Genetic overlap between mental disorders, metabolic markers may guide interventions: study

Metabolic pathways play a significant role in the development of severe mental disorders, as well as in unravelling disorder-specific aetiologies, suggests a recent study.

The authors used linkage disequilibrium score regression and bivariate gaussian mixture modeling to chart the genetic overlap of three mental disorders (ie, bipolar disorder, major depressive disorder [MDD], and schizophrenia), type 2 diabetes (T2D), coronary artery disease (CAD), and BMI with 249 circulating metabolites. They also estimated the causal associations and functionally annotated genetic variants, as well as examined enrichment across brain and body tissues.

An extensive overlap was found between all three disorders and the metabolites. The pattern of genetic associations was comparable between MDD, T2D, CAD, and BMI (Spearman’s correlation r_s>0.93), opposite in direction to the pattern seen for schizophrenia and bipolar disorder (MDD-bipolar disorder r_s=–0.74; MDD-schizophrenia r_s=–0.83).

Such genetic divergence differed from phenotypic associations, which were similar across all mental disorders. Furthermore, the metabolites displayed widespread, robust causal effects on the disorders and several cardiometabolic traits.

A total of 1,056 genes shared between the individual disorders and metabolites were mapped to disorder-specific processes associated with metabolic activity, mitochondrial function, and synaptic processes. These genes were expressed in the brain, heart, and liver.

“Severe mental disorders have strong associations with metabolites, and MDD has a distinctly different genetic relationship than bipolar disorder and schizophrenia do,” the authors said. “The ‘metabolic psychiatry’ approach applied here has high potential to guide development of targeted interventions.”