Chronic SSRI treatment induces both acute and persistent alterations in neurosteroid gene expression in NAc of female subjects

TLDR: A new study from Melcangi demonstrated that in female rats, neurosteroid genes are significantly altered during and after SSRI treatment.

What's interesting about the area the researchers measured was that this specific brain region (the NAc) is the brain's primary reward hub. It is responsible for mediating pleasurable sensations, sexual function, and motivation; anything reward oriented.

The paper noted that the following genes were significantly lowered compared to controls 1 month after withdrawal:

3α-HSD (3α-HSOR) (enzyme that turns 5α-DHP into Allopregnanolone)

3β-HSD (enzyme that turns pregnenolone into progesterone)

StAR (transport protein that helps convert cholesterol into pregnenolone)

TSPO (transport protein that also helps convert cholesterol into pregnenolone)

Each of these are genes are steps involved in the synthesis of neurosteroids. It's one entire pathway and researchers continue to find evidence that SSRIs disrupt the natural production of these neurosteroids.

While this is just in females, this study has also been conducted in male mice as well:

"together with our previous observations obtained in males, clearly indicate that SSRIs withdrawal may disrupt neurosteroidogenesis in the two sexes"

Paroxetine-Induced Alterations in Neurosteroidogenic Gene Expression in the Female Nucleus Accumbens: Insights into Post-SSRI Sexual Dysfunction