoms over the 10-year follow-up period. Global functioning was measured with Global Assessment of Functioning Scale-Split version. Multivariate and univariate analyses of variance were used to explore between-group differences in level and course of cognitive performance as global functioning. A multivariate analysis with four cognitive domains as dependent variables, showed significant group differences in performance when including healthy controls and the negative symptom groups. The groups with no and mild negative symptoms outperformed the group with sustained levels of negative symptoms on verbal learning and memory. The group with no negative symptoms also outperformed the group with sustained negative symptoms on the cognitive composite score. Significant improvements on verbal learning and memory, executive functioning and the cognitive composite were detected for the entire sample. No differences in cognitive course were detected. There was a significant improvement in global functioning as measured by the GAF-F over the follow-up period ( p &amp;lt; 0.001), without any time x group interactions ( p = 0.25). Participants with sustained negative symptoms had a significantly lower level of global functioning at 10-year follow-up with an additional independent effect of the cognitive composite score, compared to all other groups. Individuals with an early illness course characterized by absence of negative symptoms form a group with better cognitive and functional outcomes than the impairments typically associated with schizophrenia. Individuals with sustained levels of negative symptoms on the other hand may require a combined focus on both negative and cognitive symptoms.

• Høegh, Margrethe Collier; Melle, Ingrid; Aminoff, Sofie Ragnhild; Olsen, Stine Holmstul; Lunding, Synve Hoffart & Ueland, Torill [Show all 7 contributors for this article] (2022). Affective lability and social functioning in severe mental disorders. European Archives of Psychiatry and Clinical Neuroscience. ISSN 0940-1334. 272, p. 873–885. doi: 10.1007/s00406-022-01380-1. Full text in Research Archive Show summary

  Abstract Social functioning is impaired in severe mental disorders despite clinical remission, illustrating the need to identify other mechanisms that hinder psychosocial recovery. Affective lability is elevated and associated with an increased clinical burden in psychosis spectrum disorders. We aimed to investigate putative associations between affective lability and social functioning in 293 participants with severe mental disorders (schizophrenia- and bipolar spectrum), and if such an association was independent of well-established predictors of social impairments. The Affective Lability Scale (ALS-SF) was used to measure affective lability covering the dimensions of anxiety-depression, depression-elation and anger. The interpersonal domain of the Social Functioning Scale (SFS) was used to measure social functioning. Correlation analyses were conducted to investigate associations between affective lability and social functioning, followed by a hierarchical multiple regression and follow-up analyses in diagnostic subgroups. Features related to premorbid and clinical characteristics were entered as independent variables together with the ALS-SF scores. We found that higher scores on all ALS-SF subdimensions were significantly associated with lower social functioning ( p  &lt; 0.005) in the total sample. For the anxiety-depression dimension of the ALS-SF, this association persisted after controlling for potential confounders such as premorbid social functioning, duration of untreated illness and current symptoms ( p  = 0.019). Our results indicate that elevated affective lability may have a negative impact on social functioning in severe mental disorders, which warrants further investigation. Clinically, it might be fruitful to target affective lability in severe mental disorders to improve psychosocial outcomes.

• Haugen, Ingvild; Stubberud, Jan Egil; Haug, Elisabeth; McGurk, Susan R.; Hovik, Kjell Tore & Ueland, Torill [Show all 7 contributors for this article] (2022). A randomized controlled trial of Goal Management Training for executive functioning in schizophrenia spectrum disorders or psychosis risk syndromes. BMC Psychiatry. 22(1). doi: 10.1186/s12888-022-04197-3. Full text in Research Archive Show summary

  Background Executive functioning is essential to daily life and severely impaired in schizophrenia and psychosis risk syndromes. Goal Management Training (GMT) is a theoretically founded, empirically supported, metacognitive strategy training program designed to improve executive functioning. Methods A randomized controlled parallel group trial compared GMT with treatment as usual among 81 participants (GMT, n = 39 versus Wait List Controls, n = 42) recruited from an early intervention for psychosis setting. Computer generated random allocation was performed by someone independent from the study team and raters post-intervention were unaware of allocation. The primary objective was to assess the impact of GMT administered in small groups for 5 weeks on executive functioning. The secondary objective was to explore the potential of the intervention in influencing daily life functioning and clinical symptoms. Results GMT improved self-reported executive functioning, measured with the Behavior Rating Inventory of Executive Function – Adult version (BRIEF-A), significantly more than treatment as usual. A linear mixed model for repeated measures, including all partial data according to the principle of intention to treat, showed a significant group x time interaction effect assessed immediately after intervention (post-test) and 6 months after intervention (follow-up), F = 8.40, p .005, r .37. Improvement occurred in both groups in objective executive functioning as measured by neuropsychological tests, functional capacity, daily life functioning and symptoms of psychosis rated by clinicians. Self-reported clinical symptoms measured with the Symptoms Check List (SCL-10) improved significantly more after GMT than after treatment as usual, F = 5.78, p .019, r .29. Two participants withdrew due to strenuous testing and one due to adverse effects. Conclusions GMT had clinically reliable and lasting effects on subjective executive function. The intervention is a valuable addition to available treatment with considerable gains at low cost. Trial registration Registered at clinicaltrials.gov NCT03048695 09/02/2017.

• Haugen, Ingvild; Stubberud, Jan; Ueland, Torill; Haug, Elisabeth & Øie, Merete Glenne (2021). Executive dysfunction in schizophrenia: Predictors of the discrepancy between subjective and objective measures. Schizophrenia Research: Cognition. 26. doi: 10.1016/j.scog.2021.100201. Full text in Research Archive Show summary

  This study aimed to investigate what characterizes individuals with schizophrenia who experience more or less subjective executive dysfunction in everyday life compared to objective executive performance on neuropsychological tests. Sixty-six participants with broad schizophrenia spectrum disorders completed a comprehensive assessment of executive function. Discrepancies between performance on neuropsychological tests (objective) and an extensive self-report questionnaire (subjective) of central executive functions (inhibition, shifting and working memory) were calculated. Higher level of self-efficacy was the best predictor of experiencing fewer subjective cognitive complaints compared to objective performance, followed by higher levels of disorganized symptoms. Depressive symptoms did not predict discrepancy between subjective and objective executive function. Higher estimated IQ predicted greater subjective working memory difficulties in everyday life despite better objective performance. Results may aid clinicians in the assessment and remediation of cognitive impairment. Low self-efficacy may identify individuals who are not able to utilize their potential executive functions in daily life. Interventions aimed at fostering self-efficacy ought to be included in cognitive remediation for these individuals. Disorganized symptoms could prove useful in identifying individuals who are in need of cognitive remediation for executive dysfunction, despite that they overestimate their skills. These individuals may benefit from efforts to increase insight into cognitive dysfunction. Keywords: Cognition; Cognitive impairment; Executive function; Psychosis; Schizophrenia; Self-efficacy; Subjective assessment. © 2021 The Authors.

