Poststroke emotional disturbances and a tryptophan hydroxylase 2 gene polymorphism.

Mihye Ko,Hyun-Wook Nah,Hasup Song,Sang-Eun Jun,Smi Choi-Kwon,Jong S Kim,Ju Han Kim,Kyung-Hee Cho

doi:10.1002/brb3.892

Abstract

ObjectivesEmotional dysfunction is a common finding in stroke patients. Despite reports on serotonergic involvement in the etiology of poststroke emotional dysfunction (PSED), the role of serotonin synthesizing tryptophan hydroxylase 2 (TPH2) genes in the development of PSED remains unclear.MethodsGenotyping of TPH2 rs4641528 and rs10879355 was performed from genomic DNA of 383 stroke patients collected previously and stored at −70°C. Potential associations between TPH2 genes and poststroke depression (PSD), poststroke emotional incontinence (PSEI), and poststroke anger proneness (PSAP) were investigated 3 months poststroke.ResultsAmong the 383 patients, 69 (18%) had PSD, 41 (11%) had PSEI, and 93 (24%) had PSAP. The TPH2 rs4641528 genotype frequencies differed significantly between patients with and without either PSD or PSEI, although no significant differences were found between the patients with and without PSAP. In multiple logistic regression analysis, PSD was related to the National Institutes of Health Stroke Scale (NIHSS) score at admission (95% confidence interval [CI]: 1.047–1.230, p < .01), modified Rankin scale score at 3 months (95% CI: 0.135–0.848, p < .05), and TPH2 rs4641528 C allele (95% CI: 1.039–5.631, p < .05), whereas PSEI was associated only with the NIHSS score at admission (95% CI: 1.053–1.259, p < .01) and the TPH2 rs4641528 C allele (95% CI: 1.029–11.678, p < .05).ConclusionsOur findings suggest that the TPH2 rs4641528 C allele may play a role in the pathogenesis of PSD and PSEI but not PSAP in Korean stroke patients.

Highlights

Emotional dysfunction, which includes depression, emotional incontinence, and anger proneness, is commonly observed in stroke patients (Kim & Choi-Kwon, 2000; Kim, Choi, Kwon, & Seo, 2002; Choi-K won et al, 2012; Hackett, Yang, Anderson, Horrocks, & House, 2010)
We investigated for the first time the association between the tryptophan hydroxylase 2 (TPH2) SNPs and poststroke emotional dysfunction (PSED), including poststroke depression (PSD), poststroke emotional incontinence (PSEI), and poststroke anger proneness (PSAP)
We found that carrying the C allele of rs4641528 in the TPH2 gene was associated with PSD and PSEI 3 months poststroke

Summary

| INTRODUCTION

Emotional dysfunction, which includes depression, emotional incontinence, and anger proneness, is commonly observed in stroke patients (Kim & Choi-Kwon, 2000; Kim, Choi, Kwon, & Seo, 2002; Choi-K won et al, 2012; Hackett, Yang, Anderson, Horrocks, & House, 2010). In a recent meta-analysis, homozygous short variation in the serotonin transporter-linked polymorphic region (5-HTTLPR) was found to be a risk factor for PSED (Mak, Kong, Mak, Sharma, & Ho, 2013). We postulated that the tryptophan hydroxylase 2 (TPH2) genes responsible for serotonin synthesis may be associated with PSED. The aim of this study, was to investigate whether TPH2 gene polymorphisms were associated with PSED. This is a secondary data analysis from a parent study (Choi-K won et al, 2012; Choi‐Kwon et al, 2013). The design and methods of the study were published previously (Choi-Kwon et al, 2012) and are briefly summarized here

| Procedures

Findings

| DISCUSSION