Neural activation to peer acceptance and rejection in relation to concurrent and prospective depression risk in adolescent and pre-adolescent girls

Abstract

Neurobiological sensitivity to peer interactions is a proposed marker of risk for adolescent depression. We investigated neural response to peer rejection and acceptance in relation to concurrent and prospective depression risk in adolescent and pre-adolescent girls. Participants were 76 girls (M_age=13, 45% racial/ethnic minorities) varying in depression risk: 22 with current major depressive disorder (MDD), 30 at High Risk for MDD based on parental history, and 24 at Low Risk with no psychiatric history. Girls participated in the Chatroom-Interact task-involving rejection and acceptance feedback from fictitious peers-while undergoing functional magnetic resonance neuroimaging. Activation in response to peer rejection and acceptance was extracted from regions of interest. Depressive symptoms were assessed at 6- and 12-month follow-up. Girls with MDD showed blunted left subgenual anterior cingulate response to acceptance versus girls in High and Low Risk groups. Girls in the High Risk group showed greater right temporo-parietal junction (rTPJ) and right anterior insula (AI) activation to both acceptance and rejection versus girls in the MDD (rTPJ) and Low Risk (rTPJ, AI) groups. Greater rTPJ response to rejection was associated with fewer depressive symptoms at 12-months and mediated the association between High Risk group status and 12-month depressive symptoms; greater rTPJ response to acceptance mediated the association between High Risk and increased 12-month depressive symptoms. Our finding of associations between altered neural response to peer interactions and concurrent and prospective depression risk/resilience highlights the importance of neural underpinnings of social cognition as risk and compensatory adaptations along the pathway to depression.

Keywords: Acceptance; Adolescence; Anterior cingulate cortex; Anterior insula; Brain development; Chatroom Interact; Depression; FMRI; Female; Girls; Major depressive disorder; Peer relationships; Rejection; Sex differences; Social; Temporoparietal junction.

Figure 1.

Chatroom Interact Task. NOTE. Sample screenshots from the Chatroom-Interact task in the MRI scanner. During each run, each of the three participants (i.e., actual participant, two putative peers) took turns selecting whom to interact with to discuss 15 different common teen interests (i.e., music, movies, friends) while the others observed (left – “Choice”). For each topic, the person who was selected was shown with highlights around their photograph’s border (“accept” condition); the person who was not selected would have an “X” superimposed on their photograph (“reject” condition) (right – “Feedback”).

Figure 2.

Regions of Interest. NOTE. L = left, R = right. mPFC = medial prefrontal cortex; sgACC = subgenual anterior cingulate cortex; AI = anterior insula; pTPJ = posterior temporo-parietal junction; VS = ventral striatum.

Figure 2.

Regions of Interest. NOTE. L = left, R = right. mPFC = medial prefrontal cortex; sgACC = subgenual anterior cingulate cortex; AI = anterior insula; pTPJ = posterior temporo-parietal junction; VS = ventral striatum.

Figure 3.

Impact of depression risk group on response to peer acceptance and rejection in the (A) right temporo-parietal junction, (B) right anterior insula, and (C) left subgenual anterior cingulate cortex. NOTE: TPJ = temporo-parietal junction; AI = anterior insula; sgACC = subgenual anterior cingulate cortex. Low Risk = girls at lower risk of depression with no personal or parental psychiatric history; High Risk = girls at higher risk for depression based on parental history of depression; MDD = Girls with current major depressive disorder. Panels A and B represent main effects of depression risk group on Right TPJ and Right AI activation during peer interactions (rejection and acceptance, vs. baseline); Panel C represents an interaction of depression risk group by peer interaction condition (being accepted vs. baseline; being rejected vs. baseline) on Left sgACC activation. Bars represent mean activation (and standard error); dots represent individual data points. * p < .05.

Figure 3.

Impact of depression risk group on response to peer acceptance and rejection in the (A) right temporo-parietal junction, (B) right anterior insula, and (C) left subgenual anterior cingulate cortex. NOTE: TPJ = temporo-parietal junction; AI = anterior insula; sgACC = subgenual anterior cingulate cortex. Low Risk = girls at lower risk of depression with no personal or parental psychiatric history; High Risk = girls at higher risk for depression based on parental history of depression; MDD = Girls with current major depressive disorder. Panels A and B represent main effects of depression risk group on Right TPJ and Right AI activation during peer interactions (rejection and acceptance, vs. baseline); Panel C represents an interaction of depression risk group by peer interaction condition (being accepted vs. baseline; being rejected vs. baseline) on Left sgACC activation. Bars represent mean activation (and standard error); dots represent individual data points. * p < .05.

Figure 4.

Activation of the right temporo-parietal junction as a mediator of the association between depression risk group and depressive symptom scores at (A) 6-month (no mediation) and (B) 12-month follow-up (significant mediation for High Risk group). NOTE: Mediation model examining right temporo-parietal junction (rTPJ) response to peer acceptance and rejection (being selected or rejected during the Chatroom-Interact task) as mediators between depression risk group (Low Risk, High Risk, MDD) and depressive symptoms at (A) 6- and (B) 12-month follow-up. Depression risk group was entered as a multi-categorical predictor, with the Low Risk group as the reference level; High Risk and MDD (in the figure) thus represent effects related to being in the High Risk and MDD groups relative to being in the Low Risk group. Depressive symptoms were measured with the Children’s Depression Rating Scale-Revised (Mayes et al., 2010). Age was included as a covariate to the mediator and outcome variables. rTPJ responses to acceptance and to rejection were entered as parallel mediators. Coefficients and 95% confidence intervals (CIs) of the indirect effects are shown in text at the bottom of each figure, with significant indirect effects indicative of mediation [estimated as the product of path a (predictor to mediator; depression group to TPJ response) and path b (mediator to outcome; TPJ response to 12-month depressive symptoms) (Hayes, 2022; Zhao et al., 2010)] highlighted in bold. Unstandardized regression coefficients are represented on each path. Solid lines represent significant relationships, * p < .05, ** p < .01, *** p < .001. In Figure 4B, ‡ represents p = .055. Dashed lines represent associations that were not statistically significant.