SLC6A4 and major depressive disorder: Along these lines, while SSRIs function pharmacologically to perturb 5-HT signaling in brain via inhibition of the 5-HT transporter (SLC6A4/SERT)—a phenomenon that contributed to the development of the ‘monoamine hypothesis of depression’14—it remains unclear whether serotonergic dysfunction itself promotes MDD-related pathologies, or how therapeutics might work mechanistically to promote symptomatic alleviation in MDD individuals.