Serotonin Transporter Gene 5-HTTLPR Polymorphism as a Protective Factor Against the Progression of Post-Stroke Depression

Abstract

Polymorphisms in the 5-HTT and BDNF genes are shown to affect their function at the molecular and serum level. Prior work has tried to correlate the polymorphisms with post-stroke depression (PSD), the results nevertheless remain indefinitive. A plausible reason accounting for the uncertainty relates to the small sample of each published trial. In this study, we have performed a comprehensive meta-analysis in order to evaluate the effects of 5-HTT and BDNF polymorphisms (5-HTTLPR, STin2 VNTR, 5-HTR2a 102 T/C, Val66Met) on genetic risk of PSD. Human case-control trials were identified by computer-assisted and manual searches. The article search was performed until October 2014. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed effects meta-analysis to measure the effects 5-HTT and BDNF polymorphisms exerted on PSD. We also performed test of heterogeneity, test of publication bias, and sensitivity analysis to examine the reliability and stability of combined effects. 5-HTTLPR was clearly associated with genetic risk of PSD. The association seemed to be more pronounced in the homozygous model (OR = 0.34, 95% CI = 0.23-0.51, P(Q-test) = 0.63). Both the heterozygous model and the recessive model showed 50% decreased risk of PSD (OR = 0.50, 95% CI = 0.37-0.67, P(Q-test) = 0.91; OR = 0.50, 95% CI = 0.36-0.70, P(Q-test) = 0.43, respectively). Such significant association was also detected for Caucasian and Asian. These results were reliable and stable based on related analyses. Taken together, 5-HTTLPR polymorphism of the 5-HTT gene seems to protect against the occurrence of PSD. Small sample size for the polymorphisms within 5-HTT and BDNF genes may have caused underestimated associations, and a larger study is required to further assess the relations.

Post Stroke Depression

“…The elevation of IL-6 in patients that have strokes could possibly predict the development of poststroke depression [23,24]. In another meta-analysis, brain-derived neurotrophic factor (BDNF) was found to be involved in the development of depression and poststroke depression [25,26]. In these studies, a low serum level of BDNF in the acute phase after a stroke was associated with the development of poststroke depression.…”

“…BDNF is inherently involved in hippocampal plasticity and memory [27]. One study found a significant negative relationship between BDNF and NIHSS [25][26][27]. In rodent models, low levels of BDNF in the hippocampus that had an acute stroke exhibited depressed behavior, however if BDNF was overexpressed there was a marked decrease in depressed behavior [21].…”

“…There have also been studies that have shown a genetic contribution to poststroke depression. Multiple studies have evaluated the 5-HT gene located on New Insight into Cerebrovascular Diseases -An Updated Comprehensive Review 6 chromosome 17q11.1-17q12, which encodes the serotonin transporter [25][26][27]. In a meta-analysis of 7 studies, there was a significant relationship between 5-HTTLPR polymorphism and the development of poststroke depression symptoms.…”

“…In a meta-analysis of 7 studies, there was a significant relationship between 5-HTTLPR polymorphism and the development of poststroke depression symptoms. 5-HTTLPR is an exon of the 5-HT transporter gene polymorphism [25,26]. The hypothesis is that this gene polymorphism responds to the increased activity of the amygdala when responding to negative stimuli.…”

“…The hypothesis is that this gene polymorphism responds to the increased activity of the amygdala when responding to negative stimuli. An increase in 5-HTTLPR serum level has been positively associated with threefold increased risk of developing poststroke depression [25][26][27][28]. Another 5-HT polymorphism that has been analyzed is the STin2 VNTR, which is located within intron 2.…”