Healthy individuals treated with clomipramine: an fMRI study of brain activity during autobiographical recall of emotions

Abstract

Various functional magnetic resonance imaging studies addressed the effects of antidepressant drugs on brain functioning in healthy subjects; however, none specifically investigated positive mood changes to antidepressant drug. Sixteen subjects with no personal or family history of psychiatric disorders were selected from an ongoing 4-week open trial of small doses of clomipramine. Follow-up interviews documented clear positive treatment effects in six subjects, with reduced irritability and tension in social interactions, improved decision making, higher self-confidence and brighter mood. These subjects were then included in a placebo-controlled confirmatory trial and were scanned immediately after 4 weeks of clomipramine use and again 4 weeks after the last dose of clomipramine. The functional magnetic resonance imaging (fMRI) scans were run during emotion-eliciting stimuli. Repeated-measures analysis of variance of brain activity patterns showed significant interactions between group and treatment status during induced irritability (P<0.005 cluster-based) but not during happiness. Individuals displaying a positive subjective response do clomipramine had higher frontoparietal cortex activity during irritability than during happiness and neutral emotion, and higher temporo-parieto-occipital cortex activity during irritability than during happiness. We conclude that antidepressants not only induce positive mood responses but also act upon autobiographical recall of negative emotions.

Figure 1

Timelines for each arm of the clomipramine drug trial, group allocation and sequencing of the two functional magnetic resonance imaging (fMRI) scanning sessions for the two groups (responders and non-responders to clomipramine).

Figure 2

The areas highlighted in yellow and red represent blood oxygen level-dependent signal interaction of medication and group effects for the difference of irritability and happiness emotional states, located in the left temporo–parieto–occipital cortex (coronal view, on the left) and in the left frontoparietal cortex (axial view, on the right), and their respective Talairach–Tournoux Atlas coordinates (radiological convention).