Marit Haram

• 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.

• 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.

• 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.

• 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.

• Sartorius, Alina Marie; Rokicki, Jaroslav; Birkeland, Siri; Bettella, Francesco; Barth, Claudia & Lange, Ann-Marie Glasø de [Show all 17 contributors for this article] (2024). An evolutionary timeline of the oxytocin signaling pathway. Communications Biology. 7(1). doi: 10.1038/s42003-024-06094-9. Full text in Research Archive Show summary

  Oxytocin is a neuropeptide associated with both psychological and somatic processes like parturition and social bonding. Although oxytocin homologs have been identified in many species, the evolutionary timeline of the entire oxytocin signaling gene pathway has yet to be described. Using protein sequence similarity searches, microsynteny, and phylostratigraphy, we assigned the genes supporting the oxytocin pathway to different phylostrata based on when we found they likely arose in evolution. We show that the majority (64%) of genes in the pathway are ‘modern’. Most of the modern genes evolved around the emergence of vertebrates or jawed vertebrates (540 - 530 million years ago, ‘mya’), including OXTR, OXT and CD38. Of those, 45% were under positive selection at some point during vertebrate evolution. We also found that 18% of the genes in the oxytocin pathway are ‘ancient’, meaning their emergence dates back to cellular organisms and opisthokonta (3500–1100 mya). The remaining genes (18%) that evolved after ancient and before modern genes were classified as ‘medium-aged’. Functional analyses revealed that, in humans, medium-aged oxytocin pathway genes are highly expressed in contractile organs, while modern genes in the oxytocin pathway are primarily expressed in the brain and muscle tissue.

• 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.

• 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
• 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.

• 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
• Werner, Maren Caroline Frogner; Wirgenes, Katrine Verena; Shadrin, Alexey; Lunding, Synve Hoffart; Rødevand, Linn & Hjell, Gabriela [Show all 15 contributors for this article] (2022). Immune marker levels in severe mental disorders: associations with polygenic risk scores of related mental phenotypes and psoriasis. Translational Psychiatry. 12(1). doi: 10.1038/s41398-022-01811-6. Full text in Research Archive Show summary

  Several lines of evidence implicate immune abnormalities in the pathophysiology of severe mental disorders (SMD) and comorbid mental disorders. Here, we use the data from genome-wide association studies (GWAS) of autoimmune diseases and mental phenotypes associated with SMD to disentangle genetic susceptibilities of immune abnormalities in SMD. We included 1004 patients with SMD and 947 healthy controls (HC) and measured plasma levels of IL-1Ra, sIL-2R, gp130, sTNFR-1, IL-18, APRIL, and ICAM-1. Polygenic risk scores (PRS) of six autoimmune disorders, CRP, and 10 SMD-related mental phenotypes were calculated from GWAS. General linear models were applied to assess the association of PRS with immune marker abnormalities. We found negative associations between PRS of educational attainment and IL-1Ra (P = 0.01) and IL-18 (P = 0.01). There were nominal positive associations between PRS of psoriasis and sgp130 (P = 0.02) and PRS of anxiety and IL-18 (P = 0.03), and nominal negative associations between PRS of anxiety and sIL-2R (P = 0.02) and PRS of educational attainment and sIL-2R (P = 0.03). Associations explained minor amounts of the immune marker plasma-level difference between SMD and HC. Different PRS and immune marker associations in the SMD group compared to HC were shown for PRS of extraversion and IL-1Ra ([interaction effect (IE), P = 0.002), and nominally for PRS of openness and IL-1Ra (IE, P = 0.02) and sTNFR-1 (IE, P = 0.04). Our findings indicate polygenic susceptibilities to immune abnormalities in SMD involving genetic overlap with SMD-related mental phenotypes and psoriasis. Associations might suggest immune genetic factors of SMD subgroups characterized by autoimmune or specific mental features.

