Adolescents With Major Depression Demonstrate Increased Amygdala Activation

University of California, San Diego, CA 92123, USA.
Journal of the American Academy of Child and Adolescent Psychiatry (Impact Factor: 6.35). 01/2010; 49(1):42-51. DOI: 10.1097/00004583-201001000-00008
Source: PubMed

ABSTRACT Functional neuroimaging studies have led to a significantly deeper understanding of the underlying neural correlates and the development of several mature models of depression in adults. In contrast, our current understanding of the underlying neural substrates of adolescent depression is very limited. Although numerous studies have consistently demonstrated a hyperactive amygdala in depressed adults, the few published pediatric studies have reported opposite results in the amygdala. Thus, the main purpose of this study was to further our knowledge of the underlying neural substrates of adolescent depression by examining the bilateral amygdala specifically and the whole brain in depressed adolescents compared to healthy controls.
Twelve unmedicated adolescents diagnosed with current major depressive disorder without a comorbid psychiatric disorder and 12 well-matched controls ages 13 to 17 years performed a facial-emotion matching task during functional magnetic resonance imaging at 3 T.
Region-of-interest analyses demonstrated: (1) significant bilateral amygdala activation in depressed and healthy adolescents, and (2) significantly greater left amygdala activation in depressed adolescents compared to controls. Whole-brain analysis revealed areas of significantly different brain activity in depressed adolescents compared to controls.
These results suggest that (1) depressed adolescents without a comorbid psychiatric disorder exhibit an abnormally hyperactive amygdala compared to healthy controls; (2) models of adult depression might be extended to include depressed adolescents; and (3) neuropsychiatric interventions that have been developed in depressed adults should be further examined in adolescents.

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    • "Importantly, heightened amygdala and hippocampus response to threat-related stimuli has also been observed in children, adolescents, and adults with depression (e.g. Barch et al., 2012; Beesdo et al., 2009; Bishop et al., 2004; Etkin et al., 2004; Ewbank et al., 2009; Gaffrey et al., 2011; Thomas et al., 2001b; Yang et al., 2010). Amygdala hyperresponsivity is similarly present in unaffected children at risk for depression (based on parental history of depression; Monk et al., 2008), suggesting that these differences may precede the development of psychopathology and that genetic risk and/or early environmental factors may play a key role. "
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    ABSTRACT: Accumulating evidence suggests a role for stress exposure, particularly during early life, and for variation in genes involved in stress response pathways in neural responsivity to emotional stimuli. Understanding how individual differences in these factors predict differences in emotional responsivity may be important for understanding both normative emotional development and for understanding the mechanisms underlying internalizing disorders, like anxiety and depression, that have often been related to increased amygdala and hippocampus responses to negatively valenced emotional stimuli. The present study examined whether stress exposure and genetic profile scores (10 single nucleotide polymorphisms within four hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predict individual differences in amygdala and hippocampus responses to fearful vs. neutral faces in school-age children (7-12 year olds; N=107). Experience of more stressful and traumatic life events predicted greater left amygdala responses to negative emotional stimuli. Genetic profile scores interacted with sex and pubertal status to predict amygdala and hippocampus responses. Specifically, genetic profile scores were a stronger predictor of amygdala and hippocampus responses among pubertal vs. prepubertal children where they positively predicted responses to fearful faces among pubertal girls and positively predicted responses to neutral faces among pubertal boys. The current results suggest that genetic and environmental stress-related factors may be important in normative individual differences in responsivity to negative emotional stimuli, a potential mechanism underlying internalizing disorders. Further, sex and pubertal development may be key moderators of the effects of stress-system genetic variation on amygdala and hippocampus responsivity, potentially relating to sex differences in stress-related psychopathology. Copyright © 2015. Published by Elsevier Inc.
    01/2015; 109. DOI:10.1016/j.neuroimage.2015.01.017
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    • "Previous work in this sample also showed that greater right amygdala sad versus neutral face activity in school-age children was related to poorer sadness regulation skills summing across all three subscales of the CEMS (Pagliaccio et al., 2013). This is highly relevant for the wellreplicated finding that people with depression show elevated amygdala responses to emotional stimuli and that greater depression severity correlates with greater amygdala responses to these stimuli (e.g., Barch et al., 2012; Beesdo et al., 2009; Gaffrey et al., 2011; Pagliaccio et al., 2011; Yang et al., 2010). First, these findings suggest that exploring individual differences in constructs, like emotion regulation, may be key to understanding the underlying neural and psychological deficits in depression (Aldao, Nolen-Hoeksema, & Schweizer, 2010; Garnefski & Kraaij, 2006; Joormann & Gotlib , 2010; Silk, Steinberg, & Morris, 2003). "
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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.
    Development and Psychopathology 11/2014; 26:1289–1303. DOI:10.1017/S0954579414001035 · 4.89 Impact Factor
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    • "A better relationship between neuroscience and clinical research may result in better diagnoses and increased understanding in the future (Pine et al., 2008). However, studies investigating underlying neurobiological mechanisms generally focus on adolescents with a specific disorder, without fully taking comorbidity and dimensionality into account (e.g., Brotman et al., 2007; McClure et al., 2007; Monk et al., 2008b; Yang et al., 2010; Perlman et al., 2012; Strawn et al., 2012). In the current study we included a group of adolescents with depression and/or anxiety disorders "
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    ABSTRACT: Depressive and anxiety disorders are often first diagnosed during adolescence and it is known that they persist into adulthood. Previous studies often tried to dissociate depressive and anxiety disorders, but high comorbidity makes this difficult and maybe even impossible. The goal of this study was to use neuroimaging to test what the unique contribution is of depression and anxiety symptomatology on emotional processing and amygdala activation, and to compare the results with a healthy control group. We included 25 adolescents with depressive and/or anxiety disorders and 26 healthy adolescents. Participants performed an emotional face processing task while in the MRI scanner. We were particularly interested in the relation between depression/anxiety symptomatology and patterns of amygdala activation. There were no significant differences in activation patterns between the control group and the clinical group on whole brain level and ROI level. However, we found that dimensional scores on an anxiety but not a depression subscale significantly predicted brain activation in the right amygdala when processing fearful, happy and neutral faces. These results suggest that anxiety symptoms are a better predictor for differentiating activation patterns in the amygdala than depression symptoms. Although the current study includes a relatively large sample of treatment naïve adolescents with depression/anxiety disorders, results might be influenced by differences between studies in recruitment strategies or methodology. Future research should include larger samples with a more equal distribution of adolescents with a clinical diagnosis of depression and/or anxiety. To conclude, this study shows that abnormal amygdala responses to emotional faces in depression and anxiety seems to be more dependent on anxiety symptoms than on depression symptoms, and thereby highlights the need for more research to better characterize clinical groups in future studies.
    Frontiers in Human Neuroscience 06/2014; 8. DOI:10.3389/fnhum.2014.00393 · 2.90 Impact Factor

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