Htr1a, also known as 5-hydroxytryptamine receptor 1A, is a key receptor in the serotonin system. It functions as a presynaptic autoreceptor on raphe neurons and a postsynaptic receptor in regions like the hippocampus, cortex, and hypothalamus, regulating mood, emotion, and stress response. The serotonin system it belongs to is crucial for normal neural function [6].

Genetic polymorphisms of Htr1a have been widely studied. The rs6295 polymorphism of Htr1a may increase the risk for suicidal behavior according to one meta-analysis, specifically in the recessive model (OR = 2.21, 95% CI = 1.80-2.71, P < 0.001) when comparing suicidal behavior (SB) cases to healthy controls [1]. In schizophrenia, the rs6295 polymorphism may impact the improvement of negative symptoms during antipsychotic drug treatment, with C allele carriers showing greater improvement than G allele carriers (P = 0.04, standardized mean difference =-0.14, 95％CI = 0.01 to 0.28) [2]. Htr1a has also been associated with attention-deficit/hyperactive disorder (ADHD), though the exact role is yet to be fully elucidated [3]. In triple-negative breast cancer, Htr1a inhibits cancer progression via TGF-β canonical and noncanonical pathways [4]. Additionally, Htr1a methylation, along with its interaction with stress/genotype, is associated with antidepressant efficacy, and its methylation status may predict treatment response in major depressive disorder (MDD) patients [5,7].

In conclusion, Htr1a is essential for the regulation of the serotonin system, influencing mood, emotion, and stress-related responses. Studies on Htr1a, especially those focusing on its genetic polymorphisms, have revealed its potential roles in various mental health conditions such as suicidal behavior, schizophrenia, and MDD, as well as in diseases like triple-negative breast cancer and ADHD. Understanding Htr1a can provide valuable insights into the pathogenesis of these diseases and potentially lead to new treatment strategies.

References:

1. Hernández-Díaz, Yazmin, Tovilla-Zárate, Carlos Alfonso, Castillo-Avila, Rosa Giannina, Villar-Juárez, Guillermo Efrén, González-Castro, Thelma Beatriz. 2022. Association between the HTR1A rs6295 gene polymorphism and suicidal behavior: an updated meta-analysis. In European archives of psychiatry and clinical neuroscience, 273, 5-14. doi:10.1007/s00406-022-01500-x. https://pubmed.ncbi.nlm.nih.gov/36214900/

2. Takekita, Yoshiteru, Fabbri, Chiara, Kato, Masaki, Kinoshita, Toshihiko, Serretti, Alessandro. 2016. HTR1A Polymorphisms and Clinical Efficacy of Antipsychotic Drug Treatment in Schizophrenia: A Meta-Analysis. In The international journal of neuropsychopharmacology, 19, . doi:10.1093/ijnp/pyv125. https://pubmed.ncbi.nlm.nih.gov/26568455/

3. Kessi, Miriam, Duan, Haolin, Xiong, Juan, Peng, Jing, Yin, Fei. 2022. Attention-deficit/hyperactive disorder updates. In Frontiers in molecular neuroscience, 15, 925049. doi:10.3389/fnmol.2022.925049. https://pubmed.ncbi.nlm.nih.gov/36211978/

4. Liu, Qiqi, Sun, Hefen, Liu, Yang, Li, Liangdong, Jin, Wei. 2022. HTR1A Inhibits the Progression of Triple-Negative Breast Cancer via TGF-β Canonical and Noncanonical Pathways. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 9, e2105672. doi:10.1002/advs.202105672. https://pubmed.ncbi.nlm.nih.gov/35199941/

5. Xu, Zhi, Chen, Zimu, Shen, Tian, Yuan, Yonggui, Zhang, Zhijun. 2021. The impact of HTR1A and HTR1B methylation combined with stress/genotype on early antidepressant efficacy. In Psychiatry and clinical neurosciences, 76, 51-57. doi:10.1111/pcn.13314. https://pubmed.ncbi.nlm.nih.gov/34773671/

6. Le François, Brice, Czesak, Margaret, Steubl, Dominik, Albert, Paul R. 2008. Transcriptional regulation at a HTR1A polymorphism associated with mental illness. In Neuropharmacology, 55, 977-85. doi:10.1016/j.neuropharm.2008.06.046. https://pubmed.ncbi.nlm.nih.gov/18639564/

7. Wang, Peipei, Lv, Qinyu, Mao, Yemeng, Cai, Weimin, Fang, Yiru. 2017. HTR1A/1B DNA methylation may predict escitalopram treatment response in depressed Chinese Han patients. In Journal of affective disorders, 228, 222-228. doi:10.1016/j.jad.2017.12.010. https://pubmed.ncbi.nlm.nih.gov/29275155/