Martin Steen Tesli

• Schwaba, Ted; Sullivan, Margaret L. Clapp; Akingbuwa, Wonuola A.; Ilves, Kerli; Tanksley, Peter T. & Williams, Camille M. [Show all 138 contributors for this article] (2026). Robust inference and correlates from genetic associations with personality. Nature. ISSN 0028-0836. doi: 10.1038/s41586-026-10992-9. Full text in Research Archive
• Corfield, Elizabeth Claire; Shadrin, Alexey; Frei, Oleksandr; Rahman, Mohammad Zillur; Akdeniz, Bayram Cevdet & Filiz, Tahir Tekin [Show all 29 contributors for this article] (2026). Family genetic designs in MoBa provide insights into health and functioning. Nature. ISSN 0028-0836. doi: 10.1038/s41586-026-10926-5. Full text in Research Archive Show summary

  Genome-wide association studies using large, population-based samples of unrelated individuals have discovered thousands of genetic associations with health and disease1. These studies can help explain genetic and environmental risks. However, increasing evidence suggests that population-based estimates, while precise, can also reflect confounding that affects their use and interpretation. This confounding can be overcome using data from genotyped family members, such as nuclear mother–father–child trios2,3. However, samples of genotyped families are rare4,5,6,7,8,9,10,11. Here we illustrate some of the advantages of familial data using the Norwegian Mother, Father and Child Cohort Study (MoBa), a population-based cohort of parents and offspring with extensive genotype data (n ≈ 230,000) (ref. 3), along with broad and longitudinal phenotyping of health and functioning. We provide an overview of MoBa and describe the quality control of genotype data tailored to this extensively related sample. We then use trio data to illustrate how family-based genomic designs can identify distinct direct and indirect sources of genetic influence and structural confounding. As examples, we analyse children’s height, educational achievement, depressive symptoms and sleep duration. These demonstrations highlight MoBa as a broadly valuable resource for advancing understanding of health and functioning across the lifecourse and generations.

• Streit, Fabian; Awasthi, Swapnil; Hall, Alisha S.M.; Braun, Alice; Niarchou, Maria & Marouli, Eirini [Show all 152 contributors for this article] (2026). Genome-wide association analyses of borderline personality disorder identify 11 loci and highlight shared risk with mental and somatic disorders. Nature Genetics. ISSN 1061-4036. 58, p. 1831–1844. doi: 10.1038/s41588-026-02654-3. Full text in Research Archive Show summary

  Borderline personality disorder (BPD) is a severe mental health condition influenced by environmental risk factors (for example, interpersonal trauma) and genetic factors. We conducted the largest genome-wide association study (GWAS) meta-analysis of BPD so far, with a discovery sample of 12,339 cases and 1,041,717 controls, and a replication study of 685 cases and 107,750 controls (all participants of European ancestry). We identified 11 independent associated genomic loci and 9 risk genes in gene-based analyses. We observed a single-nucleotide polymorphism heritability of 17.3% and derived polygenic scores (PGS) that predicted 4.6% of the phenotypic variance in BPD on the liability scale. BPD showed the strongest positive genetic correlations with GWAS of post-traumatic stress disorder, depression, attention deficit hyperactivity disorder, antisocial behavior, and measures of suicide and self-harm. Phenome-wide analyses in Vanderbilt University Medical Center Biobank and UK Biobank using BPD-PGS confirmed these associations and also identified associations with other medical conditions, including obstructive pulmonary disease and diabetes. These analyses highlight BPD as a polygenic disorder, with the genetic risk showing substantial overlap with psychiatric and physical health conditions.

• Tesli, Natalia; Jaholkowski, Piotr Pawel; Rokicki, Jaroslav; Jangmo, Andreas; Ziaka, Laoura & Shadrin, Alexey [Show all 9 contributors for this article] (2026). Adolescents at the crossroads: genetic associations between psychotic symptoms and antisocial traits | European Child & Adolescent Psychiatry | Springer Nature Link. European Child and Adolescent Psychiatry. ISSN 1018-8827. doi: 10.1007/s00787-026-03153-w. Full text in Research Archive Show summary

  Antisocial behaviour in youth has serious consequences at individual and societal level. Adolescence is also a critical period for the emergence of prodromal psychosis symptoms. Their co-occurrence may aggravate aggression and lead to severe adverse outcomes. Common genetic risk for psychosis, antisocial behaviour, and substance use has been suggested, but the putatively shared genetic architecture is unknown, and evidence in youth is limited. Here we examined whether common genetic liability indexed by polygenic risk scores (PRSs) relates to these complex traits in the Norwegian Mother, Father and Child Cohort Study (MoBa; n = 18960). Antisocial psychopathology was operationalised as three complementary dimensions: conduct-disorder (CD) traits, oppositional-defiant disorder (ODD) traits, and psychopathy traits. We first quantified phenotypic correlations between psychotic-like experiences (PLEs) and the antisocial dimensions. We then evaluated PRS-phenotype associations (single-PRS and joint multivariable models) using PRSs for antisocial behaviour (PRSASB) and schizophrenia (PRSSCZ), in addition to PRS for alcohol use disorder (PRSAUD). We found phenotypic correlations between antisocial traits and PLEs (rs=0.13–0.34, p < 0.0001). This overlap was reflected at the genetic level, as we found associations between PRSASB and PLEs (p = 0.0004). The associations between PRSSCZ and antisocial traits were present for CD (p = 0.005) and ODD (p = 0.003) traits. Both PLEs and antisocial traits were associated with PRSAUD. Patterns persisted in mutually adjusted models. These findings indicate cross-trait associations between polygenic liability for SCZ, ASB, AUD and adolescent PLEs and antisocial dimensions in the general youth population, consistent with partially shared common genetic influences. Future studies should further delineate underlying biological mechanisms.

• Kirkøen, Benedicte; Eriksen, Astrid M.A.; Broderstad, Ann Ragnhild; Høye, Anne; Johansson, Jonas & Sivertsen, Børge [Show all 15 contributors for this article] (2026). Trends in anxiety and depressive symptoms among adults in Norway based on eight population-based surveys from 1995 to 2024. Discover Mental Health. doi: 10.1007/s44192-026-00522-4. Full text in Research Archive Show summary

  Abstract Background Increasing symptoms of anxiety and depression among adolescents and emerging adults are well documented, while less attention has been given to how these symptoms have evolved among adults of all ages. We aim to describe the development of symptoms of anxiety and depression for women and men in the adult population in Norway over the past three decades. Methods For the first time, we synthesize data from all population-based, cross-sectional surveys of symptoms of anxiety and depression among adults in Norway. Data were extracted from the Living Condition Survey (1998–2012, and 2015–2019), HUNT (1995/97-2017/19), the Tromsø Study (2001–2015/16), SAMINOR (2003/04–2012), Quality of Life Survey (2021–2024), the FHUS Agder (2019–2023), FHUS Oslo (2020–2024), and the Student’s Health and Wellbeing Study (SHoT, 2010–2022). Changes over time in symptoms were examined though sex and age stratified regression models. Results Data from 30 separate data collections include 584 173 adults aged 18–89 years between 1995 and 2024. We observe a clear increase in symptoms of anxiety and depression among young adults, especially among young women. Among individuals in midlife, findings are mixed, with most studies indicating stability or only minor fluctuations. In contrast, the symptoms of older adults appears to have remained stable or even improved. Conclusions Results show divergent trends in symptoms of anxiety and depression among adults. There has been an increase in symptoms among young adults, while symptoms remain stable or improved in old age. The results highlight the need for targeted preventive efforts among younger adults and for careful continued observation.

• Tesli, Martin Steen; Hjellvik, Vidar; Lergenmuller, Simon; Hjell, Gabriela; Jangmo, Andreas & Haram, Marit [Show all 13 contributors for this article] (2026). Socioeconomic Position and Somatic Comorbidity in Mental Disorders. Acta Psychiatrica Scandinavica. ISSN 0001-690X. doi: 10.1111/acps.70113. Full text in Research Archive Show summary

  Introduction Individuals with mental disorders face an elevated risk for somatic noncommunicable diseases (NCD), such as cardiovascular disease (CVDs), chronic obstructive pulmonary disease (COPD), diabetes, and cancer. Low socioeconomic position (SEP) is linked to both mental disorders and somatic NCDs, but its role in this association remains unclear. Here, we provide a comprehensive overview of how associations between mental disorders and somatic NCDs vary by SEP indicators. Methods Data on all adult individuals resident in Norway from 01.01.2008 to 01.01.2010 (N = 3,589,719) were derived from a nationwide registry linkage including information on primary and secondary health care, dispensed drugs, causes of death, and socioeconomic factors. We assessed four broad types of mental disorders (psychotic, bipolar, depressive and anxiety disorders) and four categories of somatic NCDs (CVD, COPD, diabetes, cancer) diagnosed during follow-up from 01.01.2010 to 31.12.2020. Educational attainment and household income were used as SEP indicators, in addition to parental educational attainment. Cox regression models estimated hazard ratios for somatic NCDs among individuals with mental disorders compared to the general population, adjusting for and stratifying by SEP, sex, and age. Results All mental disorders were associated with an increased risk of somatic NCDs, strongest for COPD and weakest for cancer. Risk increased with disorder severity, with psychotic and bipolar disorders showing the strongest associations. Young adults with psychosis had a 4–5-fold increased risk of diabetes and COPD. Low SEP was associated with both mental disorders and somatic NCDs with moderate attenuating effects in their co-occurrence and little variation across SEP strata. Conclusion We found an increased risk of somatic NCDs in individuals with mental disorders and identified young adults with psychosis as a particularly vulnerable subgroup. Low SEP compounds this burden, underscoring the need for integrated mental and somatic healthcare strategies.

• Veloz, Maria Fernanda Vinueza; Bhatta, Laxmi; Jones, Paul Remy; Tesli, Martin Steen; Smith, George Davey & Davies, Neil Martin [Show all 8 contributors for this article] (2025). Educational attainment and mental health outcomes: A within-sibship Mendelian randomization study. Psychological Medicine. ISSN 0033-2917. 55, p. 1–10. doi: 10.1017/s0033291725101736. Full text in Research Archive Show summary

  Abstract Background Observational studies indicate that higher educational attainment (EA) is associated with a lower risk of many mental health conditions (MHC). We assessed to what extent this association is influenced by genetic nurture and demographic factors (i.e., assortative mating and population structure). Methods We conducted a within-sibship Mendelian randomization (MR) study. The sample consisted of 61 880 siblings (27 507 sibships) from the Trøndelag Health Study-HUNT (Norway) and UK Biobank (United Kingdom). MHC outcomes included symptom scores for anxiety, depression, and neuroticism, measured using the Hospital Anxiety and Depression Scale, the 7-item Generalized Anxiety Disorder Scale, the 9-item Patient Health Questionnaire, and the Eysenck Personality Questionnaire, along with self-reported psychotropic medication use. Results One standard deviation (SD) increase in liability to EA was associated with lower anxiety (−0.20 SD [95% CI: −0.26, −0.14]), depression (−0.11 SD [−0.43, −0.22]), and neuroticism scores (−0.30 SD [−0.53, −0.06]), as well as lower odds of psychotropic medication use (OR: 0.60 [0.52, 0.69]). Within-sibship MR estimates remained consistent with population-based estimates: anxiety (−0.17 SD [−0.33, −0.00]); depression (−0.18 SD [−1.26, 0.89]); neuroticism (−0.29 SD [−0.43, −0.15]); psychotropic medication use (OR, 0.52 [0.34, 0.82]). Conclusions Higher EA or genetic liability to education reduces symptoms of anxiety, neuroticism, and psychotropic medication use. These mental health benefits do not seem to be explained by EA-linked genetic nurture or demographic factors. Regarding depression, results were less conclusive due to imprecise estimates, though beneficial effects of genetic liability to higher EA are possible and warrant further investigation.

• Savinen, Suvi; Stavseth, Marianne Riksheim; Bukten, Anne; Tesli, Martin Steen; Fazel, Seena & Chang, Zheng (2025). Prediction of reoffending in people released from prison in Norway: external validation of the OxRec risk assessment tool. Psychology, Crime and Law. ISSN 1068-316X. p. 1–12. doi: 10.1080/1068316x.2025.2581796. Full text in Research Archive Show summary

  Scalable and evidence-based methods for risk assessment are increasingly required in the criminal justice system. The aim of this study was to externally validate the OxRec risk prediction tool using Norwegian data. Predictors were extracted from administrative registers. Outcomes included violent and any reoffending within 1 and 2 years after prison release. OxRec’s predictive performance was tested in terms of discrimination, calibration, and classification according to predetermined thresholds. A total of 26,863 individuals (median age = 36 [IQR 27–46]; 90% male) were included, of whom 29% and 39% reoffended within 1 and 2 years, respectively. After recalibration, discrimination of OxRec was good, with AUCs ranging from 0.721 to 0.774. Sensitivity and specificity depended on the outcome, with sensitivity ranging from 72% to 86% and specificity from 44% to 70%. The model was well-calibrated. To conclude, a recalibrated version of the OxRec tool demonstrated good predictive performance for risk of violent reoffending and any reoffending within 1 and 2 years after release from prison. It has the potential to be implemented in the Norwegian criminal justice system to supplement professional judgement and assist with providing appropriate support measures upon prison release.

• Grotzinger, Andrew D.; Werme, Josefin; Peyrot, Wouter J.; Frei, Oleksandr; Leeuw, Christiaan de & Bicks, Lucy K. [Show all 72 contributors for this article] (2025). Mapping the genetic landscape across 14 psychiatric disorders. Nature. ISSN 0028-0836. 649(8096), p. 406–415. doi: 10.1038/s41586-025-09820-3. Full text in Research Archive Show summary

  Psychiatric disorders display high levels of comorbidity and genetic overlap, challenging current diagnostic boundaries. For disorders for which diagnostic separation has been most debated, such as schizophrenia and bipolar disorder, genomic methods have revealed that the majority of genetic signal is shared. While over a hundred pleiotropic loci have been identified by recent cross-disorder analyses, the full scope of shared and disorder-specific genetic influences remains poorly defined. Here we addressed this gap by triangulating across a suite of cutting-edge statistical and functional genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders (1,056,201 cases). Using genetic association data from common variants, we identified and characterized five underlying genomic factors that explained the majority of the genetic variance of the individual disorders (around 66% on average) and were associated with 238 pleiotropic loci. The two factors defined by (1) Schizophrenia and bipolar disorders (SB factor); and (2) major depression, PTSD and anxiety (Internalizing factor) showed high levels of polygenic overlap and local genetic correlation and very few disorder-specific loci. The genetic signal shared across all 14 disorders was enriched for broad biological processes (for example, transcriptional regulation), while more specific pathways were shared at the level of the individual factors. The shared genetic signal across the SB factor was substantially enriched in genes expressed in excitatory neurons, whereas the Internalizing factor was associated with oligodendrocyte biology. These observations may inform a more neurobiologically valid psychiatric nosology and implicate targets for therapeutic development designed to treat commonly occurring comorbid presentations.

