Ingrid Torp Johansen

• Wachtelaer, Eva; Trippaers, Chloë; Andreassen, Ole; Johansen, Ingrid Torp; Steen, Nils Eiel & Ask, Helga [Show all 11 contributors for this article] (2026). Post-infection mental illness: Mapping pathways of vulnerability and resilience in VIRAL-MInds. Brain, Behavior, and Immunity. ISSN 0889-1591. 134. doi: 10.1016/j.bbi.2026.106291. Full text in Research Archive
• Ormerod, Monica Bettina E. Greenwood; Sheikh, Mashhood Ahmed; Ueland, Thor; Hjell, Gabriela; Rødevand, Linn & Sæther, Linn Sofie [Show all 15 contributors for this article] (2025). Minor immunomodulatory effects of psychotropics suggested in severe mental disorders: Associations of antipsychotics with beta defensin 2, antidepressants with C-reactive protein, and mood stabilizers with soluble interleukin 2 receptor. European psychiatry. ISSN 0924-9338. 68(1). doi: 10.1192/j.eurpsy.2025.10104. Full text in Research Archive Show summary

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

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

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

• Ormerod, Monica Bettina E. Greenwood; Ueland, Thor; Aas, Monica; Hjell, Gabriela; Rødevand, Linn & Sæther, Linn Sofie [Show all 16 contributors for this article] (2025). Limited evidence of association between dysregulated immune marker levels and telomere length in severe mental disorders. Acta Neuropsychiatrica. ISSN 0924-2708. 37. doi: 10.1017/neu.2024.62. Full text in Research Archive Show summary

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

• Andreou, Dimitrios; Steen, Nils Eiel; Mørch-Johnsen, Lynn Egeland; Jørgensen, Kjetil Nordbø; Wortinger, Laura Anne & Barth, Claudia [Show all 19 contributors for this article] (2024). Toxoplasma gondii infection associated with inflammasome activation and neuronal injury. Scientific Reports. 14(1). doi: 10.1038/s41598-024-55887-9. Full text in Research Archive Show summary

  Toxoplasma gondii (TOXO) infection typically results in chronic latency due to its ability to form cysts in the brain and other organs. Latent toxoplasmosis could promote innate immune responses and impact brain function. A large body of evidence has linked TOXO infection to severe mental illness (SMI). We hypothesized that TOXO immunoglobulin G (IgG) seropositivity, reflecting previous infection and current latency, is associated with increased circulating neuron-specific enolase (NSE), a marker of brain damage, and interleukin-18 (IL-18), an innate immune marker, mainly in SMI. We included 735 patients with SMI (schizophrenia or bipolar spectrum) (mean age 32 years, 47% women), and 518 healthy controls (HC) (mean age 33 years, 43% women). TOXO IgG, expressed as seropositivity/seronegativity, NSE and IL-18 were measured with immunoassays. We searched for main and interaction effects of TOXO, patient/control status and sex on NSE and IL-18. In the whole sample as well as among patients and HC separately, IL-18 and NSE concentrations were positively correlated (p < 0.001). TOXO seropositive participants had significantly higher NSE (3713 vs. 2200 pg/ml, p < 0.001) and IL-18 levels (1068 vs. 674 pg/ml, p < 0.001) than seronegative participants, and evaluation within patients and HC separately showed similar results. Post-hoc analysis on cytomegalovirus and herpes simplex virus 1 IgG status showed no associations with NSE or IL-18 which may suggest TOXO specificity. These results may indicate ongoing inflammasome activation and neuronal injury in people with TOXO infections unrelated to diagnosis.

