Catherine Harmer

Reinecke A, Waldenmaier L, Cooper MJ, Harmer CJ. Changes in automatic threat processing precede and predict clinical changes with exposure-based cognitive-behavior therapy for panic disorder. Biol Psychiatry. 2013, 73(11):1064-70

Browning M, Holmes EA, Charles M, Cowen PJ, Harmer CJ. Using attentional bias modification as a cognitive vaccine against depression. Biol Psychiatry. 2012 Oct 1;72(7):572-9

Di Simplicio M, Norbury R, Harmer CJ. Short-term antidepressant administration reduces negative self-referential processing in the medial prefrontal cortex in subjects at risk for depression. Mol Psychiatry. 2012, 17: 503-510

Browning M, Holmes EA, Murphy SE, Goodwin GM, Harmer CJ. Lateral prefrontal cortex mediates the cognitive modification of attentional bias. Biol Psychiatry.  2010, 67:919-25.

McCabe C, Mishor Z, Cowen PJ, Harmer CJ. Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment. Biol Psychiatry. 2010, 67:439-45.

Harmer CJ, O'Sullivan U, Favaron E, Massey-Chase R, Ayres R, Reinecke A, Goodwin GM, Cowen PJ. Effect of acute antidepressant administration on negative affective bias in depressed patients. Am J Psychiatry. 2009, 166:1178-84.

Harmer CJ, Goodwin GM, Cowen PJ. Why do antidepressants take so long to work? A cognitive neuropsychological model of antidepressant drug action. Br J Psychiatry. 2009, 195: 102-8

Harmer CJ, Mackay CE, Reid CB, Cowen PJ, Goodwin GM. Antidepressant drug treatment modifies the neural processing of nonconscious threat cues. Biol Psychiatry. 2006, 59:816-20.

Hayward G, Goodwin GM, Cowen PJ, Harmer CJ. Low-dose tryptophan depletion in  recovered depressed patients induces changes in cognitive processing without depressive symptoms. Biol Psychiatry. 2005,57:517-24.

Harmer CJ, Shelley NC, Cowen PJ, Goodwin GM. Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Am J Psychiatry. 2004,161:1256-63.

• Jonassen, Rune; Øverli, Øyvind; Hilland, Eva; Nilsen, Hilde; Esbensen, Qin Ying & Lirussi, Lisa [Show all 13 contributors for this article] (2026). Serotonin transporter polymorphism (5-HTTLPR) is associated with post-awakening cortisol measures in previous depression. Comprehensive Psychoneuroendocrinology. 27, p. 1–7. doi: 10.1016/j.cpnec.2026.100363. Full text in Research Archive Show summary

  Elevated cortisol levels have been linked to major depressive disorder (MDD), but cortisol dynamics vary substantially across individuals and clinical states. Genetic variation in the serotonin transporter polymorphism (5-HTTLPR) has been proposed as one contributor to differences in hypothalamic-pituitary-adrenal axis functioning. The present study examined associations between cortisol awakening measures and 5-HTTLPR genotype groups in individuals with a history of depression compared with healthy controls, and explored whether current depressive symptom severity was related to cortisol indices. A total of 108 individuals with a history of depression were genotyped and compared with 59 healthy controls. Participants completed structured diagnostic interviews and self-reported depressive symptoms. Salivary cortisol was sampled in the evening and at five consecutive timepoints after awakening (15-min intervals). Cortisol was analyzed using a linear mixed-effects model of repeated measures and by cortisol awakening response (CAR) summary indices: area under the curve with respect to ground (AUCg) and area under the curve with respect to increase (AUCi). Cortisol changed significantly over time, but there was no evidence that genotype groups differed in the overall cortisol timecourse. In CAR summary analyses, group differences were observed for AUCg, whereas AUCi did not show corresponding group differences. Regression analyses indicated that BDI-II was not associated with AUCg or AUCi after adjustment for covariates. These findings suggest that 5-HTTLPR-related differences, when present, may be more detectable in overall post-awakening cortisol output than in baseline-relative increase.

• Hagen, Hallvard Solbø; Røssberg, Jan Ivar; Harmer, Catherine; Jonassen, Rune; Landrø, Nils Inge & Bø, Ragnhild (2025). Attention bias at baseline does not moderate the effect of attention bias modification for residual depressive symptoms. Journal of Behavior Therapy and Experimental Psychiatry. ISSN 0005-7916. 90, p. 1–8. doi: 10.1016/j.jbtep.2025.102073. Full text in Research Archive
• Klonteig, Sandra; Walsh, Annabel E.L.; Jonassen, Rune; Browning, Michael; Harmer, Catherine & Martens, Marieke A.G. (2025). Treatment response to bupropion: an investigation of changes in resting-state functional connectivity in patients with major depressive disorder. Psychopharmacology. ISSN 0033-3158. doi: 10.1007/s00213-025-06993-7. Full text in Research Archive Show summary

