Brain activation to emotional words in depressed vs healthy subjects

Abstract

Depression involves either enhanced processing of negative stimuli or diminished processing of positive stimuli. We used functional magnetic resonance imaging to assess brain activation in depressed vs healthy participants. Fifteen participants diagnosed with major depressive disorder and 15 controls were scanned during a lexical decision task involving neutral, happy, sad, and threat-related words. For happy words, depressed subjects exhibited less activation than did controls to happy words in fronto-temporal and limbic regions. For sad words, depressed subjects showed more activation than did controls in the inferior parietal lobule and less activation in the superior temporal gyrus and cerebellum, suggesting a complex activation pattern that varies for neural sub-circuits that may be associated with di¡erent cognitive or behavioral processes. INTRODUCTIONCognitive theories of depression have focused primarily on enhanced processing of negative stimuli as an explanation for the etiology and maintenance of depression [1,2]. Consistent with these formulations, depressed subjects have been found to exhibit faster responses to negative stimuli than they do to neutral or positive stimuli [3,4]. A different conceptualization of depression focuses on the absence of positive affect [5]. Consistent with this perspective, studies of depressed individuals have documented significantly diminished responsiveness to positive (but not negative) stimuli [6,7].Taken together, depression appears to be associated with increased processing of negative stimuli and/or diminished processing of positive stimuli. We used fMRI and a lexical decision task to address the question of whether these response biases are related to differential activation patterns between depressed and healthy control subjects. We predicted that, relative to normal controls, depressed participants would exhibit increased activation to sad (relative to neutral) words and/or decreased activation to happy (relative to neutral) words in brain regions associated with affective reactivity, attention, or single-word processing, such as the amygdala, insula, parietal lobules, and frontal and temporal cortical regions. SUBJECTS AND METHODSSubjects: Fifteen individuals with diagnosed major depressive disorder (MDD: 12 females, mean age 35.1 years) and 15 non-depressed control (12 females, mean age 30.7 years) subjects with no psychiatric history participated in this study. Seven of the depressed participants were taking antidepressant medications (two were taking tricyclic antidepressants, one was taking tricyclic and selective serotonin reuptake inhibitors (SSRI) antidepressants, and four were taking other types of antidepressants). There was no significant age difference between the groups. All participants were between the ages of 18 and 60, had no reported history of brain injury, lifetime history of primary psychotic ideations, social phobia, panic disorder or mania, no reported substance abuse within the past 6 months, no behavioral indications of possible impa...

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