• Johansen, Ingrid Torp; Steen, Nils Eiel; Rødevand, Linn; Lunding, Synve Hoffart; Hjell, Gabriela & Ormerod, Monica Bettina E. Greenwood [Show all 11 contributors for this article] (2024). Sex differences in autonomic adverse effects related to antipsychotic treatment and associated hormone profiles. Schizophrenia. 10. doi: 10.1038/s41537-023-00430-4. Full text in Research Archive Show summary

  Autonomic adverse effects of antipsychotic drugs (APs) cause clinical challenges, but few studies have investigated sex differences and their underlying biological pathways. Sex-specific regulation of relevant hormones could be involved. We investigated sex differences in autonomic adverse effects related to olanzapine, quetiapine, risperidone, and aripiprazole, and the role of hormones related to APs. Patients with severe mental disorders (N = 1318) were included and grouped based on AP monotherapy: olanzapine (N = 364), quetiapine (N = 211), risperidone (N = 102), aripiprazole (N = 138), and no AP (N = 503). Autonomic symptoms from the Udvalg for Kliniske Undersøgelser (UKU) side effect scale was analyzed with logistic regression, adjusting for age, diagnosis, and polypharmacy. Further, we analyzed associations between autonomic symptoms and hormones related to APs. We found associations between autonomic adverse effects and APs, with sex-specific risk for palpitations/tachycardia associated with hormonal changes related to APs. Results showed increased salivation associated with aripiprazole, reduced salivation with quetiapine, and nausea/vomiting and palpitations/tachycardia with olanzapine, and higher risk of nausea/vomiting, diarrhea, constipation, polyuria/polydipsia, and palpitations/tachycardia in females. Significant sex x AP interaction was found for palpitations/tachycardia, with higher risk in risperidone-treated males, which was associated with different hormone profiles of prolactin, cortisol, and insulin. Our findings implicate a role of several hormones in the sex-specific autonomic adverse effects related to APs.

• Aas, Monica; Andreassen, Ole; Gjerstad, Johannes; Rødevand, Linn; Hjell, Gabriela & Johansen, Ingrid Torp [Show all 12 contributors for this article] (2023). Expression of ANK3 moderates the association between childhood trauma and affective traits in severe mental disorders. Scientific Reports. 13:13845, p. 1–9. doi: 10.1038/s41598-023-40310-6. Full text in Research Archive Show summary

  Exposure to early life trauma increases the risk of psychopathology later in life. Here we investigated if ANK3 mRNA levels influence the relationship between childhood trauma experiences and clinical characteristics in mental disorders. A sample of 174 patients with bipolar disorder and 291 patients with schizophrenia spectrum disorder were included. Patients were diagnosed using the Structured Clinical Interview for DSM-IV, and childhood trauma was assessed using the childhood trauma questionnaire. Age at illness onset and number of psychotic and affective episodes were assessed from interview and medical records. Current depressive symptoms were measured using the calgary depression scale for schizophrenia and the inventory for depressive symptomatology. ANK3 expression was analyzed in whole blood using the Illumina HumanHT-12 v4 Expression BeadChip. Analyses were carried out with the Process adjusted for confounders. Within the total sample, patients with both high ANK3 expression and with the most severe childhood sexual abuse had more manic/hypomanic episodes and an earlier age at onset of the first episode. ANK3 mRNA levels also moderated the relationship between emotional neglect and manic/hypomanic episodes. Our results suggest that ANK3 expression levels moderate the association between specific types of childhood trauma and affective traits in mental disorders.

• Hjell, Gabriela; Rokicki, Jaroslav; Szabo, Attila; Holst, Rene; Tesli, Natalia & Bell, Christina [Show all 19 contributors for this article] (2023). Impulsivity across severe mental disorders: a cross-sectional study of immune markers and psychopharmacotherapy. BMC Psychiatry. 23(1). doi: 10.1186/s12888-023-05154-4. Full text in Research Archive Show summary