  Rationale Bupropion’s unique pharmacology as a dopaminergic and noradrenergic reuptake inhibitor distinguishes it from other antidepressants. Studies on a number of other antidepressants have demonstrated modulation of resting-state functional connectivity (rsFC). However, how bupropion affects rsFC in patients with major depressive disorder (MDD) remains unknown. Objectives To identify rsFC changes in MDD patients receiving bupropion treatment relative to a sample of controls. Method Thirty-nine MDD patients received 300 mg (titrated from 150 mg) Bupropion daily for 6 weeks. 40 controls received no treatment. All participants underwent MRI scans at baseline and after 2 weeks. Mood and symptom severity were assessed at baseline, week 2, and week 6. Comparisons of rsFC were made at baseline and for changes from baseline to the 2-week follow-up. Correlations between symptoms and rsFC were also assessed. Results In this explorative study, no significant baseline differences were found between patients and controls. Crossover interaction effects between groups and time were observed. Network analysis identified changed rsFC between the cerebellar network and left superior and middle temporal gyrus. Seed analysis showed changed rsFC between the insula and areas in the sensorimotor and occipital cortex as well as precuneus. No relationships were found between changes in symptoms at week 6 and rsFC changes at week 2. Conclusions This study is the first to examine bupropion’s effects on rsFC in MDD patients, revealing rsFC changes that may be important for bupropion’s mode of action. These preliminary findings provide a foundation for further investigation into bupropion and its underlying mechanisms, which may have important implications for depression treatment.

• Bø, Ragnhild; Jonassen, Rune; Harmer, Catherine; Øverli, Øyvind; Nilsen, Hilde & Esbensen, Qin Ying [Show all 13 contributors for this article] (2025). 5-HTTLPR does not moderate the effect of attention bias modification for depression: a randomized sham-controlled trial. Translational Psychiatry. 15, p. 1–6. doi: 10.1038/s41398-025-03581-3. Full text in Research Archive Show summary

  Abstract The 5-HTTLPR polymorphism in the serotonin transporter gene SLC6A4 has previously been dubbed a plasticity marker. Within the 5-HTTLPR polymorphism, a SNP (rs25531) in the L-allele in the promoter region, affects the transcription efficacy of the SCL6A4 , leading to functionally important differences related to serotonin transporter availability in the synapses. 5-HTTLPR has been implicated in magnitude of negative attentional bias, a causal risk factor for depression, and the modifiability of attentional biases both in positive and negative directions. Hence, this genotype may moderate the outcomes of attention bias modification (ABM) targeted at reducing depressive symptoms. We conducted a registered randomized sham-controlled trial of ABM in a sample of 301 participants with a history of Major Depressive Disorder (MDD) who had residual symptoms. They were randomized and underwent 14 days of two daily session of either ABM or sham at home. Of these, 264 provided genetic samples for determining the functionally important variant of the gene SLC6A4 . We investigated if the SNP ( rs25531 ) moderated the effect of ABM on symptoms of depression (HDRS, BDI-II) and anxiety (BAI), and attention bias post-intervention. None of the outcomes were moderated by the allelic variation in the promoter region of 5-HTTLPR . Limitations include low level of depressive symptoms, lack of data on ethnicity, current and prenatal level of stress, and early traumatic experiences. The 5-HTTLPR polymorphism did not moderate the effect of ABM on the symptom scales, nor attentional bias. Combination or interactions with other genes may be required for prescribing personalized interventions.

• Hagen, Hallvard Solbø; Røssberg, Jan Ivar; Harmer, Catherine; Jonassen, Rune; Landrø, Nils Inge & Bø, Ragnhild (2024). Does rumination moderate the effect of attention bias modification for depressive symptoms? Journal of Affective Disorders Reports. 17. doi: 10.1016/j.jadr.2024.100824. Full text in Research Archive Show summary

  Background: Current treatment of major depressive disorders still leave many patients with modest improvement. Attention Bias Modification (ABM) is an approach that may serve as an adjuvant therapy for subgroups of pa- tients. We examined whether rumination, often found to be associated with a negative attentional bias, acts as a moderating variable in a computerized ABM procedure in participants with recurrent depression. Methods: A total of 301 patients were randomized to receive either active - or sham ABM twice daily for 14 days. A regression-based moderator analysis was applied to evaluate whether baseline brooding, from the Rumination Response Scale (RRS-B), moderated the effect of ABM on Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory II (BDI-II). Results: There was no significant interaction effect of ABM and RRS-B on HDRS or BDI-II at post-intervention or at 1 month follow-up. In addition, no correlation was found for pre-training attention bias and RRS-B. Limitations: : Generalizability is limited to individuals with non-clinical symptom scores. Conclusions: There was no moderator effect of brooding rumination on clinical depression scales in the largest clinical study on ABM to date.

• Bø, Ragnhild; Kraft, Brage; Skilbrei, August; Jonassen, Rune; Harmer, Catherine & Landrø, Nils Inge (2024). Inhibition moderates the effect of attentional bias modification for reducing residual depressive symptoms: A randomized sham-controlled clinical trial. Journal of Behavior Therapy and Experimental Psychiatry. ISSN 0005-7916. 85(101982). doi: 10.1016/j.jbtep.2024.101982. Full text in Research Archive Show summary