• Bahrami, Shahram; Shadrin, Alexey A.; Frei, Oleksandr; O`Connell, Kevin; Bettella, Francesco & Krull, Florian [Show all 15 contributors for this article] (2021). Genetic loci shared between major depression and intelligence with mixed directions of effect. Nature Human Behaviour. p. 1–9. doi: 10.1038/s41562-020-01031-2. Full text in Research Archive
• Aas, Monica; Ueland, Torill; Mørch, Ragni Helene; Laskemoen, Jannicke Fjæra; Lunding, Synve Hoffart & Reponen, Elina Johanna [Show all 11 contributors for this article] (2021). Physical activity and childhood trauma experiences in patients with schizophrenia or bipolar disorders. World Journal of Biological Psychiatry. ISSN 1562-2975. 22(8), p. 637–645. doi: 10.1080/15622975.2021.1907707. Full text in Research Archive Show summary

  Background Physical activity promotes resilience and reduces stress. Here we aimed to clarify the impact of physical activity and childhood trauma experiences on current mood and cognitive function in patients with schizophrenia (SZ) or bipolar disorders (BD). Methods Three-hundred-and-six patients with DSM-IV schizophrenia (SZ) or bipolar disorder (BD) were included in the study. Diagnoses were assessed using the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Physical activity was measured as hours spent on any regular physical activity per week. All patients underwent a neuropsychological test battery. History of Childhood trauma was assessed using the Childhood Trauma Questionnaire and mood symptoms were assessed with the Inventory of Depressive Symptoms. Results Patients with childhood trauma who were physically inactive (˂90 min per week) had the most severe clinical profile, characterised by the highest depressive symptoms (p ˂ 0.001) and lowest performance on working memory tasks (p ˂ 0.001). Among patients with childhood trauma, those who were physically active (≥90 min per week) had better working memory performance than physically inactive patients (p = 0.02). Discussion A history of childhood trauma was associated with poorer working memory and more depressive symptoms only in patients who were physically inactive, suggesting a possible protective factor of physical activity in severe mental disorder.

• Valstad, Mathias; Roelfs, Daniel; Slapø, Nora Berz; Timpe, Clara Marie Fides; Rai, Ahsan & Matziorinis, Anna Maria [Show all 24 contributors for this article] (2021). Evidence for Reduced Long-Term Potentiation-Like Visual Cortical Plasticity in Schizophrenia and Bipolar Disorder. Schizophrenia Bulletin. ISSN 0586-7614. 47(6), p. 1751–1760. doi: 10.1093/schbul/sbab049. Full text in Research Archive Show summary

  Several lines of research suggest that impairments in long-term potentiation (LTP)-like synaptic plasticity might be a key pathophysiological mechanism in schizophrenia (SZ) and bipolar disorder type I (BDI) and II (BDII). Using modulations of visually evoked potentials (VEP) of the electroencephalogram, impaired LTP-like visual cortical plasticity has been implicated in patients with BDII, while there has been conflicting evidence in SZ, a lack of research in BDI, and mixed results regarding associations with symptom severity, mood states, and medication. We measured the VEP of patients with SZ spectrum disorders (n = 31), BDI (n = 34), BDII (n = 33), and other BD spectrum disorders (n = 2), and age-matched healthy control (HC) participants (n = 200) before and after prolonged visual stimulation. Compared to HCs, modulation of VEP component N1b, but not C1 or P1, was impaired both in patients within the SZ spectrum (χ 2 = 35.1, P = 3.1 × 10−9) and BD spectrum (χ 2 = 7.0, P = 8.2 × 10−3), including BDI (χ 2 = 6.4, P = .012), but not BDII (χ 2 = 2.2, P = .14). N1b modulation was also more severely impaired in SZ spectrum than BD spectrum patients (χ 2 = 14.2, P = 1.7 × 10−4). N1b modulation was not significantly associated with Positive and Negative Syndrome Scale (PANSS) negative or positive symptoms scores, number of psychotic episodes, Montgomery and Åsberg Depression Rating Scale (MADRS) scores, or Young Mania Rating Scale (YMRS) scores after multiple comparison correction, although a nominal association was observed between N1b modulation and PANSS negative symptoms scores among SZ spectrum patients. These results suggest that LTP-like plasticity is impaired in SZ and BD. Adding to previous genetic, pharmacological, and electrophysiological evidence, these results implicate aberrant synaptic plasticity as a mechanism underlying SZ and BD.

• Andreou, Dimitrios; Jørgensen, Kjetil Nordbø; Bakke, Laura A Wortinger; Engen, Kristine; Vaskinn, Anja & Ueland, Torill [Show all 9 contributors for this article] (2021). Cytomegalovirus infection and IQ in patients with severe mental illness and healthy individuals. Psychiatry Research. ISSN 0165-1781. doi: 10.1016/j.psychres.2021.113929. Full text in Research Archive Show summary

  Cytomegalovirus (CMV) infection in immunocompetent adults is usually asymptomatic, but results in lifelong latency. Infection occurring congenitally or in immunodeficiency can lead to cognitive impairment. We aimed to investigate the associations between CMV exposure and intelligence quotient (IQ) in patients with schizophrenia spectrum disorders (SZS), bipolar spectrum disorders (BDS) and healthy controls (HC). CMV immunoglobulin G antibody concentrations were measured by immunoassay and expressed as dichotomous measures (seropositive/CMV+ vs. seronegative/CMV-). Based on a significant CMV-by-diagnosis-by-sex interaction on IQ, we investigated main and interaction effects of CMV and sex on IQ in each diagnostic category. Significant CMV-by-sex interactions were found in patient groups. In SZS, CMV+ female patients (n = 50) had significantly lower IQ than CMV- female patients (n = 33), whereas CMV+ (n = 48) and CMV- (n = 45) male patients did not differ in IQ. In BDS, CMV+ (n = 49) and CMV- (n = 37) female patients did not differ in IQ, whereas CMV+ male patients (n = 33) had significantly higher IQ than CMV- male patients (n = 32). Among HC, CMV+ (n = 138) and CMV- (n = 118) male participants as well as CMV+ (n = 125) and CMV- (n = 93) female participants did not differ in IQ. Our findings suggest that CMV exposure may affect IQ in patients with severe mental illness but not HC.

• Lunding, Synve Hoffart; Simonsen, Carmen Elisabeth; Aas, Monica; Rødevand, Linn; Werner, Maren Caroline Frogner & Laskemoen, Jannicke Fjæra [Show all 13 contributors for this article] (2021). Childhood trauma and cardiometabolic risk in severe mental disorders: The mediating role of cognitive control. European psychiatry. ISSN 0924-9338. 64(1). doi: 10.1192/j.eurpsy.2021.14. Full text in Research Archive Show summary

  Background Cardiometabolic risk is increased in severe mental disorders (SMDs), and there appears to be a relationship between childhood trauma and cardiometabolic risk, possibly related to adverse health behavior. The current study examined the association between childhood trauma and serum lipids and adiposity in SMDs and the potential mediating role of cognitive and personality characteristics. Methods Participants with schizophrenia and bipolar spectrum disorders (N = 819) were included, cardiometabolic risk factors (serum lipids, body mass index, and waist circumference) were measured, and history of childhood trauma was assessed by the Childhood Trauma Questionnaire. Cognitive and personality characteristics were available in subsamples, with assessments of cognitive control, impulsiveness, self-esteem, and affective lability. Linear regressions and mediation analyses with Hayes’ PROCESS were performed, adjusting for age, sex, antipsychotic agent propensity of metabolic side-effect, and diagnostic group. Results Experience of three or more subtypes of childhood trauma was positively associated with waist circumference in patients with SMDs (p = 0.014). There were no other significant associations between trauma variables and lipid or adiposity measures in the total sample. Cognitive control was a significant mediator between experience of one or two subtypes of childhood trauma and waist circumference. Conclusions The results indicate childhood trauma as a predisposing factor for increased waist circumference in individuals with SMDs. Poorer cognitive control, suggestive of adverse health behavior, might be a mediating factor of the association, and the findings indicate the potential importance of increased focus on these factors in prevention and treatment regimens targeting cardiometabolic health.