  Background Impulsivity is a transdiagnostic feature linked to severe clinical expression and a potential target for psychopharmacological strategies. Biological underpinnings are largely unknown, but involvement of immune dysregulation has been indicated, and the effects of psychopharmacological agents vary. We investigated if impulsivity was associated with circulating immune marker levels and with a range of psychopharmacological treatment regimens in severe mental disorders. Methods Impulsivity was assessed in a sample (N = 657) of patients with schizophrenia or schizophreniform disorder (SCZ) (N = 116) or bipolar disorder (BD) (N = 159) and healthy participants (N = 382) using the Barratt Impulsiveness Scale (BIS-11) questionnaire. Plasma levels of systemic immune markers (RANTES, IL-1RA, IL-18, IL-18BP, sTNFR-1) were measured by enzyme immunoassays. Patients underwent thorough clinical assessment, including evaluation of psychotropic medication. Associations were assessed using linear regressions. Results Impulsivity was positively associated with SCZ (p < 0.001) and BD (p < 0.001) diagnosis and negatively associated with age (p < 0.05), but not significantly associated with any of the circulating immune markers independently of diagnostic status. Among patients, impulsivity was negatively associated with lithium treatment (p = 0.003) and positively associated with antidepressant treatment (p = 0.011) after controlling for diagnosis, psychotropic co-medications, manic symptoms, and depressive symptoms. Conclusions We report elevated impulsivity across SCZ and BD but no associations to systemic immune dysregulation based on the current immune marker selection. The present study reveals associations between impulsivity in severe mental disorders and treatment with lithium and antidepressants, with opposite directions. Future studies are warranted to determine the causal directionality of the observed associations with psychopharmacotherapy.

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

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

• Johansen, Ingrid Torp; Steen, Nils Eiel; Rødevand, Linn; Werner, Maren Caroline Frogner; Lunding, Synve Hoffart & Hjell, Gabriela [Show all 12 contributors for this article] (2022). Sex-specific associations between metabolic hormones, severe mental disorders and antipsychotic treatment. Psychoneuroendocrinology. ISSN 0306-4530. 146. doi: 10.1016/j.psyneuen.2022.105927. Full text in Research Archive
• Hjell, Gabriela; Szabo, Attila; Mørch-Johnsen, Lynn Egeland; Holst, Rene; Tesli, Natalia & Bell, Christina [Show all 18 contributors for this article] (2022). Interleukin-18 signaling system links to agitation in severe mental disorders. Psychoneuroendocrinology. ISSN 0306-4530. 140:105721, p. 1–8. doi: 10.1016/j.psyneuen.2022.105721. Full text in Research Archive Show summary

  Objective Agitation is a challenging clinical feature in severe mental disorders, but its biological correlates are largely unknown. Inflammasome-related abnormalities have been linked to severe mental disorders and implicated in animal models of agitation. We investigated if levels of circulating inflammasome-related immune markers were associated with agitation in severe mental disorders. Methods Individuals with a psychotic or affective disorder (N = 660) underwent blood sampling and clinical characterization. Plasma levels of interleukin (IL)‐18, IL-18 binding protein (IL-18BP), IL-18 receptor 1 (IL-18R1), IL-18 receptor accessory protein (IL-18RAP), and IL-1 receptor antagonist (IL-1RA) were measured. Agitation levels were estimated with the Positive and Negative Syndrome Scale Excited Component. Multiple linear- and logistic regression were used to investigate the associations between agitation and the immune markers, while controlling for confounders. The influence of psychotic and affective symptoms was assessed in follow-up analyses. Results Agitation was positively associated with IL-18BP (β = 0.13, t = 3.41, p = 0.0007) after controlling for multiple confounders, including BMI, smoking, medication, and substance use. Adjustment for psychotic, manic, and depressive symptoms did not affect the results. There were no significant associations between agitation and the other investigated immune markers (IL-1RA (β = 0.06, t = 1.27, p = 0.20), IL-18 (β = 0.05, t = 1.25, p = 0.21), IL-18R1 (β = 0.04, t = 1.01, p = 0.31), IL-18RAP (odds ratio = 0.96, p = 0.30)). In a subsample (N = 463), we also adjusted for cortisol levels, which yielded unaltered results. Conclusion Our findings add to the accumulating evidence of immune system disturbances in severe mental disorders and suggest the IL-18 system as a part of the biological correlate of agitation independent of affective and psychotic symptoms.

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

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

• 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.

• 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.

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