• Werner, Maren Caroline Frogner; Wirgenes, Katrine Verena; Shadrin, Alexey; Lunding, Synve Hoffart; Rødevand, Linn & Hjell, Gabriela [Show all 15 contributors for this article] (2022). Limited association between infections, autoimmune disease and genetic risk and immune activation in severe mental disorders. Progress in Neuro-psychopharmacology and Biological Psychiatry. ISSN 0278-5846. 116. doi: 10.1016/j.pnpbp.2022.110511. Full text in Research Archive Show summary

  Background Low-grade inflammation may be part of the underlying mechanism of schizophrenia and bipolar disorder. We investigated if genetic susceptibility, infections or autoimmunity could explain the immune activation. Methods Seven immune markers were selected based on indicated associations to severe mental disorders (IL-1Ra, sIL-2R, IL-18, sgp130, sTNFR-1, APRIL, ICAM-1) and measured in plasma of patients with schizophrenia (SCZ, N = 732) and bipolar spectrum disorders (BD, N = 460) and healthy controls (HC, N = 938). Information on rate of infections and autoimmune diseases were obtained from Norwegian national health registries for a twelve-year period. Polygenic risk scores (PRS) of SCZ and BD were calculated from genome-wide association studies. Analysis of covariance were used to test effects of infection rate, autoimmune disease and PRS on differences in immune markers between patients and HC. Results Infection rate differed between all groups (BD > HC > SCZ, all p < 0.001) whereas autoimmune disease was more frequent in BD compared to SCZ (p = 0.004) and HC (p = 0.003). sIL-2R was positively associated with autoimmune disease (p = 0.001) and negatively associated with PRS of SCZ (p = 0.006) across SCZ and HC; however, associations represented only small changes in the difference of sIL-2R levels between SCZ and HC. Conclusion There were few significant associations between rate of infections, autoimmune disease or PRS and altered immune markers in SCZ and BD, and the detected associations represented only small changes in the immune aberrations. The findings suggest that most of the low-grade inflammation in SCZ and BD is explained by other factors than the underlying PRS, autoimmunity and infection rates.

• Johansen, Ingrid Torp; Steen, Nils Eiel; Haram, Marit; Rødevand, Linn; Werner, Maren Caroline Frogner & Lunding, Synve Hoffart [Show all 13 contributors for this article] (2022). Sex differences in antipsychotic-related triglyceride levels are associated with metabolic hormone differences in patients with severe mental disorders. Schizophrenia Research. ISSN 0920-9964. 243, p. 55–63. doi: 10.1016/j.schres.2022.02.015. Full text in Research Archive Show summary

  Background Adverse effects of antipsychotics (AP) contribute to cardiovascular disease (CVD) risk in patients with severe mental disorders (SMD). We investigated sex differences in AP-related CVD risk factors and the role of metabolic hormones. Methods Patients with SMD (N = 1791) receiving AP with different CVD risk were recruited and grouped into olanzapine and/or clozapine (N = 532), other APs (N = 744) or no use of APs (N = 515). Associations between CVD risk factor (total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), body mass index (BMI), glucose, blood pressure), sex and AP groups were tested in multiple linear regression with interactions, controlling for diagnostic group, lifestyle factors, polypharmacy, age and ethnicity. Next, we tested associations between sex differences in AP-related CVD risk factors and metabolic regulatory hormones. Results AP groups and male sex were significantly associated with higher levels of LDL-C, TG and BMI, and lower levels of HDL-C. Significant interaction between AP groups and sex were found for TG (p = 0.017), with larger increase in males. Serum adiponectin, insulin, cortisol, leptin, testosterone, free thyroxine and thyroid-stimulating hormone (TSH) were associated with TG levels (all p ≤ 0.001), and a significant interaction with sex for insulin (p = 0.005), cortisol (p = 0.016), leptin (p < 0.001) and TSH (p = 0.001). Conclusions We found more severe AP-related CVD risk factors in male patients with SMD. The male-dependent increase in TG levels was associated with leptin, insulin, cortisol and TSH levels. Clinicians treating patients with SMD should be aware of increased vulnerability for AP-related lipid abnormalities in males.

