Elsevier

NeuroImage

Volume 61, Issue 3, 2 July 2012, Pages 686-693
NeuroImage

Neural correlates of emotion regulation deficits in remitted depression: The influence of regulation strategy, habitual regulation use, and emotional valence

https://doi.org/10.1016/j.neuroimage.2012.03.089Get rights and content

Abstract

Regulating emotions through reappraisal has been shown to elicit abnormal neural activation patterns in currently depressed patients. It is, however, unclear if this deficit generalizes to other emotion regulation strategies, if it persists when patients recover, and if it is related to habitual use of reappraisal strategies. Therefore, we measured the neural responses to emotional images with functional magnetic resonance imaging in remitted patients with previous episodes of major depression and healthy controls. While viewing the images participants regulated the elicited emotions using either a reappraisal or a distraction strategy. Habitual reappraisal use was measured with the Cognitive Emotion Regulation Questionnaire. Depressed patients showed a selective deficit in down-regulating amygdala responses to negative emotional stimuli using reappraisal. This down-regulation of amygdala activity was strongest in participants high in habitual reappraisal use. Activity in the regulating control-network including anterior cingulate and lateral orbitofrontal cortex was increased during both emotion regulation strategies. The findings in remitted patients with previous episodes of major depression suggest that altered emotion regulation is a trait-marker for depression. This interpretation is supported by the relation of habitual reappraisal use to amygdala down-regulation success.

Highlights

► We investigated the neural correlates of emotion regulation in depression. ► The data show that impaired amygdala regulation persists into remission. ► The deficit is specific to a reappraisal and not a distraction regulation strategy. ► Only the down-regulation of negative, not positive stimuli is impaired. ► Patients show stronger activation in the control network to achieve regulation.

Introduction

Altered affective processing is one of the defining characteristics of major depressive disorder (MDD). Its neural signature includes hyperactivity in a number of brain structures involved in emotion detection and generation (Drevets et al., 2002, Sheline et al., 2001). A critical question is whether the altered emotional responsivity in MDD is mirrored by impaired regulation of emotion. In contrast to a relatively large number of studies on automatic emotion regulation as assessed with simple emotion viewing paradigms (Dannlowski et al., 2009, Ritchey et al., 2011), there is only little evidence regarding the non-automatic cognitive control of emotions tested through explicit instructions to regulate current affect. The few data on cognitive control of emotions suggest a deficit in the capability to down-regulate amygdala activity to negative emotional stimuli (Beauregard et al., 2006), and altered connectivity between the amygdala and prefrontal control regions (Erk et al., 2010, Johnstone et al., 2007). Four major questions arise from these studies.

First, the specific cognitive regulation strategy that previous studies applied was reappraisal, which requires participants to reinterpret the meaning of emotional stimuli yielding them less negative and arousing (Gross, 2001). It is unclear, however, if the deficit in cognitive emotion regulation is restricted to reappraisal or generalizes to other emotion regulation strategies. Recent evidence in healthy participants demonstrated that reappraisal and an attentional control strategy (distraction) recruit overlapping, but distinct neural networks. While both strategies activated dorsolateral prefrontal (dlPFC) and parietal cortices, orbitofrontal cortex (OFC) activation was specific to using reappraisal, while distraction yielded more extensive activation in parietal and dorsomedial prefrontal/anterior cingulate cortex (dmPFC, ACC; Kanske et al., 2011, McRae et al., 2010). The tested strategies also differed in their effectiveness in amygdala down-regulation, with distraction yielding stronger and more extended down-regulation of the amygdala activity. The specific networks involved in emotion regulation have been shown to be differentially affected in depression. Lateral parts of the OFC show hyperactivation (Drevets, 2007), while for dorsal ACC and dlPFC, hyper- as well as hypoactivation have been reported (Disner et al., 2011, Wagner et al., 2006). Increased activation in control regions has been interpreted as a compensatory mechanism, which might also apply for emotion regulation in depression (Wagner et al., 2006). Furthermore, a recent meta-analysis showed structural changes in depression to be located more consistently in the OFC (Arnone et al., 2012). We, therefore, asked if emotion regulation deficits in depressed patients might differ between strategies.