• Høegh, Margrethe Collier; Melle, Ingrid; Aminoff, Sofie Ragnhild; Haatveit, Beathe; Olsen, Stine Holmstul & Huflåtten, Idun Bernadotte [Show all 8 contributors for this article] (2021). Characterization of affective lability across subgroups of psychosis spectrum disorders. International journal of bipolar disorders. 9.34, p. 1–10. doi: 10.1186/s40345-021-00238-0. Full text in Research Archive Show summary

  Background Affective lability is elevated and associated with increased clinical burden in psychosis spectrum disorders. The extent to which the level, structure and dispersion of affective lability varies between the specific disorders included in the psychosis spectrum is however unclear. To have potential value as a treatment target, further characterization of affective lability in these populations is necessary. The main aim of our study was to investigate differences in the architecture of affective lability in different psychosis spectrum disorders, and if putative differences remained when we controlled for current symptom status. Methods Affective lability was measured with The Affective Lability Scale Short Form (ALS-SF) in participants with schizophrenia (SZ, n = 76), bipolar I disorder (BD-I, n = 105), bipolar II disorder (BD-II, n = 68) and a mixed psychosis-affective group (MP, n = 48). Multiple analyses of covariance were conducted to compare the ALS-SF total and subdimension scores of the diagnostic groups, correcting for current psychotic, affective and anxiety symptoms, substance use and sex. Double generalized linear models were performed to compare the dispersion of affective lability in the different groups. Results Overall group differences in affective lability remained significant after adjusting for covariates (p = .001). BD-II had higher affective lability compared to SZ and BD-I (p = .004), with no significant differences between SZ and BD-I. There were no significant differences in the contributions of ALS-SF dimensions to the total affective lability or in dispersion of affective lability between the groups. Conclusions This study provides the construct of affective lability in psychosis spectrum disorders with more granular details that may have implications for research and clinical care. It demonstrates that despite overlap in core symptom profiles, BD-I is more similar to SZ than it is to BD-II concerning affective lability and the BD groups should consequently be studied apart. Further, affective lability appears to be characterized by fluctuations between depressive- and other affective states across different psychosis spectrum disorders, indicating that affective lability may be related to internalizing problems in these disorders. Finally, although the level varies between groups, affective lability is evenly spread and not driven by extremes across psychosis spectrum disorders and should be assessed irrespective of diagnosis.

• Smelror, Runar; Johannessen, Cecilie Haggag; Wedervang-Resell, Kirsten; Jørgensen, Kjetil Nordbø; Barth, Claudia & Andreou, Dimitrios [Show all 11 contributors for this article] (2021). Cognitive Impairment Profile in Adolescent Early-Onset Psychosis Usingthe MATRICS Battery: Age and Sex Effects. Neuropsychology. ISSN 0894-4105. 35(3), p. 300–309. doi: 10.1037/neu0000723. Full text in Research Archive
• Klungsøyr, Ole; Lystad, June Ullevoldsæter; Bull, Helen; Evensen, Stig; Ueland, Torill & Falkum, Erik (2021). G-estimation of causal pathways in vocational rehabilitation for adults with psychotic disorders – a secondary analysis of a randomized trial. BMC Psychiatry. 21(1), p. 1–13. doi: 10.1186/s12888-021-03349-1. Full text in Research Archive Show summary

  Background: Vocational rehabilitation (VR) has increasingly become an important intervention targeting poor occupational functioning in schizophrenia. The Norwegian Job Management Program (JUMP), sought to enhance occupational outcomes by augmenting VR with either cognitive behavioral therapy (CBT) techniques aiming to improve psychotic symptoms or cognitive remediation (CR) aiming to improve cognition. CBT is standard treatment in schizophrenia, but recent meta-analyses question the effect of CBT on negative psychotic symptoms. It is of interest to study the causal role of psychotic symptoms and cognitive functioning on occupational functioning. Methods: Data from the JUMP VR – program, was reanalyzed with a causal inference method to assess the causal effects of reduced symptoms / improved neurocognitive functioning on occupational functioning measured by number of working hours per week. Participants (N = 131) had been randomized to either VR + CBT (N = 68) or VR + CR (N = 63). Large improvements in number of working hours were demonstrated in both intervention groups (nonsignificant group difference). G-estimation was used to assess the strength and nature of the causal effects, adjusted for time-varying confounding and selection – bias from loss to follow-up. Results: Significant causal effects of reduction in each of four dimensions of symptoms and improved neurocognition respectively, on number of working hours were found (separate models). The effect of negative symptoms was the strongest and increased in magnitude during the whole observation period, while the effect of two other symptoms and neurocognition was constant. Adjusted for confounding (including potential feedback), the causal effect of a hypothetical change in negative symptoms equal to the average improvement in the CBT group corresponded to an increase in working hours of 3.2 h per week (95% CI: 1.11, 5.35). Conclusion: High performance of g-estimation in a small psychiatric data set with few repeated measures and time-varying confounding and effects, was demonstrated. Augmented vocational rehabilitation showed causal effects of intervention targets with the strongest and increasing effect from negative symptoms on number of working hours. Combination of therapy and activation (indirect and direct approach) might explain improvement in both cognition and negative symptoms, and shed some light on effective ingredients for improved treatment of negative symptoms.

• Wortinger, Laura Anne; Jørgensen, Kjetil Nordbø; Barth, Claudia; Nerland, Stener; Smelror, Runar Elle & Vaskinn, Anja [Show all 9 contributors for this article] (2021). Significant association between intracranial volume and verbal intellectual abilities in patients with schizophrenia and a history of birth asphyxia. Psychological Medicine. ISSN 0033-2917. p. 1–10. doi: 10.1017/S0033291721000489. Full text in Research Archive Show summary

  Background The etiology of schizophrenia (SZ) is proposed to include an interplay between a genetic risk for disease development and the biological environment of pregnancy and birth, where early adversities may contribute to the poorer developmental outcome. We investigated whether a history of birth asphyxia (ASP) moderates the relationship between intracranial volume (ICV) and intelligence in SZ, bipolar disorder (BD) and healthy controls (HC). Methods Two hundred seventy-nine adult patients (18–42 years) on the SZ and BD spectrums and 216 HC were evaluated for ASP based on information from the Medical Birth Registry of Norway. Participants underwent structural magnetic resonance imaging (MRI) to estimate ICV and intelligence quotient (IQ) assessment using the Wechsler Abbreviated Scale of Intelligence (WASI). Multiple linear regressions were used for analyses. Results We found a significant three-way interaction (ICV × ASP × diagnosis) on the outcome variable, IQ, indicating that the correlation between ICV and IQ was stronger in patients with SZ who experienced ASP compared to SZ patients without ASP. This moderation by ASP was not found in BD or HC groups. In patients with SZ, the interaction between ICV and a history of the ASP was specifically related to the verbal subcomponent of IQ as measured by WASI. Conclusions The significant positive association between ICV and IQ in patients with SZ who had experienced ASP might indicate abnormal neurodevelopment. Our findings give support for ICV together with verbal intellectual abilities as clinically relevant markers that can be added to prediction tools to enhance evaluations of SZ risk.

• Engen, Magnus Johan; Lyngstad, Siv Hege; Ueland, Torill; Simonsen, Carmen Elisabeth; Vaskinn, Anja & Smeland, Olav Bjerkehagen [Show all 11 contributors for this article] (2020). Polygenic scores for schizophrenia and general cognitive ability: associations with six cognitive domains, premorbid intelligence, and cognitive composite score in individuals with a psychotic disorder and in healthy controls. Translational Psychiatry. 10:416(416), p. 1–9. doi: 10.1038/s41398-020-01094-9. Full text in Research Archive Show summary

  Cognitive impairments are considered core features in schizophrenia and other psychotic disorders. Cognitive impairments are, to a lesser degree, also documented in healthy first-degree relatives. Although recent studies have shown (negative) genetic correlations between schizophrenia and general cognitive ability, the association between polygenic risk for schizophrenia and individual cognitive phenotypes remains unclear. We here investigated the association between a polygenic score for schizophrenia (SCZPGS) and six well-defined cognitive domains, in addition to a composite measure of cognitive ability and a measure of premorbid intellectual ability in 731 participants with a psychotic disorder and 851 healthy controls. We also investigated the association between a PGS for general cognitive ability (COGPGS) and the same cognitive domains in the same sample. We found no significant associations between the SCZPGS and any cognitive phenotypes, in either patients with a psychotic disorder or healthy controls. For COGPGS we observed stronger associations with cognitive phenotypes in healthy controls than in participants with psychotic disorders. In healthy controls, the association between COGPGS (at the p value threshold of ≥0.01) and working memory remained significant after Bonferroni correction (β = 0.12, p = 8.6 × 10−5). Altogether, the lack of associations between SCZPGS and COGPGS with cognitive performance in participants with psychotic disorders suggests that either environmental factors or unassessed genetic factors play a role in the development of cognitive impairments in psychotic disorders. Working memory should be further studied as an important cognitive phenotype.