• Birkenæs, Viktoria; Elvsåshagen, Torbjørn; Westlye, Lars Tjelta; Høegh, Margrethe Collier; Haram, Marit & Werner, Maren Caroline Frogner [Show all 14 contributors for this article] (2021). Telomeres are shorter and associated with number of suicide attempts in affective disorders. Journal of Affective Disorders. ISSN 0165-0327. 295, p. 1032–1039. doi: 10.1016/j.jad.2021.08.135. Full text in Research Archive
• Valstad, Mathias; Roelfs, Daniel; Slapø, Nora Berz; Timpe, Clara Marie Fides; Rai, Ahsan & Matziorinis, Anna Maria [Show all 24 contributors for this article] (2021). Evidence for Reduced Long-Term Potentiation-Like Visual Cortical Plasticity in Schizophrenia and Bipolar Disorder. Schizophrenia Bulletin. ISSN 0586-7614. 47(6), p. 1751–1760. doi: 10.1093/schbul/sbab049. Full text in Research Archive Show summary

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

• Winterton, Adriano; Bettella, Francesco; Lange, Ann-Marie Glasø de; Haram, Marit; Steen, Nils Eiel & Westlye, Lars Tjelta [Show all 8 contributors for this article] (2021). Oxytocin-pathway polygenic scores for severe mental disorders and metabolic phenotypes in the UK Biobank. Translational Psychiatry. doi: 10.1038/s41398-021-01725-9. Full text in Research Archive Show summary

  Abstract Oxytocin is a neuromodulator and hormone that is typically associated with social cognition and behavior. In light of its purported effects on social cognition and behavior, research has investigated its potential as a treatment for psychiatric illnesses characterized by social dysfunction, such as schizophrenia and bipolar disorder. While the results of these trials have been mixed, more recent evidence suggests that the oxytocin system is also linked with cardiometabolic conditions for which individuals with severe mental disorders are at a higher risk for developing. To investigate whether the oxytocin system has a pleiotropic effect on the etiology of severe mental illness and cardiometabolic conditions, we explored oxytocin’s role in the shared genetic liability of schizophrenia, bipolar disorder, type-2 diabetes, and several phenotypes linked with cardiovascular disease and type 2 diabetes risk using a polygenic pathway-specific approach. Analysis of a large sample with about 480,000 individuals (UK Biobank) revealed statistically significant associations across the range of phenotypes analyzed. By comparing these effects to those of polygenic scores calculated from 100 random gene sets, we also demonstrated the specificity of many of these significant results. Altogether, our results suggest that the shared effect of oxytocin-system dysfunction could help partially explain the co-occurrence of social and cardiometabolic dysfunction in severe mental illnesses.

• Werner, Maren Caroline Frogner; Wirgenes, Katrine Verena; Haram, Marit; Bettella, Francesco; Lunding, Synve Hoffart & Rødevand, Linn Nilsen [Show all 12 contributors for this article] (2020). Indicated association between polygenic risk score and treatment-resistance in a naturalistic sample of patients with schizophrenia spectrum disorders. Schizophrenia Research. ISSN 0920-9964. 218, p. 55–62. doi: 10.1016/j.schres.2020.03.006. Full text in Research Archive Show summary

  Background One third of people diagnosed with schizophrenia fail to respond adequately to antipsychotic medication, resulting in persisting disabling symptoms, higher rates of hospitalization and higher costs for society. In an effort to better understand the mechanisms behind resistance to antipsychotic treatment in schizophrenia, we investigated its potential relationship to the genetic architecture of the disorder. Methods Patients diagnosed with a schizophrenia spectrum disorder (N = 321) were classified as either being treatment-resistant (N = 108) or non-treatment-resistant (N = 213) to antipsychotic medication using defined consensus criteria. A schizophrenia polygenic risk score based on genome-wide association studies (GWAS) was calculated for each patient and binary logistic regression was performed to investigate the association between polygenetic risk and treatment resistance. We adjusted for principal components, batch number, age and sex. Additional analyses were performed to investigate associations with demographic and clinical variables. Results High levels of polygenic risk score for schizophrenia significantly predicted treatment resistance (p = 0.003). The positive predictive value of the model was 61.5% and the negative predictive value was 71.7%. The association was significant for one (p = 0.01) out of five tested SNP significance thresholds. Season of birth was able to predict treatment-resistance in the regression model (p = 0.05). Conclusions The study indicates that treatment-resistance to antipsychotic medication is associated with higher polygenetic risk of schizophrenia, suggesting a link between antipsychotics mechanism of action and the genetic underpinnings of the disorder.

