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

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 (13=-0.18, p = 0.01), and more severe negative and general symptomatology as measured by PANSS (13=0.19, p = 0.007 and 13=0.18, p = 0.01, respectively). In SZ, lower cortisol/CRP ratio was also associated with poorer verbal memory, learning, and processing speed (13=-0.20 p = 0.007, 13=-0.19 p = 0.01, 13=-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.