Reduced Amygdala Habituation to Anticipated Social Rejection in Youth with Major Depressive Disorder

• In Event: Challenges to developing biology and mental health

Abstract

Depression has been associated with differential amygdala response to negative stimuli (Drevets, 2003; Whalen et al., 2002). Adults and youth experiencing major depression (MDD) or at-risk of developing depression due to familial histories have been found to show increased amygdala activation to threatening or negative emotional stimuli (Yang et al., 2010; Berhe et al., 2022). In addition to differences in activation, typical patterns of amygdala habituation to repeated emotional stimuli (e.g., Plitchta et al., 2014) may be attenuated in youth with internalizing disorders (van den Bulk et al., 2016). To better understand how MDD risk may impact the temporal dynamics of amygdala response in adolescents, the current study examined how the time-course of amygdala response to anticipated social rejection—a potent threat in adolescence—varied as a function of depression risk in teenage girls.

Three groups of 10- to 17-year-old girls (22 with MDD, 30 at-risk of MDD based on parental history, and 24 low-risk (control group), based on clinical interviews; 45% racial/ethnic minorities) completed the Chatroom Select task, in which they were putatively selected or rejected for discussions by mean (70% rejecting) or nice (30% rejecting) peer confederates. Using beta-series analysis (e.g., Yin et al., 2018), we examined the temporal dynamics of neural response to the anticipation of peer feedback across trials with the mean confederate (i.e., in a high rejection context), in the amygdala and in control regions of interest associated with processing threat and reward (medial prefrontal cortex, ventral striatum, anterior insula, subgenual anterior cingulate cortex [sgACC]; Forbes et al., 2020). Linear mixed-effects models were fit to each region’s betas for all mean confederate trials, to examine whether linear and quadratic changes in response across trials varied as a function of depression group status, controlling for age (including a random slope and intercept per person).

Activation in the left sgACC was higher in the at-risk group than in the other groups (p=.01) across all anticipation trials. The trajectory of response across trials varied by depression group in the right amygdala (p=.04): whereas the low-risk and at-risk girls showed evidence of amygdala habituation to repeated threat of rejection (i.e., decreasing activation with an eventual plateau), girls with MDD instead showed consistently high amygdala activation across trials (Figure 1). Control analyses with the nice confederate trials did not replicate this pattern, suggesting specificity to the social context of heightened rejection threat.

These findings suggest that girls with MDD—but importantly, not necessarily those at familial risk for depression—show temporally extended activation of the amygdala when anticipating social rejection. Although future work should link this neural pattern to behavioural indicators, these results are suggestive of altered neural processing of interpersonal interactions in youth with MDD. Given that amygdala activation to negative social cues can decrease following successful treatment in adults (Ruhé et al., 2012), our findings highlight anticipatory processing of social cues as a potential target for intervention in youth experiencing depression.

Authors

• Michele Morningstar, Queen’s University
  Presenting Author

• Madelaine Gravelle

• Daniel P Dickstein, McLean Hospital

• Jennifer S. Silk, University of Pittsburgh

• Ron E Dahl, University of California, Berkeley

• Eric Nelson, Nationwide Children's Hospital

• Laura R Stroud, Brown Medical School and The Miriam Hospital