The serotonin transporter and the activity regulated cytoskeleton-associated protein genes in antidepressant response and resistance: 5-HTTLPR and other variants

Objective: Previous evidence suggested the involvement of serotonin transporter (SLC6A4) and activity regulated cytoskeleton-associated protein (ARC) in antidepressant action. This study investigated their role in antidepressant efficacy and treatment-resistant depression (TRD). Methods: Three samples (n total = 648) were investigated to test the association between treatment outcomes (response, remission, symptom improvement, and TRD) and 11 polymorphisms within SLC6A4 and ARC genes. The possible modulating effect of age and gender was considered. Response and remission were also investigated using a fixed-effects meta-analysis of the three samples. Results: SLC6A4 5-HTTLPR/rs25531 effects on symptom improvement were modulated by age (better improvement in L/LA carriers in older subjects) and gender (better improvement in L/LA female carriers). SLC6A4 STin2 long alleles were associated with remission and lower risk of TRD. Preliminary evidence of association between ARC rs11167152/rs10110456 and different outcomes was found. Conclusions: 5-HTTLPR/rs25531 effect on antidepressant efficacy was modulated by age, in line with previous literature data. STin2 effect on antidepressant efficacy was in line with previous meta-analyses. A new possible effect of ARC variants on antidepressant efficacy was observed; however, further studies in larger samples are needed to confirm their role.