• Bauer, Anna E.; Jaholkowski, Piotr Pawel; Lu, Yi; Guintivano, Jerry; Hannigan, Laurie John & Corfield, Elizabeth Claire [Show all 14 contributors for this article] (2025). Identification and validation of postpartum depression subtypes: a population-based cohort study. EClinicalMedicine. 89, p. 103540–103540. doi: 10.1016/j.eclinm.2025.103540. Full text in Research Archive Show summary

  Background Postpartum depression (PPD) affects 18% of postpartum women globally. PPD is a heterogeneous condition with diverse presentations, which may differ in underlying etiology, potential outcomes, and optimal treatment. This study aimed to identify and validate PPD subtypes using comprehensive phenotypic and genetic data from a large, nationwide cohort. Methods In this population-based cohort study, we used data from the Norwegian Mother, Father, and Child Cohort Study and Medical Birth Registry of Norway (MoBa), and applied unsupervised clustering (Uniform Manifold Approximation and Projection [UMAP] + Density-Based Spatial Clustering of Applications with Noise [DBSCAN]) to identify PPD subtypes among 7859 women with PPD (training set n = 5239). All pregnant women in Norway were eligible to enroll in MoBa between Jun 1, 1999 and Dec 31, 2008. Among women with their first recorded pregnancies in MoBa, they were considered to have clinically significant PPD if they scored ≥8 on the 6-item version of the Edinburgh Postnatal Depression Scale (EPDS) (equivalent to ≥11 on the full EPDS) administered at six months after birth. Input variables included psychiatric symptom severity, psychiatric history, trauma history, pain, and substance use. We then characterized clusters and tested associations with perinatal-relevant auxiliary variables and polygenic scores (PGS) for eight psychiatric and neurodevelopmental conditions. Findings were validated in a reserved test set (n = 2620). Findings Nine clusters were identified in the training set (n = 5239), with seven replicating in the independent test set (n = 2620). Clusters were differentiated by symptom severity, onset timing, trauma history, and pain during pregnancy. In the training set, the cluster with the most severe symptoms was characterized by depression + trauma and comprised 28% [1483/5239] of training sample. This cluster showed marked socioeconomic adversity and elevated genetic risk for psychiatric conditions compared to other clusters (ADHD PGS OR 1.19, 95% CI 1.12–1.28; major depression PGS OR 1.15, 95% CI 1.07–1.23; PTSD PGS OR 1.09, 95% CI 1.02–1.17). In the test set, this cluster also comprised 28% [729/2620] and showed consistent associations with ADHD (OR 1.23, 95% CI 1.12–1.35), major depression (OR 1.09, 95% CI 0.99–1.20), and PTSD (OR 1.17, 95% CI 1.06–1.29). Conversely, the mild PPD cluster (10% [498/5239] of training sample) showed a protective profile (ADHD PGS OR 0.81, 95% CI 0.73–0.90; major depression PGS OR 0.85, 95% CI 0.77–0.94). In the test set, it represented 10% (263/2620), with consistent protective associations for ADHD (OR 0.84, 95% CI 0.72–0.96) and major depression (OR 0.77, 95% CI 0.67–0.89). Two early-onset clusters demonstrated distinct profiles despite similar symptom severity. The cluster characterized as early-onset PPD + pain (6% of training set [310/5239] and 7% of test set [178/2620]) had the highest prevalence of somatic conditions, including migraines (19% [58/310] training; 15% [26/178] test), nausea (47% [144/310] training; 53% [94/178] test), prenatal hospitalization (41% [128/310] training; 35% [62/178] test), and birth by caesarean section (10% [31/310] training; 8% [14/178] test), whereas the cluster characterized as early-onset PPD + anger (6% [307/5239] of training sample; 6% [158/2620] of test sample) showed many fewer physical health burdens. The clusters in the training and testing set had moderate to high concordance (ARI = 0.76 [95% CI 0.74, 0.77], FMI = 0.79 [95% CI 0.77, 0.81]).

• Bergstedt, Jacob; Kõiv, Kadri; Jangmo, Andreas; Haram, Marit; Jaholkowski, Piotr Pawel & Treur, Jorien L. [Show all 21 contributors for this article] (2025). Associations of Genetic Liability to Six Psychiatric Disorders With Cardiometabolic Diseases. medRxiv. doi: 10.1101/2025.03.11.25323757. Full text in Research Archive Show summary

  Abstract IMPORTANCE Individuals with psychiatric disorders have increased risk of cardiometabolic diseases (CMDs). Evaluating how psychiatric genetic liability relates to CMD may clarify mechanisms. OBJECTIVE Identify genetic overlap between psychiatric disorders and CMDs independent of cross-disorder pleiotropy, BMI, and smoking. DESIGN, SETTING, AND PARTICIPANTS Three Northern European cohorts (the Swedish Twin Registry, the Estonian Biobank, and the Norwegian Mother, Father and Child Cohort Study [MoBa]) totaling 355,159 individuals. Associations with CMDs were estimated as adjusted odds ratios (AORs) from logistic models mutually adjusted for all psychiatric PRSs and in models additionally adjusting for body mass index (BMI) and smoking. Cohort-specific AORs were pooled by inverse-variance weighting. MAIN OUTCOMES AND MEASURES Exposures were PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), anxiety disorder, posttraumatic stress disorder (PTSD), bipolar disorder, and schizophrenia. Outcomes were diagnoses of CMDs (hyperlipidemia, obesity, type 2 diabetes, hypertensive diseases, arteriosclerosis, ischemic heart disease, heart failure, thromboembolic disease, cerebrovascular disease, and arrhythmias), ascertained from electronic health records. RESULTS The MDD PRS was associated with increased risk of all CMDs across analyses (AORs ranged from 1.13 [95% CI, 1.10-1.15] for heart failure to 1.02 [95% CI, 1.00-1.05] for arrhythmias). The ADHD PRS was associated with increased risk of all CMDs (AOR ranged from 1.11 [95% CI, 1.09-1.12] for obesity to 1.02 [95% CI, 1.01-1.03] for hyperlipidemia), however associations where attenuated when adjusting for BMI and smoking (lifestyle adjusted AOR for obesity: 1.03 [95% CI, 1.02-1.05]). When not mutually adjusting for all psychiatric PRSs, anxiety disorder and PTSD PRSs were associated with all CMDs; these associations diminished after adjustment. The bipolar and schizophrenia PRSs were inversely associated with most CMDs (AOR for schizophrenia PRS and obesity, 0.93 [95% CI, 0.92-0.94]). CONCLUSIONS AND RELEVANCE Associations between psychiatric PRSs and CMDs diverged: ADHD, MDD, anxiety disorder, and PTSD PRSs were positively associated with CMDs, whereas bipolar and schizophrenia PRSs were inversely associated. Genetic liability to MDD showed robust associations with CMDs independent of cross-disorder pleiotropy, BMI, and smoking status, whereas associations between the ADHD PRS and CMDs were largely attenuated after adjustment for BMI and smoking. Key Points Question Is genetic liability to specific psychiatric disorders associated with an increased risk of clinically diagnosed cardiometabolic diseases even after adjusting for cross-disorder psychiatric pleiotropy, body mass index, and smoking status? Findings In this study of cohorts in Sweden, Estonia, and Norway, genetic liability to major depressive disorder (MDD) showed stronger associations with cardiometabolic disease (CMD) compared to other psychiatric disorders. Genetic liability to anxiety disorder and PTSD showed associations with CMD that were attenuated when adjusting for cross-disorder psychiatric pleiotropy. Genetic liability to ADHD showed strong associations with obesity and type 2 diabetes that were strongly attenuated when adjusting for body mass index, and smoking status. Genetic liability to schizophrenia showed inverse associations with CMD. Meaning These findings suggest that MDD has a distinctive genetic relationship with CMD compared to other psychiatric disorders and that the well-established phenotypic association between schizophrenia and CMD is not related to genetic factors.

• Shorter, John R.; Pasman, Joëlle A.; Kurvits, Siim; Jangmo, Andreas; Naamanka, Joonas & Harder, Arvid [Show all 31 contributors for this article] (2025). Genome-wide association analyses identify distinct genetic architectures for early-onset and late-onset depression. Nature Genetics. ISSN 1061-4036. 57, p. 2972–2979. doi: 10.1038/s41588-025-02396-8. Full text in Research Archive Show summary

  Major depressive disorder (MDD) is a common and heterogeneous disorder of complex etiology. Studying more homogeneous groups stratified according to clinical characteristics, such as age of onset, can improve the identification of the underlying genetic causes and lead to more targeted treatment strategies. We leveraged Nordic biobanks with longitudinal health registries to investigate differences in the genetic architectures of early-onset (eoMDD; n  = 46,708 cases) and late-onset (loMDD; n  = 37,168 cases) MDD. We identified 12 genomic loci for eoMDD and two for loMDD. Overall, the two MDD subtypes correlated moderately (genetic correlation, r g  = 0.58) and differed in their genetic correlations with related traits. These findings suggest that eoMDD and loMDD have partially distinct genetic signatures, with a specific developmental brain signature for eoMDD. Importantly, we demonstrate that polygenic risk scores (PRS) for eoMDD predict suicide attempts within the first 10 years after the initial diagnosis: the absolute risk for suicide attempt was 26% in the top PRS decile, compared to 12% and 20% in the bottom decile and the intermediate group, respectively. Taken together, our findings can inform precision psychiatry approaches for MDD.

• Haram, Marit; Jangmo, Andreas; Jaholkowski, Piotr Pawel; Pasman, Joëlle; Meijsen, Joeri & Shorter, John R. [Show all 15 contributors for this article] (2025). Associations of polygenic risk scores for major depression and depression severity: an investigation of 105 623 individuals with 16 years follow-up. Molecular Psychiatry. ISSN 1359-4184. p. 1–8. doi: 10.1038/s41380-025-03243-2. Full text in Research Archive Show summary

  Genetic risk could be informative for identifying individuals at risk of depression with severe outcomes. With the novel approach of combined health care registries and self-report measures related to depression, the authors aimed to identify the impact of polygenic risk scores (PRS) for major depression on self report measures and a diagnosis of depression across diagnostic thresholds. The study sample comprised participants from the Norwegian Mother, Father and Child Cohort Study with linked information of depression diagnoses during 2006–2022 from health registries. Linear and logistic models were used to estimate the associations between PRS for major depression and self-reported measures related to depression (Symptom Checklist- 5, Satisfaction With Life Scale, Rosenberg Self-Esteem Scale), and a diagnosis of depression. Analyses were performed in groups stratified by level of depression severity defined by registrations in primary and specialist health care. Among the 105 623 individuals included in the study, mean (SD) age was 33.9 (5.3) and 58.5% were female. The associations between PRS for major depression and Rosenberg Self-Esteem Scale were more prominent in individuals with a history of inpatient status compared to outpatient status (β = 0.095, cluster robust 95% CI 0.029–0.162; P  = 0.005) and status of primary care (β = 0.098, cluster robust 95% CI 0.035–0.160; P  = 0.002). PRS for major depression were associated with a diagnosis of depression in all groups of depression severity, with highest effect sizes for more severe types (history of inpatient status: OR = 1.85, cluster robust 95% CI 1.75–1.94; P  < 0.01). The results provide new knowledge of how PRS for major depression vary with depression severity.

• O'Connell, Kevin Sean; Koromina, Maria; Veen, Tracy van der; Boltz, Toni; David, Friederike S. & Yang, Jessica Mei Kay [Show all 313 contributors for this article] (2025). Genomics yields biological and phenotypic insights into bipolar disorder. Nature. ISSN 0028-0836. 639, p. 968–975. doi: 10.1038/s41586-024-08468-9. Full text in Research Archive Show summary

  Bipolar disorder is a leading contributor to the global burden of disease1. Despite high heritability (60–80%), the majority of the underlying genetic determinants remain unknown2. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings3, and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder4, highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder.

• Adams, Mark J.; Streit, Fabian; Meng, Xiangrui; Awasthi, Swapnil; Adey, Brett N. & Choi, Karmel W. [Show all 51 contributors for this article] (2025). Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies. Cell. ISSN 0092-8674. 188(3), p. 640–652.e9. doi: 10.1016/j.cell.2024.12.002. Full text in Research Archive Show summary

  In a genome-wide association study (GWAS) meta-analysis of 688,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries across diverse and admixed ancestries, we identify 697 associations at 635 loci, 293 of which are novel. Using fine-mapping and functional tools, we find 308 high-confidence gene associations and enrichment of postsynaptic density and receptor clustering. A neural cell-type enrichment analysis utilizing single-cell data implicates excitatory, inhibitory, and medium spiny neurons and the involvement of amygdala neurons in both mouse and human single-cell analyses. The associations are enriched for antidepressant targets and provide potential repurposing opportunities. Polygenic scores trained using European or multi-ancestry data predicted MD status across all ancestries, explaining up to 5.8% of MD liability variance in Europeans. These findings advance our global understanding of MD and reveal biological targets that may be used to target and develop pharmacotherapies addressing the unmet need for effective treatment.

• Bramness, Jørgen Gustav; Hjellvik, Vidar; Høye, Anne; Tesli, Martin Steen; Haram, Marit & Nystad, Wenche [Show all 7 contributors for this article] (2024). The epidemiology of major depression among adults in Norway: an observational study on the concurrence between population surveys and registry data – a NCDNOR project. BMC Public Health. 24(1). doi: 10.1186/s12889-024-18754-w. Full text in Research Archive Show summary

  Background Mental health problems, and major depression in particular, are important public health issues. Following trends in the prevalence of major depression is difficult because of the costs and complications of diagnostic interviews and general population self-report health surveys. Scandinavian countries, however, have several central, population-based health registries. We aimed to investigate how well these registries capture the epidemiology of major depression in the population. Methods In two Norwegian regional surveys of general population health, each repeated after 10 years, responders were asked to report depressive symptoms using the Hopkins Symptom Checklist (HSCL) or the Hospital Anxiety and Depression Scale (HADS). Data were linked to three central health registries capturing contact with primary care, specialist care and prescriptions for antidepressants, to investigate how well these registries reflected self-reported depressive symptoms. Results Most responders scored low on Hopkins Symptom Checklist (HSCL) and the Hospital Anxiety and Depression Scale (HADS), but 10% and 13%, respectively, scored above cut-off, with only minor changes between the two survey times. Females scored higher than males. Older people scored lower than younger, and a social gradient was visible. Around 12% of those who scored above the cut-off on either scale were recorded in the central health registries during the following year. This correlation was highest in primary care data, followed by prescription data and lowest in specialist care. Females were more often recorded in registries (p < 0.001), as were younger people (p < 0.001). Conclusions There was a strong association between scores on screening for major depression in the general population surveys and being recorded in central health registries. There was a low sensitivity of these registries. and there was some variation in how sensitive the central health registries were in picking up depression, especially for males and older people. However, the stability of the measures over time suggests we may get an impression of the prevalence of major depression in the general population by using data from the central health registries. A combination of primary care data, prescription data and specialist care data have a higher sensitivity.