• Smelror, Runar; Rund, Bjørn Rishovd; Lonning, Vera Louise Hiorth; Jørgensen, Kjetil Nordbø; Wedervang-Resell, Kirsten & Andreassen, Ole Andreas [Show all 9 contributors for this article] (2020). Negative and disorganized symptoms mediate the relationship between verbal learning and global functioning in adolescents with early-onset psychosis. European Child and Adolescent Psychiatry. ISSN 1018-8827. doi: 10.1007/s00787-020-01479-7. Full text in Research Archive Show summary

  Neurocognitive deficits are associated with impaired global functioning and psychotic symptoms. However, whether symptoms can mediate the relationship between neurocognition and global functioning in adolescent psychosis is unclear. Here, we investigated if symptoms assessed with the Positive And Negative Syndrome Scale (PANSS), mediated the relationship between neurocognitive performance and global functioning in adolescents with non-affective early-onset psychotic disorders (EOP). Sixty-one adolescent EOP patients (age 12–18 years) from 2 Norwegian clinical cohorts were included. Linear regression models were applied to investigate associations between neurocognitive domains from the MATRICS Consensus Cognitive Battery (MCCB) and global functioning. PANSS symptoms were analyzed using the Wallwork/Fortgang five-factor model. Using the INDIRECT macro for SPSS, mediation effects were tested using bootstrapping with 95% bias corrected confidence intervals. Verbal learning was positively associated with global functioning (P < 0.001) and negatively associated with the disorganized symptom factor (P = 0.002), controlling for age, sex and cohort. Testing of indirect effects, controlling for age, sex and cohort, showed that the Negative (point estimate = 1.56, 95% CI 0.22, 3.47) and Disorganized (point estimate = 1.24, 95% CI 0.05, 3.69) symptom factors significantly mediated the relationship between verbal learning and global functioning. We found that verbal learning, negative and disorganized symptoms influenced global functioning in adolescents with EOP, while reality-distorted positive symptoms did not. These results suggest that assessing these domains in EOP is helpful for planning treatment and rehabilitation programs focusing on functional outcome.

• Hjelseng, Ingrid Varvin; Vaskinn, Anja; Ueland, Torill; Lunding, Synve Hoffart; Reponen, Elina Johanna & Steen, Nils Eiel [Show all 8 contributors for this article] (2020). Childhood Trauma Is Associated With Poorer Social Functioning in Severe Mental Disorders Both During an Active Illness Phase and in Remission. Schizophrenia Research. ISSN 0920-9964. doi: 10.1016/j.schres.2020.03.015. Full text in Research Archive
• Vaskinn, Anja; Haatveit, Beathe; Melle, Ingrid; Andreassen, Ole Andreas; Ueland, Torill & Sundet, Kjetil Søren (2020). Cognitive Heterogeneity Across Schizophrenia and Bipolar Disorder: A Cluster Analysis of Intellectual Trajectories. Journal of the International Neuropsychological Society. ISSN 1355-6177. 26(9), p. 860–872. doi: 10.1017/S1355617720000442. Full text in Research Archive
• Widing, Line Hustad; Simonsen, Carmen Elisabeth; Flaaten, Camilla Bärthel; Haatveit, Beathe; Vik, Ruth Kristine & Wold, Kristin Fjelnseth [Show all 9 contributors for this article] (2020). Symptom Profiles in Psychotic Disorder Not Otherwise Specified. Frontiers in Psychiatry. 11. doi: 10.3389/fpsyt.2020.580444. Full text in Research Archive Show summary

  Introduction: Approximately 10% of patients with psychotic disorders receive the diagnosis “Psychotic disorder not otherwise specified” (PNOS). However, there is a lack of knowledge about the clinical presentations captured by this diagnosis in the mental health services. Therefore, we examined the symptom profiles of participants with PNOS compared to participants with bipolar disorder (BD) and schizophrenia spectrum disorder (SZ) diagnoses. Methods: We here included 1,221 participants from the Thematically Organized Psychosis-study at Oslo University Hospital; 792 with SZ, 283 with BD, and 146 with PNOS, assessed with SCID-I for DSM-IV. The participants with PNOS were categorized into subgroups based on SCID information. The GAF, PANSS, Alcohol Use Disorders Identification Test (AUDIT), and Drug Use Disorders Identification Test (DUDIT) were used to assess function, clinical symptoms, and substance use. Results: In the PNOS group, 44% did not meet the criteria for any specific psychotic disorder, 35.5% had contradictory information making a specific diagnosis difficult, and 20.5% had inadequate information to make a specific diagnosis. The most frequent reason for a PNOS diagnosis was difficulty ruling out a substance-induced psychotic disorder (n = 41, 28%). Participants with PNOS were younger and more often first-episode than participants with BD and SZ. They were intermediate between BD and SZ for GAF scores (BD>PNOS>SZ) and PANSS scores (BD<PNOS<SZ) and more often scored above the clinical cut-off for substance misuse as measured by the AUDIT (BD = PNOS<SZ), DUDIT (BD = SZ<PNOS) and for the combination of both these measures. Conclusions: A PNOS diagnosis is more common in first-episode than in multi-episode patients. The diagnosis captures a heterogeneous group of psychotic syndromes, with a severity of symptoms and functional loss that is intermediate between BD and SZ.

• Hammar, Åsa; Semkovska, Maria; Borgen, Ida Maria Henriksen; Myklebost, Sunniva Brurok; Ronold, Eivind Haga & Sveen, Thea [Show all 9 contributors for this article] (2020). A pilot study of cognitive remediation in remitted major depressive disorder patients. Applied neuropsychology: Adult. ISSN 2327-9095. p. 1–11. doi: 10.1080/23279095.2020.1726919. Full text in Research Archive Show summary

  Major depressive disorder (MDD) is associated with working memory (WM) impairments. These deficits often persist following remission and are associated with rumination, a recognized risk factor for depression relapse. The efficacy of WM-targeted cognitive remediation as a potential relapse prevention tool has not been investigated. The present pilot study aimed to investigate the feasibility, acceptability, and cognitive benefits of a WM-targeted cognitive remediation program in remitted depression. Twenty-eight MDD participants in remission were recruited. The intervention consisted of twenty-five 30–40-minute training sessions, coupled with weekly coaching, administered over a 5-week period. Before and after the intervention, a battery of objective neuropsychological tests and self-report measures was administered. Key outcomes were WM, inhibition and rumination. Acceptability of the intervention was observed, with 83% showing high motivation, along with WM gains for all completers (n = 18, 64% of recruited participants). The cognitive remediation selectively improved targeted WM functions, as measured by objective tests. This did not translate into self-reported improvements in everyday WM or inhibition. However, all but one completer achieved at least one personal goal related to WM and 44% achieved two or, the maximum possible, three such goals. For remitters whose WM was significantly enhanced after the intervention, the cognitive remediation also decreased dysphoric-mood related rumination. The successful pilot testing of the WM-targeted intervention supports the conduct of a fully powered randomized controlled trial as a relapse prevention approach in remitted MDD.

