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: 8.93). 01/2011; 69(8):734-41. DOI: 10.1016/j.biopsych.2010.12.004
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Child abuse is the most significant environmental risk factor for the development of mood disorders, which occur twice as frequently in women as in men. To determine whether juvenile social subjugation (JSS) of rats induces mood disorder-like symptoms, we exposed 28 day-old male and female rats to daily aggressive acts from aggressive male residents. Each rat received pins, kicks, and dominance postures from the resident for 10 min per day for 10 days. When the rats were adults, we tested their anxiety- and depression-like behaviors. In addition, we measured circulating basal and stress-evoked corticosterone (CORT) levels, and weighed the adrenal glands. Although the amount of JSS was indistinguishable between males and females, females were nonetheless more severely affected by the experience. Subjugated females became immobile more quickly during forced swim tests, and made fewer investigatory approaches during the social interaction test than control females. Juvenile social subjugation increased closed arm time in the elevated plus maze of males and females, but the effect of social subjugation was greater in females. Finally, stress-evoked CORT levels were significantly higher, and adrenal gland weights were significantly heavier, in subjugated females relative to their controls and to subjugated males. Our results demonstrate that JSS increases depression- and anxiety-like behaviors and sensitizes the stress response system in a sex-specific manner.
    Hormones and Behavior 11/2011; 61(1):91-9. · 3.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Adolescence is a period of major risk for depression, which is associated with negative personal, social, and educational outcomes. Yet, in comparison to adult models of depression, very little is known about the specific psychosocial stressors that contribute to adolescent depression, and whether these can be targeted by interventions. In this review, we consider the role of peer rejection. First, we present a comprehensive review of studies using innovative experimental paradigms to understand the role of peer rejection in adolescent depression. We show how reciprocal relationships between peer rejection and depressive symptoms across adolescence powerfully shape and maintain maladaptive trajectories. Second, we consider how cognitive biases and their neurobiological substrates may explain why some adolescents are more vulnerable to the effects of, and perhaps exposure to, peer rejection compared to others. Finally, we draw attention to emerging cognitive and functional magnetic resonance imaging-based neurofeedback training, which by modifying aspects of information processing may promote more adaptive responses to peer rejection. A better understanding of the mechanisms underlying adolescent depression may not only alleviate symptoms during a period of substantial developmental challenges, but may also reduce the burden of the disorder across the lifespan.
    Depression and Anxiety 04/2013; · 4.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Major Depressive Disorder (MDD) is a leading cause of disease burden worldwide. With the rapid growth of neuroimaging research on relatively small samples, meta-analytic techniques are becoming increasingly important. Here, we aim to clarify the support in fMRI literature for three leading neurobiological models of MDD: limbic-cortical, cortico-striatal and the default mode network. Searches of PubMed and Web of Knowledge, and manual searches, were undertaken in early 2011. Data from 34 case-control comparisons (n=1165) and 6 treatment studies (n=105) were analysed separately with two meta-analytic methods for imaging data: Activation Likelihood Estimation and Gaussian-Process Regression. There was broad support for limbic-cortical and cortico-striatal models in the case-control data. Evidence for the role of the default mode network was weaker. Treatment-sensitive regions were primarily in lateral frontal areas. In any meta-analysis, the increase in the statistical power of the inference comes with the risk of aggregating heterogeneous study pools. While we believe that this wide range of paradigms allows identification of key regions of dysfunction in MDD (regardless of task), we attempted to minimise such risks by employing GPR, which models such heterogeneity. The focus of treatment effects in frontal areas indicates that dysregulation here may represent a biomarker of treatment response. Since the dysregulation in many subcortical regions in the case-control comparisons appeared insensitive to treatment, we propose that these act as trait vulnerability markers, or perhaps treatment insensitivity. Our findings allow these models of MDD to be applied to fMRI literature with some confidence.
    Journal of affective disorders 07/2013; · 3.76 Impact Factor


Available from
May 31, 2014