  Objectives: Residual symptoms represent risk factor for relapse. Attention bias modification (ABM) may reduce clinical and sub-clinical depressive symptoms, indicating that is may be of relevance when preventing relapse. Current evidence suggests that executive functions may moderate the outcome of interventions targeting depressive symptoms. Methods: We assessed inhibition and shifting as indicators of executive functioning by means of the Color-Word Interference Test (i.e., “Stroop task”). These baseline characteristics were investigated as moderator of the effect of ABM on depression symptoms in a double-blinded randomized sham-controlled trial of ABM including patients with a history of recurrent depression (N = 301). Inclusion and follow-ups took place from January 2015 to October 2016. The trial was retrospectively registered #NCT02658682 January 2016. Results: The moderation analysis was based on the interaction term ABM x Stroop. Scaled inhibition scores ≤10.8, but not shifting ability, moderated the effect of ABM compared to sham on clinician-rated depression (HDRS). The difference from the 15th to the 85th percentile of the inhibition score was about 1 HDRS-point, indicating a small effect size. No moderation was found when self-reported depression and AB were the outcome. Post-hoc power calculation indicates risk of Type-II error. Conclusion: When targeting depressive symptoms, ABM seems to be somewhat more effective in patients with weak inhibitory control. This suggests that evaluating the level of inhibition in individual patients could provide some information when making decisions about prescribing ABM to reduce residual symptoms, but the clinical implications of this is uncertain due to an overall small effect size attributable to ABM. Future studies should examine whether inhibitory control still is a relevant moderator when comparing ABM to treatment options other than the sham control condition.

• Kraft, Brage; Bø, Ragnhild; Harmer, Catherine & Landrø, Nils Inge (2024). The effect of attentional bias modification on positive affect dynamics. Scientific Reports. 14(1), p. 23628–23628. doi: 10.1038/s41598-024-74855-x. Full text in Research Archive Show summary

  Negative attentional bias and alterations in positive affect dynamics constitute emotional vulnerability to depression. Attentional bias modification (ABM) aims to reduce emotional vulnerability to depression by fostering attentional deployment towards positive stimuli. In this randomized controlled trial, we examined whether ABM leads to changes in positive affect dynamics in a sample with an emotional vulnerability to depression (N = 65). Affect dynamics were measured based on experience sampling data gathered 14 days before and after ABM. During ABM, participants paid attention to pairs of emotional faces and responded to dots that were appearing in their place. There was an 87% chance for the dots to appear in place of the relatively more positive face, with the purpose to implicitly foster attentional focus on positive stimuli. In the control condition, there was a 50% chance of the dots to appear in place of the positive stimuli. Results showed that the lag-1 autocorrelation of affect (“inertia”) increased within the ABM group and decreased in the control group, but the findings were not robust and it was unclear whether ABM was the cause. There were no changes in the other affect dynamics indices. Improvements in depression during ABM were not associated with changes in affect dynamics, and affect dynamics post ABM did not predict depression symptoms six months later. In conclusion, the study showed no clear effect of ABM on affect dynamics.

• Bø, Ragnhild; Kraft, Brage; Jonassen, Rune; Joormann, Jutta; Harmer, Catherine & Landrø, Nils Inge (2024). The effect of ABM on attentional networks and stress-induced emotional reactivity in a mixed clinical sample with depression: A randomized sham-controlled trial. Neuroscience Applied. 3. doi: 10.1016/j.nsa.2024.104091. Full text in Research Archive Show summary

  Research on the efficacy of Attention Bias Modification for depressive symptoms has predominantly yielded unfavorable outcomes. Despite adhering to rigorous conventions in randomized controlled trials, findings from these studies have indicated minimal effect sizes, thereby raising concerns about their limited clinical significance. This may be attributed to the overlapping mechanisms in ABM and the sham comparator, both affecting attentional processes. Participants with a diagnosis of major depressive disorder, with and without comorbid anxiety (N = 101) were randomized to a two-week preregistered randomized trial of ABM compared to sham. Attentional networks were assessed prior to and after the intervention by the Attention Network Task (ANT), and emotional reactivity was assessed in response to a lab-stressor. Irrespective of condition, participants improved their performance on the alerting and executive attentional networks, but not orienting, and stress-induced emotional reactivity was marginally decreased. Changes in attentional networks predicted post-intervention depression scores. It is imperative to reconsider the employment of a sham comparator in the exploration of the clinical efficacy of ABM.

• Bø, Ragnhild; Kraft, Brage; Joormann, Jutta; Jonassen, Rune; Harmer, Catherine & Landrø, Nils Inge (2023). Cognitive predictors of stress-induced mood malleability in depression. Anxiety, Stress, & Coping. ISSN 1061-5806. 37(2), p. 278–292. doi: 10.1080/10615806.2023.2255531. Full text in Research Archive Show summary

  Background & objectives: Basic attentional control, negative biases in attention and interpretation, and rumination are all cognitive processes associated with depression; however, less is known about their predictive role in depressive mood reactivity and -recovery in response to stress, and their relation to severity of depression. Design & methods: We experimentally induced stress based on an autobiographical imagery script in a sample of 92 participants with Major Depressive Disorder with or without comorbid anxiety disorders. We used simple regression analysis for investigating the roles of state- and trait rumination, attentional networks, and attentional and interpretation biases for predicting stress-induced depressive mood reactivity and -recovery, respectively, and whether they in parallel mediated the association between cognitive processes and depression severity. Results: Stress-induced depressive mood reactivity was predicted by better orienting ability and more state rumination. Better recovery was predicted by better orienting efficiency and lower negative interpretation bias. Furthermore, the relation between state rumination and depression severity was partially mediated by depressive mood reactivity, however limited by the lack of temporal precedence in the analysis. Conclusions: We characterized the relation between cognitive processes and mood malleability in response to stress. Findings could refine theoretical models of depression if causality is established.

