Different Hypothalamic-Pituitary-Adrenal Axis Reactivity in Males and Females with Bipolar Disorder after Previous SARS-CoV-2 Infection

Extreme mood fluctuations are a hallmark of bipolar disorder (BD) and the hypothalamic-pituitary-adrenal (HPA) axis and inflammatory processes, as well as neurotrophic factors are involved in its pathogenesis. Functional impairment of several systems plays an important role in the disease activity and mood swings. The direct impact of the coronavirus disease 2019 (COVID-19) on the condition of patients with BD is not well understood. This study included 176 patients aged 18 years and older with a diagnosis of BD and a current depressive episode. Participants were divided into two groups: 89 patients (23 men, 66 women) with SARS-CoV-2 antibody levels indicating no COVID-19 and 87 patients (19 men, 68 women)  with SARS-CoV-2 antibody levels indicating COVID-19, who were examined 1–8 months after the disease. The aim of the study was to identify the parameters potentially affected by COVID-19 in patients with BD and to use this information in current treatment plans. Diagnostic interviews and self-report measures were used to assess the psychometric characteristics of patients. The severity of SARS-CoV-2 infection was evaluated using a modified WHO case report form for post-COVID-19 cases. HPA axis markers, hormones, interleukin-6 (IL-6) and neurotrophic factors were measured in blood serum. IL-6 levels were found to be significantly higher in both males and females with BD after COVID-19, than those who had not previously had COVID-19. There was a significant increase in adrenocorticotropic hormone (ACTH) level (p = 0.002) and in ACTH/cortisol ratio (p = 0.0002) was found in males with BD after COVID-19 as compared to those without previous COVID-19. In contrast, there was a significant decrease in ACTH levels (p = 0.05) in females with BD who had previously had COVID-19, compared to those who didn’t have antibodies to SARS-CoV2. These results suggest that COVID-19 may cause different neuroendocrine changes in males and females with BD. Our findings support the hypothesis that people with BD may be exposed to additional harm during SARS-CoV2 infection compared with the general population, and also highlight the role of biological sex that should be considered in the assessment and management of these patients.