Academic interests
Mental disorders. Transmission of psychological traits across generations. Genetically informative designs.
Courses taught
PSYC2231 – Biologisk psykologi og genetikk
Background
Psychologist
Tags:
PROMENTA
Publications
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Valstad, Mathias; Eilertsen, Espen Moen; Ayorech, Ziada; Cheesman, Rosa Catherine Gillespie; Demange, Perline Aline Delle & Eftedal, Nikolai Haahjem
[Show all 8 contributors for this article]
(2026).
Indirect genetic effects of siblings.
Journal of Child Psychology and Psychiatry.
ISSN 0021-9630.
doi:
10.1111/jcpp.70130.
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Background
Within-family designs are increasingly used to decompose genotype–trait associations into direct and indirect genetic effects. Many such designs, including trio designs or within-sibship designs, assume an absence of sibling indirect genetic effects.
Methods
We expand two well-known molecular genetic within-family designs, one variance component (genome-based restricted maximum likelihood) and one trait-based (structural equation modeling with polygenic indices), to estimate sibling indirect genetic effects, along with direct genetic effects. We link the Norwegian Mother, Father, and Child Cohort Study (MoBa) to Norway's national education database to model genetic effects on national standardized testing results at ages 10, 13, and 14, and on parent-rated attention-deficit hyperactivity disorder (ADHD) symptoms at ages 3 and 8 in up to 15,971 genotyped and phenotyped siblings.
Results
Estimates of direct and indirect genetic effects from the genome-based restricted maximum likelihood and the structural equation modeling with polygenic indices approaches converge, albeit with the variance component estimates typically an order of magnitude greater than the trait-based estimates. We observe no indirect genetic effects of siblings on educational performance at any age, and only slightly negative indirect genetic effects of siblings on ADHD symptoms at age 3. We argue that the latter effect might reflect parental contrasting ratings.
Conclusions
The results suggest that within-family models of educational performance are unlikely to be drastically biased by an assumption of absent sibling indirect genetic effects. Combining trait-based analyses with variance component analyses can benefit understanding of indirect genetic effects, especially when the effects are not specific to a particular mechanism.
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Slapø, Nora Berz; Jørgensen, Kjetil Nordbø; Nerland, Stener; Mørch-Johnsen, Lynn Egeland; Pettersen, Johanne Hagen & Roelfs, Daniel
[Show all 23 contributors for this article]
(2026).
Relationship between N100 amplitude and T1w/T2w-ratio in the auditory cortex in schizophrenia spectrum disorders.
Schizophrenia.
doi:
10.1038/s41537-025-00715-w.
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Schizophrenia spectrum disorders (SCZspect) are associated with altered function in the auditory cortex (AC), indicated by lower N100 amplitude of the auditory evoked potential (AEP). Although the neural substrate behind lower N100 amplitude remains elusive, myelination in the AC may play a role. This study compared N100 amplitude and magnetic resonance imaging (MRI) T1 weighted and T2 weighted ratio (T1w/T2w-ratio), as a proxy of myelination, in the primary AC (AC1) and secondary AC (AC2) between SCZspect (n = 33, 48% women) and healthy controls (HC, n = 144, 49% women). We also examined the associations between N100 amplitude and T1w/T2w-ratios across groups. We finally explored N100 amplitude and T1w/T2w-ratios and the N100-T1w/T2w-ratio associations between male and female SCZspect and HC. N100 amplitude was significantly lower in male SCZspect compared to male HC (p = 0.01) and nominally lower in SCZspect compared to HC (p = 0.03). However, T1w/T2w-ratios in AC1/AC2 did not differ between groups, and no association was found between N100 amplitude and T1w/T2w-ratio in either group. These findings suggest that sex-specific effects should be considered in SCZspect neurophysiology research. Our results do not support the hypothesis of an association between lower N100 amplitude and lower T1w/T2w-ratio in the AC1/AC2 in SCZspect. More precise assessments of intracortical myelin are needed to understand the relationship between N100 amplitude and cortical myelination in the AC in SCZspect and in healthy controls.