• Odsbu, Ingvild; Hamina, Aleksi; Hjellvik, Vidar; Handal, Marte; Haram, Marit & Tesli, Martin Steen [Show all 8 contributors for this article] (2024). Initiation of Antipsychotics During the First Year After First-Episode Psychosis: A Population-Based Study. Acta Psychiatrica Scandinavica. ISSN 0001-690X. doi: 10.1111/acps.13776. Full text in Research Archive Show summary

  Background Antipsychotics are recommended after first-episode psychosis. Knowledge on the current use patterns in real-world settings is thus important to inform clinical practice. We aimed to describe antipsychotic initiation during 1 year after first-episode psychosis and its associated factors. Methods Population-based cohort study using linked nationwide health and population registers from Norway. The study population comprised 8052 persons aged 16–45 years with first-episode psychosis diagnosed in secondary care (ICD-10 F20, F22–F29) in the period 2011–2019. Initiation of antipsychotic use was defined as being dispensed antipsychotics (ATC N05A, excl. lithium) at least once from −90 to +365 days from secondary care diagnosis of first-episode psychosis. Antipsychotic polypharmacy during follow-up was defined as having at least 90 days with overlapping drug use periods modeled using the Prescriptions to Drug Use Periods method. Adjusted risk ratios (aRRs) with 95% confidence intervals (CIs) for the association between socioeconomic and clinical factors and initiation of antipsychotic use were calculated using modified Poisson regression. Results In total, 4413 persons (54.8%) initiated antipsychotic use after first-episode psychosis with proportions ranging from 45.5% in 2012 to 62.1% in 2019. Oral formulations of olanzapine (34.9%), quetiapine (21.2%), and aripiprazole (11.6%) were most common at initiation, whereas long-acting injectables (LAIs) and clozapine were rarely used. Among the initiators, 13.8% started a polypharmacy period lasting more than 90 days. Factors associated with antipsychotic initiation were lower age (aRR 1.14, 95% CI 1.08–1.21; 26–35 years vs. 36–45 years), higher education (1.11, 1.05–1.18), being employed (1.04, 1.00–1.09), being hospitalized (1.13, 1.09–1.18), being diagnosed late in the study period (1.16, 1.11–1.22; 2017–2019 vs. 2011–2013), or with previously diagnosed bipolar disorder, depression, or anxiety disorders. Conclusions The antipsychotic use pattern is largely within the current clinical guideline. Primary non-compliance and disease severity may explain the socioeconomic and clinical differences related to initiation of antipsychotic use.

• Indregard, Anne Marthe Rustad; Nussle, Hans Martin; Hagen, Milada; Vandvik, Per Olav; Tesli, Martin Steen & Gather, Jakov [Show all 7 contributors for this article] (2024). Open-door policy versus treatment-as-usual in urban psychiatric inpatient wards: a pragmatic, randomised controlled, non-inferiority trial in Norway. The Lancet Psychiatry. ISSN 2215-0374. 11(5), p. 330–338. doi: 10.1016/S2215-0366(24)00039-7. Full text in Research Archive Show summary

  Background - Open-door policy is a recommended framework to reduce coercion in psychiatric wards. However, existing observational data might not fully capture potential increases in harm and use of coercion associated with open-door policies. In this first randomised controlled trial, we compared coercive practices in open-door policy and treatment-as-usual wards in an urban hospital setting. We hypothesised that the open-door policy would be non-inferior to treatment-as-usual on the proportion of patients exposed to coercive measures.<p> <p>Methods - We conducted a pragmatic, randomised controlled, non-inferiority trial comparing two open-door policy wards and three treatment-as-usual acute psychiatric wards at Lovisenberg Diaconal Hospital in Oslo, Norway. An exemption from the consent requirements enabled inclusion and random allocation of all patients admitted to these wards using an open list (2:3 ratio) administrated by a team of ward nurses. The primary outcome was the proportion of patient stays with one or more coercive measures, including involuntary medication, isolation or seclusion, and physical and mechanical restraints. The non-inferiority margin was set to 15%. Primary and safety analyses were assessed using the intention-to-treat population. The trial is registered with ISRCTN registry and is complete, ISRCTN16876467.<p> <p>Findings - Between Feb 10, 2021, and Feb 1, 2022, we randomly assigned 556 patients to either open-door policy wards (n=245; mean age 41·6 [SD 14·5] years; 119 [49%] male; 126 [51%] female; and 180 [73%] admitted to the ward involuntarily) or treatment-as-usual wards (n=311; mean age 41·6 [4·3] years; 172 [55%] male and 138 [45%] female; 233 [75%] admitted involuntarily). Data on race and ethnicity were not collected. The open-door policy was non-inferior to treatment-as-usual on all outcomes: the proportion of patient stays with exposure to coercion was 65 (26·5%) in open-door policy wards and 104 (33·4%) in treatment-as-usual wards (risk difference 6·9%; 95% CI –0·7 to 14·5), with a similar trend for specific measures of coercion. Reported incidents of violence against staff were 0·15 per patient stay in open-door policy wards and 0·18 in treatment-as-usual wards. There were no suicides during the randomised controlled trial period.<p> <p>Interpretation - The open-door policy could be safely implemented without increased use of coercive measures. Our findings underscore the need for more reliable and relevant randomised trials to investigate how a complex intervention, such as open-door policy, can be efficiently implemented across health-care systems and contexts.

• Bakken, Nora Refsum; Parker, Nadine; Hannigan, Laurie John; Hagen, Espen; Parekh, Pravesh & Shadrin, Alexey [Show all 15 contributors for this article] (2024). Childhood trajectories of emotional and behavioral difficulties are related to polygenic liability for mood and anxiety disorders. Journal of Child Psychology and Psychiatry. ISSN 0021-9630. 66(3), p. 350–365. doi: 10.1111/jcpp.14063. Full text in Research Archive Show summary

  Background Symptoms related to mood and anxiety disorders (emotional disorders) often present in childhood and adolescence. Some of the genetic liability for mental disorders, and emotional and behavioral difficulties seems to be shared. Yet, it is unclear how genetic liability for emotional disorders and related traits influence trajectories of childhood behavioral and emotional difficulties, and if specific developmental patterns are associated with higher genetic liability for these disorders. Methods This study uses data from a genotyped sample of children (n = 54,839) from the Norwegian Mother, Father, and Child Cohort Study (MoBa). We use latent growth models (1.5–5 years) and latent profile analyses (1.5–8 years) to quantify childhood trajectories and profiles of emotional and behavioral difficulties and diagnoses. We examine associations between these trajectories and profiles with polygenic scores for bipolar disorder (PGSBD), anxiety (PGSANX), depression (PGSDEP), and neuroticism (PGSNEUR). Results Associations between PGSDEP, PGSANX, and PGSNEUR, and emotional and behavioral difficulties in childhood were more persistent than age-specific across early childhood (1.5–5 years). Higher PGSANX and PGSDEP were associated with steeper increases in behavioral difficulties across early childhood. Latent profile analyses identified five profiles with different associations with emotional disorder diagnosis. All PGS were associated with the probability of classification into profiles characterized by some form of difficulties (vs. a normative reference profile), but only PGSBD was uniquely associated with a single developmental profile. Conclusions Genetic risk for mood disorders and related traits contribute to both a higher baseline level of, and a more rapid increase in, emotional and behavioral difficulties across early and middle childhood, with some indications for disorder-specific profiles. Our findings may inform research on developmental pathways to emotional disorders and the improvement of initiatives for early identification and targeted intervention.

• Akdeniz, Bayram Cevdet; Frei, Oleksandr; Hagen, Espen; Filiz, Tahir Tekin; Karthikeyan, Sandeep & Pasman, Joëlle [Show all 18 contributors for this article] (2024). COSGAP: COntainerized Statistical Genetics Analysis Pipelines. Bioinformatics Advances. 4(1). doi: 10.1093/bioadv/vbae067. Full text in Research Archive Show summary

  The collection and analysis of sensitive data in large-scale consortia for statistical genetics is hampered by multiple challenges, due to their non-shareable nature. Time-consuming issues in installing software frequently arise due to different operating systems, software dependencies, and limited internet access. For federated analysis across sites, it can be challenging to resolve different problems, including format requirements, data wrangling, setting up analysis on high-performance computing (HPC) facilities, etc. Easier, more standardized, automated protocols and pipelines can be solutions to overcome these issues. We have developed one such solution for statistical genetic data analysis using software container technologies. This solution, named COSGAP: “COntainerized Statistical Genetics Analysis Pipelines,” consists of already established software tools placed into Singularity containers, alongside corresponding code and instructions on how to perform statistical genetic analyses, such as genome-wide association studies, polygenic scoring, LD score regression, Gaussian Mixture Models, and gene-set analysis. Using provided helper scripts written in Python, users can obtain auto-generated scripts to conduct the desired analysis either on HPC facilities or on a personal computer. COSGAP is actively being applied by users from different countries and projects to conduct genetic data analyses without spending much effort on software installation, converting data formats, and other technical requirements.

• Jaholkowski, Piotr Pawel; Shadrin, Alexey; Jangmo, Anders Andreas Krister; Frei, Evgeniia; Woldeyohannes, Markos Tesfaye & Hindley, Guy Frederick Lanyon [Show all 23 contributors for this article] (2023). Associations Between Symptoms of Premenstrual Disorders and Polygenic Liability for Major Psychiatric Disorders. JAMA psychiatry. ISSN 2168-6238. doi: 10.1001/jamapsychiatry.2023.1137. Full text in Research Archive
• Hiller, John Kim; Jangmo, Andreas; Tesli, Martin Steen; Jaholkowski, Piotr Pawel; Hoseth, Eva Zsuzsanna & Steen, Nils Eiel [Show all 7 contributors for this article] (2023). Lipid Biomarker Research in Bipolar Disorder: A Scoping Review of Trends, Challenges, and Future Directions. Biological Psychiatry: Global Open Science. 3(4), p. 594–604. doi: 10.1016/j.bpsgos.2023.07.004. Full text in Research Archive Show summary

  Bipolar disorder (BD) is a disabling disorder with heterogeneous symptom profiles and trajectories. Like many other neuropsychiatric disorders, clinical decision making related to diagnoses and choice of treatment is based on clinical assessments alone, and risk prediction for treatment success or resistance at an individual level remains sparse. An enormous effort to add biological markers to this risk prediction is ongoing. The role of lipids in normal brain functioning is well established, and several hypotheses about the role of lipids in the pathogenesis of neuropsychiatric disorders, including BD, have been made. The frequent comorbidity between neuropsychiatric disorders and cardiovascular disease, the genetic overlap of risk genes for severe mental disorders and genes involved in lipid regulation, and the lipid-altering effects of antipsychotics and mood stabilizers indicate that lipids could hold promise as biomarkers for neuropsychiatric disorders, including BD. To date, reviews of lipid biomarkers in schizophrenia and major depression have noted caveats for future investigations, while reviews of lipid biomarker research in BD is missing. In the current scoping review, we present a comprehensive overview of trends in previous research on lipid biomarkers in BD. The current literature varies greatly in the phenotypes investigated and study designs, leading to divergent findings. Small sample size; potential confounders related to physical activity, nutritional status, and medication use; and cross-sectional designs were frequently reported limitations. Future research may benefit from pivoting toward utilization of newer laboratory techniques such as lipidomics, but consistent use of study methods across cohorts is also needed.

• Jaholkowski, Piotr; Shadrin, Alexey A.; Jangmo, Andreas; Frei, Evgeniia; Woldeyohannes, Markos Tesfaye & Hindley, Guy F. L. [Show all 23 contributors for this article] (2023). Associations Between Symptoms of Premenstrual Disorders and Polygenic Liability for Major Psychiatric Disorders. JAMA psychiatry. ISSN 2168-6238. 80(7), p. 738–742. doi: 10.1001/jamapsychiatry.2023.1137. Full text in Research Archive
• Guintivano, Jerry; Byrne, Enda M.; Kiewa, Jacqueline; Yao, Shuyang; Bauer, Anna E. & Aberg, Karolina A. [Show all 78 contributors for this article] (2023). Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression. American Journal of Psychiatry. ISSN 0002-953X. 180(12), p. 884–895. doi: 10.1176/appi.ajp.20230053. Full text in Research Archive
• Pasman, Joëlle A.; Meijsen, Joeri J.; Haram, Marit; Kowalec, Kaarina; Harder, Arvid & Xiong, Ying [Show all 23 contributors for this article] (2023). Epidemiological overview of major depressive disorder in Scandinavia using nationwide registers. The Lancet Regional Health - Europe. 29. doi: 10.1016/j.lanepe.2023.100621. Full text in Research Archive Show summary

  Background Major depressive disorder (MDD) is a common psychiatric disorder associated with a high disease burden. This study gives a comprehensive overview of the prevalence, outcomes, treatment, and genetic epidemiology of MDD within and across the Scandinavian countries. Methods This study has aimed to assess and compare across Norway, Denmark, and Sweden 1) the prevalence and trajectories of MDD and comorbidity, 2) outcomes and treatment, and 3) heritability (Denmark and Sweden only). The analyses leveraged data on 272,944 MDD cases (and 6.2 million non-cases) from Norway, Sweden, and Denmark in specialist care in national longitudinal health registers covering 1975–2013. Relying on harmonized public data global comparisons of socioeconomic and health metrics were performed to assess to what extent findings are generalizable. Findings MDD ranked among the most prevalent psychiatric disorders. For many cases, the disorder trajectory was severe, with varying proportions experiencing recurrence, developing comorbid disorders, requiring inpatient treatment, or dying of suicide. Important country differences in specialist care prevalence and treatment were observed. Heritability estimates were moderate (35–48%). In terms of socioeconomic and health indices, the Scandinavian nations were comparable to one another and grouped with other Western nations. Interpretation The Scandinavian countries were similar with regards to MDD epidemiological measures, but we show that differences in health care organization need to be taken into consideration when comparing countries. This study demonstrates the utility of using comprehensive population-wide registry data, outlining possibilities for other applications. The findings will be of use to policy makers for developing better prevention and intervention strategies.

