Neural mechanisms of cognitive reappraisal in remitted major depressive disorder

Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: .
Journal of Affective Disorders (Impact Factor: 3.38). 06/2013; DOI: 10.1016/j.jad.2013.05.073
Source: PubMed


Down-regulation of negative emotions by cognitive strategies relies on prefrontal cortical modulation of limbic brain regions, and impaired frontolimbic functioning during cognitive reappraisal has been observed in affective disorders. However, no study to date has examined cognitive reappraisal in unmedicated euthymic individuals with a history of major depressive disorder relative to symptom-matched controls. Given that a history of depression is a critical risk factor for future depressive episodes, investigating the neural mechanisms of emotion regulation in remitted major depressive disorder (rMDD) may yield novel insights into depression risk.
We assessed 37 individuals (18 rMDD, 19 controls) with functional magnetic resonance imaging (fMRI) during a task requiring cognitive reappraisal of sad images.
Both groups demonstrated decreased self-reported negative affect after cognitive reappraisal and no group differences in the effects of cognitive reappraisal on mood were evident. Functional MRI results indicated greater paracingulate gyrus (rostral anterior cingulate cortex, Brodmann area 32) activation and decreased right midfrontal gyrus (Brodmann area 6) activation during the reappraisal of sad images.
Trial-by-trial ratings of pre-regulation affect were not collected, limiting the interpretation of post-regulation negative affect scores.
Results suggest that activation of rostral anterior cingulate cortex, a region linked to the prediction of antidepressant treatment response, and of the right midfrontal gyrus, a region involved in cognitive control in the context of cognitive reappraisal, may represent endophenotypic markers of future depression risk. Future prospective studies will be needed to validate the predictive utility of these neural markers.