• Bø, Ragnhild; Kraft, Brage; Pedersen, Mads Lund; Joormann, Jutta; Jonassen, Rune & Osnes, Kåre [Show all 8 contributors for this article] (2023). The effect of attention bias modification on depressive symptoms in a comorbid sample: a randomized controlled trial. Psychological Medicine. ISSN 0033-2917. 53(13), p. 6389–6396. doi: 10.1017/S0033291722003956. Full text in Research Archive Show summary

  Background Studies investigating the long-term effect of attention bias modification (ABM) in clinical samples are lacking. This study investigates the 6-months follow-up effect of ABM on depressive symptoms in participant with major depressive disorder with and without comorbid disorders. Methods We conducted a double-blind randomized sham-controlled trial in 101 participants between 19 November 2019, and 17 August 2021. Follow-up ended 3 April 2022. Participants were allocated to ABM or sham condition twice daily for 14 consecutive days. Primary outcomes were the total score on the Beck Depression Inventory-II (BDI-II) at 6 months, mean Brief State Rumination Inventory (BSRI) score post-treatment and reduction in BSRI post-treatment. Secondary outcome was change in attentional bias (AB). The trial was preregistered in ClinicalTrials.gov (#NCT 04137367). Results A total of 118 patients aged 18–65 years were assessed for eligibility, and 101 were randomized and subjected to intention-to-treat analyses. At 6 months, ABM had no effect on depression and anxiety compared to a sham condition. While rumination decreased during the intervention, there was no effect of condition on rumination and AB. Predictor analysis did not reveal differences between participants with ongoing major depressive episode or comorbid anxiety. Conclusion Compared to sham training, there was no effect of ABM on depressive symptoms at 6-months follow-up. Since the intervention failed at modifying AB, it is unclear whether changes in AB are related to long-term outcomes.

• Bø, Ragnhild; Kraft, Brage; Jonassen, Rune; Pedersen, Mads Lund; Harmer, Catherine & Landrø, Nils Inge (2023). The long-term effects of ABM on symptom severity in patients with recurrent depression: A randomized sham-controlled trial. Journal of Affective Disorders. ISSN 0165-0327. 340, p. 886–892. doi: 10.1016/j.jad.2023.08.024. Full text in Research Archive Show summary

  Background: The present study reports on long-term outcomes of ABM over one year in self-reported and clinician-rated depression symptoms, anxiety symptoms, and relapse rates. Methods: We conducted a double-blind randomized sham-controlled trial in 301 participants with recurrent major depression disorder between January 2015 and October 2016 (#NCT02658682). Participants were allo- cated to ABM or sham condition twice daily for 14 consecutive days. Long-term effects of ABM were assessed by BDI-II, HDRS and BAI at one-, six-, and 12-months follow-up. Relapse rates at 12-months follow-up were also assessed. Results: There was no long-term effect of ABM (as compared to sham) on clinician-rated depression symptoms, on anxiety symptoms, nor in relapse rates. By 12 months follow-up, there was a small effect on self-reported depression favoring ABM over sham. Limitations: The lack of an assessment-only condition hinders comparison to natural trajectories of depression symptoms. Conclusions: The overall long-term effect of ABM was limited, and currently there is no convincing evidence for implementing this as a viable treatment option in clinical populations. We speculate if the sham condition should be replaced by another control condition when investigating the clinical utility of ABM.

• Kraft, Brage; Bø, Ragnhild; Hoorelbeke, Kristof; Koster, Ernst; Jonassen, Rune & Harmer, Catherine [Show all 7 contributors for this article] (2023). Examining attentional functioning in depression using a personalized network approach: A proof-of-principle study. Psychiatry Research Communications. 3(3). doi: 10.1016/j.psycom.2023.100137. Full text in Research Archive Show summary

  Reduced attentional functioning has been identified as an important factor in depression etiology and mainte- nance. However, current research does not fully take into account the large heterogeneity of depression, for example identifying for whom and how reduced attentional functioning plays a role. In this proof-of-principle study, we demonstrate how a personalized network approach can provide more nuanced insight into the role of attentional functioning in depression. To this end, we estimated person-specific symptom networks in a depression sample, and explored associations between reduced attentional functioning (alerting, orienting, ex- ecutive control) and symptom centrality (expected influence). Participants with ongoing and remitted depression were enrolled to 14 days of intensive assessment of depression symptoms in their daily life using a smartphone app. Based on these data, person-specific network models were estimated using vector autoregression modelling. Orienting, alerting and executive control were assessed using the Attentional Network Test in the laboratory. Person-specific networks showed large variability in symptom dynamics. Higher centrality of fatigue was asso- ciated with reduced orienting efficiency, and higher centrality of passivity was associated with reduced executive control. This study highlights the potential of assessing individual symptom dynamics when considering cognitive functioning in depression.

