Intersection of autism and mental health in SLC6A4: Genetic and neurobiological balances with SSRIs

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are a class of effective antidepressant drugs that target the serotonin transporter protein and are encoded by the solute carrier family 6 member 4 (SLC6A4) gene. Genetic variations in the SLC6A4 gene, particularly the 5-HTTLPR polymorphism, directly influence the synaptic reuptake of serotonin, thereby significantly shaping individuals' responses to SSRI treatment. Various studies have demonstrated that individuals carrying the long allele exhibit more favorable clinical outcomes compared to those carrying the short allele. Autism spectrum disorder (ASD) is a complex disorder where genetic predispositions play a strong role and affect neurodevelopmental processes. Mutations in the SLC6A4 gene have been reported to be associated with anxiety, which is frequently observed in individuals with ASD. Anxiety accompanying ASD severely impairs individuals' daily living skills and functionality, making this condition a significant mental health problem that needs to be managed. Selective serotonin reuptake inhibitors are pharmacologic agents commonly used and scientifically proven to be effective in managing symptoms such as anxiety and depression in individuals with autism. This review comprehensively addresses the key role of the SLC6A4 gene in serotonin regulation, the effects of genetic variations associated with this gene, and the potential benefits of SSRIs in treating anxiety in individuals with ASD. The findings further highlight the necessity of personalized medicine approaches based on individual genetic profiles in the treatment of comorbid psychiatric conditions in autism.

Cite this article as: Altiok U, Erbaş O. Intersection of autism and mental health in SLC6A4: Genetic and neurobiological balances with SSRIs. D J Med Sci 2025;11(1):35-42. doi: 10.5606/fng.btd.2025.166.