Elsevier

Biological Psychiatry

Volume 70, Issue 4, 15 August 2011, Pages 366-372
Biological Psychiatry

Archival Report
Mood-Linked Responses in Medial Prefrontal Cortex Predict Relapse in Patients with Recurrent Unipolar Depression

https://doi.org/10.1016/j.biopsych.2011.03.009Get rights and content

Background

Altered cognitive processing following mood challenge is associated with elevated relapse risk in remitted unipolar depressed patients, but little is known about the neural basis of this reactivity and its link to depressive relapse and prophylaxis.

Methods

Remitted unipolar depressed participants (n = 16) and healthy control subjects (n = 16) underwent functional magnetic resonance imaging (fMRI) while viewing sad and neutral film clips. Correlations were determined between emotional reactivity (neural responses to sad vs. neutral films) in remitted patients and subsequent relapse status over an 18 month follow-up period. A receiver operating characteristic analysis was used to determine signal cutoffs for predicting relapse. Emotional reactivity in relapse prognostic areas was compared between groups.

Results

Within the remitted group, relapse was predicted by medial prefrontal cortical (mPFC; Brodmann's area 32) activity and contraindicated by visual cortical activity (Brodmann's area 17). mPFC reactivity predicted rumination, whereas visual cortical reactivity predicted distress tolerance (acceptance). Compared with control participants, remitted depressed patients demonstrated a more pronounced tradeoff between mPFC and visual cortex reactivity. The difference score between mPFC and visual reactivity yielded excellent prediction of depressive relapse.

Conclusions

Medial prefrontal cortical reactivity to mood provocation in remitted unipolar depressed patients serves as a marker of relapse risk rather than successful emotion regulation. Enduring remission is characterized by normalization of the mPFC to that of healthy control subjects. Furthermore, visual cortex reactivity predicts resilience against depressive relapse, indicating a prophylactic role for sensory rather than ruminative cognitive reactivity in the processing of negative emotion.

Section snippets

Participants

Participants were right-handed adults ranging in age from 21 to 61. Sixteen participants fully remitted from unipolar depression (mean age = 44, SD = 16; 11 female) and 16 healthy control subjects (mean age = 39, SD = 13; 11 female) participated in the study (Table 1 contains further participant information). All remitted patients had a history of three or more past episodes of depression at the time of recruitment (mean number of past episodes = 4.6, SD = 2.4). All remitted patients were

Results

Patient and control groups did not differ on demographic indicators such as gender, age, employment and marital status, or ethnic distribution (Table 1). Patients demonstrated higher depression scores than control subjects at study intake [t(30) = 2.68, p < .05], although all patients were in the normal range (HRSD < 7). Emotional reactivity (ER) was operationalized through the comparison of sad and neutral film viewing periods. Sad films elicited greater reported sadness than neutral films in

Discussion

We employed sad mood provocation to conduct a prospective neuroimaging study of depressive relapse. Expansive mPFC reactivity predicted depressive relapse, encompassing both dorsal and ventral aspects of the mPFC (Figure 2, Panel A). The mPFC prediction of relapse was partially associated with patient ruminative tendencies, but much of mPFC relapse prediction was not accounted for by rumination (Figure 3, Panel A). It may be that mPFC reactivity represents other maladaptive processes during

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