The genetic risk of depression is reflected in the structure of the brain

Major depression (MD) is a severe mental disorder that affects millions of people around the world. It is manifested by a persistent decrease in mood, loss of interest in habitual activities, sleep disorders and appetite. It is believed that its development is associated with both external factors and a genetic predisposition.

Polygenic risk scores (PRS), which are cumulative indicators reflecting the impact of multiple hereditary variants, help to assess this risk. To understand how genetic risk correlates with brain anatomy, researchers from the universities of Edinburgh, Melbourne, Amsterdam and other centers conducted the largest meta-analysis involving almost 51 thousand people.

Data from 11 international projects were combined within the framework of the ENIGMA Major Depressive Disorder Working Group consortium. The participants underwent genetic testing and neuroimaging. Comparing the results, the researchers found that higher PRS values are associated with a reduced area of the cerebral cortex and a smaller total volume of the cranial cavity.

The most pronounced differences concerned the surface of the frontal lobe, primarily the left medial orbitofrontal gyrus. In addition, people with a high genetic risk of depression had smaller volumes of the thalamus, hippocampus, and globus pallidus. The same features were evident in young participants under the age of 25, although the differences were less pronounced.

Additional analysis showed a possible causal relationship between a decrease in the volume of the hippocampus and an increase in predisposition to depression.

It is especially emphasized that the results demonstrate the value of international collaborations and unified methods in neurogenetics. The new data will help to better understand the biological basis of depression and, possibly, become the foundation for personalized methods of early prevention and treatment.