Amygdala-function perturbations in healthy mid-adolescents with familial liability for depression

Functional magnetic resonance imaging (fMRI) studies have identified increased amygdala responses to negative stimuli as a risk marker of depression in adults, and as a state marker of depression in adults and adolescents. Hyperreactivity of the amygdala has been linked to negatively biased emotional processing in depression. However, no study has elucidated whether similar amygdala perturbations can be found in healthy mid-adolescents with familial liability for depression. We hypothesized that healthy 14-year-olds with relatives with depression would demonstrate increased amygdala responses to negative stimuli, as compared with their peers with no family history of mental disorders.

We investigated a community-based sample of 164 typically developing 14-year-olds without record of past or current mental disorders. Of these individuals, 28 fulfilled criteria for family history of depression, and 136 served as controls. Groups did not differ with regard to cognitive ability, depressive symptomatology, and anxiety. During fMRI they performed a perceptual discrimination task in which visual target and distractor stimuli varied systematically with regard to emotional valence.

Both a hypothesis-driven region-of-interest analysis and a whole-brain analysis of variance revealed that negative distractors elicited greater amygdala activation in adolescents with a family history of depression compared to controls. Amygdala responses also differed during the processing of negative target stimuli, but effects were reversed.

Our study demonstrates that familial liability for depression is associated with correlates of negatively biased emotional processing in healthy adolescents. Amygdala perturbations during the processing of negative stimuli might reflect an early and subtle risk marker for depression.