• Aas, Monica; Ueland, Torill; Inova, Amina; Melle, Ingrid; Andreassen, Ole Andreas & Steen, Nils Eiel (2020). Childhood Trauma Is Nominally Associated With Elevated Cortisol Metabolism in Severe Mental Disorder. Frontiers in Psychiatry. doi: 10.3389/fpsyt.2020.00391. Full text in Research Archive Show summary

  Objective: Individuals exposed to childhood trauma display longstanding modifications of the Hypothalamic–Pituitary–Adrenal (HPA) axis, as well as cognitive impairments. Schizophrenia spectrum disorder (SZ) and bipolar disorders (BD) are characterised by higher prevalence of childhood trauma, abnormal HPA axis, and cognitive dysfunction. Elevated cortisol metabolism was recently demonstrated in both disorders. However, it is yet to be established if childhood adversity is associated with cortisol metabolism in this population, and how this may be associated with cognitive function. Methods: One-hundred-and-fourteen participants with a DSM-IV SZ or BD diagnosis took part in the study. Diagnoses were evaluated by the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Estimated cortisol metabolizing activity (5α-reductase and 5β-reductase) was assessed by urinary free cortisol, and metabolites. All patients underwent cognitive assessment and completed the Childhood Trauma Questionnaire. Results: Estimated 5β-reductase activity was elevated in participant with childhood physical abuse (r = 0.26, p = 0.005). After adjusting for age, sex and diagnosis, physical abuse was still nominally associated with elevated 5β-reductase. Moreover, only high 5α-reductase activity was negatively correlated with working memory and executive performance (r = −0.23, p = 0.01; r = −0.19, p = 0.05, respectively), however this disappeared after adjusting for age, sex and diagnosis. Cortisol metabolism did not mediate the association between childhood trauma and cognitive function. Conclusions: Our study indicates that childhood physical abuse is associated with elevated cortisol metabolism (5β-reductase) in adults with a SZ or BD disorder. However, our study did not support cortisol metabolism as a mediator between childhood trauma experiences and cognitive function within these disorders.

• Høegh, Margrethe Collier; Melle, Ingrid; Aminoff, Sofie Ragnhild; Laskemoen, Jannicke Fjæra; Büchmann, Camilla Bakkalia & Ueland, Torill [Show all 7 contributors for this article] (2020). Affective lability across psychosis spectrum disorders. European psychiatry. ISSN 0924-9338. 63:e53, p. 1–8. doi: 10.1192/j.eurpsy.2020.44. Full text in Research Archive Show summary

  Background. Despite apparent clinical remission, individuals with psychotic disorders often experience significant impairments across functional domains. Thus, there is a need to search beyond management of core symptoms to optimize treatment outcomes. Affective dysregulation is considered a risk factor for poor clinical and functional outcomes in many mental disorders, but research investigating such features in psychosis, particularly in schizophrenia, is limited. We aimed to investigate the level of affective lability (AL) in participants with schizophrenia- and bipolar spectrum disorders (n = 222) compared to healthy controls (n = 140), as well as clinical correlates of AL in the diagnostic groups. Methods. The Affective Lability Scale (ALS-SF) was used to measure total score of AL and subscores covering the domains of anxiety/depression, depression/elation, and anger. An analysis of covariance was performed to compare the ALS-SF total score between groups, correcting for potential confounders, as well as standard multiple regression analyses for diagnosis-specific investigations of the relationship between AL and demographic and clinical features. Results. Both the schizophrenia- and bipolar spectrum group had significantly higher ALS-SF total score compared to controls (p < 0.001), and no significant differences between the patient groups were found. In the schizophrenia group, current psychotic and depressive symptoms were significantly and independently associated with AL (p = 0.012 and p = 0.024, respectively). Conclusions. The findings indicate that AL is elevated in psychotic disorders and that it transcends diagnostic boundaries. Further research into the causal relationship between psychotic and affective symptoms and AL, as well as its role as a potential therapeutic target in psychosis spectrum disorders, is warranted.

• Haatveit, Beathe Christin; Mørch-Johnsen, Lynn; Alnæs, Dag; Engen, Magnus Johan; Lyngstad, Siv Hege & Færden, Ann [Show all 9 contributors for this article] (2020). Divergent relationship between brain structure and cognitive functioning in patients with prominent negative symptomatology. Psychiatry Research : Neuroimaging. ISSN 0925-4927. doi: 10.1016/j.pscychresns.2020.111233. Full text in Research Archive Show summary

  Investigating commonalities in underlying pathology of cognitive dysfunction and negative symptoms in schizophrenia is important, as both are core features of the disorder and linked to brain structure abnormalities. We aimed to explore the relationship between cognition, negative symptoms and brain structure in schizophrenia. A total of 225 patients with Schizophrenia spectrum disorder and 283 healthy controls from the Norwegian Thematically Organized Psychosis (TOP) cohort were included in this study. Patients were categorized into four patient subgroups based on severity of negative symptoms: no-negative- (NNS), threshold-negative- (TNS), moderate-negative- (MNS), and prominent-negative (PNS) subgroups. MRI measures of brain volume, mean cortical thickness and surface area from pre-selected brain regions were tested for relationships with general cognitive ability and negative symptom subgroups. Positive associations were found between brain volume, thickness, surface area and cognition in the dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), fusiform gyrus (FG) and the left anterior cingulate cortex (ACC), but with no differences between subgroups. In the PNS subgroup, cognition was conversely negatively associated with brain volume in the left ACC. These results indicate that patients with prominent negative symptoms have different associations between cognition and brain structure in the left ACC, which may point to abnormal neurodevelopment.

• O`Connell, Kevin; Shadrin, Alexey A.; Smeland, Olav Bjerkehagen; Bahrami, Shahram; Frei, Oleksandr & Bettella, Francesco [Show all 24 contributors for this article] (2019). Identification of genetic loci shared between ADHD, intelligence and educational attainment. Biological Psychiatry. ISSN 0006-3223. 87(12), p. 1052–1062. doi: 10.1016/j.biopsych.2019.11.015. Full text in Research Archive Show summary

  Background Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is consistently associated with lower levels of educational attainment. A recent large genome-wide association study identified common gene variants associated with ADHD, but most of the genetic architecture remains unknown. Methods We analyzed independent genome-wide association study summary statistics for ADHD (19,099 cases and 34,194 controls), educational attainment ( N = 842,499), and general intelligence ( N = 269,867) using a conditional/conjunctional false discovery rate (FDR) statistical framework that increases power of discovery by conditioning the FDR on overlapping associations. The genetic variants identified were characterized in terms of function, expression, and biological processes. Results We identified 58 linkage disequilibrium–independent ADHD-associated loci (conditional FDR < 0.01), of which 30 were shared between ADHD and educational attainment or general intelligence (conjunctional FDR < 0.01) and 46 were novel risk loci for ADHD. Conclusions These results expand on previous genetic and epidemiological studies and support the hypothesis of a shared genetic basis between these phenotypes. Although the clinical utility of the identified loci remains to be determined, they can be used as resources to guide future studies aiming to disentangle the complex etiologies of ADHD, educational attainment, and general intelligence.

