Temporal trends of blood-based markers in various mental disorders and their relationship with brain structure

Background: Studies have identified blood-based biomarkers for various mental disorders, but their temporal trends and relationship with brain structure remain unclear. This study aimed to assess the temporal trends of blood-based 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 (n = 502,617; aged 40 to 69 years; recruited from 2006 to 2010), which included both psychiatric assessments and blood-based biomarkers. Cases were defined as individuals with a diagnosis of mental disorders at baseline and during follow-up (individuals with bipolar disorder = 1,325; depression = 36,582; schizophrenia = 1,479; anxiety = 27,220). 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 blood-based biomarker. Results: In comparison to controls, 6, 15, 10, and 47 blood-based 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 temporal trends. Some clusters displayed monotonic changes, while others reversed near the time of diagnosis. The identified blood-based 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 trends of blood-based biomarkers in various mental disorders within 10 years before and after clinical diagnosis, as well as their correlations 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.