• Jonassen, Rune; Hilland, Eva; Harmer, Catherine; Abebe, Dawit Shawel; Bergem, Anne Kristine & Skarstein, Siv (2021). Use of Over-The-Counter Analgesics for Pain and Psychological Distress Among Adolescents: A Mixed Effects Approach in Cross-Sectional Survey Data From Norway. BMC Public Health. doi: 10.21203/rs.3.rs-78057/v1. Full text in Research Archive
• Bø, Ragnhild; Kraft, Brage; Jonassen, Rune; Harmer, Catherine; Hilland, Eva & Stiles, Tore C [Show all 10 contributors for this article] (2021). Symptom severity moderates the outcome of attention bias modification for depression: An exploratory study. Journal of Psychiatric Research. ISSN 0022-3956. 138, p. 528–534. doi: 10.1016/j.jpsychires.2021.04.027. Full text in Research Archive Show summary

  A recent meta-analysis has questioned the relevance of attention bias modification (ABM) for depression outcomes. However, there might be patient characteristics not yet accounted for, that are relevant to the outcome. In the context of personalized treatment, the lack of moderator studies have limited the potential for matching ABM-treatment to individual patient characteristics. Subjects (N = 301) were randomly assigned 1:1 to receive either active or placebo Attention Bias Modification (ABM) twice daily for 14 days in a double-blind design (placebo n = 148; ABM n = 153). The outcome was change in symptoms based on the Hamilton Depression Rating Scale (HDRS). Moderator variables were self-reported depression (Beck Depression Inventory-II; BDI-II), anxiety (Beck Anxiety Inventory; BAI) and attentional bias (AB) assessed at baseline. This trial was registered with ClinicalTrials.gov, number NCT02658682. Only BAI (p for interaction = .01, Bootstrap 95% CI [0.046, 0.337]) moderated the effects of ABM on change in clinician rated depressive symptoms. Interactions were significant for BAI scores ≥8. The relative effect of the intervention increased with the highest symptom load. ABM was not effective in patients with the lowest symptom load. Future research should validate this finding and continue investigating moderators of the ABM-intervention to further enhance personalization of treatment to individual symptom characteristics.

• Jonassen, Rune; Hilland, Eva; Harmer, Catherine J.; Abebe, Dawit Shawel; Bergem, Anne Kristine & Skarstein, Siv (2021). Over-the-counter analgesics use is associated with pain and psychological distress among adolescents: a mixed effects approach in cross-sectional survey data from Norway. BMC Public Health. 21(1), p. 1–12. doi: 10.1186/s12889-021-12054-3. Full text in Research Archive Show summary

  Background: Over-the-counter analgesics (OTCA) such as Paracetamol and Ibuprofen are frequently used by adolescents, and the route of administration and access at home allows unsupervised use. Psychological distress and pain occur simultaneously and are more common among females than among males. There is a dynamic interplay between on-label pain indications and psychological distress, and frequent OTCA use or misuse can exacerbate symptoms. No studies have to date provided an overview of frequent OTCA use in a larger population-based study. The current study used survey data to explore associations between and the relative predictive value of on-label pain indication and measures of psychological distress, together with sex differences for weekly OTCA use. Methods: This study included 349,528 adolescents aged 13–19. The data was collected annually between January 2014 and December 2018 as part of the Norwegian Young Data survey. Performance analysis was conducted to explore the relative roles and associations between on-label pain indication and psychological distress in weekly OTCA use. A mixed-effects logistic regression model was used to explore the unique contributions from four domains of on-label pain indication and psychological distress as measured by a combined measure of anxiety and depression (HSCL-10) and peer-bullying involvement as victims or bullies. Results: Thirty percent of females and 13 % of males use OTCA weekly. Headache is the strongest on-label pain predictor of weekly OTCA use, followed by abdominal pain. Depression and anxiety are the strongest psychological predictor of weekly OTCA use, and higher symptom levels and being female increase the strength of this association. Anxiety and depression also predict weekly OTCA use after controlling for physiological pain. Conclusions: Sex, pain and anxiety and depression are inter-correlated and strong predictors of frequent OTCA use. Frequent OTCA use in the context of psychological distress may be a form of self-medication that can exacerbate symptoms and decrease psychosocial function. Longitudinal studies that explore causal trajectories between frequent on-label OTCA use and psychological distress are required. OTCA use among adolescents, and particularly among females, with anxiety and depression should be administered with caution and closely monitored.

• Hilland, Eva; Landrø, Nils Inge; Harmer, Catherine; Browning, Michael; Maglanoc, Luigi Angelo & Jonassen, Rune (2019). Attentional bias modification is associated with fMRI response toward negative stimuli in individuals with residual depression: a randomized controlled trial. Journal of Psychiatry & Neuroscience. ISSN 1180-4882. doi: 10.1503/jpn.180118. Full text in Research Archive Show summary

  Background: Attentional bias modification (ABM) may lead to more adaptive emotion perception and emotion regulation. Understanding the neural basis of these effects may lead to greater precision for the development of future treatments. Task-related functional MRI (fMRI) after ABM training has not been investigated in depression so far. The main aim of this randomized controlled trial was to explore differences in brain activity after ABM training, in response to emotional stimuli. Methods: A total of 134 people with previous depression, who had been treated for depression and had various degrees of residual symptoms, were randomized to 14 days of active ABM or a closely matched placebo training, followed by an fMRI emotion regulation task. The training procedure was a classical dot–probe task with emotional face stimuli. In the active ABM condition, the probes replaced the more positively valenced face of a given pair. As participants implicitly learned to predict the probe location, this would be likely to induce a more positive attentional bias. The placebo condition was identical, except for the contingency of the probe, which appeared equally behind positive and negative stimuli. We compared depression symptoms and subjective ratings of perceived negativity during fMRI between the training groups. We explored brain activation in predefined regions of interest and across the whole brain. We explored activation in areas associated with changes in attentional bias and degree of depression. Results: Compared with the placebo group, the ABM group showed reduced activation in the amygdala and the anterior cingulate cortex when passively viewing negative images. We found no group differences in predefined regions of interest associated with emotion regulation strategies. Response in the temporal cortices was associated with the degree of change in attentional bias and the degree of depressive symptoms in ABM versus placebo. Limitations: These findings should be replicated in other samples of patients with depression, and in studies using fMRI designs that allow analyses of within-group variability from baseline to follow-up. Conclusion: Attentional bias modification training has an effect on brain function in the circuitry associated with emotional appraisal and the generation of affective states. Clinicaltrials.gov identifier: NCT02931487.