• Anderssen, Jannicke Fjæra; Büchmann, Camilla Bakkalia; Barrett, Elizabeth Ann; Høegh, Margrethe Collier; Haatveit, Beathe & Vedal, Trude Seselie Jahr [Show all 10 contributors for this article] (2019). Do sleep disturbances contribute to cognitive impairments in schizophrenia spectrum and bipolar disorders? European Archives of Psychiatry and Clinical Neuroscience. ISSN 0940-1334. p. 1–11. doi: 10.1007/s00406-019-01075-0. Full text in Research Archive
• Evensen, Stig; Wisløff, Torbjørn; Lystad, June Ullevoldsæter; Bull, Helen; Martinsen, Egil Wilhelm & Ueland, Torill [Show all 7 contributors for this article] (2019). Exploring the potential cost-effectiveness of a vocational rehabilitation program for individuals with schizophrenia in a high-income welfare society. BMC Psychiatry. 19(140), p. 1–10. doi: 10.1186/s12888-019-2130-7. Full text in Research Archive Show summary

  Background Over the past decades research has shown that employment has a positive impact on quality of life, global functioning and recovery in individuals with schizophrenia. However, access to vocational rehabilitation services for this group is limited and unemployment rates remain high. In this study we explore the potential cost-effectiveness of a novel vocational rehabilitation program (The Job Management Program – JUMP) earmarked for individuals with schizophrenia in Norway. Methods The JUMP study was a vocational rehabilitation program augmented with either cognitive behaviour therapy or cognitive remediation. In addition to the JUMP protocol, we extracted treatment cost data from comprehensive and mandatory health and welfare registers. The costs over a two-year follow-up period were compared with the costs over the two-year period prior to inclusion in the study. We also compared the cost-effectiveness of JUMP with a treatment as usual group (TAU). Results We identified significant reductions in inpatient services in the JUMP group, both for those who obtained employment and those who did not. Significant reductions were also found in the TAU group, but adjusted for baseline differences the total cost for JUMP participants were € 10,621 lower than in the TAU group during the follow-up period. Conclusion In addition to supporting individuals with schizophrenia obtain employment, JUMP appears to have reduced the reliance on mental health services, which should be of interest to stakeholders. Trial registration ClinicalTrials.gov Identifier: NCT01139502 . Retrospectively registered on 6 February 2010.

• Bowie, Christopher R.; Bell, Morris D.; Fiszdon, Joanna M.; Johannesen, Jason K.; Lindenmayer, Jean-Pierre & McGurk, Susan R. [Show all 12 contributors for this article] (2019). Cognitive remediation for schizophrenia: An expert working group white paper on core techniques. Schizophrenia Research. ISSN 0920-9964. p. 1–5. doi: 10.1016/j.schres.2019.10.047. Full text in Research Archive Show summary

  Cognitive remediation is now widely recognized as an effective treatment for cognitive deficits in schizophrenia. Its effects are meaningful, durable, and related to improvements in everyday functional outcomes. As with many therapies, the evolution of cognitive remediation has resulted in treatment programs that use a variety of specific techniques, yet share common core principles. This paper is the product of a cognitive remediation expert working group consensus meeting to identify core features of the treatment and produce recommendations for its design, conduct, reporting, and implementation. Four techniques were identified as core features of cognitive remediation: facilitation by a therapist, cognitive exercise, procedures to develop problem-solving strategies, and procedures to facilitate transfer to real world functioning. Treatment techniques within each of these core features are presented to facilitate decisions for clinical trials and implementation in clinical settings.

• Simonsen, Carmen Elisabeth; Aminoff, Sofie Ragnhild; Vaskinn, Anja; Barrett, Elizabeth Ann; Færden, Ann & Ueland, Torill [Show all 9 contributors for this article] (2019). Perceived and experienced stigma in first-episode psychosis: A 1-year follow-up study. Comprehensive Psychiatry. ISSN 0010-440X. 95:152134, p. 1–8. doi: 10.1016/j.comppsych.2019.152134. Full text in Research Archive Show summary

  Objectives Perceived/experienced stigma and its relationship with clinical outcome were investigated across the first year of treatment in a large sample with first-episode psychosis (FEP). Methods FEP participants (n = 112) in the TOP study were investigated at baseline and 1-year follow-up. Perceived/experienced stigma was measured with items from the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0), assessing problems because of barriers and hindrances, and living with dignity because of attitudes and actions of others. Clinical outcome included: symptoms, global functioning, self-rated disability and self-rated life satisfaction. Results In the total sample, 46% perceived/experienced stigma at baseline, which decreased significantly to 32% at 1-year follow-up. Perceived/experienced stigma was present in 1/5 at both time-points (Sustained stigma), in 2/5 at only one time-point (Transient stigma), and in 2/5 it was not present at either time-point (No stigma). Compared to the No stigma group, the Sustained stigma group had significantly higher levels of positive, excited and depressive symptoms and self-rated disability, as well as lower levels of global functioning and life satisfaction at 1 year follow-up, while the Transient stigma group only had poorer functioning and higher self-rated disability. Yet the outcome variables improved across the first year of treatment in all three stigma groups. Conclusion Perceived/experienced stigma was common in FEP, yet the rate decreased across the first year of treatment. Although there was some clinical improvement across the first year of treatment irrespective of stigma, stigma was related to poorer clinical outcome in a bidirectional manner. This suggests that perceived/experienced stigma is an important target in the early stages of treatment.

• Bakke, Laura A. Wortinger; Engen, Kristine; Barth, Claudia; Lonning, Vera Louise Hiorth; Jørgensen, Kjetil Nordbø & Andreassen, Ole Andreas [Show all 10 contributors for this article] (2019). Obstetric complications and intelligence in patients on the schizophrenia-bipolar spectrum and healthy participants. Psychological Medicine. ISSN 0033-2917. p. 1–9. doi: 10.1017/S0033291719002046. Full text in Research Archive
• Smeland, Olav Bjerkehagen; Bahrami, Shahram; Frei, Oleksandr; Shadrin, Alexey A.; O`Connell, Kevin & Savage, Jeanne E. [Show all 15 contributors for this article] (2019). Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder, and intelligence. Molecular Psychiatry. ISSN 1359-4184. p. 1–10. doi: 10.1038/s41380-018-0332-x. Full text in Research Archive Show summary

  Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders associated with cognitive impairment, which is considered a major determinant of functional outcome. Despite this, the etiology of the cognitive impairment is poorly understood, and no satisfactory cognitive treatments exist. Increasing evidence indicates that genetic risk for SCZ may contribute to cognitive impairment, whereas the genetic relationship between BD and cognitive function remains unclear. Here, we combined large genome-wide association study data on SCZ (n = 82,315), BD (n = 51,710), and general intelligence (n = 269,867) to investigate overlap in common genetic variants using conditional false discovery rate (condFDR) analysis. We observed substantial genetic enrichment in both SCZ and BD conditional on associations with intelligence indicating polygenic overlap. Using condFDR analysis, we leveraged this enrichment to increase statistical power and identified 75 distinct genomic loci associated with both SCZ and intelligence, and 12 loci associated with both BD and intelligence at conjunctional FDR < 0.01. Among these loci, 20 are novel for SCZ, and four are novel for BD. Most SCZ risk alleles (61 of 75, 81%) were associated with poorer cognitive performance, whereas most BD risk alleles (9 of 12, 75%) were associated with better cognitive performance. A gene set analysis of the loci shared between SCZ and intelligence implicated biological processes related to neurodevelopment, synaptic integrity, and neurotransmission; the same analysis for BD was underpowered. Altogether, the study demonstrates that both SCZ and BD share genetic influences with intelligence, albeit in a different manner, providing new insights into their genetic architectures.

