Longitudinal trajectories of immunometabolic marker in various mental disorders and their relationship with brain structures

Abstract Background: Studies have identified immunometabolic biomarkers for various mental disorders, but their temporal evolution and relationship with brain structure remain unclear. This study aimed to assess the long-term trajectories of immunometabolic biomarkers across 10 years leading up to and following diagnosis and explore their association with brain structure. Methods: We conducted a nested case-control study using prospective community-based cohort data from UK Biobank, which included both psychiatric assessments and immunometabolic markers. Cases were defined as individuals with a diagnosis of mental disorders at baseline and during follow-up. Nearly 5 controls without any mental disorders were matched for each case. Multivariable linear regression was used to assess the divergence evolution between cases and controls for each psychiatric assessment and immunometabolic biomarker. Results: In comparison to controls, 6, 15, 10, and 47 immunometabolic markers exhibited significant changes over time in bipolar disorder, anxiety, schizophrenia, and depression, respectively. These biomarkers could be grouped into distinct clusters with complex, non-linear trajectories. Some clusters displayed monotonic changes, while others reversed near the time of diagnosis. The identified immunometabolic markers were associated with brain structure in the general population, including orbitofrontal, precuneus, and amygdala regions. Conclusions: These findings provide novel insights into the temporal dynamics of immunometabolic biomarkers in various mental disorders within 10 years before and after clinical diagnosis, as well as their correlation with brain structure. Monitoring and managing these biomarkers could potentially carry significant implications for the early detection and prevention of mental disorders in older adults.