MRI Study of Brain Activity and Risk for Depression in Adolescents

Parental history of major depressive disorder poses a particularly high risk for later-life MDD. In adults, MDD involves dysfunction in subcortical brain regions related to emotional responsiveness, such as the amygdala, and in cortical brain regions that interface cognitive and emotional processes. These abnormalities: i) have been found primarily in adults with specific familial forms of MDD; ii) persist after recovery from MDD, and iii) relate to anxiety. These findings raise the possibility that risk for MDD is tied to dysfunction in emotional circuits themselves or in prefrontal regions involved in regulation of emotion. If this possibility were confirmed in never-depressed adolescents at high risk for MDD, the findings would provide key insights into the developmental neurobiology of MDD. The goal of this protocol is to study the neural substrate of risk for MDD in young people. This protocol tests the hypothesis that adolescents at high risk for MDD by virtue of parental history of MDD exhibit dysfunction in prefrontal cortex, amygdala, and other subcortical regions involved in emotion and emotion regulation. This goal will be accomplished through fMRI studies of edmotion provocation in high and low-risk adolescents.

For this research, at-risk adolescents will be recruited from participants in NIMH-funded extramural studies at New York University, Brown University, and Columbia University examining the biology of risk for anxiety and depressive disorders. Over a three-year period, data on each measure of interest will be obtained in 100 high-risk probands and 100 low-risk comparisons. In addition, a sub-set of parents of these adolescents (n=100) also will be studied using identical procedures. In the present protocol, to be conducted at NIH, subjects will undergo volumetric MRI scans to assess structural abnormalities in the prefrontal cortex and medial temporal lobe. They will complete a series of out-of-scanner cognitive tasks and fMRI-based cognitive tasks. Two of these tasks measure modulation of attention to emotional stimuli; the third task measures engagement of temporal and prefrontal regions during social interactions. For these types of tasks, prior studies in adolescents with ongoing mood and anxiety disorders demonstrate hypothesized abnormalities in brain engagement. The current study is designed to examine the degree to which comparable findings emerge in unaffected adolescents at risk for mood and anxiety disorders.