Increased Amygdala Response to Positive Social Feedback in Young People with Major Depressive Disorder

Orygen Youth Health Research Centre, The University of Melbourne, Melbourne, Australia.
Biological psychiatry (Impact Factor: 10.26). 04/2011; 69(8):734-41. DOI: 10.1016/j.biopsych.2010.12.004
Source: PubMed


Studies of depressed patients have demonstrated increased amygdala activation to negative affective stimuli. In this study, we used a paradigm that employed personally relevant social stimuli, which are known to strongly activate the amygdala, to test whether the amygdala demonstrated aberrant activity in depressed participants as they responded to stimuli with positive valence.
Nineteen patients with major depressive disorder, aged 15 to 24 years, were matched with 20 healthy control participants. They completed a novel functional magnetic resonance imaging task in which they received social feedback from people who they believed had evaluated them. Voxelwise statistical parametric maps of brain response to positive social feedback and to a control feedback condition were compared to test the hypothesis that differences in neural response between depressed and control participants would arise in the amygdala.
Depressed participants showed increased neural response to the positive- versus control-feedback condition in the amygdala (p < .05, corrected). An exploratory analysis showed that depressed participants responded to faces from both feedback conditions with increased activity in regions subserving social appraisal (ventrolateral prefrontal cortex and inferior parietal cortex) and affective processing (pregenual anterior cingulate cortex and anterior insular cortex; p < .001, uncorrected).
Depressed patients responded to positive social feedback with increased amygdala activation, demonstrating that amygdala hyperresponsivity in depression is not restricted to negatively-valenced stimuli. The heightened sensitivity of depressed participants to social evaluation may help explain symptoms of depression such as social withdrawal.

