SSRI-Related Modulation of Sexual Functioning is Predicted by Pre-treatment Resting State Functional Connectivity in Healthy Men

Abstract

Sexual dysfunction related to treatment with selective serotonin reuptake inhibitors (SSRIs) is a common reason for discontinuation of otherwise effective antidepressant treatment regimens. Thus, identification of subjects at risk for this side effect remains a crucial challenge. After demonstrating task-related neural correlates of impaired sexual functioning under treatment with the SSRI paroxetine (Abler et al., 2011), we studied (1) if resting state brain function before treatment predicts subsequent development of treatment-related modulation of sexual function, and (2) which neural circuits relate to different aspects of the impairment. Effects of paroxetine and bupropion administration over 1week on subjective sexual functioning were investigated in 17 healthy male volunteers in a placebo-controlled, randomized cross-over design using the Massachusetts General Hospital Sexual Function Questionnaire. Data from a 10min eyes-closed resting state scan were used to analyze functional connectivity under placebo in previously identified brain regions, focussing on the sublenticular extended amygdala (SLEA), dopaminergic midbrain, and anterior cingulate cortex. Resting state functional connectivities of the pregenual anterior cingulate cortex (pgACC), midbrain, and insula to the SLEA sufficiently predicted the development of subjective SSRI-related decreased sexual functioning and distinguished vulnerable from resilient subjects. Furthermore, connectivity with the midbrain particularly predicted orgasm-related deficits, while connectivity with pgACC predicted sexual satisfaction. Linking SSRI-related subjective sexual functioning to pre-treatment resting state connectivities in cortico-subcortical network of sexual processing, we demonstrated the potential of novel, non-invasive and passive brain imaging techniques to guide therapeutic decisions and adjust treatment protocols in psychiatric disorders and sexual medicine.