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    • "The key finding of this study is the reduced DMN suppression in MDD patients existing even after full recovery, which mirrors findings in symptomatic-(Rose et al., 2006; Greicius et al., 2007; Sheline et al., 2009; Sheline et al., 2010; Disner et al., 2011; Zhang et al., 2011; Anticevic et al., 2012; Davey et al., 2012a; Zhu et al., 2012; Connolly et al., 2013; Guo et al., 2013; Li et al., 2013; Sambataro et al., 2013; Dutta et al., 2014; Rodriguez-Cano et al., 2014) and euthymic-(Walsh et al., 2007; Schoning et al., 2009; Smoski et al., 2013) MDD patients. This reduction of DMN suppression , which is accompanied by increased ruminative response style in our study, might therefore be interpreted as increased selfreferential processing as well as insufficient inhibition of conflicting computations in line with previous literature (Mason et al., 2007; Hamilton et al., 2011; Anticevic et al., 2012; Marchetti et al., 2012; Nejad et al., 2013). "
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    ABSTRACT: Insufficient default mode network (DMN) suppression was linked to increased rumination in symptomatic Major Depressive Disorder (MDD). Since rumination is known to predict relapse and a more severe course of MDD, we hypothesized that similar DMN alterations might also exist during full remission of MDD (rMDD), a condition known to be associated with increased relapse rates specifically in patients with adolescent onset. Within a cross-sectional functional magnetic resonance imaging study activation and functional connectivity (FC) were investigated in 120 adults comprising 78 drug-free rMDD patients with adolescent- (n = 42) and adult-onset (n = 36) as well as 42 healthy controls (HC), while performing the n-back task. Compared to HC, rMDD patients showed diminished DMN deactivation with strongest differences in the anterior-medial prefrontal cortex (amPFC), which was further linked to increased rumination response style. On a brain systems level, rMDD patients showed an increased FC between the amPFC and the dorsolateral prefrontal cortex, which constitutes a key region of the antagonistic working-memory network. Both whole-brain analyses revealed significant differences between adolescent-onset rMDD patients and HC, while adult-onset rMDD patients showed no significant effects. Results of this study demonstrate that reduced DMN suppression exists even after full recovery of depressive symptoms, which appears to be specifically pronounced in adolescent-onset MDD patients. Our results encourage the investigation of DMN suppression as a putative predictor of relapse in clinical trials, which might eventually lead to important implications for antidepressant maintenance treatment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
    Journal of Psychiatric Research 03/2015; 64. DOI:10.1016/j.jpsychires.2015.02.025 · 3.96 Impact Factor
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    • "Functional magnetic resonance imaging (fMRI) studies of emotion regulation have focused on a top-down frontolimbic regulatory network (Ochsner et al., 2004). As we have summarized previously (Smoski et al., 2013), prefrontal cortical regions, including dorsolateral prefrontal cortex (dlPFC), ventrolateral prefrontal cortex (vlPFC) and anterior cingulate cortex (ACC), mediate the modulation of emotionelicited activation in limbic regions (Ochsner and Gross, 2008). Within this regulatory circuit, activation in prefrontal cognitive control regions is negatively associated with changes in limbic activation while processing negative stimuli (Siegle et al., 2006; Urry et al., 2006). "
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    ABSTRACT: Mood disorders are characterized by impaired emotion regulation abilities, reflected in alterations in frontolimbic brain functioning during regulation. However, little is known about differences in brain function when comparing regulatory strategies. Reappraisal and emotional acceptance are effective in downregulating negative affect, and are components of effective depression psychotherapies. Investigating neural mechanisms of reappraisal versus emotional acceptance in remitted major depressive disorder (rMDD) may yield novel mechanistic insights into depression risk and prevention. Thirty-seven individuals (18 rMDD, 19 controls) were assessed during an fMRI task requiring reappraisal, emotional acceptance, or no explicit regulation while viewing sad images. Lower negative affect was reported following reappraisal than acceptance, and was lower following acceptance than no explicit regulation. In controls, the acceptance > reappraisal contrast revealed greater activation in left insular cortex and right prefrontal gyrus, and less activation in several other prefrontal regions. Compared to controls, the rMDD group had greater paracingulate and right midfrontal gyrus (BA 8) activation during reappraisal relative to acceptance. Compared to reappraisal, acceptance is associated with activation in regions linked to somatic and emotion awareness, though this activation is associated with less reduction in negative affect. Additionally, a history of MDD moderated these effects. © The Author (2015). Published by Oxford University Press. For Permissions, please email:
    Social Cognitive and Affective Neuroscience 01/2015; 10(9). DOI:10.1093/scan/nsv003 · 7.37 Impact Factor
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    • "Reappraisal may involve the utilization of cognitive control to regulate semantic representations of affective stimuli which in turn attenuate amygdala reactivity [10]. Moreover, reappraisal is generally viewed as an adaptive emotion regulation strategy which is dysfunctional in depression with less frequency of daily use [11] as well as abnormal neural activation patterns [9] [12] [13]. Therefore, reappraisal may be a promising target for disclosing the vulnerable characteristics of depression. "
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    ABSTRACT: Reappraisal is an adaptive emotion regulation strategy while the role of self-perspective in reappraisal process of depressed patients is largely unknown in terms of goals (valence/arousal) and tactics (detachment/immersion). In this study, 12 depressed individuals and 15 controls were scanned with MRI during which they either attend naturally to emotional stimuli, or adopt detachment/immersion strategy. Behaviorally, no group differences in self-reported emotion regulation effectiveness were found. In addition, we observed that (1) patients were less able to downregulate amygdala activation with recruitment of more dorsal lateral prefrontal cortex (dlPFC) when adopting detachment strategy regardless of valence, and this preserved ability to regulate emotion was inversely associated with severity of symptoms; (2) patients had deficits in upregulating amygdala activation when adopting immersion strategy, with less inferior frontal gyrus (IFG) activation and strengthening coupling of dlPFC and ventral medial prefrontal cortex (vmPFC) with amygdala; (3) comparison between groups yielded that patients showed stronger vmPFC activation under either self-detached or self-immersed condition. In conclusion, impaired modulatory effects of amygdala in depressed patients are compensated with strengthening cognitive control resources, with dissociable effects for different self-perspectives in reappraisal. These results may help clarify the role of self-perspective underlying reappraisal in major depression.
    04/2014; 2014(1):390865. DOI:10.1155/2014/390865
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