• Benjamin, Silje Beatrice Rognås; Valstad, Mathias; Elvsåshagen, Torbjørn; Jönsson, Erik Gunnar; Moberget, Torgeir & Winterton, Adriano [Show all 14 contributors for this article] (2020). Heart rate variability is associated with disease severity in psychosis spectrum disorders. Progress in Neuro-psychopharmacology and Biological Psychiatry. ISSN 0278-5846. 00:110108, p. 1–8. doi: 10.1016/j.pnpbp.2020.110108. Full text in Research Archive Show summary

  While a growing literature links cardiac autonomic dysregulation to a variety of psychiatric disorders, the relationship between cardiac autonomic functioning and specific symptoms in schizophrenia (SZ) and bipolar disorder (BD) remains elusive. Thus, we investigated heart rate variability (HRV), a proxy for vagal activity, as a biological marker for symptom severity in patients with SZ and BD. HRV was calculated in 35 patients with SZ and 52 patients with BD, as well as in 149 healthy controls. In the patient groups, symptom severity and function were measured by the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Results showed that HRV was significantly lower in both clinical groups compared to the healthy controls, with no significant HRV differences between patient groups. PANSS general psychopathology scores, GAF symptom scores, and GAF function scores showed statistically significant associations with HRV across groups. These results suggest that disease severity is associated with autonomic dysfunction and that HRV may provide a potential biomarker of disease severity in SZ and BD.

• Nerhus, Mari; Berg, Akiah Ottesen; Simonsen, Carmen Elisabeth; Haram, Marit; Haatveit, Beathe Christin & Dahl, Sandra Rinne [Show all 11 contributors for this article] (2017). Vitamin D deficiency associated with cognitive functioning in psychotic disorders. Journal of Clinical Psychiatry. ISSN 0160-6689. 78(7), p. e750–e757. doi: 10.4088/JCP.16m10880. Full text in Research Archive
• Mørch, Ragni Helene; Dieset, Ingrid; Færden, Ann; Hope, Sigrun; Aas, Monica & Nerhus, Mari [Show all 17 contributors for this article] (2017). Persistent increase in TNF and IL-1 markers in severe mental disorders suggests trait-related inflammation: a one year follow-up study. Acta Psychiatrica Scandinavica. ISSN 0001-690X. 136(4), p. 400–408. doi: 10.1111/acps.12783. Full text in Research Archive
• Quintana, Daniel; Elstad, Maja; Kaufmann, Tobias; Brandt, Christine Lycke; Haatveit, Beathe Christin & Haram, Marit [Show all 9 contributors for this article] (2016). Resting-state heart rate variability is related to respiratory frequency in individuals with severe mental illness but not healthy controls. Scientific Reports. 6:37212, p. 1–8. doi: 10.1038/srep37212. Full text in Research Archive Show summary

  Heart rate variability (HRV) has become central to biobehavioral models of self-regulation and interpersonal interaction. While research on healthy populations suggests changes in respiratory frequency do not affect short-term HRV, thus negating the need to include respiratory frequency as a HRV covariate, the nature of the relationship between these two variables in psychiatric illness is poorly understood. Therefore, the aim of this study was to investigate the association between HRV and respiratory frequency in a sample of individuals with severe psychiatric illness (n = 55) and a healthy control comparison group (n = 149). While there was no significant correlation between HF-HRV and respiration in the control group, we observed a significant negative correlation in the psychiatric illness group, with a 94.1% probability that these two relationships are different. Thus, we provide preliminary evidence suggesting that HF-HRV is related to respiratory frequency in severe mental illness, but not in healthy controls, suggesting that HRV research in this population may need to account for respiratory frequency. Future work is required to better understand the complex relationship between respiration and HRV in other clinical samples with psychiatric diseases.