• Engen, Magnus Johan; Simonsen, Carmen Elisabeth; Melle, Ingrid; Færden, Ann; Lyngstad, Siv Hege & Haatveit, Beathe [Show all 8 contributors for this article] (2019). Cognitive functioning in patients with first-episode psychosis stratified by level of negative symptoms: A 1-year follow-up study. Psychiatry Research. ISSN 0165-1781. 281, p. 1–7. doi: 10.1016/j.psychres.2019.112554. Full text in Research Archive
• Aas, Monica; Pizzagalli, Diego A.; Anderssen, Jannicke Fjæra; Reponen, Elina Johanna; Ueland, Torill & Melle, Ingrid [Show all 9 contributors for this article] (2019). Elevated hair cortisol is associated with childhood maltreatment and cognitive impairment in schizophrenia and in bipolar disorders. Schizophrenia Research. ISSN 0920-9964. doi: 10.1016/j.schres.2019.01.011. Full text in Research Archive Show summary

  Background The neural diathesis-stress model is useful to understand schizophrenia (SZ) and bipolar (BD) disorders. Childhood maltreatment could affect the Hypothalamic–Pituitary–Adrenal (HPA)-axis and lead to chronic changes in stress-sensitivity, which can be measured with hair cortisol concentrations (HCC), representing long-term, cumulative cortisol levels. Here we investigated if childhood trauma experiences are associated with chronic changes in the HPA axis in severe mental disorders. Methods Participants with SZ or BD (N = 63) and healthy controls (N = 94) were included, and HCC was measured by ELISA. History of childhood maltreatment was assessed using the Childhood Trauma Questionnaire (CTQ). Global function and symptom levels were obtained using the Global Assessment of Functioning (GAF) Scale and the Positive and Negative Syndrome Scale (PANSS). A neuropsychological test battery (MATRICS) was performed to assess cognitive functions. Results Our study shows for the first time that patients with a history of childhood maltreatment have higher HCC relative to both healthy controls and patients without a history of childhood maltreatment (P = 0.01, ƞp2 = 0.046). In addition, patients experiencing a mood episode had higher HCC than patients in remission (P = 0.03). Lastly, we are the first to show that patients with higher HCC had poorer cognitive performance, specifically working memory (P = 0.01). All associations were irrespective of diagnostic group. A factor analysis confirmed a subgroup within the patients characterized by childhood maltreatment and elevated HCC. Conclusions Findings support the neural diathesis-stress model in SZ and BD pointing to long-term changes in HPA-axis following childhood maltreatment experiences.

• Frøyhaug, Mathias; Andersson, Stein; Andreassen, Ole Andreas; Ueland, Torill & Vaskinn, Anja (2019). Theory of mind in schizophrenia and bipolar disorder: psychometric properties of the Norwegian version of the Hinting Task. Cognitive Neuropsychiatry. ISSN 1354-6805. 24(6), p. 454–469. doi: 10.1080/13546805.2019.1674645. Full text in Research Archive Show summary

  Introduction: The quality of measures used to assess theory of mind (ToM) in severe mental illness has not been sufficiently investigated. This study evaluated the psychometric properties of the Norwegian version of the Hinting Task in schizophrenia, bipolar I and II disorder and healthy controls. Methods: The study included 90 patients and 183 healthy controls. Internal consistency, ceiling effects, discriminatory power and concurrent and construct validity were investigated. Results: The Hinting Task displayed adequate levels of internal consistency for schizophrenia and bipolar I disorder. Ceiling effects emerged in all groups except the schizophrenia group. Schizophrenia patients scored significantly lower than all other groups, but no other significant group differences were detected. In the schizophrenia group, the Hinting Task’s concurrent validity was substantiated by significant correlations with measures of neurocognition, symptoms and functional capacity. In the bipolar disorder groups, however, only a few significant relationships were found. Correlations between the Hinting Task and a measure of emotion recognition indicated that construct validity was higher for schizophrenia than bipolar disorder. Conclusions: The results suggest that the Norwegian Hinting Task is suited for use in schizophrenia research and assessment, but caution is warranted when using the test for other populations.

• Gjerde, Priyanthi Borgen; Simonsen, Carmen Elisabeth; Lagerberg, Trine Vik; Steen, Nils Eiel; Ueland, Torill & Andreassen, Ole Andreas [Show all 8 contributors for this article] (2019). Improvement in verbal learning over the first year of antipsychotic treatment is associated with serum HDL levels in a cohort of first episode psychosis patients. European Archives of Psychiatry and Clinical Neuroscience. ISSN 0940-1334. p. 1–10. doi: 10.1007/s00406-019-01017-w. Full text in Research Archive Show summary

  To investigate whether changes in serum lipids are associated with cognitive performance in first episode psychosis (FEP) patients during their first year of antipsychotic drug treatment. One hundred and thirty-two antipsychotic-treated FEP patients were included through the TOP study along with 83 age- and gender-matched healthy controls (HC). Information regarding cognitive performance, psychotic symptoms, lifestyle, body mass index, serum lipids [total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides] and antipsychotic treatment was obtained at baseline and after 1 year. The cognitive test battery is comprised of assessments for verbal learning, processing speed, working memory, verbal fluency, and inhibition. Mixed-effects models were used to study the relationship between changes over time in serum lipids and cognitive domains, controlling for potential confounders. There was a significant group by HDL interaction effect for verbal learning (F = 11.12, p = 0.001), where an increase in HDL levels was associated with improvement in verbal learning in FEP patients but not in HC. Practice effects, lifestyle, and psychotic symptoms did not significantly affect this relationship. Antipsychotic-treated FEP patients who increased in HDL levels during the first year of follow-up exhibited better verbal learning capacity. Further investigations are needed to clarify the underlying mechanisms.

• Engelstad, Katharina Nymo; Rund, Bjørn Rishovd; Torgalsbøen, Anne-Kari; Lau, Bjørn; Ueland, Torill & Vaskinn, Anja (2018). Large social cognitive impairments characterize homicide offenders With schizophrenia. Psychiatry Research. ISSN 0165-1781. 272, p. 209–215. doi: 10.1016/j.psychres.2018.12.087. Full text in Research Archive
• Wolfers, Thomas; Doan, Nhat Trung; Kaufmann, Tobias; Alnæs, Dag; Moberget, Torgeir & Agartz, Ingrid [Show all 14 contributors for this article] (2018). Mapping the heterogeneous phenotype of schizophrenia and bipolar disorder using normative models. JAMA psychiatry. ISSN 2168-6238. 75(11), p. 1146–1155. doi: 10.1001/jamapsychiatry.2018.2467. Full text in Research Archive
• Srinivasan, Saurabh; Bettella, Francesco; Frei, Oleksandr; Hill, W. David; Wang, Yunpeng & Witoelar, Aree [Show all 17 contributors for this article] (2018). Enrichment of genetic markers of recent human evolution in educational and cognitive traits. Scientific Reports. 8:12585, p. 1–9. doi: 10.1038/s41598-018-30387-9. Full text in Research Archive Show summary

  Higher cognitive functions are regarded as one of the main distinctive traits of humans. Evidence for the cognitive evolution of human beings is mainly based on fossil records of an expanding cranium and an increasing complexity of material culture artefacts. However, the molecular genetic factors involved in the evolution are still relatively unexplored. Here, we investigated whether genomic regions that underwent positive selection in humans after divergence from Neanderthals are enriched for genetic association with phenotypes related to cognitive functions. We used genome wide association data from a study of college completion (N = 111,114), one of educational attainment (N = 293,623) and two different studies of general cognitive ability (N = 269,867 and 53,949). We found nominally significant polygenic enrichment of associations with college completion (p = 0.025), educational attainment (p = 0.043) and general cognitive ability (p = 0.015 and 0.025, respectively), suggesting that variants influencing these phenotypes are more prevalent in evolutionarily salient regions. The enrichment remained significant after controlling for other known genetic enrichment factors, and for affiliation to genes highly expressed in the brain. These findings support the notion that phenotypes related to higher order cognitive skills typical of humans have a recent genetic component that originated after the separation of the human and Neanderthal lineages.

