Neurons
Credit: Rost-9D / Getty Images

Genes expressed in the brain before birth may affect development of a range of mental illnesses during childhood, according to new research. A Massachusetts General Hospital (MGH) team has found a new gene “set” that helps predict risk for several neurodevelopmental disorders, including autism, ADHD, Tourette syndrome, and depression.

The team’s findings were published this week in Nature Neuroscience. The lead author is Dylan E. Hughes, of MGH’s Department of Psychiatry.

“That genetic risk factors for mental illness in kids begin to influence the brain so early on—even before birth—means that interventions that protect them from risk may also need to start earlier in life than previously expected,” said co–senior author Joshua Roffman, MD, director of MGH’s Early Brain Development Initiative, in a press release. “It is also important to note that while genes play an important part in risk for mental illness, the early life environment is also critical—and at this point, potentially easier to modify.”

The MGH team used data from the Adolescent Brain and Cognitive Development (ABCD) Study. This study of child and adolescent brain development has enrolled nearly 12,000 individuals at age 9–10 years. The MGH team set out to see whether genes associated with psychiatric illnesses in adults are similar to those associated with psychiatric symptoms in children.

“We found those relationships to be more complex than we had imagined.  For example, genetic risk for ADHD and depression were associated with a range of symptoms in children, not just those related to attention or mood,” said Roffman. “The genetic factors that shape mental illness symptoms in kids differ from the ones that shape mental illness symptoms in adults.”

Notably, the strongest genetic predictor for most mental health symptoms in ABCD participants was a new measure, a “neurodevelopmental gene set,” developed by the paper’s co–senior author, and computational geneticist, Phil H. Lee, PhD, and colleagues at the Mass General Center for Genomic Medicine. This gene set points to heightened risk for  several common neurodevelopmental disorders, including autism, ADHD, Tourette syndrome, and depression.

With their international collaborators, the MGH team determined this gene set also predicted childhood psychiatric symptoms in participants of the Netherlands’ Generation R study.

Studies of samples from brain banks also showed that the genes in this set are expressed mostly in the cerebellum, and their expression peaks before birth. Also, brain imaging data from the ABCD study indicated that children with psychiatric symptoms tended to have a slightly smaller cerebellum.

These finding all suggests that very early intervention is warranted.

The MGH team is investigating other factors during pregnancy—such as quality sleep, exercise, diet, optimal prenatal care, or psychosocial support—that may protect against risk of psychiatric disorders in children. Currently, a study called Brain health Begins Before Birth (B4) is enrolling families at MGH during pregnancy and then following children’s brain development after birth.

Also of Interest