• 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.

• 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.

• Haram, Marit; Tesli, Martin Steen; Dieset, Ingrid; Steen, Nils Eiel; Røssberg, Jan Ivar & Djurovic, Srdjan [Show all 8 contributors for this article] (2014). An attempt to identify single nucleotide polymorphisms contributing to possible relationships between personality traits and oxytocin-related genes. Neuropsychobiology. ISSN 0302-282X. 69(1), p. 25–30. doi: 10.1159/000356965. Full text in Research Archive
• Steen, Nils Eiel; Methlie, Paal; Lorentzen, Steinar; Dieset, Ingrid; Aas, Monica & Nerhus, Mari [Show all 11 contributors for this article] (2014). Altered systemic cortisol metabolism in bipolar disorder and schizophrenia spectrum disorders. Journal of Psychiatric Research. ISSN 0022-3956. 52(1), p. 57–62. doi: 10.1016/j.jpsychires.2014.01.017. Full text in Research Archive
• Nerhus, Mari; Berg, Akiah Ottesen; Haram, Marit; Kvitland, Levi Røstad; Andreassen, Ole Andreas & Melle, Ingrid (2013). Migrant background and ethnic minority status as predictors for duration of untreated psychosis. Early Intervention in Psychiatry. ISSN 1751-7885. doi: 10.1111/eip.12106. Full text in Research Archive Show summary

  AIM: The aim of the study was to explore if patients with migration and/or ethnic minority background have longer duration of untreated psychosis (DUP) than patients from the reference population, and in case to what extent this was best explained by ethnic minority status or migration background, including age at migration. METHODS: Four hundred sixty-two first-episode patients were included. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders was used for diagnostic purposes. Patients were interviewed about migration history and ethnicity using structured questionnaires. RESULTS: Being part of an ethnic minority group had a trend-level significance, and migration after the age of 6 had a statistically significant association with prolonged DUP. CONCLUSIONS: Age at migration has a moderate, but statistically significant effect on DUP. The findings indicate migrating after school start is associated with a longer DUP in immigrant populations.

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• Johnsen, Erik; Tveito, Marit; Pignatiello, Siv Elin; Strandlie, Martine; Haram, Marit & Selle, Morten Stefan (2025). Psykiatrisk spesialistkunnskap har kort halveringstid. Full text in Research Archive Show summary

  Faglig oppdaterte psykiatere er helt nødvendig for å sikre god kvalitet, pasientsikkerhet og god ressursutnyttelse.

• Løberg, Else-Marie; Mørkved, Nina; Melle, Ingrid; Haram, Marit; Malerbakken, Anne & Blindheim, Anne Alnes [Show all 7 contributors for this article] (2025). Gi mennesker med psykoselidelser traumebehandling. doi: https:/www.dagensmedisin.no/psykisk-helse-psykose-traumefokusert-kognitiv-atferdsterapi/gi-mennesker-med-psykoselidelser-traumebehandling/717866. Full text in Research Archive Show summary

  Det er på tide at våre myndigheter prioriterer denne pasientgruppen for kunnskapsbasert traumebehandling. Vi håper de tar utfordringen.

• 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
• Jaholkowski, Piotr Pawel; Haram, Marit & Andreassen, Ole (2023). Etiologic Studies of Premenstrual Disorders Require Prospective Confirmation of Affective Cyclicity - Reply. JAMA psychiatry. ISSN 2168-6238. 80(11), p. 1175–1176. doi: 10.1001/jamapsychiatry.2023.3290. 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
• Kvitland, Levi Røstad; Ringen, Petter Andreas; Aminoff, Sofie Ragnhild; Haram, Marit; Hellvin, Tone & Lagerberg, Trine Vik [Show all 9 contributors for this article] (2013). Cannabis use in the early phase of bipolar disorder: clinical characteristics in a cross-sectional sample. Bipolar Disorders. ISSN 1398-5647. 15, p. 118–118. Full text in Research Archive

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