• Aas, Monica; Djurovic, Srdjan; Ueland, Torill; Mørch, Ragni Helene; Anderssen, Jannicke Fjæra & Reponen, Elina Johanna [Show all 11 contributors for this article] (2018). The relationship between physical activity, clinical and cognitive characteristics and BDNF mRNA levels in patients with severe mental disorders. World Journal of Biological Psychiatry. ISSN 1562-2975. doi: 10.1080/15622975.2018.1557345. Full text in Research Archive
• Dieset, Ingrid; Mørch, Ragni Helene; Hope, Sigrun; Hoseth, Eva Zsuzsanna; Reponen, Elina Johanna & Gran, Jon Michael [Show all 16 contributors for this article] (2018). An association between YKL-40 and type 2 diabetes in psychotic disorders. Acta Psychiatrica Scandinavica. ISSN 0001-690X. 139, p. 37–45. doi: 10.1111/acps.12971. Full text in Research Archive
• Simonsen, Carmen Elisabeth; Færden, Ann; Ueland, Torill; Vaskinn, Anja; Bjella, Thomas & Andreassen, Ole Andreas [Show all 8 contributors for this article] (2018). Self-rated disability in first treated episode of psychosis: A 1-year follow-up study. Comprehensive Psychiatry. ISSN 0010-440X. 85, p. 48–54. doi: 10.1016/j.comppsych.2018.06.004. Full text in Research Archive Show summary

  Objectives: Knowledge about self-rated disability over time in psychotic disorders is limited. How self-rateddisability relates to clinician-rated global functioning, self-rated life satisfaction and symptomatology wasinvestigated across thefirst year of treatment in early psychosis. Methods: Participants withfirst treated episode of psychosis (n= 115) were investigated at baseline and 1-yearfollow-up. Self-rated Disability was measured with World Health Organization- Disability Assessment Schedule2.0. Clinician-rated global functioning, self-rated life satisfaction, and symptomatology were measured withappropriate scales. Results: Average self-rated disability infirst-treated episode of psychosis was high, corresponding with the 10%highest in a general population sample. However, 37% werenotdisabled at a clinically significant level afterone year. Self-rated disability was highest in the two social domains (Getting along with people and Participationin society), but improved significantly from baseline to 1-year. At 1-year follow-up self-rated disability hadsignificant weak to medium correlations with clinician-rated global functioning and positive symptoms,and mainly medium to strong correlations with life satisfaction and depressive symptoms. Yet only baselinedepression significantly predicted disability after one year. Conclusion: Self-rated disability infirst treated episode of psychosis is high, but improves across thefirst year,indicating signs of early recovery. Moreover,self-rateddisability isrelated, but distinct fromclinician-ratedglobalfunctioning and self-rated life satisfaction, suggesting that self-rated disability should also be assessed in order tomore fully describe outcomes infirst episode psychosis. Thefindings highlight the need for specialised treatmentof depression and social disability in early psychosis.

• Smelror, Runar; Jørgensen, Kjetil Nordbø; Lonning, Vera Louise Hiorth; Kelleher, Ian; Cannon, Mary & DeRosse, Pamela [Show all 16 contributors for this article] (2018). Healthy adolescent performance with standardized scoring tables for the MATRICS Consensus Cognitive Battery: A multisite study. Schizophrenia Bulletin. ISSN 0586-7614. 45(4), p. 773–783. doi: 10.1093/schbul/sby131. Full text in Research Archive
• Tønnesen, Siren; Kaufmann, Tobias; Doan, Nhat Trung; Alnæs, Dag; Palomera, Aldo Còrdova & Meer, Dennis van der [Show all 15 contributors for this article] (2018). White matter aberrations and age-related trajectories in patients with schizophrenia and bipolar disorder revealed by diffusion tensor imaging. Scientific Reports. 8. doi: 10.1038/s41598-018-32355-9. Full text in Research Archive Show summary

  Supported by histological and genetic evidence implicating myelin, neuroinflammation and oligodendrocyte dysfunction in schizophrenia spectrum disorders (SZ), diffusion tensor imaging (DTI) studies have consistently shown white matter (WM) abnormalities when compared to healthy controls (HC). The diagnostic specificity remains unclear, with bipolar disorders (BD) frequently conceptualized as a less severe clinical manifestation along a psychotic spectrum. Further, the age-related dynamics and possible sex differences of WM abnormalities in SZ and BD are currently understudied. Using tract-based spatial statistics (TBSS) we compared DTI-based microstructural indices between SZ (n = 128), BD (n = 61), and HC (n = 293). We tested for age-by-group and sex-by-group interactions, computed effect sizes within different age-bins and within genders. TBSS revealed global reductions in fractional anisotropy (FA) and increases in radial (RD) diffusivity in SZ compared to HC, with strongest effects in the body and splenium of the corpus callosum, and lower FA in SZ compared to BD in right inferior longitudinal fasciculus and right inferior fronto-occipital fasciculus, and no significant differences between BD and HC. The results were not strongly dependent on age or sex. Despite lack of significant group-by-age interactions, a sliding-window approach supported widespread WM involvement in SZ with most profound differences in FA from the late 20 s.

• Akkouh, Ibrahim; Ueland, Torill; Andreassen, Ole Andreas; Brattbakk, Hans-Richard; Steen, Vidar Martin & Hughes, Timothy [Show all 7 contributors for this article] (2018). Expression of TCN1 in Blood is Negatively Associated with Verbal Declarative Memory Performance. Scientific Reports. 8:12654, p. 1–11. doi: 10.1038/s41598-018-30898-5. Full text in Research Archive Show summary

  Memory is indispensable for normal cognitive functioning, and the ability to store and retrieve information is central to mental health and disease. The molecular mechanisms underlying complex memory functions are largely unknown, but multiple genome-wide association studies suggest that gene regulation may play a role in memory dysfunction. We performed a global gene expression analysis using a large and balanced case-control sample (n = 754) consisting of healthy controls and schizophrenia and bipolar disorder patients. Our aim was to discover genes that are differentially expressed in relation to memory performance. Gene expression in blood was measured using Illumina HumanHT-12 v4 Expression BeadChip and memory performance was assessed with the updated California Verbal Learning Test (CVLT-II). We found that elevated expression of the vitamin B12-related gene TCN1 (haptocorrin) was significantly associated with poorer memory performance after correcting for multiple testing (β = −1.50, p = 3.75e-08). This finding was validated by quantitative real-time PCR and followed up with additional analyses adjusting for confounding variables. We also attempted to replicate the finding in an independent case-control sample (n = 578). The relationship between TCN1 expression and memory impairment was comparable to that of important determinants of memory function such as age and sex, suggesting that TCN1 could be a clinically relevant marker of memory performance. Thus, we identify TCN1 as a novel genetic finding associated with poor memory function. This finding may have important implications for the diagnosis and treatment of vitamin B12-related conditions.

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• Ueland, Torill; Grimstad, Kristoffer; Sørensen, Håkon; Øie, Merete Glenne & Vaskinn, Anja (2026). Reply to Stip and colleagues. Schizophrenia Research: Cognition. 45, p. 1–3. doi: 10.1016/j.scog.2026.100429. Full text in Research Archive
• Smeland, Olav Bjerkehagen; Bahrami, Shahram; Frei, Oleksandr; Shadrin, Alexey; O'Connell, Kevin & Savage, Jeanne [Show all 15 contributors for this article] (2019). Correction: Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder, and intelligence (Molecular Psychiatry, (2020), 25, 4, (844-853), 10.1038/s41380-018-0332-x). Molecular Psychiatry. ISSN 1359-4184. 25(4), p. 914–914. doi: 10.1038/s41380-019-0456-7. Full text in Research Archive
• Smeland, Olav Bjerkehagen; Bahrami, Shahram; Frei, Oleksandr; Shadrin, Alexey A.; Savage, Jeanne E. & Watanabe, Kyoko [Show all 14 contributors for this article] (2018). Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder and intelligence. Full text in Research Archive

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