• Demontis, Ditte; Walters, G. Bragi; Athanasiadis, Georgios; Walters, Raymond; Therrien, Karen & Nielsen, Trine Tollerup [Show all 88 contributors for this article] (2023). Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains. Nature Genetics. ISSN 1061-4036. 55, p. 198–208. doi: 10.1038/s41588-022-01285-8. Full text in Research Archive
• Tesli, Natalia; Jaholkowski, Piotr Pawel; Jaholkowski, Piotr Pawel; Haukvik, Unn Kristin Hansen; Jangmo, Andreas & Haram, Marit [Show all 16 contributors for this article] (2023). Conduct disorder - a comprehensive exploration of comorbidity patterns, genetic and environmental risk factors. Psychiatry Research. ISSN 0165-1781. 331, p. 1–10. doi: 10.1016/j.psychres.2023.115628. Full text in Research Archive
• Reponen, Elina Johanna; Ueland, Thor; Rokicki, Jaroslav; Bettella, Francesco; Aas, Monica & Werner, Maren Caroline Frogner [Show all 10 contributors for this article] (2023). Polygenic risk for schizophrenia and bipolar disorder in relation to cardiovascular biomarkers. European Archives of Psychiatry and Clinical Neuroscience. ISSN 0940-1334. doi: 10.1007/s00406-023-01591-0. Full text in Research Archive Show summary

  Individuals with schizophrenia and bipolar disorder are at an increased risk of cardiovascular disease (CVD), and a range of biomarkers related to CVD risk have been found to be abnormal in these patients. Common genetic factors are a putative underlying mechanism, alongside lifestyle factors and antipsychotic medication. However, the extent to which the altered CVD biomarkers are related to genetic factors involved in schizophrenia and bipolar disorder is unknown. In a sample including 699 patients with schizophrenia, 391 with bipolar disorder, and 822 healthy controls, we evaluated 8 CVD risk biomarkers, including BMI, and fasting plasma levels of CVD biomarkers from a subsample. Polygenic risk scores (PGRS) were obtained from genome-wide associations studies (GWAS) of schizophrenia and bipolar disorder from the Psychiatric Genomics Consortium. The CVD biomarkers were used as outcome variables in linear regression models including schizophrenia and bipolar disorder PGRS as predictors, age, sex, diagnostic category, batch and 10 principal components as covariates, controlling for multiple testing by Bonferroni correction for the number of independent tests. Bipolar disorder PGRS was significantly (p = 0.03) negatively associated with BMI after multiple testing correction, and schizophrenia PGRS was nominally negatively associated with BMI. There were no other significant associations between bipolar or schizophrenia PGRS, and other investigated CVD biomarkers. Despite a range of abnormal CVD risk biomarkers in psychotic disorders, we only found a significant negative association between bipolar disorder PGRS and BMI. This has previously been shown for schizophrenia PGRS and BMI, and warrants further exploration.

• Tesli, Martin Steen; Nesvåg, Ragnar; Haukvik, Unn Kristin Hansen; Gustavson, Kristin; Tesli, Natalia & Friestad, Christine [Show all 12 contributors for this article] (2023). Common genetic and environmental risk for personality disorders and psychotic-like experiences in young adult twins. Acta Psychiatrica Scandinavica. ISSN 0001-690X. 148(6), p. 561–569. doi: 10.1111/acps.13596. Full text in Research Archive Show summary

  Abstract Introduction Psychotic‐like experiences (PLE) have been associated with the subsequent emergence of psychotic disorders as well as several other domains of psychopathology. In this twin study, we estimated the genetic and environmental correlations between PLE and 10 personality disorders (PD). Methods Diagnoses of 10 PDs according to the Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV) and PLE from the Composite International Diagnostic Interview (CIDI) were retrieved for 2793 young adult twins from the Norwegian Twin Registry. Risk for having a PD and PLEs was modeled using item response theory. Biometric twin models were fitted to estimate the genetic and environmental correlations between PDs and PLEs. Co‐twin control analysis was performed to estimate additional within‐family risk for PLEs when having a PD. Results Phenotypic overlap between PDs and PLEs ranged from 14% to 44% in males and from 11% to 39% in females, with the highest overlap for borderline PD in both sexes. In general, we found higher genetic correlations ( r  = 0.14–0.72) than environmental correlations ( r  = 0.06–0.28) between PDs and PLEs. The highest genetic correlations between PLE and PDs were found for borderline ( r  = 0.72), paranoid ( r  = 0.56), schizotypal ( r  = 0.56) and antisocial PD (r = 0.49). Conclusion We found that the co‐occurrence between PDs and PLE is the best explained by shared genetic determinants, with minor contributions from environmental factors. Interestingly, borderline PD was highly genetically correlated with PLE, warranting molecular genetic studies of this association.

• Langlete, Petter; Tesli, Martin Steen; Veneti, Lamprini; Starrfelt, Jostein; Elstrøm, Petter & Meijerink, Hinta (2023). Estimated vaccine effectiveness against SARS-CoV-2 Delta and Omicron infections among health care workers and the general adult population in Norway, August 2021 – January 2022. Vaccine. ISSN 0264-410X. 41(26), p. 3923–3929. doi: 10.1016/j.vaccine.2023.05.022. Full text in Research Archive Show summary

  Background Health care workers (HCW) have a higher exposure to SARS-CoV-2 virus than other professionals and to protect both HCW and patients, HCW have been prioritized for vaccination against SARS-CoV-2 in many countries. Estimating the COVID-19 vaccine effectiveness among HCW is important to provide recommendations to protect risk groups. Methods We estimated vaccine effectiveness against SARS-CoV-2 infections using Cox proportional hazard models among HCW with comparisons in the general population, from 1 August 2021 to 28 January 2022. Vaccine status is specified as a time-varying covariate and all models incorporated explicit time and were adjusted for age, sex, comorbidities, county of residence, country of birth, and living conditions. Data from the adult Norwegian population (aged 18-67 years) and HCW workplace data (as registered 1 January 2021) were collated from the National Preparedness Register for COVID-19 (Beredt C19). Results Vaccine effectiveness was higher for Delta than for the Omicron variant in HCW (71 % compared to 19 %) as well as in non-HCW (69 % compared to -32 %). For the Omicron variant a 3rd dose provides significantly better protection against infection than 2 doses in both HCW (33 %) and non-HCW (10 %). Further, HCW seem to have better vaccine effectiveness than non-HCW for the Omicron, but not for the Delta variant. Conclusions Vaccine effectiveness were comparable between HCW and non-HCW for the delta variant, but significantly higher in HCW than non-HCW for the omicron variant. Both HCW and non-HCW got increased protection from a third dose.

• Bakken, Nora R.; Parker, Nadine; Hannigan, Laurie J.; Hagen, Espen; Parekh, Pravesh & Shadrin, Alexey [Show all 15 contributors for this article] (2023). Childhood trajectories of emotional and behavioral difficulties are related to polygenic liability for mood and anxiety disorders. medRxiv. doi: 10.1101/2023.11.21.23298804. Full text in Research Archive
• Tesli, Natalia; Bell, Christina; Hjell, Gabriela; Fischer-Vieler, Thomas; Maximov, Ivan & Richard, Geneviève [Show all 14 contributors for this article] (2022). The age of violence: Mapping brain age in psychosis and psychopathy. NeuroImage: Clinical. 36. doi: 10.1016/j.nicl.2022.103181. Full text in Research Archive Show summary

  Young chronological age is one of the strongest predictors for antisocial behaviour in the general population and for violent offending in individuals with psychotic disorders. An individual's age can be predicted with high accuracy using neuroimaging and machine-learning. The deviation between predicted and chronological age, i.e., brain age gap (BAG) has been suggested to reflect brain health, likely relating partly to neurodevelopmental and aging-related processes and specific disease mechanisms. Higher BAG has been demonstrated in patients with psychotic disorders. However, little is known about the brain-age in violent offenders with psychosis and the possible associations with psychopathy traits. We estimated brain-age in 782 male individuals using T1-weighted MRI scans. Three machine learning models (random forest, extreme gradient boosting with and without hyper parameter tuning) were first trained and tested on healthy controls (HC, n = 586). The obtained BAGs were compared between HC and age matched violent offenders with psychosis (PSY-V, n = 38), violent offenders without psychosis (NPV, n = 20) and non-violent psychosis patients (PSY-NV, n = 138). We ran additional comparisons between BAG of PSY-V and PSY-NV and associations with Positive and Negative Syndrome Scale (PANSS) total score as a measure of psychosis symptoms. Psychopathy traits in the violence groups were assessed with Psychopathy Checklist-revised (PCL-R) and investigated for associations with BAG. We found significantly higher BAG in PSY-V compared with HC (4.9 years, Cohen's d = 0.87) and in PSY-NV compared with HC (2.7 years, d = 0.41). Total PCL-R scores were negatively associated with BAG in the violence groups (d = 1.17, p < 0.05). Additionally, there was a positive association between psychosis symptoms and BAG in the psychosis groups (d = 1.12, p < 0.05). While the significant BAG differences related to psychosis and not violence suggest larger BAG for psychosis, the negative associations between BAG and psychopathy suggest a complex interplay with psychopathy traits. This proof-of-concept application of brain age prediction in severe mental disorders with a history of violence and psychopathy traits should be tested and replicated in larger samples.

• Rødevand, Linn; Tesli, Martin Steen & Andreassen, Ole (2022). Cardiovascular disease risk in people with severe mental disorders: An update and call for action. Current Opinion in Psychiatry. ISSN 0951-7367. 35(4), p. 277–284. doi: 10.1097/YCO.0000000000000797. Full text in Research Archive
• Havdahl, Alexandra; Wootton, Robyn E; Leppert, Beate; Riglin, Lucy; Ask, Helga & Tesli, Martin Steen [Show all 16 contributors for this article] (2022). Associations between Pregnancy-Related Predisposing Factors for Offspring Neurodevelopmental Conditions and Parental Genetic Liability to Attention-Deficit/Hyperactivity Disorder, Autism, and Schizophrenia: The Norwegian Mother, Father and Child Cohort Study (MoBa). JAMA psychiatry. ISSN 2168-6238. 79(8), p. 799–810. doi: 10.1001/jamapsychiatry.2022.1728. Full text in Research Archive Show summary

  Importance Several maternal exposures during pregnancy are considered predisposing factors for offspring neurodevelopmental conditions. However, many of these exposures may be noncausal and biased by maternal genetic liability. Objective To assess whether pregnancy-related predisposing factors for offspring neurodevelopmental conditions are associated with maternal genetic liability for attention-deficit/hyperactivity disorder (ADHD), autism, and schizophrenia and to compare associations for maternal genetic liability with those for paternal genetic liability, which could indicate that paternal exposures are not suitable negative controls for maternal exposures. Design, Setting, and Participants The Norwegian Mother, Father and Child Cohort Study (MoBa) is a population-based pregnancy cohort that recruited parents from June 1999 to December 2008. Polygenic scores (PGS) for ADHD, autism, and schizophrenia were derived in mothers and fathers. The associations between maternal PGS and 37 pregnancy-related measures were estimated, and these results were compared with those from paternal PGS predicting paternal measures during the mother’s pregnancy. Analysis took place between March 2021 and March 2022. Exposures PGS for ADHD, autism, and schizophrenia, calculated (using discovery effect size estimates and threshold of P < .05) from the largest available genome-wide association studies. Main Outcomes and Measures Self-reported pregnancy-related measures capturing lifestyle behaviors, metabolism, infectious and autoimmune diseases, other physical health conditions, and medication use. Results Data were available for up to 14 539 mothers (mean [SD] age, 30.00 [4.45] years) and 14 897 fathers (mean [SD] age, 32.46 [5.13] years) of European ancestry. Modest but robust associations were observed between specific pregnancy-related measures and maternal PGS, including ADHD PGS with asthma (odds ratio [OR], 1.15 [95% CI, 1.06-1.25]), smoking (OR, 1.26 [95% CI, 1.19-1.33]), prepregnancy body mass index (β, 0.25 [95% CI, 0.18-0.31]), pregnancy weight gain (β, 0.20 [95% CI, 0.10-0.30]), taking folate (OR, 0.92 [95% CI, 0.88-0.96]), and not taking supplements (OR, 1.09 [95% CI, 1.04-1.14]). Schizophrenia PGS was associated with coffee consumption (OR, 1.09 [95% CI, 1.05-1.12]), smoking (OR, 1.12 [95% CI, 1.06-1.19]), prepregnancy body mass index (β, −0.18 [95% CI, −0.25 to −0.11]), and pregnancy weight gain (β, 0.17 [95% CI, 0.07-0.27]). All 3 PGSs associated with symptoms of depression/anxiety (ADHD: OR, 1.15 [95% CI, 1.09-1.22]; autism: OR, 1.13 [95% CI, 1.06-1.19]; schizophrenia: OR, 1.13 [95% CI, 1.07-1.20]). Associations were largely consistent for maternal and paternal PGS, except ADHD PGS and smoking (fathers: OR, 1.13 [95% CI, 1.09-1.17]). Conclusions and Relevance In this study, genetic liability to neurodevelopmental conditions that is passed from mothers to children was associated with several pregnancy-related factors and may therefore confound associations between these pregnancy-related factors and offspring neurodevelopment that have previously been thought to be causal. It is crucial that future study designs account for genetic confounding to obtain valid causal inferences so that accurate advice can be given to pregnant individuals.

• Weiner, Daniel J.; Ling, Emi; Erdin, Serkan; Tai, Derek J. C.; Yadav, Rachita & Grove, Jakob [Show all 110 contributors for this article] (2022). Statistical and functional convergence of common and rare genetic influences on autism at chromosome 16p. Nature Genetics. ISSN 1061-4036. 54(11), p. 1630–1639. doi: 10.1038/s41588-022-01203-y. Full text in Research Archive Show summary

  The canonical paradigm for converting genetic association to mechanism involves iteratively mapping individual associations to the proximal genes through which they act. In contrast, in the present study we demonstrate the feasibility of extracting biological insights from a very large region of the genome and leverage this strategy to study the genetic influences on autism. Using a new statistical approach, we identified the 33-Mb p-arm of chromosome 16 (16p) as harboring the greatest excess of autism’s common polygenic influences. The region also includes the mechanistically cryptic and autism-associated 16p11.2 copy number variant. Analysis of RNA-sequencing data revealed that both the common polygenic influences within 16p and the 16p11.2 deletion were associated with decreased average gene expression across 16p. The transcriptional effects of the rare deletion and diffuse common variation were correlated at the level of individual genes and analysis of Hi-C data revealed patterns of chromatin contact that may explain this transcriptional convergence. These results reflect a new approach for extracting biological insight from genetic association data and suggest convergence of common and rare genetic influences on autism at 16p.

• Ystrøm, Eivind; Degerud, Eirik Magnus Meek; Tesli, Martin Steen; Høye, Anne; Reichborn-Kjennerud, Ted & Næss, Øyvind Erik (2022). Alcohol consumption and lower risk of cardiovascular and all-cause mortality: The impact of accounting for familial factors in twins. Psychological Medicine. ISSN 0033-2917. doi: 10.1017/S0033291722000812. Full text in Research Archive Show summary

  Background. A moderate to high alcohol consumption is associated with a lower risk of cardiovascular disease (CVD) mortality in comparison with low consumption. The mechanisms underlying this association are not clear and have been suggested to be caused by residual confounding. The main objective of this study was to separate the familial and individual risk for CVD mortality and all-cause mortality related to alcohol consumption. This will be done by estimating the risk for CVD mortality and all-cause mortality in twin pairs discordant for alcohol consumption.<p> <p>Methods. Alcohol consumption was assessed at two time points using self-report questionnaires in the Norwegian Twin Registry. Data on CVD mortality was obtained from the Norwegian Cause of Death Registry. Exposure–outcome associations for all-cause mortality and mortality due to other causes than CVD were estimated for comparison. <p>Results. Coming from a family with moderate to high alcohol consumption was protective against cardiovascular death (HR = 0.54, 95% CI 0.65–0.83). Moderate and high alcohol consumption levels were associated with a slightly increased risk of CVD mortality at the individual level (HR = 1.33, 95% CI 1.02–1.73). There was no association between alcohol consumption and all-cause mortality both at the familial nor at the individual level. <p>Conclusions. The protective association of moderate to high alcohol consumption with a lower risk of CVD mortality was accounted for by familial factors in this study of twins. Early life genetic and environmental familial factors may mask an absence of health effect of moderate to high alcohol consumption on cardiovascular mortality.

