BACKGROUND: Polymorphisms of the gene encoding the serotonin transporter-specifically, length variation in the serotonin--transporter-linked polymorphic region (5-HTTLPR), a single-nucleotide polymorphism in the 5-HTTLPR (rs25531), and variable number of tandem repeats (VNTR) in the second intron 2 (STin2)--have been implicated in the development of post-stroke depression (PSD).<br /><br />OBJECTIVE: To evaluate the association between polymorphisms of the serotonin transporter gene and PSD in the medical literature.<br /><br />METHODS: Random-effects meta-analyses were conducted on cross-sectional, case-control and cohort studies examining relations between polymorphisms of the gene encoding the serotonin transporter and the risk of developing PSD.<br /><br />RESULTS: Four studies comprising 260 stroke patients with PSD and 381 without were included. Our analyses showed a significant and positive association between the homozygous short variation (S) allele genotype of the 5-HTTLPR (SS) and PSD (random-effects pooled OR 2.05, 95% CI 1.41 to 2.98, z=3.79, p<0.001). Our analyses also showed a significant and negative association between the homozygous long variation (L) allele genotype of the 5-HTTLPR (LL) and PSD (random-effects OR 0.52, 95% CI 0.27 to 0.97, z=-2.07, p=0.039). No statistically significant association of PSD with heterozygous S and L allele genotype for 5-HTTLPR or other polymorphisms with rs25531 and STin2 VNTR was found. Heterogeneity and publication bias were not statistically significant. The major limitation of this meta-analysis is that we could not assess the interaction between stroke, environmental stress and PSD.<br /><br />CONCLUSIONS: The 5-HTTLPR SS genotype may be a risk factor for PSD. The 5-HTTLPR LL genotype showed a significant negative association with PSD. Further research to assess the sensitivity and specificity of predicting the risk of developing PSD by screening for the 5-HTTLPR genotype in stroke patients is required.
Mak, K. K., Kong, W. Y., Mak, A., Sharma, V. K., & Ho, R. C. M. (2013). Polymorphisms of the serotonin transporter gene and post-stroke depression: A meta-analysis. Journal of Neurology, Neurosurgery and Psychiatry, 84(3), 322–328. https://doi.org/10.1136/jnnp-2012-303791