Implications of childhood subcortical volumes on psychiatric disorders: A mendelian randomization study

Previous studies have reported a link between subcortical volumes and psychiatric disorders. However, it is challenging to directly determine the associations between these phenotypes because of the limits of observational researches. This study aimed to assess the associations between childhood subcortical volumes and psychiatric disorders through Mendelian randomisation (MR) analysis.

The two-sample MR method was carried out to genetically analyse the causal associations between childhood subcortical volumes and various psychiatric disorders, such as anorexia nervosa (AN), generalized anxiety disorders (GAD), bipolar disorder (BD), obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), schizophrenia (SCZ), and Tourette's syndrome (TS), using genome-wide association studies (GWASs) data. The inverse variance-weighted method was employed as the main analysis, and sensitivity analysis was also conducted.

It was revealed that 3 subcortical volumes were positively associated with psychiatric disorders, while 6 subcortical volumes were negatively associated. The analysis revealed significant causal effects, indicating an increased risk of psychiatric disorders associated with genetic liability and specific brain structures. Notable associations included bilateral accumbens volume with BD (P_FDR = 0.047), OCD (P_FDR = 0.025) and PTSD (P_FDR = 0.047); bilateral pallidum volume interacting with prenatal stress and OCD (P_FDR = 0.023); and bilateral thalamus volume interacting with postnatal stress and PTSD (P_FDR = 0.047). Conversely, the study identified risk-decreasing associations for subcortical volumes and several psychiatric disorders, such as bilateral accumbens volume interacting with postnatal stress and AN (P_FDR = 0.047), TS (P_FDR = 0.047); bilateral caudate volume interacting with postnatal stress and GAD (P_FDR = 0.008); bilateral pallidum volume interacting with prenatal stress and BD (P_FDR = 0.025), PTSD (P_FDR = 0.047); bilateral pallidum volume interacting with postnatal stress and PTSD (P_FDR = 0.047); bilateral thalamus volume interacting with postnatal stress and SCZ (P_FDR = 0.031); and bilateral accumbens volume interacting with prenatal stress and TS (P_FDR = 0.013).

The findings indicated the genetical associations between childhood subcortical volumes and psychiatric disorders, varied predispositions of specific subcortical structures in different forms of psychosis. Replication in larger samples will be essential to acquire a better understanding of the interactions between subcortical volumes and psychiatric disorders.