Amygdala and Nucleus Accumbens Activation to Emotional Facial Expressions in Children and Adolescents at Risk for Major Depression

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 \u3c .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

Stress Responsivity and HPA Axis Activity in Juveniles: Results From a Home-Based CO 2 Inhalation Study

Objective: A previous laboratory-based study found elevated cortisol levels in anxious children susceptible to CO 2 -induced panic, but the effects of parent diagnosis were not considered. The current home-based study tested the hypothesis that parental panic disorder and offspring response to CO 2 are associated with elevated cortisol levels in juvenile offspring. Method: A total of 131 offspring (ages 9–19) of parents with panic disorder, major depression, and no mental disorder underwent CO 2inhalation. Parent and child diagnoses were assessed. Salivary cortisol was assayed before and after CO2 inhalation. Results: Neither parents with panic disorder, parents with major depression, or offspring anxiety predicted offspring cortisol levels. Independent of parent and child diagnoses, anxiety response to CO 2 predicted elevated cortisol levels in offspring. Conclusions: As in adults, anxiety response to CO 2 in juveniles is associated with elevated cortisol levels, but elevated cortisol levels are not related to parent or child diagnoses