Temporal trends of blood-based markers in various psychiatric disorders and their cross-sectional brain structure associations

Introduction

More than 14% of adults aged 60 and above suffer from a psychiatric disorder, and the prevalence increases with age^1,2. Considering the rapid aging of the global population^3,4, it is expected that a growing number of elderly individuals will experience psychiatric disorders in the coming years. Psychiatric disorders are often accompanied by a multitude of debilitating symptoms⁵, including emotional dissonance, cognition decline, motor dysfunction and disturbances of the metabolic and immune system^{6, 7, 8, 9, 10–11}. These alterations not only have an impact on health in their own right but also increase the risk of other adverse health outcomes, encompassing neurodegenerative disorders¹², cardiovascular disease^13,14 and cognitive impairment². They can also result in a substantial reduction in life expectancy (10–20 years)^{15, 16–17}. Early intervention at the onset of psychiatric disorders can improve a range of outcomes¹⁸. However, older adults frequently face insufficient recognition and undertreatment of their psychiatric health conditions.

Recent evidence has revealed that metabolic markers in psychiatric disorders change compared with controls and differ significantly between different psychiatric disorders^{19, 20, 21–22}. There are also studies that identified causal roles for certain metabolites in psychiatric disorders, suggesting that metabolic dysregulation contributes to the development of psychiatric disorders^11,23,24. Various immune biomarkers, such as C-reactive protein (CRP) and immune cell count, have also been associated with psychiatric disorders^{25, 26, 27–28}. However, a comprehensive understanding of the temporal trends of these blood-based biomarkers throughout the pre- and post-diagnostic phases of various psychiatric disorders is currently lacking. Understanding these trends is crucial because it can reveal early signs of psychiatric disorders, allowing for timely interventions. Traditional case-control or causal studies often focus on a single point in time, whereas examining the temporal trends can provide insights into the progression and underlying mechanisms of these disorders. Additionally, the association between different blood-based biomarkers and brain imaging findings remains uninvestigated. Understanding their relationship could reveal which biomarkers can be intervened on to reduce the impact of the disease on the brain.

This study leverages data from the UK Biobank (UKB)²⁹ to examine temporal trends of blood-based biomarkers in psychiatric disorders. The cohort includes over 500,000...