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Available from: Murat Yucel, Oct 09, 2015
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    • "Several recent studies have documented anxiety-and mood-related correlates using novel neuroimaging paradigms that simulate social interactions (Jarcho et al., 2013). Although findings vary across studies, activation in amygdala, striatum and medial prefrontal cortex (mPFC) consistently differentiate anxious/depressed from healthy individuals (Guyer et al., 2008; Gunther Moor et al., 2010; Davey et al., 2011; Masten et al., 2011; Lau et al., 2012; Silk et al., 2014; Somerville et al., 2013; Guyer et al., 2014). These regions are thought to function interactively to ascribe salience, generate predictions and create flexible patterns of behavior within a motivated social context (Phelps et al., 2004; Schiller et al., 2008; Haber and Knutson, 2010; Pessoa and Adolphs, 2010). "
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    ABSTRACT: Adolescence is the time of peak onset for many anxiety disorders, particularly Social Anxiety Disorder. Research using simulated social interactions consistently finds differential activation in several brain regions in anxious (vs. non-anxious) youth, including amygdala, striatum, and medial prefrontal cortex. However, few studies examined the anticipation of peer interactions, a key component in the etiology and maintenance of anxiety disorders. Youth completed the Chatroom Task while undergoing functional magnetic resonance imaging. Patterns of neural activation were assessed in anxious and non-anxious youth as they were cued to anticipate social feedback from peers. Anxious participants evidenced greater amygdala activation and rostral anterior cingulate (rACC)↔amygdala coupling than non-anxious participants during anticipation of feedback from peers they had previously rejected; anxious participants also evidenced less nucleus accumbens activation during anticipation of feedback from selected peers. Finally, anxiety interacted with age in rACC: in anxious participants, age was positively associated with activation to anticipated feedback from rejected peers and negatively for selected peers, whereas the opposite pattern emerged for non-anxious youth. Overall, anxious youth showed greater reactivity in anticipation of feedback from rejected peers, and thus may ascribe greater salience to these potential interactions and increase the likelihood of avoidance behavior. © The Author (2014). Published by Oxford University Press. For Permissions, please email:
    Social Cognitive and Affective Neuroscience 12/2014; 10(8). DOI:10.1093/scan/nsu165 · 7.37 Impact Factor
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    • "Although PFC regions associated with cognitive reappraisal undergo protracted maturation during adolescence (Cohen Kadosh, et al., 2013), data from typically-developing youths reveal a remarkably similar network of regions involved in ER to that in adults (Levesque, et al., 2004; McRae, et al., 2012; Pitskel, et al., 2011). In line with studies of uninstructed ER in depressed adults (Dannlowski, et al., 2007; Tang, et al., 2007; Victor, et al., 2010) and adolescents (Davey, et al., 2011; Masten, et al., 2011), one recent study found depressed adolescents showed greater activity than controls in the right amygdala in the maintain (versus reappraisal) condition (Perlman, et al., 2012). Also replicating adult studies (Kong, et al., 2013), this study showed there was less connectivity between the amygdala and the insula and medial PFC during this condition, suggesting adolescent depression may be associated with impaired neural control over affective responses. "
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    ABSTRACT: Depression is the most common psychiatric disorder in adolescence, and is characterised by an inability to down-regulate negative emotional responses to stress. Adult studies suggest this may be associated with reduced functional connectivity between prefrontal and subcortical regions, yet the neurological mechanisms in adolescence remain unclear. We developed a novel, age-appropriate, reappraisal paradigm to investigate functional connectivity during reappraisal of a real-life source of stress in 15 depressed and 15 non-depressed adolescents. During fMRI, participants i) attended to, and ii) implemented reappraisal techniques (learnt prior to fMRI) in response to, rejection. Reappraisal reduced negative mood and belief in negative thoughts in both groups alike, however during reappraisal (versus attend) trials, depressed adolescents showed greater connectivity between the right frontal pole and numerous subcortical and cortical regions than non-depressed adolescents. These findings tentatively suggest that, when instructed, depressed adolescents do have the ability to engage neural networks involved in emotion regulation, possibly because adolescence reflects a period of heightened plasticity. These data support the value of cognitive reappraisal as a treatment tool, identify neural markers that could be used to optimise current therapies, and lay the foundations for developing novel neuroscientific techniques for the treatment of adolescent depression. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Journal of Psychiatric Research 12/2014; 61. DOI:10.1016/j.jpsychires.2014.11.016 · 3.96 Impact Factor
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    • "One possibility related to our choice of fMRI task is that the mPFC is especially sensitive to social rewards, and depression particularly disrupts responding to a social reward in that region rather than in the VS. Also, unlike a previous study using this social reward task with late adolescents (Davey et al., 2011), we did not find that depression was related to amygdala response to social reward. That study took a group-differences approach, however, comparing a group of clinically depressed young people with a group of healthy young people. "
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    ABSTRACT: Anhedonia, a cardinal symptom of depression defined as difficulty experiencing pleasure, is also a possible endophenotype and prognostic factor for the development of depression. The onset of depression typically occurs during adolescence, a period in which social status and affiliation are especially salient. The medial prefrontal cortex (mPFC), a region implicated in reward, self-relevant processing, and social cognition, exhibits altered function in adults with anhedonia, but its association with adolescent anhedonia has yet to be investigated. We examined neural response to social reward in 27 late adolescents, 18-21years old, who varied in social anhedonia. Participants reported their social anhedonia, completed ratings of photos of unfamiliar peers, and underwent a functional magnetic resonance imaging task involving feedback about being liked. Adolescents with higher social anhedonia exhibited greater mPFC activation in response to mutual liking (i.e., being liked by someone they also liked) relative to received liking (i.e., being liked by someone whom they did not like). This association held after controlling for severity of current depressive symptoms, although depressive severity was also associated with greater mPFC response. Adolescents with higher levels of social anhedonia also had stronger positive connectivity between the nucleus accumbens and the mPFC during mutual versus received liking. These results, the first on the pathophysiology of adolescent anhedonia, support altered neural reward-circuit response to social reward in young people with social anhedonia.
    Brain and Cognition 01/2014; 89. DOI:10.1016/j.bandc.2013.12.004 · 2.48 Impact Factor
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