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Mäki-Marttunen, Tuomo; Blackwell, Kim T.; Akkouh, Ibrahim Ahmed; Shadrin, Alexey; Valstad, Mathias & Elvsåshagen, Torbjørn
[Show all 10 contributors for this article]
(2024).
Genetic mechanisms for impaired synaptic plasticity in schizophrenia revealed by computational modeling.
Proceedings of the National Academy of Sciences of the United States of America (PNAS).
ISSN 0027-8424.
121(34).
doi:
10.1073/pnas.2312511121.
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Schizophrenia phenotypes are suggestive of impaired cortical plasticity in the disease, but the mechanisms of these deficits are unknown. Genomic association studies have implicated a large number of genes that regulate neuromodulation and plasticity, indicating that the plasticity deficits have a genetic origin. Here, we used biochemically detailed computational modeling of postsynaptic plasticity to investigate how schizophrenia-associated genes regulate long-term potentiation (LTP) and depression (LTD). We combined our model with data from postmortem RNA expression studies (CommonMind gene-expression datasets) to assess the consequences of altered expression of plasticity-regulating genes for the amplitude of LTP and LTD. Our results show that the expression alterations observed post mortem, especially those in the anterior cingulate cortex, lead to impaired protein kinase A (PKA)-pathway-mediated LTP in synapses containing GluR1 receptors. We validated these findings using a genotyped electroencephalogram (EEG) dataset where polygenic risk scores for synaptic and ion channel-encoding genes as well as modulation of visual evoked potentials were determined for 286 healthy controls. Our results provide a possible genetic mechanism for plasticity impairments in schizophrenia, which can lead to improved understanding and, ultimately, treatment of the disorder.
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Slapø, Nora Berz; Nerland, Stener; Jørgensen, Kjetil Nordbø; Mørch-Johnsen, Lynn Egeland; Pettersen, Johanne Hagen & Roelfs, Daniel
[Show all 22 contributors for this article]
(2023).
Auditory Cortex Thickness Is Associated With N100 Amplitude in Schizophrenia Spectrum Disorders.
Schizophrenia Bulletin Open.
4(1).
doi:
10.1093/schizbullopen/sgad015.
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Background and Hypothesis: The auditory cortex (AC) may play a central role in the pathophysiology of schizophrenia and auditory hallucinations (AH). Previous schizophrenia studies report thinner AC and impaired AC function, as indicated by decreased N100 amplitude of the auditory evoked potential. However, whether these structural and functional alterations link to AH in schizophrenia remain poorly understood. Study Design: Patients with a schizophrenia spectrum disorder (SCZspect), including patients with a lifetime experience of AH (AH+), without (AH−), and healthy controls underwent magnetic resonance imaging (39 SCZ spect, 22 AH+, 17 AH−, and 146 HC) and electroencephalography (33 SCZ spect, 17 AH+, 16 AH−, and 144 HC). Cortical thickness of the primary (AC1, Heschl’s gyrus) and secondary (AC2, Heschl’s sulcus, and the planum temporale) AC was compared between SCZ spect and controls and between AH+, AH−, and controls. To examine if the association between AC thickness and N100 amplitude differed between groups, we used regression models with interaction terms. Study Results: N100 amplitude was nominally smaller in SCZ spect (P = .03, d = 0.42) and in AH− (P = .020, d = 0.61), while AC2 was nominally thinner in AH+ (P = .02, d = 0.53) compared with controls. AC1 thickness was positively associated with N100 amplitude in SCZspect (t = 2.56, P = .016) and AH− (t= 3.18, P = .008), while AC2 thickness was positively associated with N100 amplitude in SCZspect (t = 2.37, P = .024) and in AH+ (t = 2.68, P = .019). Conclusions: The novel indings of positive associations between AC thickness and N100 amplitude in SCZ spect, suggest that a common neural substrate may underlie AC thickness and N100 amplitude alterations.
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Slapø, Nora Berz; Jørgensen, Kjetil Nordbø; Elvsåshagen, Torbjørn; Nerland, Stener; Roelfs, Daniel & Valstad, Mathias
[Show all 18 contributors for this article]
(2023).
