Human HTR1A blocking peptide

Estrogen and serotonin play vital roles in the mechanism of premenstrual dysphoric disorder (PMDD). Cognitive deficit in the premenstrual phase contributes to impaired life function among women with PMDD. The aim of this study was to evaluate the difficulties in cognitive control and working memory (WM) in PMDD and to explore the effects of gonadotropic hormone and polymorphism of serotonin 1A receptor (HTR1A; rs6295) on cognitive deficit in PMDD. Women with PMDD completed diagnostic interviewing, questionnaire assessment, the Go/Nogo task, 2-back and 3-back tasks, and gonadotropic hormone analysis in the premenstrual and follicular phases. Further, they were followed up for two menstrual cycles to confirm two consecutive symptomatic cycles. A total of 59 subjects with PMDD and 74 controls completed all evaluation, fulfilled the criteria, and entered into the final analysis. The results demonstrated cognitive control and WM decline in the premenstrual among women with PMDD. The G/G genotype of HTR1A (rs6295) was found to be associated with impaired WM in the premenstrual phase and premenstrual decline of cognitive function. It also contributed to the vulnerability of cognitive function to the menstrual cycle effect and PMDD effect. As the G/G genotype of HTR1A (rs6295) involves in reducing serotonin neurotransmission, our results provide insight into the serotonin mechanism of cognitive function among women with PMDD.

Serotonergic system-related genes are likely to be involved in mechanisms underlying attention deficit hyperactivity disorder (ADHD). We investigated the association of serotonin the 1A receptor C-1019G single nucleotide polymorphism (HTR1A C-1019G SNP) and tryptophan hydroxylase 2 gene -703GIT (TPH2 - 703G/T) SNP with ADHD. All of the ADHD subjects completed a comprehensive and standardized diagnostic and psychological evaluation battery including the parents' Korean version of the ADHD Rating Scale-IV (ARS). The genotype and allele frequencies of 78 ADHD patients and 107 normal controls were analyzed for 5-HTR1A C-1019G and TPH2 -703G/T. There were statistically significant differences in the genotype distributions and allele frequencies of FITR1A C-1019G between the ADHD group and the control group. The homozygous allele C frequency was significantly higher in ADHD patients than in controls. However, no differences in either genotype distribution or in allele frequencies of TPH2 -703G1T were observed between the ADHD patients and the controls. In the ADHD patients, ANCOVA revealed that there were no significant differences in the subscales and total score between the ADHD probands with the CC genotype and those with the CG and GG genotypes in ARS and the Continuous Performance Test (CPT) when adjusting for age and gender. The odds ratio comparing the CC genotype group with the CG genotype group and the C allele with G was 2.12 and 1.79 respectively. Therefore, genotype CC was associated with higher risk of ADHD. Our results suggest that the H1'R1A C-1019G SNP may affect susceptibility to ADHD. Further investigation with a larger number of subjects is needed in order to confirm this finding. (C) 2010 Elsevier Inc. All rights reserved.