Effect of Serotonin-Related Gene Polymorphisms on Pathogenesis and Treatment Response in Korean Schizophrenic Patients

Abstract

Serotonin has been implicated in the pathophysiology of several psychiatric disorders including schizophrenia. Serotonergic system-related genes may be good candidates in investigating the genetic basis of schizophrenia. We aimed to investigate the associations of HTR1A C-1019G, HTR2A-1438A/G, TPH1 218A/C, and TPH2-703G/T variants with schizophrenia. A total of 202 patients with schizophrenia and 165 normal controls were genotyped for HTR1A C-1019G, HTR2A-1438A/G, TPH1 218A/C, and TPH2-703G/T single nucleotide polymorphisms (SNPs). In order to assess the severity of a patient's psychiatric symptoms, the brief psychiatric rating scale (BPRS), the positive and negative symptom scale (PANSS), and the Calgary depression scale for Schizophrenia (CDSS) were administered. Genotype and allele frequencies were compared between groups via χ(2) statistics. Associations between the genotypes of candidate SNPs with the severity of symptoms were examined with ANOVA by comparing the mean scores of BPRS, PANSS, and CDSS according to genotype. No significant differences in the genotype distributions and allele frequencies of four SNPs were found between patients with schizophrenia and normal controls. There was a trend towards association of HTR1A C-1019G polymorphism with negative symptom. Negative symptom score of PANSS was lower in the patients with CC genotype than in the G allele carriers. These results suggested that C allele might be associated with lesser negative symptom. More studies are needed to confirm these findings. In the future, we plan to study the associations between schizophrenia and other genetic polymorphisms.

TPH2 gene polymorphisms in the regulatory region are associated with paranoid schizophrenia in Northern Han Chinese

“…Prior to our study, no studies had reported an association between genetic variations in the TPH2 gene and schizophrenia (De Luca et al, 2005a;Higashi et al, 2007;Shiroiwa et al, 2010;Tee et al, 2010, Kim andYoon, 2011;Zhang et al, 2011). There are several possible explanations for our novel results.…”

“…In contrast to TPH1, genetic studies have shown an association between TPH2 and suicidal behavior (Zill et al, 2004b;Li and He, 2006a), major depression (Zill et al, 2004c), panic disorder (Maron et al, 2007), chronic fatigue syndrome (Goertzelet et al, 2006;Smith et al, 2006) and Tourette syndrome (Mössner et al, 2007). However, no evidence has been found for a role of TPH2 in schizophrenia, despite several studies in this area (De Luca et al, 2005a;Higashi et al, 2007;Shiroiwa et al, 2010;Tee et al, 2010;Kim and Yoon, 2011;Zhang et al, 2011). It is noteworthy that a certain number of these studies focused mainly on the rs4570625 (-703G/T), a common polymorphic SNP in the putative promoter (Kennedy et al, 2003) that has been reported to be associated with the attention deficit hyperactivity disorder (ADHD) (Walitza et al, 2005), emotional processing (Herrmann et al, 2007), personality traits, and disorders related to emotional dysregulation (Gutknecht et al, 2007;Reuter et al, 2007).…”

Evaluation of association of common variants in HTR1A and HTR5A with schizophrenia and executive function

“…So far, some studies have investigated the association of HTR1A gene with SCZ in different populations including American, Korean, Japanese and Han Chinese populations2829303132333435, and the significant association was found in American29, Japanese33 and Han Chinese populations3435. Thus, the association of HTR1A gene with SCZ is not specific to a certain ethnic group.…”

“…HTR1A is the most abundantly expressed 5-HT receptor subtype in the mammalian brain, and HTR5A is expressed in the central nervous system, a significant portion of cortical pyramidal neurons2627. Previous studies have investigated the association between only a few HTR1A variants and SCZ, but they have produced conflicting results2829303132333435. So far, HTR5A has been studied less than other HTRs .…”

Serotonin-Related Polymorphisms in TPH1 and HTR5A Genes Are Not Associated with Escitalopram Treatment Response in Korean Patients with Major Depression

“…However, several other candidate genes may influence the antidepressant treatment response [37]. For example, the TPH2 gene may have an important effect on susceptibility to suicidal behavior in MDD patients [41] and on the therapeutic response to antidepressants [36]. The correlation between functional polymorphisms associated with serotonergic neurotransmission and antidepressant treatment response has been widely studied [42,43,44].…”