Cortisol and C-reactive protein (CRP) regulation in severe mental disorders

Amina Inova; Viktoria Birkenæs; Daniel S Quintana; Monica B E G Ormerod; Torill Ueland; Thor Ueland; Srdjan Djurovic; Ole Andreassen; Nils Eiel Steen; Monica Aas

doi:10.1016/j.psyneuen.2024.107272

Cortisol and C-reactive protein (CRP) regulation in severe mental disorders

Psychoneuroendocrinology. 2024 Dec 25:172:107272. doi: 10.1016/j.psyneuen.2024.107272. Online ahead of print.

Authors

Affiliations

¹ Institute of Clinical Medicine, University of Oslo, Norway.
² Centre for Precision Psychiatry, Division of Mental Health and Addiction, University of Oslo and Oslo University Hospital, Oslo, Norway; PsychGen Center for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
³ Department of Psychology, University of Oslo, Oslo, Norway; NevSom, Department of Rare Disorders, Oslo University Hospital, Oslo, Norway.
⁴ Institute of Clinical Medicine, University of Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁵ Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
⁶ Institute of Clinical Medicine, University of Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Thrombosis Research Center (TREC), Division of internal medicine, University hospital of North Norway, Tromsø, Norway.
⁷ Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
⁸ Institute of Clinical Medicine, University of Oslo, Norway; Centre for Precision Psychiatry, Division of Mental Health and Addiction, University of Oslo and Oslo University Hospital, Oslo, Norway.
⁹ Institute of Clinical Medicine, University of Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Division of Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway.
¹⁰ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK. Electronic address: monica.aas@kcl.ac.uk.

PMID: 39740359
DOI: 10.1016/j.psyneuen.2024.107272

Abstract

Background: People with schizophrenia (SZ) and bipolar disorder (BD) show abnormalities in the biological stress system and low-grade inflammation. However, whether the hypothalamic-pituitary-adrenal (HPA) axis-immune regulation is disrupted in SZ and BD, is yet to be determined.

Methods: Cortisol and C-reactive protein (CRP) were measured in blood samples collected at or before 10 am in participants with SZ (N = 257), BD (N = 153), and healthy controls (N = 40). Cortisol/CRP ratio was calculated as an indicator of the balance between HPA axis activity and inflammatory activity, called HPA axis-immune regulation. Global functioning and symptom levels were obtained using the Global Assessment of Functioning (GAF) Scale and Positive and Negative Syndrome Scale (PANSS). Standardized neuropsychological tests were used to assess cognitive function. All analyses were adjusted for demographic variables (age and sex) and the time of blood sampling.

Results: Participants with a SZ or BD diagnosis had lower cortisol/CRP ratios (F=5.93, p = 0.003) compared to healthy controls. The difference was no longer statistically significant (p > 0.1) when BMI was added as a covariate to the model. Within patients, those on psychotropic treatment (n = 337) had lower cortisol/CRP ratio than those not taking psychotropic agents (n = 59) (F=4.72, p = 0.03). Compared to HC, only patients on regular psychotropic agents had lower cortisol/CRP ratio (p = 0.02). Within the SZ group, lower cortisol/CRP ratio was associated with having poorer general functioning as measured by GAF (ß=-0.18, p = 0.01), and more severe negative and general symptomatology as measured by PANSS (ß=0.19, p = 0.007 and ß=0.18, p = 0.01, respectively). In SZ, lower cortisol/CRP ratio was also associated with poorer verbal memory, learning, and processing speed (ß=-0.20 p = 0.007, ß=-0.19 p = 0.01, ß=-0.25, p > 0.001, respectively). No associations were observed between cortisol/CRP ratio and clinical and cognitive functioning in the BD group.

Conclusion: These findings may indicate HPA axis-immune dysregulation in SZ. Our study further indicates that disrupted HPA axis-immune regulation in people with SZ and BD is associated with psychotropic treatment and fat mass, highlighting the clinical importance of weight control and regular psychotropic treatment follow-ups within this group.

Keywords: Bipolar disorders; Clinical features; Cognitive functioning; Cortisol and CRP ratio; Schizophrenia.