Genes Expressed in Prenatal Brain Linked to Risk of Childhood Psychiatric Disorders

Using data from a long-term study of adolescent brain development, a team led by scientists from Massachusetts General Hospital has identified a set of genes that, when expressed in the fetal brain, appear to increase the risk of certain psychiatric disorders during childhood. The risk of psychiatric disorders arises early in life and polygenic risk scores (PGSs) have helped provide insights into the biological origins of these illnesses. Still, the clinical potential of PGSs in children are limited, in part because psychiatric symptoms in children tend to be poorly differentiated but can coalesce into discrete mental illnesses in late adolescence. In a study appearing in this week's Nature Neuroscience, the researchers leveraged data from the Adolescent Brain and Cognitive Development Study, which has enrolled nearly 12,000 children between the ages of 9 to 10 years, to evaluate the relationships of disease-specific and cross-disorder PGSs to dimensional psychopathology in mid-childhood. They identify a narrow neurodevelopmental PGS — comprising overlapping genetic variants across attention deficit/hyperactivity disorder, autism, depression, and Tourette syndrome — that predicted psychiatric symptoms through early adolescence with greater sensitivity than other scores. Notably, genes associated with this PGS were preferentially expressed in the cerebellum, where their expression peaked prenatally. "These findings," the study's authors write, "suggest a mechanism through which altered fetal cerebellar development instantiates risk for a wide range of childhood psychopathology."