• Tesli, Martin Steen; Degerud, Eirik Magnus Meek; Plana-Ripoll, Oleguer; Gustavson, Kristin; Torvik, Fartein Ask & Ystrøm, Eivind [Show all 13 contributors for this article] (2022). Educational attainment and mortality in schizophrenia. Acta Psychiatrica Scandinavica. ISSN 0001-690X. 145(5), p. 481–493. doi: 10.1111/acps.13407. Full text in Research Archive Show summary

  Background Individuals suffering from schizophrenia have a reduced life expectancy with cardiovascular disease (CVD) as a major contributor. Low educational attainment is associated with schizophrenia, as well as with all-cause and CVD mortality. However, it is unknown to what extent low educational attainment can explain the increased mortality in individuals with schizophrenia. Aim Here, we quantify associations between educational attainment and all-cause and CVD mortality in individuals with schizophrenia, and compare them with the corresponding associations in the general population. Method All Norwegian citizens born between January 1, 1925, and December 31, 1959, were followed up from January 1, 1990, to December 31, 2014. The total sample included 1,852,113 individuals, of which 6548 were registered with schizophrenia. We estimated hazard ratios (HR) for all-cause and CVD mortality with Cox models, in addition to life years lost. Educational attainment for index persons and their parents were included in the models. Results In the general population individuals with low educational attainment had higher risk of all-cause (HR: 1.48 [95% CI: 1.47–1.49]) and CVD (HR: 1.59 [95% CI: 1.57–1.61]) mortality. In individuals with schizophrenia these estimates were substantially lower (all-cause: HR: 1.13 [95% CI: 1.05–1.21] and CVD: HR: 1.12 [95% CI: 0.98–1.27]). Low educational attainment accounted for 3.28 (3.21–3.35) life years lost in males and 2.48 (2.42–2.55) years in females in the general population, but was not significantly associated with life years lost in individuals with schizophrenia. Results were similar for parental educational attainment. Conclusions Our results indicate that while individuals with schizophrenia in general have lower educational attainment and higher mortality rates compared with the general population, the association between educational attainment and mortality is smaller in schizophrenia subjects than in the general population.

• Pingault, Jean-Baptiste; Barkhuizen, Wikus; Wang, Biyao; Hannigan, Laurie John; Eilertsen, Espen Moen & Corfield, Elizabeth Claire [Show all 16 contributors for this article] (2022). Genetic nurture versus genetic transmission of risk for ADHD traits in the Norwegian Mother, Father and Child Cohort Study. Molecular Psychiatry. ISSN 1359-4184. doi: 10.1038/s41380-022-01863-6. Full text in Research Archive Show summary

  Identifying mechanisms underlying the intergenerational transmission of risk for attention-deficit/hyperactivity disorder (ADHD) traits can inform interventions and provide insights into the role of parents in shaping their children’s outcomes. We investigated whether genetic transmission and genetic nurture (environmentally mediated effects) underlie associations between polygenic scores indexing parental risk and protective factors and their offspring’s ADHD traits. This birth cohort study included 19,506 genotyped mother-father-offspring trios from the Norwegian Mother, Father and Child Cohort Study. Polygenic scores were calculated for parental factors previously associated with ADHD, including psychopathology, substance use, neuroticism, educational attainment, and cognitive performance. Mothers reported on their 8-year-old children’s ADHD traits (n = 9,454 children) using the Parent/Teacher Rating Scale for Disruptive Behaviour Disorders. We found that associations between ADHD maternal and paternal polygenic scores and child ADHD traits decreased significantly when adjusting for the child polygenic score (pΔβ = 9.95 × 10−17 for maternal and pΔβ = 1.48 × 10−14 for paternal estimates), suggesting genetic transmission of ADHD risk. Similar patterns suggesting genetic transmission of risk were observed for smoking, educational attainment, and cognition. The maternal polygenic score for neuroticism remained associated with children’s ADHD ratings even after adjusting for the child polygenic score, indicating genetic nurture. There was no robust evidence of genetic nurture for other parental factors. Our findings indicate that the intergenerational transmission of risk for ADHD traits is largely explained by the transmission of genetic variants from parents to offspring rather than by genetic nurture. Observational associations between parental factors and childhood ADHD outcomes should not be interpreted as evidence for predominantly environmentally mediated effects.

• Hughes, Amanda M.; Sanderson, Eleanor; Morris, Tim; Ayorech, Ziada; Tesli, Martin Steen & Ask, Helga [Show all 16 contributors for this article] (2022). Body mass index and childhood symptoms of depression, anxiety, and attention-deficit hyperactivity disorder: A within-family Mendelian randomization study. eLIFE. 11. doi: 10.7554/eLife.74320. Full text in Research Archive Show summary

  Background: Higher BMI in childhood is associated with emotional and behavioural problems, but these associations may not be causal. Results of previous genetic studies imply causal effects but may reflect influence of demography and the family environment. Methods: This study used data on 40,949 8-year-old children and their parents from the Norwegian Mother, Father and Child Cohort Study (MoBa) and Medical Birth Registry of Norway (MBRN). We investigated the impact of BMI on symptoms of depression, anxiety, and attention-deficit hyperactivity disorder (ADHD) at age 8. We applied within-family Mendelian randomization, which accounts for familial effects by controlling for parental genotype. Results: Within-family Mendelian randomization estimates using genetic variants associated with BMI in adults suggested that a child’s own BMI increased their depressive symptoms (per 5 kg/m2 increase in BMI, beta = 0.26 S.D., CI = −0.01,0.52, p=0.06) and ADHD symptoms (beta = 0.38 S.D., CI = 0.09,0.63, p=0.009). These estimates also suggested maternal BMI, or related factors, may independently affect a child’s depressive symptoms (per 5 kg/m2 increase in maternal BMI, beta = 0.11 S.D., CI:0.02,0.09, p=0.01). However, within-family Mendelian randomization using genetic variants associated with retrospectively-reported childhood body size did not support an impact of BMI on these outcomes. There was little evidence from any estimate that the parents’ BMI affected the child’s ADHD symptoms, or that the child’s or parents’ BMI affected the child’s anxiety symptoms. Conclusions: We found inconsistent evidence that a child’s BMI affected their depressive and ADHD symptoms, and little evidence that a child’s BMI affected their anxiety symptoms. There was limited evidence of an influence of parents’ BMI. Genetic studies in samples of unrelated individuals, or using genetic variants associated with adult BMI, may have overestimated the causal effects of a child’s own BMI. Funding: This research was funded by the Health Foundation. It is part of the HARVEST collaboration, supported by the Research Council of Norway. Individual co-author funding: the European Research Council, the South-Eastern Norway Regional Health Authority, the Research Council of Norway, Helse Vest, the Novo Nordisk Foundation, the University of Bergen, the South-Eastern Norway Regional Health Authority, the Trond Mohn Foundation, the Western Norway Regional Health Authority, the Norwegian Diabetes Association, the UK Medical Research Council. The Medical Research Council (MRC) and the University of Bristol support the MRC Integrative Epidemiology Unit.

• Akdeniz, Bayram Cevdet; Frei, Oleksandr; Hagen, Espen; Filiz, Tahir Tekin; Karthikeyan, Sandeep & Pasman, Joëlle [Show all 18 contributors for this article] (2022). COGEDAP: A COmprehensive GEnomic Data Analysis Platform. arXiv.org. ISSN 2331-8422. Full text in Research Archive
• Torgersen, Kristin Stensland; Rahman, Zillur; Bahrami, Shahram; Hindley, Guy Frederick Lanyon; Parker, Nadine & Frei, Oleksandr [Show all 14 contributors for this article] (2022). Shared genetic loci between depression and cardiometabolic traits. PLoS Genetics. ISSN 1553-7390. 18(5). doi: 10.1371/journal.pgen.1010161. Full text in Research Archive Show summary

  Epidemiological and clinical studies have found associations between depression and cardiovascular disease risk factors, and coronary artery disease patients with depression have worse prognosis. The genetic relationship between depression and these cardiovascular phenotypes is not known. We here investigated overlap at the genome-wide level and in individual loci between depression, coronary artery disease and cardiovascular risk factors. We used the bivariate causal mixture model (MiXeR) to quantify genome-wide polygenic overlap and the conditional/conjunctional false discovery rate (pleioFDR) method to identify shared loci, based on genome-wide association study summary statistics on depression (n = 450,619), coronary artery disease (n = 502,713) and nine cardiovascular risk factors (n = 204,402–776,078). Genetic loci were functionally annotated using FUnctional Mapping and Annotation (FUMA). Of 13.9K variants influencing depression, 9.5K (SD 1.0K) were shared with body-mass index. Of 4.4K variants influencing systolic blood pressure, 2K were shared with depression. ConjFDR identified 79 unique loci associated with depression and coronary artery disease or cardiovascular risk factors. Six genomic loci were associated jointly with depression and coronary artery disease, 69 with blood pressure, 49 with lipids, 9 with type 2 diabetes and 8 with c-reactive protein at conjFDR < 0.05. Loci associated with increased risk for depression were also associated with increased risk of coronary artery disease and higher total cholesterol, low-density lipoprotein and c-reactive protein levels, while there was a mixed pattern of effect direction for the other risk factors. Functional analyses of the shared loci implicated metabolism of alpha-linolenic acid pathway for type 2 diabetes. Our results showed polygenic overlap between depression, coronary artery disease and several cardiovascular risk factors and suggest molecular mechanisms underlying the association between depression and increased cardiovascular disease risk.

• Bakken, Nora Refsum; Hannigan, Laurie John; Shadrin, Alexey; Hindley, Guy Frederick Lanyon; Ask, Helga & Reichborn-Kjennerud, Ted [Show all 9 contributors for this article] (2022). Childhood temperamental, emotional, and behavioral characteristics associated with mood and anxiety disorders in adolescence: A prospective study. Acta Psychiatrica Scandinavica. ISSN 0001-690X. 147(2), p. 217–228. doi: 10.1111/acps.13522. Full text in Research Archive Show summary

  Background Mood and anxiety disorders account for a large share of the global burden of disability. Some studies suggest that early signs may emerge already in childhood. However, there is a lack of well-powered, prospective studies investigating how and when childhood mental traits and trajectories relate to adolescent mood and anxiety disorders. Methods We here examine cross-sectional and longitudinal association between maternally reported temperamental traits, emotional and behavioral problems in childhood (0.5–8 years) and clinical diagnosis of mood or anxiety (“emotional”) disorders in adolescence (10–18 years), using the prospective Norwegian Mother, Father and Child Cohort Study (MoBa) of 110,367 children. Results Logistic regression analyses showed consistent and increasing associations between childhood negative emotionality, behavioral and emotional problems and adolescent diagnosis of emotional disorders, present from 6 months of age (negative emotionality). Latent profile analysis incorporating latent growth models identified five developmental profiles of emotional and behavioral problems. A profile of early increasing behavioral and emotional problems with combined symptoms at 8 years (1.3% of sample) was the profile most strongly associated with emotional disorders in adolescence (OR vs. reference: 5.00, 95% CI: 3.70–6.30). Conclusions We found a consistent and increasing association between negative emotionality, behavioral and emotional problems in early to middle childhood and mood and anxiety disorders in adolescence. A developmental profile coherent with early and increasing disruptive mood dysregulation across childhood was the profile strongest associated with adolescent emotional disorders. Our results highlight the importance of early emotional dysregulation and childhood as a formative period in the development of adolescent mood and anxiety disorders, supporting potential for prevention and early intervention initiatives.

• Kinge, Jonas Minet; Øverland, Simon Nygaard; Flatø, Martin; Dieleman, Joseph; Røgeberg, Ole Jørgen & Magnus, Maria Christine [Show all 13 contributors for this article] (2021). Parental income and mental disorders in children and adolescents: prospective register-based study. International Journal of Epidemiology. ISSN 0300-5771. 50(5), p. 1615–1627. doi: 10.1093/ije/dyab066. Full text in Research Archive Show summary

  Background Children with low-income parents have a higher risk of mental disorders, although it is unclear whether other parental characteristics or genetic confounding explain these associations and whether it is true for all mental disorders. Methods In this registry-based study of all children in Norway (n = 1 354 393) aged 5–17 years from 2008 to 2016, we examined whether parental income was associated with childhood diagnoses of mental disorders identified through national registries from primary healthcare, hospitalizations and specialist outpatient services. Results There were substantial differences in mental disorders by parental income, except for eating disorders in girls. In the bottom 1% of parental income, 16.9% [95% confidence interval (CI): 15.6, 18.3] of boys had a mental disorder compared with 4.1% (95% CI: 3.3, 4.8) in the top 1%. Among girls, there were 14.2% (95% CI: 12.9, 15.5) in the lowest, compared with 3.2% (95% CI: 2.5, 3.9) in the highest parental-income percentile. Differences were mainly attributable to attention-deficit hyperactivity disorder in boys and anxiety and depression in girls. There were more mental disorders in children whose parents had mental disorders or low education, or lived in separate households. Still, parental income remained associated with children’s mental disorders after accounting for parents’ mental disorders and other factors, and associations were also present among adopted children. Conclusions Mental disorders were 3- to 4-fold more prevalent in children with parents in the lowest compared with the highest income percentiles. Parents’ own mental disorders, other socio-demographic factors and genetic confounding did not fully explain these associations.

• Tesli, Natalia; Rokicki, Jaroslav; Maximov, Ivan; Bell, Christina; Hjell, Gabriela & Gurholt, Tiril Pedersen [Show all 17 contributors for this article] (2021). White Matter Matters: Unraveling Violence in Psychosis and Psychopathy. Schizophrenia Bulletin Open. 2(1). doi: 10.1093/schizbullopen/sgab026. Full text in Research Archive Show summary

  Individuals with psychotic disorders have an increased risk of committing acts of violence. Neurobiological support for the extent to which violence in psychosis is driven by psychotic symptoms and/or antisocial traits could have clinical and legal implications. Neuroimaging studies have reported white matter (WM) abnormalities in individuals with psychosis and in those with antisocial traits. However, it is unknown whether WM abnormalities in psychosis patients with a history of violence (violent-PSY) resemble those found in nonviolent psychosis patients (nonviolent PSY), violent nonpsychotic individuals (violent non-PSY), or both. Diffusion tensor imaging scans from 301 males including violent-PSY (n = 28), violent non-PSY (n = 20), nonviolent PSY (n = 58), and healthy controls (HC, n = 195) were analyzed with tract-based spatial statistics. Fractional anisotropy (FA), mean, axial and radial (RD) diffusivity were compared between groups. Psychopathic traits in the violent groups were measured with Psychopathy Checklist-revisited (PCL-R). Violent-PSY had globally lower FA and higher RD, compared with nonviolent PSY. Both psychosis groups and violent non-PSY group had widespread disruptions in WM compared with HC. There were no significant WM differences between violent-PSY and violent non-PSY. PCL-R scores did not differ between the violence groups and were associated with higher RD in corpus callosum. Here we demonstrate a widespread pattern of reduced WM integrity in violent-PSY compared with nonviolent PSY. The lack of significant WM and PCL-R differences between the violence groups, together with the positive association between PCL-R and WM deficits in violent-PSY and violent non-PSY may indicate shared neurobiological underpinnings of trait violence.