Second, as previous studies investigated emotion regulation in currently depressed but not remitted patients (Beauregard et al., 2006, Erk et al., 2010, Johnstone et al., 2007), we do not know if the deficit persists when patients recover. Because of high relapse rates (Hardeveld et al., 2010), remission is a vulnerable clinical state also characterized by greater sensitivity to mood challenges that predict recurrence (Segal et al., 1999) and related changes in orbitofrontal and cingulate activation patterns (Liotti et al., 2002). It remains to be investigated if altered regulation of emotion also reflects a trait-marker for depression and is not necessarily linked to present symptoms.

Third, it has been shown that depression is related to habitual differences in the use of emotion regulation through reappraisal. A recent meta-analysis, for example, reported reduced reappraisal use in depression (Aldao et al., 2010). Interestingly, habitual reappraisal use is also related to incremented emotional responding in currently remitted patients (Joormann and Gotlib, 2010). Nevertheless, it still needs to be tested if these habitual differences are related to impaired amygdala regulation during reappraisal use in neuroimaging experiments.

Fourth, previous studies concentrated on the down-regulation of negative emotion (Beauregard et al., 2006, Erk et al., 2010, Johnstone et al., 2007), which may be suggestive because of the excess of negative emotion in depression. Nevertheless, it is unclear if the deficit is selective to negative emotion or generalizes to positive emotion as well.

To address these questions, we examined two different cognitive emotion regulation strategies, reappraisal and distraction, in patients with previous depressive episodes currently in remission. While reappraisal is a form of cognitive change of emotion, distraction requires attentional control to divert attention to the performance of a parallel task, reducing the resources available for emotional processing (Ochsner and Gross, 2005). To differentiate the control of negative and positive emotion we used pictures of different valence and measured neural responses while patients applied emotion regulation with functional magnetic resonance imaging (fMRI). We also assessed habitual differences in the use of reappraisal using a validated questionnaire (Garnefski and Kraaij, 2007). This allowed testing four major hypotheses. First, if the deficits in regulating emotions are specific to the reappraisal strategy, than application of the distraction strategy should not yield any differences between healthy participants and MDD patients. Candidate regions for alterations include the amygdala as the major site for regulation effects, and the OFC and ACC/dmPFC as part of the control networks for reappraisal and distraction, respectively. In the amygdala we expect impairments to show in reduced down-regulation of activity in depression. In contrast, in line with the concept of compensatory hyperactivation, patients should show an activation increase in control regions. Second, if emotion regulation deficits are a trait-marker for depression we expect to also observe this in remitted MDD patients. Third, we expect to find a relation of neural activation changes during emotion regulation to habitual use of emotion regulation. Fourth, as depression is mainly characterized by excessive negative emotion, the deficits should be specific to down-regulating negative, but not positive emotion.

Section snippets

Participants

Twenty-six remitted patients with MDD and 26 healthy controls (HC), matched for age, sex, handedness, and education participated in the study. Three patients and one control had to be excluded from the analysis due to technical problems at the time of measurement or excessive movement artifacts in the fMRI data, leaving N = 23 remitted patients with major depression and 25 controls for data analyses (see Table 1 for demographic and illness-related characteristics of the final sample).

Patients

Post-experimental valence and arousal rating

The rating of the images after the regulation experiment yielded the same pattern as the normative IAPS ratings (see supplemental data ST1). Negative and positive pictures were rated as more arousing than neutral pictures (F(1,46) = 90.2, p < .001; F(1,46) = 125.0, p < .001, respectively). Valence was also significantly different between the picture sets (positive > neutral > negative; F(1,46) = 293.3, p < .001; F(1,46) = 113.9, p < .001, respectively). There were no differences between MDD patients and HCs (all p >

Discussion

The present results yield new insights into the crucial role of emotion regulation deficits in depression. We extend previous findings of impaired down-regulation of amygdala activity in currently symptomatic MDD patients to the remitted state. We also show that this amygdala effect is specific to reappraisal and not general to all emotion regulation strategies. Interestingly, to achieve amygdala down-regulation, patients show compensatory hyperactivation in the respective regulatory network

Acknowledgment

We wish to thank Johanna Forneck and Heike Schmidt for help with the data acquisition and two anonymous reviewers for their helpful comments on a previous version of this manuscript.

The present work was funded by a grant from the Deutsche Forschungsgemeinschaft (We3638/3-1).

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