Altered neural function to happy faces in adolescents with and at risk for depression

Abstract

Background There is accumulating evidence of alterations in neural circuitry underlying the processing of social-affective information in adolescent Major Depressive Disorder (MDD). However the extent to which such alterations are present in youth at risk for mood disorders remains unclear. Method Whole-brain blood oxygenation level-dependent task responses and functional connectivity using generalized psychophysiological interaction (gPPI) analyses to mild and intense happy face stimuli was examined in 29 adolescents with MDD (MDD; M age, 16.0, SD 1.2 years), 38 healthy adolescents at risk of a mood disorder, by virtue of having a parent diagnosed with either Bipolar Disorder (BD) or MDD (Mood-risk; M age 13.4, SD 2.5 years) and 43 healthy control adolescents, having parents with no psychiatric disorder (HC; M age 14.6, SD 2.2 years). Results Relative to HC adolescents, Mood-risk adolescents showed elevated right dorsolateral prefrontal cortex (DLPFC) activation to 100% intensity happy (vs. neutral) faces and concomitant lowered ventral putamen activity to 50% intensity happy (vs. neutral) faces. gPPI analyses revealed that MDD adolescents showed significantly lower right DLPFC functional connectivity with the ventrolateral PFC (VLPFC) compared to HC to all happy faces. Limitations The current study is limited by the smaller number of healthy offspring at risk for MDD compared to BD. Conclusions Because Mood-risk adolescents were healthy at the time of the scan, elevated DLPFC and lowered ventral striatal activity in Mood-risk adolescents may be associated with risk or resiliency. In contrast, altered DLPFC-VLPFC functional connectivity in MDD adolescents may be associated with depressed mood state. Such alterations may affect social-affective development and progression to a mood disorder in Mood-risk adolescents. Future longitudinal follow-up studies are needed to directly answer this research question.

Reward Processing and Risk for Depression Across Development

“…As such, more advanced pubertal development could contribute to differences in striatal response to reward between high- and low-risk groups. Pubertal development was reported in only four of the nine MDD-risk studies discussed above [50, 58, 67, 68]. Although high-risk offspring tend show earlier pubertal onset in large-scale studies investigating puberty and psychopathology [63], MDD-risk was related to more advanced pubertal development in only one of the studies reviewed here [68].…”

“…Two of the MDD-risk studies discussed above also included a currently depressed group to address this issue. Both studies reported similar striatal responses to reward, happy faces [68] or money [51] in healthy high-risk and depressed adolescents. These results suggest that blunted striatal response to reward is not simply a ‘scar’ of MDD, but rather is present to the same degree in never-depressed high-risk groups.…”

“…Pubertal development was reported in only four of the nine MDD-risk studies discussed above [50, 58, 67, 68]. Although high-risk offspring tend show earlier pubertal onset in large-scale studies investigating puberty and psychopathology [63], MDD-risk was related to more advanced pubertal development in only one of the studies reviewed here [68]. Importantly, the effects of MDD-risk were unchanged when controlling for puberty [50, 67, 68].…”

“…Although high-risk offspring tend show earlier pubertal onset in large-scale studies investigating puberty and psychopathology [63], MDD-risk was related to more advanced pubertal development in only one of the studies reviewed here [68]. Importantly, the effects of MDD-risk were unchanged when controlling for puberty [50, 67, 68]. Thus, it seems unlikely that more advanced self-reported pubertal development in high-risk groups (relative to low-risk groups) accounted for risk-related differences in striatal response.…”

“…Although all of the MDD-risk studies discussed here included a negative feedback condition (loss of candy/money/points [51, 58–60, 67], aversive taste/picture [52], social rejection [50], or negative faces [49, 68]), only four studies reported on risk effects for both reward and negative feedback [49, 52, 58, 67] (note, [59] focused on the feedback negativity, which is the difference between loss- and gain-related ERPs). The four studies that investigated response to negative feedback all reported greater reactivity in high-risk groups.…”