Abstract
Introduction:
Background: Major depressive disorder is one of the most diagnosed diseases especially in Western countries. While more and more antidepressant drugs are prescribed, the mechanisms how those drugs work on neural basis and how specific side-effects like sexual dysfunction may occur, still remain poorly understood.
Aim: The aim of our study was to look for alterations in restingstate fMRI, before and during antidepressant treatment, which could explain if not predict sexual side-effects. We therefore chose two common antidepressants with different side-effect spectra: Paroxetine, a selective serotonine reuptake inhibitor, often blamed of causing sexual dysfunction, and Bupropion as a dopamine-norepinephrine reuptake inhibitor, rarely decreasing if not increasing sexual performance. Both drugs were investigated in healthy subjects in a randomized, double-blind, placebo-controlled clinical trial to account for intra-subject effects under all three conditions identifying possible targets of treatment response.
Methods:
18 healthy volunteers were included in a randomized trial taking either Bupropion (BUP), Paroxetine (PAR) or Placebo (PLAC) for one week, with a two-week wash-out phase between trials. They completed an fMRI-trial including a 10min eyes-closed restingstate scan in a 3Tesla scanner. Drug-intake was controlled by plasma-levels. Restingstate analysis was performed using DPARSF (Chao-Gan and Yu-Feng, 2010). Functional connectivity (FC) was analyzed for the sublenticular extended amygdala (SLEA), previously found to predict sexual dysfunction under PAR (Metzger et al. 2013). Sexual dysfunction was assessed by self-report with the 5-item Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ) after each pharmacological trial.
Results:
Effects of interest for PLAC, BUP and PAR on SLEA-seeded connectivity were found bilaterally in pgACC, pMCC, lateral temporal cortex (p<0.005, corr.). While connectivity with pgACC showed effects of same directionality for both BUP and PAR, differential effects were found in pMCC with an increase in connectivity with SLEA under PAR and in the lateral temporal cortex with an increase in connectivity under BUP compared to PLAC (p<0.005, corr.).
A positive correlation was observed between the change in sexual functioning from PLAC to PAR with functional connectivity between SLEA and midbrain, pgACC and nucleus accumbens while connectivity with LOC was negatively correlated (all p<0.05).
Conclusions:
According to previous findings of SLEA-seeded connectivity predicting sexual side-effects, we could show, that changes in SLEA-seeded connectivity changed along with sexual functional and were moreover differentially effected by PAR and BUP.
