Neurobiological correlates of comorbidity in disorders across the affective disorders-psychosis spectrum

Disorders across the affective disorders-psychosis spectrum such as major depressive disorder (MDD), bipolar disorder (BD), schizoaffective disorder (SCA), and schizophrenia (SCZ), have overlapping symptomatology and high comorbidity rates with other mental disorders. So far, however, it is largely unclear why some of the patients develop comorbidities. In particular, the specific genetic architecture of comorbidity and its relationship with brain structure remain poorly understood. Therefore, we performed systematic analyses of clinical, genetics and brain structural measures to gain further insights into the neurobiological correlates of mental disorder's comorbidity. We investigated a sub-sample of the Marburg/Münster Cohort Study (MACS), comprising DSM-IV-TR diagnosed patients with a single disorder in the affective disorders-psychosis spectrum (SD, n = 470, MDD; BD; SCA; SCZ), with additional mental disorder's comorbidities (COM, n = 310), and healthy controls (HC, n = 649). We investigated group differences regarding a) the global severity index (based on SCL90-R), b) a cross-disorder polygenic risk score (PRS) calculated with PRS-continuous shrinkage (PRS-CS) using the summary statistics of a large genome-wide association study across mental disorders, and c) whole brain grey matter volume (GMV). The SCL90-R score significantly differed between groups (COM > SD > HC). While SD and COM did not differ in cross-disorder PRS and GMV, SD and COM versus HC displayed increased cross-disorder PRS and decreased GMV in the bilateral insula, the left middle temporal, the left inferior parietal, and several frontal gyri. Our results thus suggest that disorders in the affective disorders-psychosis spectrum with or without additional comorbidities differ in self-reported clinical data, but not on genetic or brain structural levels.