Subgenual anterior cingulate activation to valenced emotional stimuli in major depression

Department of Psychology, Stanford University, Stanford, California 94305-2130, USA.
Neuroreport (Impact Factor: 1.52). 12/2005; 16(16):1731-4. DOI: 10.1097/01.wnr.0000183901.70030.82
Source: PubMed


Major depression has been associated with anomalous activation in the subgenual anterior cingulate cortex, but its response to emotional stimuli is poorly understood. The primary goal of this study was to compare levels of activation in the subgenual anterior cingulate cortex of diagnosed depressed and nondepressed participants in response to happy and sad facial expressions of affect. Whereas cognitive theories of depression predict increased activation to negative stimuli, depressed participants were found to exhibit increased activation to both types of stimuli in the subgenual anterior cingulate cortex. Importantly, the loci were in different regions of the subgenual anterior cingulate cortex, suggesting that there is functional specialization in the processing of negatively and positively valenced stimuli.

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Available from: Ian H Gotlib
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    • "Each child performed two task runs with no stimuli repetition. In addition, prior to performing this task, all children underwent a mood induction in the scanner based on prior work (Gotlib et al., 2005). We included this mood manipulation because affective processing biases (Scher, Ingram & Segal, 2005) and hyperactivity of limbic regions (Ramel et al., 2007) can be reactivated in individuals with a past history of MDD following a mood induction and can be elicited using mood induction in nondepressed children at risk due to maternal MDD history (Joormann & Gotlib, 2006; Joormann, Talbot, & Gotlib, 2007; Taylor & Ingram, 1999). "
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    ABSTRACT: Structural and functional alterations in a variety of brain regions have been associated with depression and risk for depression across the life span. A majority of these regions are associated with emotion reactivity and/or regulation. However, it is generally unclear what mechanistic role these alterations play in the etiology of depression. A first step toward understanding this is to characterize the relationships between variation in brain structure/function and individual differences in depression severity and related processes, particularly emotion regulation. To this end, the current study examines how brain structure and function predict concurrent and longitudinal measures of depression symptomology and emotion regulation skills in psychiatrically healthy school-age children (N ¼ 60). Specifically, we found that smaller hippocampus volumes and greater responses to sad faces in emotion reactivity regions predict increased depressive symptoms at the time of scan, whereas larger amygdala volumes, smaller insula volumes, and greater responses in emotion reactivity regions predict decreased emotion regulation skills. In addition, larger insula volumes predict improvements in emotion regulation skills even after accounting for emotion regulation at the time of scan. Understanding brain–behavior relationships in psychiatrically healthy samples, especially early in development, will help inform normative developmental trajectories and neural alterations in depression and other affective pathology.
    Full-text · Article · Nov 2014 · Development and Psychopathology
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    • "Similarly, the amygdala rapidly reacts to the emotional significance of stimuli (Victor et al., 2010) and is involved in processing facial displays of affect (Fitzgerald et al., 2006). Abnormal processing of emotional stimuli has been consistently implicated in MDD and is thought to increase risk of disease development, maintenance and relapse (Foland-Ross and Gotlib, 2012; Mathews and MacLeod, 2005). Mayberg and others have suggested that depressive symptomatology is a consequence of hypo-activity in neocortical structures and hyperactivity in paralimbic structures (Mayberg, 1997; Stuhrmann et al., 2011). "
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    ABSTRACT: Background Major depressive disorder (MDD) often begins during adolescence when the brain is still maturing. To better understand the neurobiological underpinnings of MDD early in development, this study examined brain function in response to emotional faces in adolescents with MDD and healthy (HC) adolescents using functional magnetic resonance imaging (fMRI). Method Thirty-two unmedicated adolescents with MDD and 23 healthy age- and gender-matched controls completed an fMRI task viewing happy and fearful faces. Fronto-limbic regions of interest (ROI; bilateral amygdala, insula, subgenual and rostral anterior cingulate cortices) and whole-brain analyses were conducted to examine between-group differences in brain function. Results ROI analyses revealed that patients had greater bilateral amygdala activity than HC in response to viewing fearful versus happy faces, which remained significant when controlling for comorbid anxiety. Whole-brain analyses revealed that adolescents with MDD had lower activation compared to HC in a right hemisphere cluster comprised of the insula, superior/middle temporal gyrus, and Heschl׳s gyrus when viewing fearful faces. Brain activity in the subgenual anterior cingulate cortex was inversely correlated with depression severity. Limitations Limitations include a cross-sectional design with a modest sample size and use of a limited range of emotional stimuli. Conclusions Results replicate previous studies that suggest emotion processing in adolescent MDD is associated with abnormalities within fronto-limbic brain regions. Findings implicate elevated amygdalar arousal to negative stimuli in adolescents with depression and provide new evidence for a deficit in functioning of the saliency network, which may be a future target for early intervention and MDD treatment.
    Full-text · Article · Oct 2014 · Journal of Affective Disorders
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    • "NA has been reported to show negative correlation with the strength of amygdala–sACC connectivity during a task in which participants processed negative affective stimuli (Pezawas et al. 2005) – that is, participants with high levels of NA showed reduced connectivity . This result is in contrast to studies in depressed participants, in which the regions have been reported to show both increased activation to negatively valenced stimuli (Sheline et al. 2001; Gotlib et al. 2005) and increased connectivity (Matthews et al. 2008; Almeida et al. 2011; Wilson et al. 2014). "
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    ABSTRACT: Background: The amygdala and subgenual anterior cingulate cortex (sACC) are key brain regions for the generation of negative affect. In this longitudinal fMRI study of adolescents we investigated how amygdala-sACC connectivity was correlated with negative affectivity (NA) both cross-sectionally and longitudinally, and examined its relationship to the onset of first-episode depression. Method: Fifty-six adolescents who were part of a larger longitudinal study of adolescent development were included. They had no history of mental illness at the time of their baseline scan (mean age 16.5 years) and had a follow-up scan 2 years later (mean age 18.8 years). We used resting-state functional-connectivity MRI to investigate whether cross-sectional and change measures of amygdala-sACC connectivity were (i) correlated with NA and its change over time, and (ii) related to the onset of first-episode depression. Results: The magnitude of amygdala connectivity with sACC showed significant positive correlation with NA at both time-points. Further analysis confirmed that change in amygdala-sACC connectivity between assessments was correlated with change in NA. Eight participants developed a first episode of depression between the baseline and follow-up assessments: they showed increased amygdala-sACC connectivity at follow-up. Conclusions: Amygdala-sACC connectivity is associated with NA in adolescence, with change in connectivity between these regions showing positive correlation with change in NA. Our observation that the onset of depression was associated with an increase in connectivity between the regions provides support for the neurobiological 'scar' hypothesis of depression.
    Full-text · Article · Aug 2014 · Psychological Medicine
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