Relationship between function and structure in the visual cortex in healthy individuals and in patients with severe mental disorders.
Psychiatry Research : Neuroimaging.
ISSN 0925-4927.
332.
doi:
10.1016/j.pscychresns.2023.111633.
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Patients with schizophrenia spectrum disorders (SCZspect) and bipolar disorders (BD) show impaired function in the primary visual cortex (V1), indicated by altered visual evoked potential (VEP). While the neural substrate for altered VEP in these patients remains elusive, altered V1 structure may play a role. One previous study found a positive relationship between the amplitude of the P100 component of the VEP and V1 surface area, but not V1 thickness, in a small sample of healthy individuals. Here, we aimed to replicate these findings in a larger healthy control (HC) sample (n = 307) and to examine the same relationship in patients with SCZspect (n = 30) or BD (n = 45). We also compared the mean P100 amplitude, V1 surface area and V1 thickness between controls and patients and found no significant group differences. In HC only, we found a significant positive P100-V1 surface area association, while there were no significant P100-V1 thickness relationships in HC, SCZspect or BD. Together, our results confirm previous findings of a positive P100-V1 surface area association in HC, whereas larger patient samples are needed to further clarify the function-structure relationship in V1 in SCZspect and BD.
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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.
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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.
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Valstad, Mathias; Moberget, Torgeir; Roelfs, Daniël Thomas Heimen; Slapø, Nora Berz; Timpe, Clara Marie Fides & Beck, Dani
[Show all 18 contributors for this article]
(2020).
Experience-dependent modulation of the visual evoked potential: Testing effect sizes, retention over time, and associations with age in 415 healthy individuals.
NeuroImage.
ISSN 1053-8119.
doi:
10.1016/j.neuroimage.2020.117302.
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Experience-dependent modulation of the visual evoked potential (VEP) is a promising proxy measure of synaptic plasticity in the cerebral cortex. However, existing studies are limited by small to moderate sample sizes as well as by considerable variability in how VEP modulation is quantified. In the present study, we used a large sample (n = 415) of healthy volunteers to compare different quantifications of VEP modulation with regards to effect sizes and retention of the modulation effect over time. We observed significant modulation for VEP components C1 (Cohen's d = 0.53), P1 (d = 0.66), N1 (d=-0.27), N1b (d=-0.66), but not P2 (d = 0.08), and in three clusters of total power modulation, 2–4 min after 2 Hz prolonged visual stimulation. For components N1 (d=-0.21) and N1b (d=-0.38), as well for the total power clusters, this effect was retained after 54–56 min, by which time also the P2 component had gained modulation (d = 0.54). Moderate to high correlations (0.39≤ρ≤0.69) between modulation at different postintervention blocks revealed a relatively high temporal stability in the modulation effect for each VEP component. However, different VEP components also showed markedly different temporal retention patterns. Finally, participant age correlated negatively with C1 (χ2=30.4), and positively with P1 modulation (χ2=13.4), whereas P2 modulation was larger for female participants (χ2=15.4). There were no effects of either age or sex on N1 and N1b potentiation. These results provide strong support for VEP modulation, and especially N1b modulation, as a robust measure of synaptic plasticity, but underscore the need to differentiate between components, and to control for demographic confounders.
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Benjamin, Silje Beatrice Rognås; Valstad, Mathias; Elvsåshagen, Torbjørn; Jönsson, Erik Gunnar; Moberget, Torgeir & Winterton, Adriano
[Show all 14 contributors for this article]
(2020).
Heart rate variability is associated with disease severity in psychosis spectrum disorders.
Progress in Neuro-psychopharmacology and Biological Psychiatry.
ISSN 0278-5846.
00:110108,
p. 1–8.
doi:
10.1016/j.pnpbp.2020.110108.