• Reponen, Elina Johanna; Tesli, Martin Steen; Dieset, Ingrid; Steen, Nils Eiel; Vedal, Trude Seselie Jahr & Szabo, Attila [Show all 12 contributors for this article] (2021). Adiponectin Is Related to Cardiovascular Risk in Severe Mental Illness Independent of Antipsychotic Treatment. Frontiers in Psychiatry. 12. doi: 10.3389/fpsyt.2021.623192. Full text in Research Archive Show summary

  Background: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) associated with elevated cardiovascular disease (CVD) risk, including obesity. Leptin and adiponectin are secreted by adipose tissue, with pro- and anti-inflammatory properties, respectively. The second generation antipsychotics (AP) olanzapine, clozapine, and quetiapine have been associated with high leptin levels in SMI. However, the link between inflammatory dysregulation of leptin and adiponectin and CVD risk in SMI, and how this risk is influenced by body mass and AP medication, is still not completely understood. We investigated herein if leptin, adiponectin or their ratio (L/A ratio) could predict increased CVD risk in SCZ, BD, and in subgroups according to use of antipsychotic (AP) treatment, independent of other cardio-metabolic risk factors.<p> <p>Methods: We measured fasting plasma levels of leptin and adiponectin, and calculated the L/A ratio in n = 1,092 patients with SCZ and BD, in subgroups according to AP treatment, and in n = 176 healthy controls (HC). Differences in the levels of adipokines and L/A between groups were examined in multivariate analysis of covariance, and the correlations between adipokines and body mass index (BMI) with linear regression. CVD risk was defined by total cholesterol/high-density lipoprotein (TC/HDL) and triglyceride/HDL (TG/HDL) ratios. The adipokines and L/A ratios ability to discriminate individuals with TG/HDL and TC/HDL ratios above threshold levels was explored by ROC analysis, and we investigated the possible influence of other cardio-metabolic risk factors on the association in logistic regression analyses.<p> <p>Results: We observed higher leptin levels and L/A ratios in SMI compared with HC but found no differences in adiponectin. Both adipokines were highly correlated with BMI. The low adiponectin levels showed a fair discrimination in ROC analysis of individuals with CVD risk, with AUC between 0.7 and 0.8 for both TC/HDL and TG/HDL, in all groups examined regardless of diagnosis or AP treatment. Adiponectin remained significantly associated with an elevated TC/HDL and TG/HDL ratio in SMI, also after further adjustment with other cardio-metabolic risk factors.<p> <p>Conclusions: Adiponectin is not dysregulated in SMI but is associated with CVD risk regardless of AP treatment regime.

• Askeland, Ragna Bugge; Hannigan, Laurie J.; Ask, Helga; Ayorech, Ziada; Tesli, Martin Steen & Corfield, Elizabeth [Show all 12 contributors for this article] (2021). Early manifestations of genetic risk for neurodevelopmental disorders. Journal of Child Psychology and Psychiatry. ISSN 0021-9630. p. 1–10. doi: 10.1111/jcpp.13528. Full text in Research Archive Show summary

  Background: Attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (autism) and schizophrenia are highly heritable neurodevelopmental disorders, affecting the lives of many individuals. It is important to increase our understanding of how the polygenic risk for neurodevelopmental disorders manifests during childhood in boys and girls. Methods: Polygenic risk scores (PRS) for ADHD, autism and schizophrenia were calculated in a subsample of 15 205 children from the Norwegian Mother, Father and Child Cohort Study (MoBa). Mother-reported traits of repetitive behavior, social communication, language and motor difficulties, hyperactivity and inattention were measured in children at 6 and 18 months, 3, 5 and 8 years. Linear regression models in a multigroup framework were used to investigate associations between the three PRS and dimensional trait measures in MoBa, using sex as a grouping variable. Results: Before the age of 2, the ADHD PRS was robustly associated with hyperactivity and inattention, with increasing strength up to 8 years, and with language difficulties at age 5 and 8. The autism PRS was robustly associated with language difficulties at 18 months, motor difficulties at 36 months, and hyperactivity and inattention at 8 years. We did not identify robust associations for the schizophrenia PRS. In general, the PRS associations were similar in boys and girls. The association between ADHD PRS and hyperactivity at 18 months was, however, stronger in boys. Conclusions: Polygenic risk for autism and ADHD in the general population manifests early in childhood and broadly across behavioral measures of neurodevelopmental traits.

• Hannigan, Laurie John; Askeland, Ragna Bugge; Ask, Helga; Tesli, Martin; Corfield, Elizabeth & Ayorech, Ziada [Show all 15 contributors for this article] (2021). Genetic Liability for Schizophrenia and Childhood Psychopathology in the General Population. Schizophrenia Bulletin. ISSN 0586-7614. 47(4), p. 1179–1189. doi: 10.1093/schbul/sbaa193. Full text in Research Archive Show summary

  Abstract Genetic liability for schizophrenia is associated with psychopathology in early life. It is not clear if these associations are time dependent during childhood, nor if they are specific across different forms of psychopathology. Using genotype and questionnaire data on children (N = 15 105) from the Norwegian Mother, Father and Child Cohort Study, we used schizophrenia polygenic risk scores to test developmental stability in associations with measures of emotional and behavioral problems between 18 months and 5 years, and domain specificity in associations with symptoms of depression, anxiety, conduct problems, oppositionality, inattention, and hyperactivity at 8 years. We then sought to identify symptom profiles—across development and domains—associated with schizophrenia polygenic liability. We found evidence for developmental stability in associations between schizophrenia polygenic risk scores and emotional and behavioral problems, with the latter being mediated specifically via the rate of change in symptoms (β slope = 0.032; 95% CI: 0.007–0.057). At age 8, associations were better explained by a model of symptom-specific polygenic effects rather than effects mediated via a general psychopathology factor or by domain-specific factors. Overall, individuals with higher schizophrenia polygenic risk scores were more likely (OR = 1.310 [95% CIs: 1.122–1.528]) to have a profile of increasing behavioral and emotional symptoms in early childhood, followed by elevated symptoms of conduct disorder, oppositionality, hyperactivity, and inattention by age 8. Schizophrenia-associated alleles are linked to specific patterns of early-life psychopathology. The associations are small, but findings of this nature can help us better understand the developmental emergence of schizophrenia.

• Martin, Joanna; Agha, Sharifah Shameem; Eyre, Olga; Riglin, Lucy; Langley, Kate & Hubbard, Leon [Show all 57 contributors for this article] (2021). Sex differences in anxiety and depression in children with attention deficit hyperactivity disorder: Investigating genetic liability and comorbidity. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. ISSN 1552-4841. 186(7), p. 412–422. doi: 10.1002/ajmg.b.32842. Full text in Research Archive
• Smeland, Olav Bjerkehagen; Shadrin, Alexey A.; Bahrami, Shahram; Broce, Iris J.; Tesli, Martin Steen & Frei, Oleksandr [Show all 22 contributors for this article] (2020). Genome-wide Association Analysis of Parkinson’s Disease and Schizophrenia Reveals Shared Genetic Architecture and Identifies Novel Risk Loci. Biological Psychiatry. ISSN 0006-3223. 89(3), p. 227–235. doi: 10.1016/j.biopsych.2020.01.026. Full text in Research Archive Show summary

  BACKGROUND:Parkinson’s disease (PD) and schizophrenia (SCZ) are heritable brain disorders that involvedysregulation of the dopaminergic system. Epidemiological studies have reported potential comorbidity between thedisorders, and movement disturbances are common in patients with SCZ before treatment with antipsychotic drugs.Despite this, little is known about shared genetic etiology between the disorders.METHODS:We analyzed recent large genome-wide association studies on patients with SCZ (N= 77,096) and PD(N= 417,508) using a conditional/conjunctional false discovery rate (FDR) approach to evaluate overlap incommon genetic variants and improve statistical power for genetic discovery. Using a variety of biologicalresources, we functionally characterized the identified genomic loci.RESULTS:We observed genetic enrichment in PD conditional onassociations with SCZ and vice versa, indicatingpolygenic overlap. We then leveraged this cross-trait enrichment using conditional FDR analysis and identified 9 novel PDrisk loci and 1 novel SCZ locus at conditional FDR,.01. Furthermore, we identified 9 genomic loci jointly associated withPD and SCZ at conjunctional FDR,.05. There was an even distribution of antagonistic and agonistic effect directionsamong the shared loci, in line with the insignificant genetic correlation between the disorders. Of 67 genes mapped to theshared loci, 65 are expressed in the human brain and show cell type–specific expression profiles.CONCLUSIONS:Altogether, the study increases understanding of the genetic architectures underlying SCZ and PD,indicating that common molecular genetic mechanisms may contribute to overlapping pathophysiological and clinicalfeatures between the disorders.

• Tesli, Natalia; Meer, Dennis van der; Rokicki, Jaroslav; Storvestre, Guttorm Breivik; Røsæg, Cato & Jensen, Arvid [Show all 14 contributors for this article] (2020). Hippocampal subfield and amygdala nuclei volumes in schizophrenia patients with a history of violence. European Archives of Psychiatry and Clinical Neuroscience. ISSN 0940-1334. doi: 10.1007/s00406-020-01098-y. Full text in Research Archive Show summary

  Schizophrenia (SCZ) is associated with an increased risk of violence compared to the general population. Previous studies have indicated smaller hippocampal and amygdala volumes in violent than non-violent psychotic patients. However, little is known about volumetric differences at the subdivision level of these structures. In the present study, hippocampal subfields and amygdala nuclei volumes were estimated with FreeSurfer from 3 T MRI of SCZ patients with (SCZ-V, n = 24) and without (SCZ-NV, n = 51) a history of severe violence and 90 healthy controls (HC). Volumetric differences between groups were explored with a general linear model covarying for confounders, in addition to follow-up analyses in patient groups controlling for clinical characteristics such as antipsychotic medication, duration of illness and illicit substance use. SCZ-V had smaller total hippocampal volume and smaller CA1, HATA, fimbria, and molecular layer of DG volumes compared to HC. Total amygdala volume together with basal nucleus, accessory basal nucleus, CTA, and paralaminar nucleus volumes were smaller in SCZ-V compared to HC. In SCZ-NV, compared to HC, the observed smaller volumes were limited to basal and paralaminar nucleus. There were no significant differences in hippocampal subfield and amygdala nuclei volumes between SCZ-V and SCZ-NV. Follow-up analyses showed that the results in patient groups were not affected by clinical characteristics. The results suggest that smaller hippocampal subfield and amygdala nuclei volumes may be relevant to violence risk in SCZ. However, the neurobiological signature of violence in SCZ should be further investigated in larger cohorts.

• Akingbuwa, Wonuola A.; Hammerschlag, Anke R.; Jami, Eshim S.; Allegrini, Andrea G.; Karhunen, Ville & Sallis, Hannah [Show all 35 contributors for this article] (2020). Genetic Associations Between Childhood Psychopathology and Adult Depression and Associated Traits in 42 998 Individuals: A Meta-analysis. JAMA psychiatry. ISSN 2168-6238. 77(7), p. 715–728. doi: 10.1001/jamapsychiatry.2020.0527. Full text in Research Archive
• Reponen, Elina Johanna; Dieset, Ingrid; Tesli, Martin Steen; Mørch, Ragni Helene; Aas, Monica & Vedal, Trude Seselie Jahr [Show all 18 contributors for this article] (2020). Atherogenic lipid ratios related to myeloperoxidase and C-reactive protein levels in psychotic disorders. Frontiers in Psychiatry. 11(672). doi: 10.3389/fpsyt.2020.00672. Full text in Research Archive Show summary

  Background: Cardiovascular disease (CVD) is a major cause of premature death in patients with psychotic disorders, where dyslipidemia occurs frequently. In the pathogenesis of these serious mental disorders, a low-grade inflammation seems to be a possible contributor. Concurrently, systemic inflammation and its interplay with dyslipidemia is a central driver in the pathogenesis of CVD. We hypothesize that evaluation of atherogenic lipid ratios together with inflammatory markers reflecting different inflammatory pathways with relevance for atherogenesis, could give novel information on immune-related mechanisms involved in early CVD risk in patients with psychotic disorders. Methods: As a measure for CVD risk we calculated atherogenic lipid ratios using established sex-specific cut-offs: Total cholesterol/high-density lipoprotein; HDL-c (TC/HDL) and triglyceride/HDL-c (TG/HDL) were evaluated in 571 schizophrenia (SCZ) and 247 bipolar disorder (BD) patients, and in 99 healthy controls (HC). In addition, as a measure of low-grade inflammation, we measured fasting plasma levels of nine stable atherogenic inflammatory markers in patients (SCZ, BD) and in HC. The elevated inflammatory markers and CVD risk in patients, as reflected by TC/HDL and TG/HDL, were further assessed in multivariable analyses adjusting for comorbid cardio-metabolic risk factors. Results: A markedly higher proportion (26%-31%) of patients had increased TC/HDL and TG/HDL ratios compared with HC. Plasma levels of high-sensitivity C-reactive protein (hs-CRP) and myeloperoxidase (MPO) were higher (p<0.05, p<0.001) in patients with psychotic disorders than in HC, and hs-CRP and MPO were independently associated with atherogenic lipid ratios in the multivariable analyses. Conclusions: Our findings suggest that low-grade inflammation and abnormal neutrophil activation may cause increased CVD risk in patients with psychotic disorders. These mechanisms should be further examined to determine the potential for development of novel risk evaluation strategies. Keywords: CVD risk; bipolar disorder; dyslipidemia; inflammatory biomarkers; schizophrenia.

• Sønmez, Nasrettin; Romm, Kristin Lie; Østefjells, Tiril; Grande, Marit; Jensen, Lene Hunnicke & Hummelen, Benjamin [Show all 9 contributors for this article] (2019). Cognitive behavior therapy in early psychosis with a focus on depression and low self-esteem: A randomized controlled trial. Comprehensive Psychiatry. ISSN 0010-440X. 97. doi: 10.1016/j.comppsych.2019.152157. Full text in Research Archive Show summary

  Background Patients in early phases of psychosis often struggle with depressive symptoms and low self-esteem. The main aims of the present study were to examine whether cognitive behavior therapy (CBT) compared to treatment as usual (TAU) would reduce depressive symptoms (primary outcome) and increase self-esteem (secondary outcome). Furthermore, we wanted to examine whether CBT reduces symptoms measured with the PANSS (positive, negative, cognitive, or excited symptoms) or increases general functioning compared to TAU. Methods A total of 63 early psychosis patients were included and randomly assigned to receive either CBT (maximum 26 sessions) or TAU for a period of up to six months. A linear mixed model was used for longitudinal analysis, with a focus on whether patients in the CBT group or the TAU group changed differently to one another between the baseline and 15-month follow-up. Results There were no differences between the CBT group and TAU group regarding improvements in depressive symptoms measured with the Calgary Depression Scale for Schizophrenia (P = 0.188) or self-esteem measured with the Rosenberg Self-Esteem Scale (P = 0.580). However, patients in the CBT group improved significantly more on negative symptoms (P = 0.002) and social functioning (P = 0.001). Conclusions We did not find CBT to be more effective than TAU in reducing depressive symptoms or increasing self-esteem in patients with early psychosis. However, CBT seems to improve negative symptoms and functioning. These results still need to be replicated in further studies as the present one was merely an exploratory analysis.

