Common and distinct amygdala-function perturbations in depressed vs anxious adolescents

Abstract

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 x emotion x attention interactions, P < or = .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.

Figure 1

Amygdala activation to fearful faces in patients with anxiety and major depressive disorder (MDD) relative to healthy controls for select attention conditions. A, Left amygdala activation to fearful faces relative to fixation (error bars reflect standard errors) displaying the group (healthy controls, MDD with and without anxiety disorder, anxiety disorder alone) × attention condition interaction. A similar activation pattern was found for the right amygdala and when patients with comorbid MDD/anxiety were excluded (not shown). B and C, Left amygdala activation to fearful faces during afraid ratings vs passive viewing (“fearful-afraid vs fearful-passive” contrast) showing significantly enhanced activation among both anxiety and MDD groups compared with healthy controls, with no difference between patients with anxiety and patients with MDD. D and E, The fearful-afraid vs fearful-passive contrast evidences significantly greater left amygdala activation in patients with anxiety alone than in controls (D) (Montreal Neurological Institute [MNI] coordinates: −20, −2, −20, P=.001 (shown in figure); −10, −4, −16, P=.002; MNI coordinates are small-volume corrected) and in patients with MDD alone than in controls (E) (MNI coordinates: −20, 4, −16, P=.007; small-volume corrected). Highlighted areas indicate regions where the differences in blood oxygen level–dependent activation between groups were significant (for display purposes, uncorrected threshold was set at P=.0005 [D] and P=.005 [E]).

Figure 2

Differential amygdala activation in patients with major depressive disorder (MDD) and patients with anxiety during passive viewing of fearful vs other face-emotion types. A, Left amygdala activation to passively viewed facial expressions relative to fixation (error bars reflect standard errors) among patients with MDD (with and without comorbid anxiety disorder), patients with anxiety disorder, and healthy controls displaying the group × face-emotion interaction in the passive viewing condition. A similar activation pattern was found for the right amygdala and when patients with comorbid MDD/anxiety were excluded (not shown). B and C, Patients with anxiety and those with MDD showed opposite and significantly different left (shown in figure) and right amygdala responses to fearful faces vs happy faces passively viewed (“fearful-passive vs happy-passive” contrast). Patients with MDD and those with anxiety also differed from healthy controls in left amygdala activation in this contrast. D, The fearful-passive vs happy-passive contrast evidences significantly greater left and right amygdala activation in patients with anxiety than in patients with MDD even when those with MDD with comorbid anxiety were excluded (Montreal Neurological Institute coordinates: left, −16, 2, −16, P=.01, small-volume corrected; right, 22, 0, −14, P=.001, small-volume corrected). Highlighted areas indicate regions where the differences in blood oxygen level–dependent activation between groups were significant (for display purposes, uncorrected threshold was set at P=.005).

Figure 3

Orbitofrontal cortex (OFC) activation in the “fearful-afraid vs fearful-passive” contrast in patients with major depressive disorder (MDD) and anxiety. A and B, Left OFC activation to fearful faces during afraid ratings vs passive viewing (fearful-afraid vs fearful-passive contrast) (error bars reflect standard errors) showing significantly enhanced activation among patients with anxiety compared with healthy controls. C, The fearful-afraid vs fearful-passive contrast evidences significantly greater left lateral OFC activation in patients with anxiety than in controls (Montreal Neurological Institute coordinates: left, −50, 22, −2, P=.046 (shown in figure); −14, 18, −10, P=.05, small-volume corrected). Highlighted areas indicate regions where the differences in blood oxygen level–dependent activation between groups were significant (for display purposes, uncorrected threshold was set at P=.005).

Figure 4

Orbitofrontal cortex (OFC) activation in the “fearful-passive vs happy-passive” contrast in patients with major depressive disorder (MDD) and anxiety. A and B, Right OFC activation to fearful faces during passive viewing of fearful vs happy faces (fearful-passive vs happy-passive contrast) (error bars reflect standard errors) showing significantly enhanced activation among patients with anxiety compared with those with MDD and healthy controls. C, The fearful-passive vs happy-passive contrast evidences significantly greater right lateral OFC activation in patients with anxiety than in those with MDD (with and without comorbid anxiety) (Montreal Neurological Institute coordinates: 32, 24, −18, P=.005, small-volume corrected; no suprathreshold voxels emerge for the anxiety vs MDD-alone comparison). Highlighted areas indicate regions where the differences in blood oxygen level–dependent activation between groups were significant (for display purposes, uncorrected threshold was set at P=.0005).