Abnormal emotional and neural responses to romantic rejection and acceptance in depressed women

Abstract

Introduction: Responding adaptively to one's social environment is a key factor predicting the course of major depressive disorder (MDD). Socially rejecting events can exacerbate, whereas socially accepting events can ameliorate depressive symptoms. The neural responses to rejection and acceptance in MDD are relatively unexplored.

Methods: We used functional magnetic resonance imaging (fMRI) to measure neural responses to romantic rejection and acceptance in women diagnosed with current MDD (n = 19) and a matched group of healthy controls (HCs) (n = 19). During fMRI, participants received rejecting, accepting, and neutral feedback from self-selected potential romantic partners.

Results: In women with MDD but not HCs, rejection significantly increased activity in the right anterior insula relative to neutral feedback. Greater activation during rejection was found in the dorsal anterior cingulate cortex in MDD compared to HCs. Women with MDD reported stronger emotional responses than HCs to both rejection and acceptance. In addition, left and right nucleus accumbens (NAcc) activity mediated the relationship between trait reward responsiveness and increased ratings of feeling "happy and accepted" following acceptance in HCs, but not the MDD group.

Discussion: Women with MDD were behaviorally and neurally hyperresponsive to rejection. Although both groups were behaviorally responsive to acceptance, in MDD this was dissociated from NAcc activity. These findings highlight abnormal behavioral and neural responses to social cues in MDD, with implications for disease prognosis and the development of novel and sensitive biomarkers for MDD focused on neural pathways for social-affective processing.

Limitations: Conclusions may be limited to depressed women in a romantic context.

Figure 1

Task design. Each trial began with the participant’s own headshot for 500ms, the addition of the question “Does this person like me?” along with picture from a highly-rated profile (500ms), followed by the feedback (4000ms). A rejection trial is shown. Rejection trials contained the feedback “very likely no” or “definitely no”, acceptance trials contained the feedback “very likely yes” or “definitely yes”, and neutral trials contained the feedback “not completed” to indicate that this person had not yet completed his rating of the participant. Four trials of the same feedback type were presented in one block, and cross-hair fixations (10–14s) were presented between blocks.

Figure 2

Emotional states reported following different types of feedback, by group: a) Mean ratings (± standard error) of “sad and rejected” increased following rejection and decreased following acceptance in participants with MDD; b) mean ratings of “happy and accepted” decreased following rejection and increased following acceptance in participants with MDD; c) Participants with MDD had a significantly greater desire for social interaction following acceptance; d) Participants with MDD had significantly increased self-esteem following acceptance. All four state measures had a significant effect of group, and a significant interaction between group and feedback type. HCs had an increase in “sad and rejected” (P = .028) following rejection, and an increase in self-esteem (P = .028) and “happy and accepted” (P = .024) following acceptance that did not survive correction for multiple comparisons (corrected P = .0125). ^P<.05, *P<.0125, **P<.01, ***P<.001

Figure 3

Significant activity (P_{FWE-whole-brain} < .001, voxel-wise analysis) in right AI during Rej>Neu trials in participants with MDD, but not HCs. AI, anterior insula; MDD, major depressive disorder group; HC, healthy control group; Rej>Neu, rejection - neutral contrast.

Figure 4

(a) Strong evidence for mediation by both left and right NAcc of the relationship between BAS-RR and state “happy and accepted” changes during Acc>Neu in HCs. The posterior probability for α (correlation between the independent variable to the mediator) is computed using MCMC parameter estimates, followed by the posterior probability for path β (a partial correlation between the mediator and the dependent variable, controlling for the independent variable). Evidence for a correlation between the independent and dependent variables, controlling for the mediator, is represented by path τ′. The probability for a mediation effect of the mediator on the path between the independent and dependent variable is computed by multiplying the posterior probabilities α and β. Bayes Factor (BF) greater than 1 indicates evidence in favor of the model. Numbers in blue correspond to the model including the left NAcc, and numbers in red correspond to the right NAcc. BF₁₀ is the Bayes Factor for the mediation model as a whole; p(α≠0|D) is the probability that the relationship α exists, given the data; p(β≠0|D) is the probability that the relationship β exists, given the data and controlling for the effects of α; p(τ≠0|D) is the probability that the relationship τ exists, given the data and before accounting for the mediator; p(τ′≠0|D) is the probability that the relationship τ exists, given the data and after accounting for the mediator; α̂, β̂, τ̂′, and τ̂ represent the mean coefficients for their respective paths. (b) Correlations between left NAcc activity and state “happy and accepted” changes during Acc>Neu in HC group (Pearson’s r = .81, P < .001) and MDD group (r = −.02, P = .93); (c) Correlations between right NAcc activity and state “happy and accepted” changes during Acc>Neu in HC group (r = .72, P >.001) and MDD group (r = −.004, P = .99). Participants indicated how “happy” and “accepted” they felt on a 1–5 Likert-type scale following Acc and Neu blocks. Scores for each item were averaged together within each condition. Values reported here are the averaged scores during Acc minus the averaged scores during Neu.