Neural activity changes to emotional stimuli in healthy individuals under chronic use of clomipramine

Abstract

Previous functional magnetic resonance imaging (fMRI) studies examined neural activity responses to emotive stimuli in healthy individuals after acute/subacute administration of antidepressants. We now report the effects of repeated use of the antidepressant clomipramine on fMRI data acquired during presentation of emotion-provoking and neutral stimuli on healthy volunteers. A total of 12 volunteers were evaluated with fMRI after receiving low doses of clomipramine for 4 weeks and again after 4 weeks of washout. Fear-, happiness-, anger-provoking and neutral pictures from the International Affective Picture System (IAPS) were used. Data analysis was performed with statistical parametric mapping (P < 0.05). Paired t-test comparisons for each condition between medicated and unmedicated states showed, to negative valence paradigms, decrease in brain activity in the amygdala when participants were medicated. We also demonstrated, across both positive and negative valence paradigms, consistent decreases in brain activity in the medicated state in the anterior cingulate gyrus and insula. This is the first report of modulatory effects of repeated antidepressant use on the central representation of somatic states in response to emotions of both negative and positive valences in healthy individuals. Also, our results corroborate findings of antidepressant-induced temporolimbic activity changes to emotion-provoking stimuli obtained in studies of subjects treated acutely with such agents.

Fig. 1

Selected regions of interest where there were foci of significantly decreased neural activity when healthy volunteers (n=12) were medicated versus unmedicated while viewing emotion-provoking paradigm (paired t-tests, p<0.05 corrected for multiple comparisons). Foci of significance were overlaid on coronal and sagittal brain slices spatially normalized into the Montreal Neurologic Institute coordinates system. A. Happiness paradigm; B. Fear paradigm and C. Anger paradigm. Significant differences were detected across the three emotion-provoking paradigms in the insula (shown on the sections on the superior side of the illustration), and in the anterior cingulate gyrus (shown on the inferior slices). Brain slices correspond to coronal view (superior panel) an sagittal view (inferior panel). Left side of the brain corresponds to the left side of the picture. The numbers at the right upper corner at each frame represent standard coordinates in the y (coronal view) and x (sagittal view) axis.