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While a growing literature links cardiac autonomic dysregulation to a variety of psychiatric disorders, the relationship between cardiac autonomic functioning and specific symptoms in schizophrenia (SZ) and bipolar disorder (BD) remains elusive. Thus, we investigated heart rate variability (HRV), a proxy for vagal activity, as a biological marker for symptom severity in patients with SZ and BD. HRV was calculated in 35 patients with SZ and 52 patients with BD, as well as in 149 healthy controls. In the patient groups, symptom severity and function were measured by the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Results showed that HRV was significantly lower in both clinical groups compared to the healthy controls, with no significant HRV differences between patient groups. PANSS general psychopathology scores, GAF symptom scores, and GAF function scores showed statistically significant associations with HRV across groups. These results suggest that disease severity is associated with autonomic dysfunction and that HRV may provide a potential biomarker of disease severity in SZ and BD.
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Quintana, Daniel; Westlye, Lars Tjelta; Hope, Sigrun; Nærland, Terje; Elvsåshagen, Torbjørn & Dørum, Erlend Solberg
[Show all 16 contributors for this article]
(2017).
Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial.
Translational Psychiatry.
e1136(7),
p. 1–9.
doi:
10.1038/tp.2017.103.
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Valstad, Mathias; Alvares, Gail A.; Andreassen, Ole Andreas; Westlye, Lars Tjelta & Quintana, Daniel
(2016).
The relationship between central and peripheral oxytocin concentrations: a systematic review and meta-analysis protocol.
Systematic Reviews.
5(49).
doi:
10.1186/s13643-016-0225-5.
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Background Research examining the effects of oxytocin (OT) interventions on psychiatric, social-behavioral, and social-cognitive outcomes regularly collect peripheral levels of OT as markers of central bioavailability. Such inferences rest on the assumption that central and peripheral levels of OT are directly associated. However, conflicting evidence from coordinated sampling of central and peripheral OT question the validity of this assumption. The purpose of this meta-analysis is to evaluate the correlation between central and peripheral OT, as well as to account for potential heterogeneity in the literature. Methods/design Studies that report coordinated sampling of central and peripheral OT in humans and animals will be identified. Research investigating concentrations in both basal states and after exogenous administration will be considered. PubMed and Embase databases will be searched, along with citation lists of retrieved articles. Peer-reviewed studies written in English published from 1971 onwards will be included in the meta-analysis. Data will be extracted from eligible studies for a random-effects meta-analysis. For each study, a summary effect size, heterogeneity, risk of bias, publication bias, and the effect of categorical and continuous moderator variables will be determined. Discussion This systematic review and meta-analysis will identify and synthesize evidence to determine if there is an association between central and peripheral OT concentrations. If significant associations are observed, evidence would provide a rationale for future research to use peripheral measures as a proxy for central OT concentrations. Systematic review registration PROSPERO CRD42015027864
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Ofstad, Sverre Berg; Demange, Perline Aline Delle; Ayorech, Ziada; Valstad, Mathias & Ystrom, Eivind
(2026).
Temporal Trends in the Severity and Impairment of Childhood and Adolescent ADHD: A Population-Wide Genetic Study in Norway.
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By calculating family genetic risk scores for the entire for the entire Norwegian population for birth years 1992-2019, ages 6-16 (N ≈ 1.5M) we show that the reduction in functional impairment over time is largely attributed to a diagnostic expansion of less genetically severe cases. Those who are diagnosed today have lower levels of genetic risk, while simulatenously, there has been no change in the relationship between GPA at age 16 and genetic risk for ADHD.
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Ofstad, Sverre Berg; Demange, Perline Aline Delle; Ayorech, Ziada; Valstad, Mathias & Ystrom, Eivind
(2026).
Temporal Trends in the Severity and Impairment of Childhood and Adolescent ADHD: A Population-Wide Genetic Study in Norway.
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By calculating family genetic risk scores for the entire for the entire Norwegian population for birth years 1992-2019, ages 6-16 (N ≈ 1.5M) we show that the reduction in functional impairment over time is largely attributed to a diagnostic expansion of less genetically severe cases. Those who are diagnosed today have lower levels of genetic risk, while simulatenously, there has been no change in the relationship between GPA at age 16 and genetic risk for ADHD.