• Mahmood, Javed Iqbal; Grotmol, Kjersti Støen; Tesli, Martin Steen; Moum, Torbjørn Åge; Andreassen, Ole Andreas & Tyssen, Reidar (2019). Life satisfaction in Norwegian medical doctors: a 15-year longitudinal study of work-related predictors. BMC Health Services Research. 19:729, p. 1–10. doi: 10.1186/s12913-019-4599-7. Full text in Research Archive Show summary

  Background Despite many recent studies on burn-out and dissatisfaction among American medical doctors, less is known about doctors in the Scandinavian public health service. The aims of this study were to analyse long-term work-related predictors of life satisfaction among established doctors in Norway and to identify predictors in a subgroup of doctors who reported a decline in life satisfaction. Methods Two nationwide cohorts of doctors (n = 1052), who graduated medical school 6 years apart, were surveyed at graduation from medical school (T1, 1993/94 and 1999), and 4 (T2), 10 (T3), and 15 (T4) years later. Work-related predictors of life satisfaction (three items) obtained at T2 to T4 were analysed. Individual and lifestyle confounders were controlled for using mixed-models repeated-measures analyses, and logistic regression analyses were applied to identify predictors of the decrease in life satisfaction. Results Ninety per cent (947/1052) responded at least once, and 42% (450/1052) responded at all four times. Work-related predictors of higher life satisfaction in the adjusted model were work–home stress (β = − 0.20, 95% confidence interval [CI] = − 0.25 to − 0.16, p < 0.001), perceived job demands (β = − 0.10, CI = − 0.15 to − 0.05, p < 0.001), and colleague support (β = 0.05, CI = 0.04 to 0.07, p < 0.001). The new adjusted individual predictors that we identified included female gender, reality weakness trait, and problematic drinking behaviour. Neuroticism trait and low colleague support predicted a decrease in life satisfaction. Conclusions Work–home stress, perceived job demands, and colleague support were the most important predictors of life satisfaction related to doctors’ work. When personality traits were controlled for, female doctors were more satisfied with their life than male doctors. These findings suggest that improving work-related factors with targeted interventions, including a supportive work environment, may increase life satisfaction among doctors.

• Ask, Helga; Gustavson, Kristin; Ystrøm, Eivind; Havdahl, Karoline Alexandra; Tesli, Martin Steen & Askeland, Ragna Bugge [Show all 7 contributors for this article] (2018). Association of Gestational Age at Birth With Symptoms of Attention-Deficit/Hyperactivity Disorder in Children. JAMA pediatrics. ISSN 2168-6203. 172(8), p. 749–756. doi: 10.1001/jamapediatrics.2018.1315. Full text in Research Archive
• Smeland, Olav Bjerkehagen; Wang, Yunpeng; Lo, Min-Tzu; Li, Wen; Frei, Oleksandr & Witoelar, Aree [Show all 13 contributors for this article] (2017). Identification of genetic loci shared between schizophrenia and the Big Five personality traits. Scientific Reports. 7:2222(1), p. 1–9. doi: 10.1038/s41598-017-02346-3. Full text in Research Archive Show summary

  Schizophrenia is associated with differences in personality traits, and recent studies suggest that personality traits and schizophrenia share a genetic basis. Here we aimed to identify specific genetic loci shared between schizophrenia and the Big Five personality traits using a Bayesian statistical framework. Using summary statistics from genome-wide association studies (GWAS) on personality traits in the 23andMe cohort (n = 59,225) and schizophrenia in the Psychiatric Genomics Consortium cohort (n = 82,315), we evaluated overlap in common genetic variants. The Big Five personality traits neuroticism, extraversion, openness, agreeableness and conscientiousness were measured using a web implementation of the Big Five Inventory. Applying the conditional false discovery rate approach, we increased discovery of genetic loci and identified two loci shared between neuroticism and schizophrenia and six loci shared between openness and schizophrenia. The study provides new insights into the relationship between personality traits and schizophrenia by highlighting genetic loci involved in their common genetic etiology.

• Aas, Monica; Kauppi, Karolina; Brandt, Christine Lycke; Tesli, Martin Steen; Kaufmann, Tobias & Steen, Nils Eiel [Show all 10 contributors for this article] (2017). Childhood trauma is associated with increased brain responses to emotionally negative as compared with positive faces in patients with psychotic disorders. Psychological Medicine. ISSN 0033-2917. 47(4), p. 669–679. doi: 10.1017/S0033291716002762. Full text in Research Archive
• Aas, Monica; Melle, Ingrid; Bettella, Francesco; Djurovic, Srdjan; Hellard, Stephanie Le & Bjella, Thomas [Show all 12 contributors for this article] (2017). Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not. Psychological Medicine. ISSN 0033-2917. 48(1), p. 43–49. doi: 10.1017/S0033291717001209. Full text in Research Archive Show summary

  Background Schizophrenia (SZ) and bipolar disorder (BD) are heritable, polygenic disorders with shared clinical and genetic components, suggesting a psychosis continuum. Cannabis use is a well-documented environmental risk factor in psychotic disorders. In the current study, we investigated the relationship between SZ genetic load and cannabis use before illness onset in SZ and BD spectrums. Since frequent early cannabis use (age <18 years) is believed to increase the risk of developing psychosis more than later use, follow-up analyses were conducted comparing early use to later use and no use. Methods We assigned a SZ-polygenic risk score (PGRS) to each individual in our independent sample (N = 381 SZ spectrum cases, 220 BD spectrum cases and 415 healthy controls), calculated from the results of the Psychiatric Genomics Consortium (PGC) SZ case–control study (N = 81 535). SZ-PGRS in patients who used cannabis weekly to daily in the period before first illness episode was compared with that of those who never or infrequently used cannabis. Results Patients with weekly to daily cannabis use before illness onset had the highest SZ-PGRS (p = 0.02, Cohen's d = 0.33). The largest difference was found between patients with daily or weekly cannabis use before illness onset <18 years of age and patients with no or infrequent use of cannabis (p = 0.003, Cohen's d = 0.42). Conclusions Our study supports an association between high SZ-PGRS and frequent cannabis use before illness onset in psychosis continuum disorders.

• Mahmood, Javed Iqbal; Grotmol, Kjersti Støen; Tesli, Martin Steen; Vaglum, Per Jørgen Wiggen & Tyssen, Reidar (2017). Contextual factors and mental distress as possible predictors of hazardous drinking in Norwegian medical doctors: a 15-year longitudinal nationwide study. European Addiction Research. ISSN 1022-6877. 23(1), p. 19–27. doi: 10.1159/000452442. Full text in Research Archive
• Steen, Nils Eiel; Aas, Monica; Simonsen, Carmen Elisabeth; Dieset, Ingrid; Tesli, Martin Steen & Nerhus, Mari [Show all 13 contributors for this article] (2016). Serum levels of second-generation antipsychotics are associated with cognitive function in psychotic disorders. World Journal of Biological Psychiatry. ISSN 1562-2975. 18(6), p. 471–482. doi: 10.1080/15622975.2016.1245441. Full text in Research Archive
• Steen, Nils Eiel; Aas, Monica; Simonsen, Carmen Elisabeth; Dieset, Ingrid; Tesli, Martin Steen & Nerhus, Mari [Show all 13 contributors for this article] (2016). Serum concentrations of mood stabilizers are associated with memory, but not other cognitive domains in psychosis spectrum disorders; explorative analyses in a naturalistic setting. International journal of bipolar disorders. 4(24). doi: 10.1186/s40345-016-0067-z. Full text in Research Archive Show summary

  Background Mood stabilizers like lithium and anticonvulsants are used in bipolar and related psychotic disorders. There is a lack of knowledge of the relationship of these medications and cognition in the psychosis spectrum. We studied the association between serum concentration of mood stabilizers and cognitive performance in a well-characterized sample of bipolar and schizophrenia spectrum disorders. Methods Serum concentrations of valproate, lamotrigine, and lithium were analyzed for associations to performance on neuropsychological tests in six cognitive domains in individuals with bipolar disorder (n = 167) and in a combined sample of individuals with bipolar or schizophrenia spectrum disorders (n = 217). Linear regression with adjustments for gender, age, and symptom levels of depression, mania, and psychosis were applied for the association analyses. Results There were negative associations between serum levels of valproate and short term delayed recall (bipolar: p = 0.043; combined: p = 0.044) and working memory (bipolar: p = 0.043). A positive association was suggested between serum level of lithium and working memory (bipolar: p = 0.039). There were no other significant relationships between serum levels of valproate, lamotrigine, or lithium and neuropsychological test performance in neither the bipolar disorder nor the combined group. Conclusions Serum levels of mood stabilizers were unrelated to cognitive performance in most domains, indicating that higher dose does not lead to broader cognitive impairments in bipolar and related psychotic disorder patients. However, worsened memory with increasing levels of valproate suggests cautious dosing of anticonvulsants, while increasing lithium level seems to be associated with improved memory. The findings should be interpreted with caution due to the explorative, naturalistic design.

• Haram, Marit; Bettella, Francesco; Brandt, Christine Lycke; Quintana, Daniel; Nerhus, Mari & Bjella, Thomas [Show all 11 contributors for this article] (2016). Contribution of oxytocin receptor polymorphisms to amygdala activation in schizophrenia spectrum disorders. BJPsych Open. 2(6), p. 353–358. doi: 10.1192/bjpo.bp.116.003376. Full text in Research Archive Show summary

  Background Oxytocin has been proposed to mediate amygdala dysfunction associated with altered emotion processing in schizophrenia, but the contribution of oxytocin pathway genes is yet to be investigated. Aims To identify potential different contributions of three oxytocin receptor polymorphisms (rs53576, rs237902 and rs2254298) between patients with schizophrenia spectrum disorders (SCZ), affective spectrum disorders (AD) and healthy controls (HC). Method In a total of 346 participants (104 with SCZ, 100 with AD, and 142 HC) underwent genotyping and functional magnetic resonance imaging (fMRI) during an emotional faces matching paradigm. Genetic association analyses were performed to test the possible effects on task-induced BOLD amygdala response to fearful/angry faces. Results In participants with SCZ, the rs237902 G allele was associated with low amygdala activation (left hemisphere: b=−4.99, Bonferroni corrected P=0.04) and interaction analyses showed that this association was disorder specific (left hemisphere: Bonferroni corrected P=0.003; right hemisphere: Bonferroni corrected P=0.03). There were no associations between oxytocin polymorphisms and amygdala activation in the total sample, among AD patients or HC. Conclusions Rs237902 was associated with amygdala activation in response to fearful/angry faces only in patients with SCZ. Our findings indicate that the endogenous oxytocin system could serve as a contributing factor in biological underpinnings of emotion processing and that this contribution is disorder specific.

• Tesli, Martin Steen; Wirgenes, Katrine Verena; Hughes, Timothy; Bettella, Francesco; Athanasiu, Lavinia & Hoseth, Eva Zsuzsanna [Show all 14 contributors for this article] (2016). VRK2 gene expression in schizophrenia, bipolar disorder and healthy controls. British Journal of Psychiatry. ISSN 0007-1250. 209(2), p. 114–120. doi: 10.1192/bjp.bp.115.161950. Full text in Research Archive
• Athanasiu, Lavinia; Smorr, Lisa-Lena H; Tesli, Martin Steen; Røssberg, Jan Ivar; Sønderby, Ida Elken & Spigset, Olav [Show all 8 contributors for this article] (2015). Genome-wide association study identifies common variants associated with pharmacokinetics of psychotropic drugs. Journal of Psychopharmacology. ISSN 0269-8811. 29(8), p. 884–891. doi: 10.1177/0269881115584469. Full text in Research Archive
• Hughes, Timothy; Hansson, Lars Johan Axel; Sønderby, Ida Elken; Athanasiu, Lavinia; Zuber, Verena & Tesli, Martin Steen [Show all 13 contributors for this article] (2015). A Loss-of-Function Variant in a Minor Isoform of ANK3 Protects Against Bipolar Disorder and Schizophrenia. Biological Psychiatry. ISSN 0006-3223. doi: 10.1016/j.biopsych.2015.09.021. Full text in Research Archive
• Haram, Marit; Tesli, Martin Steen; Bettella, Franscesco; Djurovic, Srdjan; Andreassen, Ole Andreas & Melle, Ingrid (2015). Association between genetic variation in the oxytocin receptor gene and emotional withdrawal, but not between oxytocin pathway genes and diagnosis in psychotic disorders. Frontiers in Human Neuroscience. 9, p. 1–7. doi: 10.3389/fnhum.2015.00009. Full text in Research Archive Show summary

  Social dysfunction is common in patients with psychotic disorders. Oxytocin is a neuropeptide with a central role in social behavior. This study aims to explore the relationship between oxytocin pathway genes and symptoms related to social dysfunction in patients with psychotic disorders. We performed association analyses between four oxytocin pathway genes (OXT, OXTR, AVP, and CD38) and four areas of social behavior-related psychopathology as measured by Positive and Negative Syndrome Scale. For this purpose, we used both a polygenic risk score (PGRS) and single OXTR candidate single nucleotide polymorphism previously reported in the literature (rs53576, rs237902, and rs2254298). A total of 734 subjects with DSM-IV psychotic spectrum disorders and 420 healthy controls were included. Oxytocin pathway PGRSs were calculated based on the independent Psychiatric Genomics Consortium study sample. There was a significant association between symptom of Emotional Withdrawal and the previously reported OXTR risk allele A in rs53576. No significant associations between oxytocin pathway gene variants and a diagnosis of psychotic disorder were found. Our findings indicate that while oxytocin pathway genes do not appear to contribute to the susceptibility to psychotic disorders, variations in the OXTR gene might play a role in the development of impaired social behavior.

