Young children who are timid and stressed by new people and situations—and who have a parent with a panic disorder—are more likely than their peers to have a smaller hippocampus, a key brain structure, by the time they become adolescents, according to a study published July 21st in the journal Translational Psychiatry.

The study, conducted by a team led by Carl Schwartz, M.D., of Massachusetts General Hospital, included Jerrold Rosenbaum, M.D., a 2006 NARSAD Distinguished Investigator and Chief of Psychiatry at Massachusetts General Hospital. Their work could help scientists better understand how the hippocampus is connected to mental illnesses in conditions ranging from depression to post-traumatic stress disorder. It might also shed light on why some children with early shyness and social anxiety develop more severe mood and anxiety disorders later in life.

The hippocampus is a part of the brain thought to be involved in mood and anxiety disorders; adults with these illnesses tend to have smaller than normal hippocampi (we have two such structures, one on each side of the brain). In animals, severe chronic stress can stunt hippocampus growth. This prior finding led the investigators to wonder whether a condition called behavioral inhibition, where children as young as two show physical signs of stress and shyness in new situations, might be connected with smaller hippocampus volume in those children by the time they were teens.

The researchers used brain imaging to measure hippocampus volume in 43 girls and 40 boys at age 17. In this group, 22 of the adolescents had been diagnosed with behavioral inhibition as children. The long-term study also included information on the presence or absence of behavioral disorders in the parents of these children. The team found no difference in the average hippocampal volume of young people who had childhood behavioral inhibition and those who did not. But they did note that teens with childhood behavioral inhibition and with at least one parent who had a panic disorder had smaller hippocampi than teens who had a parent with a panic disorder but had never been diagnosed with behavioral inhibition.

The results suggest that both genetic and environmental factors might influence hippocampus size, the researchers say. Previous studies of twins have noted some genetic factors related to behavioral inhibition; children of a parent with a panic disorder may experience family stress or overprotective parenting that increases their own stress levels in a way that affects hippocampal growth. In any case, scientists would like to know whether the smaller hippocampus in adolescents could be a risk factor for mental illness, especially anxiety disorders, later in life.

Co-authors of the paper reporting the study included former NARSAD Young Investigator grantees Aude Henin, Ph.D., (2006) and Scott L. Rauch, M.D., (1993 and 1996), as well as Joseph Biederman, M.D., who received a Distinguished Investigator grant in 2002.

Read the abstract.