Neurofunctional Correlates and Pharmagological Modulation of Cognitive Inhibition in Major Depression: A Study with erfMRI

Introduction: Neurofunctional studies provided evidence that a dysfunctional fronto-cingulate circuit might be related to deficits of cognitive control in major depression. Altered prefrontal and ACC blood flow associated with cognitive deficits in the depressive state were described (George et al. 1997; Okada et al. 2003). Moreover, altered activation of the anterior cingulate cortex (ACC) has been reported to have a predictive power for antidepressant treatment response (Mayberg, 2003). Aside from influencing depressive mood, antidepressants appear to have a differential effect on cognitive functions. However, treatment-related effects of different antidepressant drugs on cognitive brain activation patterns have not been examined in more detail yet. Therefore, the present study aimed to investigate patterns of cognitive brain activation in patients with depression during the course of a 6-weeks antidepressant treatment regimen. Methods: Fifteen patients (mean age=39.6 years) with a major depressive episode (MDE) according to DSM IV were examined with fMRI drug-free and after 6 weeks of treatment with either Citalopram or Reboxetin. Fifteen age-, gender- and education-matched healthy controls were included as the comparison group. The subjects were investigated with event-related functional MRI while performing a cognitive control task (Stroop-Color-Word-Task). Results and Conclusion: Although there were no significant differences in performance between groups, the depressed subjects demonstrated reduced cognitive activation in the ACC. This regional difference could no longer be observed after remission. The patients showed also increased activation in the right prefrontal and parietal cortex compared to their baseline measurements. These results indicate a central function of the ACC for remission. A normalization of ACC activity might be accompanied by a more efficient implementation of cognitive control. Supported by the German BMBF FKZ01ZZ0105, TMWFK B30701–015/-016, IZKF grants.