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• Tesli, Martin Steen (2024). Dobbelblindet litterært eksperiment. 144(2). doi: 10.4045/tidsskr.23.0726. Full text in Research Archive
• Kjerpeseth, Lars Jøran; Hjellvik, Vidar; Ariansen, Inger; Bramness, Jørgen Gustav; Dalene, Knut Eirik & Krokstad, Steinar [Show all 12 contributors for this article] (2024). Social disparities in multimorbidity of noncommunicable diseases in Norway 2010-2020 – an emerging challenge in a single-disease-focused healthcare system. Data from the NCDNOR project. Full text in Research Archive
• Kunøe, Nikolaj; Indregard, Anne Marthe Rustad; Nussle, Hans Martin; Tesli, Martin Steen; Vandvik, Per Olav & Gather, Jakov (2024). A pragmatic randomised controlled non-inferiority trial of open-door policy versus treatment as usual in urban psychiatric inpatient wards. Full text in Research Archive
• Friestad, Christine; Tesli, Martin Steen; Rokicki, Jaroslav; Ziaka, Laoura; Heilskov, Esben Rytter & Hartberg, Cecilie Bhandari [Show all 7 contributors for this article] (2024). UNDERSTANDING AND PREVENTING VIOLENCE IN HIGH RISK INDIVIDUALS – A MIXED-METHODS APPROACH (PreVio). Full text in Research Archive
• Ziaka, Laoura; Tesli, Martin Steen; Haukvik, Unn Kristin Hansen; Rokicki, Jaroslav & Friestad, Christine (2024). Understanding and Preventing Violent Crime in Individuals with Severe Mental Disorders – a Mixed-Methods Approach (PreVio): A Study Protocol. Full text in Research Archive
• Tesli, Martin Steen; Hjellvik, Vidar; Jangmo, Anders Andreas Krister; Haram, Marit; Ariansen, Inger & Krokstad, Steinar [Show all 10 contributors for this article] (2023). A comprehensive exploration of comorbidity patterns between mental disorders and non-communicable somatic diseases. Full text in Research Archive
• Bramness, Jørgen Gustav; Hjellvik, Vidar; Høye, Anne; Tesli, Martin Steen; Haram, Marit & Nystad, Wenche [Show all 7 contributors for this article] (2023). Studying the epidemiology of depressive disorders using central health registries in a Nordic setting – the NCDNOR project. Full text in Research Archive
• Demontis, Ditte; Walters, G. Bragi; Athanasiadis, Georgios; Walters, Raymond; Therrien, Karen & Nielsen, Trine Tollerup [Show all 86 contributors for this article] (2023). Author Correction: Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains (Nature Genetics, (2023), 55, 2, (198-208), 10.1038/s41588-022-01285-8). Nature Genetics. ISSN 1061-4036. doi: 10.1038/s41588-023-01350-w. Full text in Research Archive
• Ayorech, Ziada; Davies, Neil; Smith, George Davey; Watson, Hunna J; Yilmaz, Zeynep & Bulik, Cynthia M [Show all 15 contributors for this article] (2023). Causal risk factors for childhood eating behaviours and adulthood anorexia nervosa. A between and within family Mendelian randomisation study. Full text in Research Archive
• Haram, Marit; Jangmo, Anders Andreas Krister; Koch, Elise; Plana-Ripoll, Oleguer; Bramness, Jørgen Gustav & Krokstad, Steinar [Show all 13 contributors for this article] (2023). Depression severity and life years lost. Full text in Research Archive
• Hannigan, Laurie John; Tesli, Martin Steen; Corfield, Elizabeth Claire; Bragantini, Daniela; Hegemann, Laura & Andreassen, Ole [Show all 8 contributors for this article] (2023). Genetic overlap between ADHD and cardiometabolic traits: an investigation in MoBa using polygenic transmission disequilibrium analyses. Full text in Research Archive
• Corfield, Elizabeth Claire; Frei, Oleksandr; Shadrin, Alexey; Rahman, Zillur; Lin, Aihua & Athanasiu, Lavinia [Show all 26 contributors for this article] (2022). The Norwegian Mother, Father, and Child cohort study (MoBa) genotyping data resource: the MoBaPsychGen_v1 pipeline. Full text in Research Archive
• Ystrøm, Eivind & Tesli, Martin Steen (2022). Personlighetstrekket som gir angst. [Journal]. Dagbladet. Full text in Research Archive
• Pasman, Joëlle; Shorter, John; Jangmo, Andreas; Kurvits, Siim; Meijsen, Joeri & Frei, Oleksandr [Show all 13 contributors for this article] (2022). IS GENETIC RISK FOR EARLY ONSET MAJOR DEPRESSIVE DISORDER ASSOCIATED WITH MORE SEVERE CLINICAL FEATURES THAN BROAD MAJOR DEPRESSIVE DISORDER? European Neuropsychopharmacology. ISSN 0924-977X. Full text in Research Archive
• Barkhuizen, Wikus; Pingault, Jean-Baptiste; Wang, Biyao; Hannigan, Laurie John; Eilertsen, Espen Moen & Andreassen, Ole [Show all 14 contributors for this article] (2021). Direct and indirect genetic influences involved in the intergenerational transmission of risk for ADHD in the Norwegian Mother, Father and Child Cohort. Full text in Research Archive
• Ayorech, Ziada; Davies, Neil; Wootton, Robyn; Watson, Hunna J; Hannigan, Laurie John & Askeland, Ragna Bugge [Show all 17 contributors for this article] (2021). Differential causal risk patterns in childhood eating behaviours compared to adulthood anorexia nervosa. A Mendelian randomization study. Full text in Research Archive
• Hannigan, Laurie John; Corfield, Elizabeth; Biele, Guido; Tilling, Kate; McAdams, Tom A. & Badini, Isabella [Show all 19 contributors for this article] (2021). The genomic basis of participation in the Norwegian Mother, Father and Child Cohort Study. Full text in Research Archive
• Barkhuizen, Wikus; Pingault, Jean-Baptiste; Wang, Biyao; Hannigan, Laurie John; Eilertsen, Espen Moen & Andreassen, Ole [Show all 14 contributors for this article] (2021). Direct and indirect genetic influences involved in the intergenerational transmission of risk for ADHD in the Norwegian Mother, Father and Child Cohort. Behavior Genetics. ISSN 0001-8244. 51(6), p. 692–691. Full text in Research Archive
• Hughes, Amanda; Morris, Tim; Ayorech, Ziada; Tesli, Martin Steen; Ask, Helga & Askeland, Ragna Bugge [Show all 16 contributors for this article] (2021). The causal effect of BMI on neurodevelopment: a within family Mendelian randomization study using MoBa. International Journal of Epidemiology. ISSN 0300-5771. 50(Suppl 1). doi: 10.1093/ije/dyab168.296. Full text in Research Archive
• Tesli, Martin Steen (2020). Hva er et samfunnsproblem og hva er et helseproblem i psykiatrien? Full text in Research Archive
• Askeland, Ragna Bugge; Hannigan, Laurie John; Ask, Helga; Lennox, Ziada Ayorech; Tesli, Martin Steen & Corfield, Elizabeth [Show all 9 contributors for this article] (2020). Genetic risk factors for neurodevelopmental disorders. Full text in Research Archive
• Lennox, Ziada Ayorech; Davies, Neil; Hannigan, Laurie John; Askeland, Ragna Bugge; Tesli, Martin Steen & Andreassen, Ole Andreas [Show all 14 contributors for this article] (2020). Which Metabo-Psychiatric Factors Affect the Risk of Anorexia Nervosa? A Mendelian Randomization Study. Full text in Research Archive
• Ask, Helga; Hannigan, Laurie; Davies, Neil; Gustavson, Kristin; Biele, Guido & Richardson, Thomas [Show all 15 contributors for this article] (2019). Exploring the Associations Between Health-Related Polygenic Scores and Participation in the Norwegian Mother and Child Pregnancy Cohort (MoBa). Full text in Research Archive
• Havdahl, Alexandra; Laurie, Hannigan; Askeland, Ragna Bugge; Ask, Helga; Tesli, Martin Steen & Corfield, Elizabeth [Show all 10 contributors for this article] (2019). Polygenic Risk for ADHD and Exposures During Pregnancy in the Norwegian Mother and Child Cohort Study (MoBa). Full text in Research Archive Show summary

  Background: Over the past decade, there has been an increase in studies showing associations between a broad range of lifestyle factors (e.g., smoking and alcohol intake) and health-related exposures (e.g., gestational diabetes) in pregnant women and ADHD in their children. It is, however, unclear whether the observed associations are causal or not. They may reflect confounding by unmeasured shared familial factors that influence both the maternal exposure and offspring ADHD. In the present study we assess the potential contribution of maternal polygenic risk for ADHD to pregnancy exposures linked to this disorder. Methods: We use data from the Norwegian Mother and Child pregnancy cohort study (MoBa), a prospective population-based pregnancy cohort study conducted by the Norwegian Institute of Public Health. Participants were recruited from all over Norway from 1999-2008. The women consented to participation in 40.6 % of the pregnancies. The cohort now includes 114,500 children, 95,200 mothers and 75,200 fathers. Blood samples were obtained from both parents during pregnancy and from mothers and children (umbilical cord) at birth. Genotyping is ongoing. A wide range of pregnancy exposures have been measured through the Medical Birth Registry and questionnaires. Summary statistics from the largest available genome-wide association study of ADHD (Demontis et al., 2019) were used to calculate polygenic risk scores (PRS). Results: Preliminary results from up to 9,073 mothers with available genotype and pregnancy exposure data suggest that maternal PRS for ADHD is associated with a range of pregnancy exposures, including smoking, coffee intake, non-use of nutritional supplements and use of pain medications. At WCPG, results will be presented from analyses of more than 20,000 mothers. For comparison purposes, associations between ADHD PRS and lifestyle and health-related factors in fathers (n>20,000) will be shown. Finally, we will present analyses of the extent to which accounting for genetic confounding attenuates associations between maternal pregnancy exposures and offspring ADHD in the MoBa cohort. Discussion: The results indicate that observed associations between pregnancy exposures and offspring ADHD could at least partly be explained by shared genetic influences/gene-environment correlations. Disclosure: Nothing to disclose.

• Askeland, Ragna Bugge; Hannigan, Laurie John; Ask, Helga; Tesli, Martin Steen; Corfield, Elizabeth & Andreassen, Ole Andreas [Show all 9 contributors for this article] (2019). Early manifestations of genetic risk for neurodevelopmental disorders. Full text in Research Archive
• Askeland, Ragna Bugge; Reichborn-Kjennerud, Ted; Hannigan, Laurie John; Ask, Helga; Tesli, Martin Steen & Corfield, Elizabeth [Show all 7 contributors for this article] (2019). Early manifestation of genetic risk for attention deficit/hyperactivity disorder in Norwegian children. Full text in Research Archive
• Tesli, Martin Steen; Corfield, Elizabeth; Zayats, Tetyana; Ask, Helga; Askeland, Ragna Bugge & Hannigan, Laurie [Show all 10 contributors for this article] (2019). Investigation of shared genetic risk between cardiometabolic morbidity and ADHD in a Norwegian family cohort using polygenic transmission disequilibrium test. Full text in Research Archive
• Hannigan, Laurie; Askeland, Ragna Bugge; Ask, Helga; Tesli, Martin Steen; Corfield, Elizabeth & Mcadams, Tom [Show all 10 contributors for this article] (2019). Perinatal maternal stress and early-life behavioural and emotional problems: examining the role of genetically-influenced environmental sensitivity in mothers and offspring. Full text in Research Archive
• Smeland, Olav Bjerkehagen; Witoelar, Aree; Lo, Min-Tzu; Tesli, Martin Steen; Wang, Yunpeng & Hinds, David A. [Show all 11 contributors for this article] (2016). Genetic overlap between schizophrenia and the Big Five personality traits. Full text in Research Archive
• Aas, Monica; Blokland, G. A.; Chawner, S. J; Choi, S. W; Estrada, J. & Forsingdal, A [Show all 29 contributors for this article] (2016). Summaries of plenary, symposia, and oral sessions at the XXII World Congress of Psychiatric Genetics, Copenhagen, Denmark, 12-16 October 2014. Psychiatric Genetics. ISSN 0955-8829. 26(1), p. 1–47. doi: 10.1097/YPG.0000000000000112. Full text in Research Archive
• Mahmood, Javed Iqbal; Grotmol, Kjersti Støen; Tesli, Martin Steen; Vaglum, Per Jørgen Wiggen & Tyssen, Reidar (2015). Risk factors at medical school for later hazardous drinking: a 10-year longitudinal, nationwide study. Full text in Research Archive
• Corfield, Elizabeth Claire; Frei, Oleksandr; Shadrin, Alexey; Rahman, Zillur; Lin, Aihua & Athanasiu, Lavinia [Show all 26 contributors for this article] (2022). The Norwegian Mother, Father, and Child cohort study (MoBa) genotyping data resource: MoBaPsychGen pipeline v.1. Cold Spring Harbor Laboratory Press (CSHL). doi: 10.1101/2022.06.23.496289. Full text in Research Archive Show summary

  Background: The Norwegian Mother, Father, and Child Cohort Study (MoBa) is a population-based pregnancy cohort, which includes approximately 114,500 children, 95,200 mothers, and 75,200 fathers. Genotyping of MoBa has been conducted through multiple research projects, spanning several years; using varying selection criteria, genotyping arrays, and genotyping centres. MoBa contains numerous interrelated families, which necessitated the implementation of a family-based quality control (QC) pipeline that verifies and accounts for diverse types of relatedness. Methods: The MoBaPsychGen pipeline, comprising pre-imputation QC, phasing, imputation, and post-imputation QC, was developed based on current best-practice protocols and implemented to account for the complex structure of the MoBa genotype data. The pipeline includes QC on both single nucleotide polymorphism (SNP) and individual level. Phasing and imputation were performed using the publicly available Haplotype Reference Consortium release 1.1 panel as a reference. Information from the Medical Birth Registry of Norway and MoBa questionnaires were used to identify biological sex, year of birth, reported parent-offspring (PO) relationships, and multiple births (only available in the offspring generation). Results: In total, 207,569 unique individuals (90% of the unique individuals included in the study) and 6,981,748 SNPs passed the MoBaPsychGen pipeline. The relatedness checks performed throughout the pipeline allowed identification of within-generation and across-generation first-degree, second-degree, and third-degree relatives. The individuals passing post-imputation QC comprised 64,471 families ranging in size from singletons to 84 unique individuals (singletons are included as families as other family members may not have been genotyped, imputed, or passed post-imputation QC). The relationships identified include 287 monozygotic twin pairs, 22,884 full siblings, 117,004 PO pairs, 23,299 second-degree relative pairs, and 10,828 third-degree relative pairs. Discussion: MoBa contains a highly complex relatedness structure, with a variety of family structures including singletons, PO duos, full (mother, father, child) PO trios, nuclear families, blended families, and extended families. The availability of robustly quality-controlled genetic data for such a large cohort with a unique extended family structure will allow many novel research questions to be addressed. Furthermore, the MoBaPsychGen pipeline has potential utility in similar cohorts.

• Askeland, Ragna Bugge; Hannigan, Laurie John; Ask, Helga; Ayorech, Ziada; Tesli, Martin Steen & Corfield, Elizabeth [Show all 12 contributors for this article] (2020). Early manifestations of genetic risk for neurodevelopmental disorders. PsyArXiv (Preprint artikkel). doi: 10.31234/osf.io/qbvw8. Full text in Research Archive
• Hannigan, Laurie John; Askeland, Ragna Bugge; Ask, Helga; Tesli, Martin Steen; Corfield, Elizabeth & Ayorech, Ziada [Show all 14 contributors for this article] (2020). Developmental milestones in early childhood and genetic liability to neurodevelopmental disorders. PsyArXiv (Preprint artikkel). doi: 10.31234/osf.io/x8wst. Full text in Research Archive

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