Abstract
The hypothesis for the etiology of schizophrenia involves various neurotransmitters, including 5-HT. Metabolic disorder of 5-HT is an important underlying neurobiochemical cause leading to the development of mental illness. Abnormality in the receptors involved in 5-HT synthesis and metabolism may affect the functioning of 5-HT in the central nervous system. There are seven types of 5-HT receptor families, with a total of 15 corresponding subtypes. HTR1A is the most abundantly expressed 5-HT receptor subtype in the mammalian brain. SNPs in HTR1A enhance or weaken the functioning of 5-HT by affecting HTR1A expression levels or ligand-binding activity, thereby placing HTR1A in an important role in the study of diseases of the nervous system. This study employed DNA sequencing to investigate HTR1A fragment lengths, including complete exons as well as 5′ FR and 3′ FR segments, for a total of 2,718 bp. Seven SNP loci (ss212928868, rs6295, rs6294, ss218178047, rs34118353, rs6449693, and rs878567) were found in 182 healthy volunteers and 161 patients. Among them, two SNP loci had not been reported in the National Center for Biotechnology Information (NCBI) database, promoter locus ss212928868 and exon locus ss218178047, which now have been approved by the NCBI database and assigned rs numbers, rs113195492 and rs112846276, respectively. ss212928868 and rs6294 were statistically different between control and paranoid schizophrenic women (P < 0.05), and both loci were in a state of linkage disequilibrium. However, statistical significance was lost after Bonferroni correction. Compared with the GG genotype, the GA + AA genotype had a decreased disease risk (odds ratioGA + AA = 0.3529, 95 % confidence interval = 0.1319–0.9444). The data showed that changes in SNP loci of HTR1A were different between paranoid schizophrenic and control group women. Although such differences were lost after statistical correction, studies with larger sample sizes have not been conducted. Combined with the newly discovered loci, these findings can point out possible directions for future investigations in different populations.
References
Burnet PW, Eastwood SL, Harrison PJ (1996) 5-HT1A and 5-HT2A receptor mRNAs and binding site densities are differentially altered in schizophrenia. Neuropsychopharmacology 15(5):442–455
David SP, Johnstone EC, Murphy MFG et al (2008) Genetic variation in the serotonin pathway and smoking cessation with nicotine replacement therapy: new data from the Patch in Practice trial and pooled analyses. Drug Alcohol Depend 98:77–85
Geyer MA, Vollenweider FX (2008) Serotonin research: contributions to understanding psychoses. Trends Pharmacol Sci 29(9):445–453
Hashimoto T, Nishino N, Nakai H et al (1991) Increase in serotonin 5-HT1A receptors in prefrontal and temporal cortices of brains from patients with chronic schizophrenia. Life Sci 48(4):355–363
Hashimoto T, Kitamura N, Kajimoto Y et al (1993) Differential changes in serotonin 5-HT1A and 5-HT2 receptor binding in patients with chronic schizophrenia. Psychopharmacology (Berl) 112(1 Suppl):S35–S39
Hong L, Jianxun L (2003) Progress of research on pathogenic genes of schizophrenia. Ment Illn Ment Health 3(3):231–232
Huang YY, Battistuzzi C, Oquendo MA et al (2004) Human 5-HT1A receptor C (−1019) G polymorphism and psychopathology. Int J Neuropsychopharm 7(4):441–451
Kawanishi Y, Harada S, Tachikawa H et al (1998) Novel mutations in the promoter and coding region of the human 5-HT1A receptor gene and association analysis in schizophrenia. Am J Med Genet (Neuropsychiatr Genet) 81(5):434–439
Kishi T, Tsunoka T, Ikeda M et al (2010a) Serotonin 1A receptor gene is associated with Japanese methamphetamine-induced psychosis patients. Neuropharma 58(2):452–456
Kishi T, Tsunoka T, Ikeda M et al (2010b) Serotonin 1A receptor gene is associated with Japanese methamphetamine-induced psychosis patients. Neuropharm 58(2):452–456
Lemonde S, Turecki G, Bakish D et al (2003) Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci 23(25):8788–8799
McGuffine ME, Chandler D, Somaiya D et al (1998) Autoregulation of transformer-2 alternative splicing is necessary for normal male fertility in Drosophila. Genet 149(3):1477–1486
Mclarren KW, Theriault FM, Stifani S (2001) Association with the nuclear matrix and interaction with Groucho and RUNX proteins regulate the transcription repression activity of the basic helix loop helix factor Hes1. J Biol Chem 276(2):1578–1584
Meltzer HY, Li Z, Kaneda Y et al (2003) Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry 27(7):1159–1172
Ou XM, Lemonde S, Jafar-Nejad H et al (2003) Freud-1: a neural calcium-regulated repressor of the 5-HT1A receptor gene. J Neurosic 23(19):7415–7425
Savitz J, Lucki I, Drevets WC et al (2009) 5-HT1A receptor function in major depressive disorder. Prog Neurobiol 88(1):17–31
Shaolin G (2003) Depression. People’s Medical Publishing House, Beijing, pp 45–46
Strobel A, Gutknecht L, Rothe C et al (2003) Allelic variation in 5-HT1A receptor expression is associated with anxiety- and depression-related personality traits. J Neural Transm 110(2):1445–1463
Sullivan PF, Kendler KS, Neale MC et al (2003) Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiat 60(12):1187–1192
Sumiyoshi T, Stockmeier CA, Overholser JC et al (1996) Serotonin1A receptors are increased in postmortem prefrontal cortex in schizophrenia. Brain Res 708(1–2):209–214
Szewczyk B, Albert PR, Burns AM et al (2009) Gender-specific decrease in NUDR and 5-HT1A receptor proteins in the prefrontal cortex of subjects with major depressive disorder. Int J Neuropsychopharm 12(2):155–168
World Health Organization (2001) WHO health report 2001—mental health: new understanding, new hope. World Health Organization 33–34
Wu Y, Xu Y, Sun Y et al (2008) Association between the serotonin 1A receptor C (−1019) G polymorphism and major depressive disorder in the northern Han ethnic group in China. Chin Med J 121(10):874–876
Yu S (2002) Psychiatry. Beijing People’s Medical Publishing House, Beijing, pp 393–412
Yu WY, Tsai SJ, Hong CJ et al (2006) Association study of two serotonin 1A receptor gene polymorphisms and fluoxetine treatment response in Chinese major depressive disorders. Eur Neuropsychopharm 16(7):498–503
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Special thanks to the Third People’s Hospital of Liaoning Province for providing blood samples from paranoid schizophrenic patients for this experiment.
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Zhou, X., Ding, M., Ding, C. et al. Relationship Between Genetic Polymorphisms in the HTR1A Gene and Paranoid Schizophrenia in a Northern Han Chinese Population. J Mol Neurosci 49, 625–631 (2013). https://doi.org/10.1007/s12031-012-9928-9
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DOI: https://doi.org/10.1007/s12031-012-9928-9