LAUSR

Major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BD) have both shared and discrete genetic risk factors and abnormalities in blood-based measures of inflammation and blood-brain barrier (BBB) permeability. The relationships between such genetic architectures and blood-based markers are however unclear. We investigated relationships between polygenic risk scores for these disorders and peripheral biomarkers in the UK Biobank cohort.We calculated polygenic risk scores (PRS) for samples of n = 367,329 (MDD PRS), n = 366,465 (SCZ PRS), and n = 366,383 (BD PRS) individuals from the UK Biobank cohort. We examined associations between each disorder PRS and 58 blood markers, using two generalized linear regression models: 'minimally adjusted' controlling for variables including age and sex, and 'fully adjusted' including additional lifestyle covariates such as alcohol and smoking status. In total, 15/58, 14/58 and 10/58 peripheral markers were significantly associated with MDD, SCZ and BD PRS respectively for both models. Many were disorder-specific, with 10/15 MDD PRS associations unique to MDD. Moreover, several of these disorder-specific associations for MDD and SCZ were with immune-related parameters, with mostly positive and negative associations identified for MDD and SCZ PRS respectively. This study suggests that MDD, SCZ and BD have shared and distinct peripheral markers associated with disorder-specific genetic risk. The results also implicate inflammatory dysfunction in MDD and SCZ, albeit with differences in patterns between the two conditions, and enrich our understanding of potential underlying pathophysiological mechanisms in major psychiatric disorders.