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Yang, Tianfang; Eftedal, Nikolai Haahjem; Valstad, Mathias; Reichborn-Kjennerud, Ted; Ystrom, Eivind & Czajkowski, Nikolai Olavi
(2025).
The lifespan impact of personality disorder on marital outcome: a Norwegian population study.
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Valstad, Mathias; Eftedal, Nikolai Haahjem; Yang, Tianfang; Reichborn-Kjennerud, Ted; Ystrom, Eivind & Czajkowski, Nikolai Olavi
(2025).
Epidemiology of personality disorders in Norway, 2010 to 2022.
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Czajkowski, Nikolai Olavi; Eilertsen, Espen Moen; Valstad, Mathias; Eftedal, Nikolai Haahjem & Ystrøm, Eivind
(2025).
A Bayesian Framework for Zygosity Classification and Heritability Estimation Using Nationwide Registry Data.
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Ayorech, Ziada Ng'ombo Laurel; Cheesman, Rosa Catherine Gillespie; Demange, Perline Aline Delle; Eilertsen, Espen Moen; Valstad, Mathias & Ystrøm, Eivind
(2025).
How the importance of family history and gender for receiving a depression diagnosis varies over GP’s.
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Yang, Tianfang; Ystrøm, Eivind; Valstad, Mathias; Eftedal, Nikolai Haahjem; Reichborn-Kjennerud, Ted & Czajkowski, Nikolai Olavi
(2025).
Marital Consequence of Personality Disorder: Evidence from Norwegian Registry.
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Ayorech, Ziada Ng'ombo Laurel; Cheesman, Rosa Catherine Gillespie; Demange, Perline Aline Delle; Eilertsen, Espen Moen; Valstad, Mathias & Ystrøm, Eivind
(2024).
GEOGRAPHICAL STRATIFICATION IN RECEIVING A DEPRESSION DIAGNOSIS IN THE NORWEGIAN POPULATION.
doi:
https:/www.sciencedirect.com/science/article/abs/pii/S0924977X24005455.
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Background
Depression runs in families, has a striking female preponderance, and in 2030 is predicted to be the leading cause of disease burden worldwide. Receiving a depression diagnosis is critical for access to appropriate treatment to alleviate the debilitating symptoms associated with this common disorder. Evidence that patient characteristics can contribute to who receives a diagnosis is well documented, however the extent to which GP tendencies for diagnosing depression are geographically stratified is unknown, in part due to the sparsity of large scale diagnostic data in population cohorts.
Methods
Here we capitalize on registry data for ∼ 5 million Norwegian adults including all ICPC2 depression codes, GP, clinic and residential identifiers. Multilevel models are used to test whether the role of familial risk (i.e., affected siblings) in predicting diagnosis varies as a function of geographical location and GP characteristics. In addition we test whether GP diagnosing varies by patients genetic risk and self-report symptoms by adding depression polygenic scores and symptom checklist data for a subset of the population (200,000 genotyped participants in the Norwegian Mother Father and Child study (Moba)) to our models.
Results
We provide descriptions of depression clusters across the entire Norwegian country and critical insight into the path from symptoms to diagnosis. Crucially, this novel approach informs on whether provider leniency impacts the genetic signal captured in large scale genome-wide association studies of depression.
Discussion
These results will have implications for academics, clinicians and the more than 300 million individuals and their families suffering from depression worldwide.
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Czajkowski, Nikolai Olavi; Eftedal, Nikolai Haahjem; Yang, Tianfang; Valstad, Mathias; Reichborn-Kjennerud, Ted & Ystrøm, Eivind
(2024).
The Role of Parental Personality Disorders in High School Dropout: Insights from a Nationwide Cohort Study.
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Yang, Tianfang; Ystrøm, Eivind; Valstad, Mathias; Eftedal, Nikolai Haahjem; Reichborn-Kjennerud, Ted & Czajkowski, Nikolai Olavi
(2024).
Parental Personality Disorder, Substance Abuse and Child Academic Performance: a Norwegian Registry Study.
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Published
Dec. 12, 2023 2:16 PM
- Last modified
Jan. 7, 2026 10:52 AM