• Hilland, Eva; Landrø, Nils Inge; Harmer, Catherine; Browning, Michael; Maglanoc, Luigi Angelo & Jonassen, Rune (2019). Attentional bias modification is associated with fMRI response toward negative stimuli in individuals with residual depression: a randomized controlled trial. Journal of Psychiatry & Neuroscience. ISSN 1180-4882. 45(1), p. 23–33. doi: 10.1503/jpn.180118. Full text in Research Archive
• Kraft, Brage; Jonassen, Rune; Heeren, Alexandre; Harmer, Catherine; Stiles, Tore C & Landrø, Nils Inge (2019). Attention Bias Modification in Remitted Depression Is Associated With Increased Interest and Leads to Reduced Adverse Impact of Anxiety Symptoms and Negative Cognition. Clinical Psychological Science. ISSN 2167-7026. 7(3), p. 530–544. doi: 10.1177/2167702618822480. Full text in Research Archive Show summary

  Using a computational network approach, we reanalyzed data from a randomized controlled trial of attention bias modification (ABM) tasks on residual depression symptoms. The main aim was to characterize the symptom-to-symptom changes following ABM. ABM was associated with improvements in interest, which was in turn associated with improvements in other depression symptoms. Although there were no changes in the global network strength following ABM, the comparison with symptom change in the ABM and control group suggests that ABM leads to a reduction of the association between anxiety, depressed mood, and guilt. Findings suggest that reduction in depression symptoms following ABM may have been set in motion by increased interest and involvement in everyday activities, leading to a reduction of the adverse impact of anxiety and negative cognition. ABM may be more effective in patients in whom these symptoms are prominent.

• Jonassen, Rune; Harmer, Catherine; Hilland, Eva; Maglanoc, Luigi Angelo; Kraft, Brage & Browning, Michael [Show all 10 contributors for this article] (2019). Effects of Attentional Bias Modification on residual symptoms in depression: A randomized controlled trial. BMC Psychiatry. 19(141). doi: 10.1186/s12888-019-2105-8. Full text in Research Archive Show summary

  Background Following treatment, many depressed patients have significant residual symptoms. However, large randomised controlled trials (RCT) in this population are lacking. When Attention bias modification training (ABM) leads to more positive emotional biases, associated changes in clinical symptoms have been reported. A broader and more transparent picture of the true advantage of ABM based on larger and more stringent clinical trials have been requested. The current study evaluates the early effect of two weeks ABM training on blinded clinician-rated and self-reported residual symptoms, and whether changes towards more positive attentional biases (AB) would be associated with symptom reduction. Method A total of 321 patients with a history of depression were included in a preregistered randomized controlled double-blinded trial. Patients were randomised to an emotional ABM paradigm over fourteen days or a closely matched control condition. Symptoms based on the Hamilton Rating Scale for Depression (HRSD) and Beck Depression Inventory II (BDI-II) were obtained at baseline and after ABM training. Results ABM training led to significantly greater decrease in clinician-rated symptoms of depression as compared to the control condition. No differences between ABM and placebo were found for self-reported symptoms. ABM induced a change of AB towards relatively more positive stimuli for participants that also showed greater symptom reduction. Conclusion The current study demonstrates that ABM produces early changes in blinded clinician-rated depressive symptoms and that changes in AB is linked to changes in symptoms. ABM may have practical potential in the treatment of residual depression.

• Østergaard, Tom; Lundgren, Tobias; Rosendahl, Ingvar; Zettle, Robert; Jonassen, Rune & Harmer, Catherine [Show all 9 contributors for this article] (2019). Acceptance and Commitment Therapy Preceded by Attention Bias Modification on Residual Symptoms in Depression: A 12-Month Follow-Up. Frontiers in Psychology. 10, p. 1–13. doi: 10.3389/fpsyg.2019.01995. Full text in Research Archive Show summary

  Depression is a highly recurrent disorder with limited treatment alternatives for reducing risk of subsequent episodes. Acceptance and commitment therapy (ACT) and attention bias modification (ABM) separately have shown some promise in reducing depressive symptoms. This study investigates (a) if group-based ACT had a greater impact in reducing residual symptoms of depression over a 12-month follow-up than a control condition, and (b) if preceding ACT with ABM produced added benefits. This multisite study consisted of two phases. In phase 1, participants with a history of depression, currently in remission (N = 244), were randomized to either receive 14 days of ABM or a control condition. In phase 2, a quasi- experimental design was adopted, and only phase-1 participants from the Sørlandet site (N = 124) next received an 8-week group-based ACT intervention. Self-reported and clinician-rated depression symptoms were assessed at baseline, immediately after phase 1 and at 1, 2, 6, and 12 months after the conclusion of phase 1. At 12-month follow-up, participants who received ACT exhibited fewer self-reported and clinician-rated depressive symptoms. There were no significant differences between ACT groups preceded by ABM or a control condition. There were no significant differences between ACT groups preceded by ABM or a control condition. Group-based ACT successfully decreased residual symptoms in depression over 12 months, suggesting some promise in preventing relapse.

