Amygdala Response to Fearful Faces in Anxious and Depressed Children

Thomas, Kathleen M.; Drevets, Wayne C.; Dahl, Ronald E.; Ryan, Neal D.; Birmaher, Boris; Eccard, Clayton H.; Axelson, David; Whalen, Paul J.; Casey, B. J.

doi:10.1001/archpsyc.58.11.1057

Cited by 533 publications

(385 citation statements)

References 50 publications

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“…Studies comparing neural responses to emotionally expressive faces found that the hemodynamic responses of the amygdala were increased when viewing sad faces vs neutral faces or vs fixation point baseline (Fu et al, 2004;Surguladze et al, 2005) in depressives relative to controls. In contrast, hemodynamic responses of the amygdala decreased to fearful faces vs neutral faces in depressed adults relative to controls and to fearful faces vs fixation point baseline in depressed children relative to controls (Thomas et al, 2001). However, left amygdala responses were reportedly increased in depressives vs controls when hemodynamic activity measured during exposure to fearful and happy faces presented using a backward masking technique (so that subjects were unaware of having seen the emotional faces) was compared with activity during fixation point baseline (Sheline et al, 2001).…”

Section: Introductionmentioning

confidence: 85%

Effects of a α2C-Adrenoreceptor Gene Polymorphism on Neural Responses to Facial Expressions in Depression

Neumeister

Drevets

Belfer

et al. 2006

Neuropsychopharmacol

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Alterations in processing of emotionally salient information have been reported in individuals with major depressive disorder (MDD). Evidence suggests a role for noradrenaline in the regulation of a cortico-limbic-striatal circuit that has also been implicated in the pathophysiology of MDD. Herein, we studied the physiological consequences of a common coding polymorphism of the gene for the a 2C -adrenoreceptor (AR) subtypeFthe deletion of four consecutive amino acids at codons 322-325 of the a2C-AR (a2CDel322-325-AR) in medication-free, remitted individuals with MDD (rMDD), and healthy control subjects. After injection of 10 mCi of H 2 15 O, positron emission tomography (PET) measures of neural activity were acquired while subjects were viewing unmasked sad, happy, and fearful faces. The neural responses to sad facial expressions were increased in the amygdala and decreased in the left ventral striatum in rMDD patients relative to healthy control subjects. Furthermore, we report that rMDD carriers of one or two copies of the a2CDel322-325-AR exhibit greater amygdala as well as pregenual and subgenual anterior cingulate gyrus neuronal activity in response to sad faces than healthy a2CDel322-325-AR carriers and rMDD noncarriers. These results suggest that the a2CDel322-325-AR confers a change in brain function implicating this a2-AR subtype into the pathophysiology of MDD.

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Section: Introductionmentioning

confidence: 85%

Effects of a α2C-Adrenoreceptor Gene Polymorphism on Neural Responses to Facial Expressions in Depression

Neumeister

Drevets

Belfer

et al. 2006

Neuropsychopharmacol

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“…Given the atypical emotional responses of individuals with anxious or depressive disorders, researchers have hypothesized that anomalies in neural structures involved in perceiving, evaluating, and responding to emotional stimuli may characterize these patient groups. Consistent with this hypothesis, accumulating evidence associates aberrant amygdala function, typically enhanced activity, with anxiety disorders and major depressive disorder (MDD) (2)(3)(4)(5)(6).…”

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confidence: 97%

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confidence: 99%

“…A smaller body of research in adolescents with mood and anxiety disorders has generated similar evidence of atypical amygdala responsiveness (6,(11)(12)(13), mostly hyperactivity. One study, however, found hypoactivity in a small sample of depressed females (6). Limited research has focused on youth with specific anxiety disorders; however, in a larger study comparing amygdala responses between patients with GAD and healthy peers (14), we found compelling evidence of a distinctive pattern of elevated amygdala activity in youth with GAD when their attention was constrained to their own internal emotional states.…”

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confidence: 99%

“…In particular, no study in youth has examined associations between amygdala activity and response to treatment. Such work is important in mood and anxiety disorders, given emerging data on amygdala function in these conditions (6,12), coupled with questions surrounding therapeutics. For instance, it is unclear why youth show a different pattern of responses to antidepressant medications, including a possible increased risk of suicidal ideation, than adults (19).…”

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confidence: 99%

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fMRI predictors of treatment outcome in pediatric anxiety disorders

et al. 2006

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Common and Distinct Amygdala-Function Perturbations in Depressed vs Anxious Adolescents

Beesdo¹,

Lau

Guyer

et al. 2009

Arch Gen Psychiatry

235

222

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Context Few studies directly compare amygdala function in depressive and anxiety disorders. Data from longitudinal research emphasize the need for such studies in adolescents. Objective To compare amygdala response to varying attention and emotion conditions among adolescents with major depressive disorder (MDD) or anxiety disorders, relative to adolescents with no psychopathology. Design Case-control study. Setting Government clinical research institute. Participants Eighty-seven adolescents matched on age, sex, intelligence, and social class: 26 with MDD (14 with and 12 without anxiety disorders), 16 with anxiety disorders but no depression, and 45 without psychopathology. Main Outcome Measures Blood oxygen level–dependent signal in the amygdala, measured by means of event-related functional magnetic resonance imaging. During imaging, participants viewed facial expressions (neutral, fearful, angry, and happy) while attention was constrained (afraid, hostility, and nose-width ratings) or unconstrained (passive viewing). Results Left and right amygdala activation differed as a function of diagnosis, facial expression, and attention condition both when patients with comorbid MDD and anxiety were included and when they were excluded (group × emotion × attention interactions, P≤.03). Focusing on fearful face–viewing events, patients with anxiety and those with MDD both differed in amygdala responses from healthy participants and from each other during passive viewing. However, both MDD and anxiety groups, relative to healthy participants, exhibited similar signs of amygdala hyperactivation to fearful faces when subjectively experienced fear was rated. Conclusions Adolescent MDD and anxiety disorders exhibit common and distinct functional neural correlates during face processing. Attention modulates the degree to which common or distinct amygdala perturbations manifest in these patient groups, relative to healthy peers.

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Amygdala Response to Fearful Faces in Anxious and Depressed Children

Abstract: Our results suggest that amygdala function is affected in both anxiety and depression during childhood and adolescence. Moreover, this disruption appears to be specific to the child's own rating of everyday anxiety.

Cited by 533 publications

References 50 publications

Effects of a α2C-Adrenoreceptor Gene Polymorphism on Neural Responses to Facial Expressions in Depression

Effects of a α2C-Adrenoreceptor Gene Polymorphism on Neural Responses to Facial Expressions in Depression

fMRI predictors of treatment outcome in pediatric anxiety disorders

Common and Distinct Amygdala-Function Perturbations in Depressed vs Anxious Adolescents

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