Generalized anxiety modulates frontal and limbic activation in major depression

We used functional magnetic resonance imaging and two emotional information processing tasks to examine frontal and limbic activation in ten patients with major depression and comorbid with preceding generalized anxiety (MDD/GAD) and ten non-depressed controls.Consistent with prior studies on depression, MDD/GAD patients showed hypoactivation in medial and middle frontal regions, as well as in the anterior cingulate, cingulate and insula. However, heightened anxiety in MDD/GAD patients was associated with increased activation in middle frontal regions and the insula and the effects varied with the type of emotional information presented.Our findings highlight frontal and limbic hypoactivation in patients with depression and comorbid anxiety and indicate that anxiety level may modulate frontal and limbic activation depending upon the emotional context. One implication of this finding is that divergent findings reported in the imaging literature on depression could reflect modulation of activation by anxiety level in response to different types of emotional information.Depression is characterized by reductions in brain activation in the dorsal lateral and medial frontal cortex, the anterior cingulate and limbic structures [1-4]. Recent reports suggest that up to 12% of patients with major depressive disorder (MDD) are also comorbid with generalized anxiety disorder (GAD) [5]. Some hypothesize the early onset of GAD may confer vulnerability to later-developing disorders, including depression [6]. Comorbid anxiety may also modify the psychopathology and course of depression, with patients with agitated depression showing exacerbated bodily responses while patients with non-anxious depression manifest inhibitory autonomic responses [7]. Evidence also shows anxious arousal and anxious apprehension modulate activation differently in depression [1]. However, few neuroimaging investigations have examined brain activation in patients with depression and comorbid with precedin