• Østergaard, Tom; Lundgren, Tobias; Zettle, Robert; Jonassen, Rune; Harmer, Catherine & Stiles, Tore C [Show all 8 contributors for this article] (2018). Acceptance and Commitment Therapy preceded by an experimental Attention Bias Modification procedure in recurrent depression: Study protocol for a randomized controlled trial. Trials. 19(203), p. 1–12. doi: 10.1186/s13063-018-2515-9. Full text in Research Archive Show summary

  Background This project studies the effect of group-based Acceptance and Commitment Therapy (ACT) following Attention Bias Modification (ABM) on residual symptoms in recurrent depression. ACT is a cognitive-behavioral intervention combining acceptance and mindfulness processes with commitment and behavior-change processes. ACT enjoys modest empirical support in treating depression and has also shown promising results in secondary prevention of depression. The experimental cognitive bias modification (ABM) procedure has been shown to reduce surrogate markers of depression vulnerability in patients in remission from depression. The aim of the current project is to investigate if the effect of group-based ACT on reducing residual depressive symptoms can be enhanced by preceding it with ABM. Also, assessment of the relationship between conceptually relevant therapeutic processes and outcome will be investigated. Methods/design An invitation to participate in this project was extended to 120 individuals within a larger sample who had just completed a separate randomized, multisite, clinical trial (referred to hereafter as Phase 1) in which they received either ABM (n = 60) or a control condition without bias modification (n = 60). This larger Phase-1 sample consisted of 220 persons with a history of at least two episodes of major depression who were currently in remission or not fulfilling the criteria of major depression. After its inclusion, Phase-1 participants from the Sørlandet site (n = 120) were also recruited for this study in which they received an 8-week group-based ACT intervention. Measures will be taken immediately after Phase 1, 1 month, 2 months, 6 months, and 1 year after the conclusion of Phase 1. Discussion This study sequentially combines acceptable, nondrug interventions from neuropsychology and cognitive-behavioral psychology in treating residual symptoms in depression. The results will provide information about the effectiveness of treatment and on mechanisms and processes of change that may be valuable in understanding and further developing ABM and ACT, combined and alone.

• Hilland, Eva; Landrø, Nils Inge; Harmer, Catherine; Maglanoc, Luigi Angelo & Jonassen, Rune (2018). Within-network connectivity in the salience network after attention bias modification training in residual depression: Report from a preregistered clinical trial. Frontiers in Human Neuroscience. 12. doi: 10.3389/fnhum.2018.00508. Full text in Research Archive Show summary

  Alterations in resting state networks (RSNs) are associated with emotional- and attentional control difficulties in depressed individuals. Attentional bias modification (ABM) training may lead to more adaptive emotional processing in depression, but little is known about the neural underpinnings associated with ABM. In the current study a sample of 134 previously depressed individuals were randomized into 14 days of computerized ABM- or a closely matched placebo training regime followed by a resting state magnetic resonance imaging (MRI) scan. Using independent component analysis (ICA) we examined within-network connectivity in three major RSN’s, the default mode network (DMN), the salience network (SN) and the central executive network (CEN) after 2 weeks of ABM training. We found a significant difference between the training groups within the SN, but no difference within the DMN or CEN. Moreover, a significant symptom improvement was observed in the ABM group after training.

• Jonassen, Rune; Chelnokova, Olga V; Harmer, Catherine; Leknes, Siri & Landrø, Nils Inge (2015). A single dose of antidepressant alters eye-gaze patterns across face stimuli in healthy women. Psychopharmacology. ISSN 0033-3158. 232(5), p. 953–958. doi: 10.1007/s00213-014-3729-5. Full text in Research Archive
• Aker, Martin; Bø, Ragnhild; Harmer, Catherine; Stiles, Tore C & Landrø, Nils Inge (2015). Inhibition and response to error in remitted major depression. Psychiatry Research. ISSN 0165-1781. 235, p. 116–122. doi: 10.1016/j.psychres.2015.11.038. Full text in Research Archive Show summary

  Depression is a common illness which tends to have a relapsing progression. Revealing vulnerability factors is an important step towards improved treatment and prevention. Previous studies of individuals in remission indicate that inhibitory control is more strongly impaired than other cognitive functions. Studies have mostly used Stroop tasks; it is unclear how this population performs on other measures of inhibition. Abnormal reactions to errors may also promote depression relapse, but this has rarely been studied in remitted depression. We used a Stop Signal task and Stroop inhibition task to investigate inhibitory function and post-error reaction time adjustments in 54 individuals with a history of depression and 185 never-depressed controls. Inhibitory processing was slower among the remitted depressed individuals on the Stop Signal task, but no difference was found in Stroop inhibition. The groups were not different on post-error adjustments. This finding extends the understanding of inhibitory deficiency in this population and offers insight into trait markers of depression.

