Huang Yung-Yu, Battistuzzi Cristina, Oquendo Maria A, Harkavy-Friedman Jill, Greenhill Laurence, Zalsman Gil, Brodsky Beth, Arango Victoria, Brent David A, Mann J John
Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032, USA.
Int J Neuropsychopharmacol. 2004 Dec;7(4):441-51. doi: 10.1017/S1461145704004663. Epub 2004 Oct 7.
Dysfunction of the serotonin (5-HT1A) receptor (5-HTR1A) has been implicated in mood disorders, anxiety disorders, psychosis and the action of antidepressants. A common C(-1018)G [C(-1019)G] functional polymorphism in the promoter region of the human 5-HT1A receptor gene has been reported, which may be useful in identifying psychopathology associated with altered function of the human 5-HT1A receptor. We studied the relationship of this polymorphism to psychopathology and 5-HT1A binding in prefrontal cortex. The 5-HT1A receptor genotype for the C(-1019)G polymorphism was typed in 696 unrelated psychiatric subjects, 107 unrelated healthy volunteers, and in post-mortem brain samples from 241 cases. 5-HT1A receptor binding was assayed in post-mortem prefrontal cortex using [3H]8-OH-DPAT, and specific binding determined by 1 microM 5-HT. An association of genotype distribution and allele frequency of the 5-HTR1A C(-1019)G locus was observed in schizophrenia (chi2=9.51, d.f.=2, p=0.009; chi2=9.52, d.f.=1, p=0.002; Armitage's trend test: chi2=9.07, d.f.=1, p=0.003), in substance use disorder (chi2=8.41, d.f.=2, p=0.015; chi2=8.35, d.f.=1, p=0.004; Armitage's trend test: chi2=6.27, d.f.=1, p=0.0012), and in panic attack (chi2=6.31, d.f.=2, p=0.043; chi2=6.14, d.f.=1, p=0.013; Armitage's trend test: chi2=6.27, d.f.=1, p=0.012). An association of the 5-HTR1A C(-1019)G locus with schizophrenia, substance use disorder, and panic attack was suggested by our results. In post-mortem brain samples, 5-HT1A receptor binding in prefrontal cortex and suicide were not associated with genotype. The relationship does not appear to be explained by binding differences, although we cannot rule out altered receptor affinity and transduction.
血清素（5-HT1A）受体（5-HTR1A）功能失调与情绪障碍、焦虑症、精神病及抗抑郁药的作用有关。据报道，人类5-HT1A受体基因启动子区域存在常见的C（-1018）G [C（-1019）G]功能多态性，这可能有助于识别与人类5-HT1A受体功能改变相关的精神病理学。我们研究了这种多态性与精神病理学及前额叶皮质中5-HT1A结合的关系。对696名无亲缘关系的精神科受试者、107名无亲缘关系的健康志愿者以及241例尸检脑样本进行了C（-1019）G多态性的5-HT1A受体基因分型。使用[3H]8-OH-DPAT在尸检前额叶皮质中检测5-HT1A受体结合，并通过1 microM 5-HT确定特异性结合。在精神分裂症（χ2=9.51，自由度=2，p=0.009；χ2=9.52，自由度=1，p=0.002；阿米蒂奇趋势检验：χ2=9.07，自由度=1，p=0.003）、物质使用障碍（χ2=8.41，自由度=2，p=0.015；χ2=8.35，自由度=1，p=0.004；阿米蒂奇趋势检验：χ2=6.27，自由度=1，p=0.0012）和惊恐发作（χ2=6.31，自由度=2，p=0.043；χ2=6.14，自由度=1，p=0.013；阿米蒂奇趋势检验：χ2=6.27，自由度=1，p=0.012）中观察到5-HTR1A C（-1019）G位点的基因型分布和等位基因频率存在关联。我们的结果提示5-HTR1A C（-1019）G位点与精神分裂症、物质使用障碍和惊恐发作有关。在尸检脑样本中，前额叶皮质中的5-HT1A受体结合与自杀和基因型无关。尽管我们不能排除受体亲和力和转导改变的可能性，但这种关系似乎无法用结合差异来解释。
