Background: Anxiety is relatively common in depression and capable of modifying the severity and course of\r\ndepression. Yet our understanding of how anxiety modulates frontal and limbic activation in depression is limited.\r\nMethods: We used functional magnetic resonance imaging and two emotional information processing tasks to\r\nexamine frontal and limbic activation in ten patients with major depression and comorbid with preceding\r\ngeneralized anxiety (MDD/GAD) and ten non-depressed controls.\r\nResults: Consistent with prior studies on depression, MDD/GAD patients showed hypoactivation in medial and\r\nmiddle frontal regions, as well as in the anterior cingulate, cingulate and insula. However, heightened anxiety in\r\nMDD/GAD patients was associated with increased activation in middle frontal regions and the insula and the\r\neffects varied with the type of emotional information presented.\r\nConclusions: Our findings highlight frontal and limbic hypoactivation in patients with depression and comorbid\r\nanxiety and indicate that anxiety level may modulate frontal and limbic activation depending upon the emotional\r\ncontext. One implication of this finding is that divergent findings reported in the imaging literature on depression\r\ncould reflect modulation of activation by anxiety level in response to different types of emotional information.
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