• Aker, Martin; Harmer, Catherine & Landrø, Nils Inge (2014). More rumination and less effective emotion regulation in previously depressed women with preserved executive functions. BMC Psychiatry. 14(1). doi: 10.1186/s12888-014-0334-4. Full text in Research Archive Show summary

  Background: Major depressive disorder is associated with very high recurrence rates, and specific vulnerability factors that increase the risk for repeated episodes should be identified. Impaired executive functions have repeatedly been found in remitted populations. The current study included both neutral and emotional executive tasks, and we expected to find impaired performance in unmedicated previously depressed women compared to controls. Furthermore, we hypothesized that the executive functions inhibition and shifting would be related to the ability to apply cognitive reappraisal and to avoid unhealthy rumination. Methods: Inhibition and shifting data derived from neutral and emotional computerized tasks, and questionnaire data on emotion regulation and trait rumination, were obtained from previously depressed (n?=?109) and never-depressed women (n?=?64) and analyzed in independent samples t-tests. A logistic regression analysis investigated the ability of emotion regulation and rumination to predict depression vulnerability. The associations of executive functions to emotion regulation and rumination were investigated in a series of linear regression analyses. Participants on psychotropic medication were excluded from all analyses of executive performance. Results: Previously depressed participants, the majority of which had experienced recurrent episodes, matched control participants on both neutral and emotional executive tasks. However, significantly more rumination and expressive suppression, and less cognitive reappraisal, were found in the previously depressed group. Executive function was unrelated to rumination and emotion regulation in this sample. Conclusions: Previously depressed women whose executive function was intact were characterized by ruminative tendencies and more frequent use of expressive suppression. Trait rumination and expressive suppression are known to increase depression risk, but were unrelated to executive functions in this population. This indicates that unhealthy emotion regulation strategies may be targeted directly in preventive interventions.

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• Landrø, Nils Inge; Harmer, Catherine; Blackwell, Simon E.; Bø, Ragnhild; Dawson, Gerry & Goodwin, Guy [Show all 16 contributors for this article] (2023). Combining antidepressants and attention bias modification in primary health care (DEPTREAT): Protocol for a pragmatic randomized controlled trial. Contemporary Clinical Trials. ISSN 1551-7144. 133. doi: 10.1016/j.cct.2023.107326. Full text in Research Archive Show summary

  Background Major depressive disorder (MDD) is a highly prevalent psychiatric condition associated with significant disability, mortality and economic burden. A large proportion of MDD patients are treated in primary health care in the local community. Attentional Bias Modification (ABM) training in combination with antidepressants could be an effective treatment. Here we test the hypothesis that adding an ABM procedure to regular treatment with antidepressants in primary health care will result in further improvement of symptoms compared to treatment with antidepressants alone (treatment as usual, TAU) and as compared to an active comparison condition. Methods A total of 246 patients with a diagnosis of MDD will be included in this study. The study is a three-armed pragmatic randomized controlled trial comparing the efficacy of ABM as add-on to treatment with antidepressants in primary care (ABM condition) compared to standard antidepressant treatment (TAU condition). In a third group participants will complete the same schedule of intermediate assessments as the ABM condition in addition to TAU, but no ABM, thus controlling for the non-training-specific aspects of the ABM condition (Antidepressant active comparison group). Discussion The clinical outcome of this study may help develop easily accessible, low-cost treatment of depression in primary health care. Moreover, the study aims to broaden our knowledge of optimal treatment for patients with a MDD by providing adjunct treatment to facilitate recovery and long-term gain.

• Østergaard, Tom; Lundgren, Tobias; Rosendahl, Ingvar; Zettle, Robert D.; Jonassen, Rune & Harmer, Catherine [Show all 9 contributors for this article] (2023). Corrigendum: Acceptance and commitment therapy preceded by attention bias modification on residual symptoms in depression: a 12-month follow-up (Frontiers in Psychology, (2019), 10, (1995), 10.3389/fpsyg.2019.01995). Frontiers in Psychology. 14. doi: 10.3389/fpsyg.2023.1233621. Full text in Research Archive
• Bø, Ragnhild; Kraft, Brage; Jonassen, Rune; Harmer, Catherine & Landrø, Nils Inge (2022). The effect of attentional bias modification on attentional bias change is related to increased emotional reactivity. Full text in Research Archive
• Hilland, Eva; Landrø, Nils Inge; Harmer, Catherine; Maglanoc, Luigi Angelo; Browning, Michael & Jonassen, Rune (2018). Attentional Bias Modification alters fMRI response towards negative stimuli in depression. Full text in Research Archive
• Jonassen, Rune; Hilland, Eva; Harmer, Catherine; Berge, Torkil; Maglanoc, Luigi Angelo & Kraft, Brage [Show all 9 contributors for this article] (2017). Attentional Bias Modification reduces symptom severity in major depression: Preliminary analysis from an ongoing longitudinal RCT study. Full text in Research Archive
• Jonassen, Rune; Hilland, Eva; Harmer, Catherine; Berge, Torkil; Maglanoc, Luigi Angelo & Kraft, Brage [Show all 9 contributors for this article] (2016). Attention bias modification reduces symptom severity in Major Depression. Preliminary analysis from an ongoing longitudinal RCT study. Full text in Research Archive
• Jonassen, Rune; Chelnokova, Olga V; Harmer, Catherine; Leknes, Siri & Landrø, Nils Inge (2014). A single dose of antidepressant alters eye-gaze patterns across face stimuli in healthy women. Full text in Research Archive

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