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.

Associations Between Daily Affective Instability and Connectomics in Functional Subnetworks in Remitted Patients with Recurrent Major Depressive Disorder

“…In line with this, the FPS has been found to be involved in functions related to cognitive control (Laird et al, 2011). Indeed, two studies that induced irritability by recalling autobiographical experiences found increased prefrontal activation during irritability scripts compared with neutral scripts in HCs (Cerqueira et al, 2010(Cerqueira et al, , 2014. These findings suggest that our result of higher local efficiency in the FPS may act as a compensatory mechanism to control cognitively (fluctuating) feelings of irritation and frustration.…”

Neural correlates of self-perceptions in adolescents with major depressive disorder

“…Previous studies of healthy individuals who were given controlled doses of citalopram, fluvoxamine, as well as other psychotropic medications, showed drug-related variations in neural activation during a variety of fMRI tasks, suggesting that these medication may affect global network function. Additionally, there is evidence that psychotropic medications specifically affect neural recruitment during emotional processing and induce positive mood responses and affect recall of negative emotions ( Cerqueira et al, 2014 ). Therefore, while developmental alterations in the self-referential processing network from adolescence into adulthood is likely, medication effects should also not be ignored when interpreting these differences.…”

The Anti-inflammatory Effect of the Tricyclic Antidepressant Clomipramine and Its High Penetration in the Brain Might Be Useful to Prevent the Psychiatric Consequences of SARS-CoV-2 Infection

“…However, its anticholinergic effects require further investigations, especially in the context of SARS-CoV-2 infection. Clomipramine has already been assessed in healthy volunteers (without psychiatric pathology), and was well tolerated without mood changes (e.g., mania) at the doses used for patients with mood disorders ( Cardoso de Almeida et al, 2010 ; Cerqueira et al, 2014 ).…”