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Objective. Offspring of parents with major depressive disorder (MDD) face three-fold higher risk for MDD than offspring without a family history. Although MDD is a major cause of morbidity and mortality, neural correlates of risk for MDD remain poorly understood. This study compares amygdala and nucleus accumbens activation in children and adolescents at high and low risk for MDD under varying attentional and emotional conditions. Methods. Thirty-nine juveniles, 17 offspring of parents with MDD (high-risk group) and 22 offspring of parents without histories of MDD, anxiety or psychotic disorders (low-risk group) completed a functional magnetic resonance imaging study. During imaging, subjects viewed faces that varied in intensity of emotional expressions across blocks of trials; while attention was unconstrained (passive viewing), and constrained (rate nose width on face; rate subjective fear while viewing face). Results. When attention was unconstrained, high-risk, relative to low-risk, subjects showed greater amygdala and nucleus accumbens (NAcc) activation to fearful faces, and lower NAcc activation to happy faces (p values < .05, small volume corrected for the amygdala and NAcc). No group differences emerged in amygdala or NAcc activation during constrained attention. Exploratory analysis showed that constraining attention was associated with greater medial prefrontal cortex activation in the high-risk than low-risk group. Conclusions. Amygdala and NAcc responses to affective stimuli may reflect vulnerability for MDD. Constraining attention may normalize emotion-related neural function, possibly via engagement of the medial prefrontal cortex; face-viewing with unconstrained attention may engage aberrant processes associated with risk for MDD.


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Monk, C.S., Klein, R.G., Telzer, E.H., Schroth, E.A., Mannuzza, S., Moulton, J.L., Guardino, M., Masten, C.L., McClure-Tone, E.B., Fromm, S., Blair, R.J.R., Pine, D.S., Ernst, M. (2008). Amygdala and nucleus accumbens activation to emotional facial expressions in children and adolescents at risk for major depression. American Journal of Psychiatry, 165(1), 90-98. DOI: 10.1176/appi.ajp.2007.06111917

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