Patriquin Michelle A, Hamon Sara C, Harding Mark J, Nielsen Ellen M, Newton Thomas F, De La Garza Richard, Nielsen David A
aThe Menninger Clinic bThe Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine cMichael E. DeBakey Veterans Affairs Medical Center; Houston, Texas dStatistical and Genetic Consulting LLC, Daren, Connecticut, USA.
Psychiatr Genet. 2017 Oct;27(5):178-186. doi: 10.1097/YPG.0000000000000178.
This study investigated variants of tryptophan hydroxylase (TPH)1, TPH2, and SLC6A4 in the moderation of the subjective effects of cocaine.
Non-treatment-seeking cocaine-dependent individuals (N=66) were intravenously administered saline and cocaine (40 mg) in a randomized order. Participants self-reported subjective effects of cocaine using a visual analog scale starting before administration of saline or cocaine (-15 min) to up to 20 min after infusion. Self-report ratings on the visual analog scale ranged from 0 (no effect) to 100 (greatest effect). Participants were genotyped for the TPH1 rs1799913, TPH2 rs4290270, and SLC6A4 5-HTTLPR variants. Repeated-measures analysis of covariance was used to examine changes in subjective effect scores over time while controlling for population structure.
Participants carrying the TPH1 rs1799913 A allele reported greater subjective response to cocaine for 'stimulated' and 'access' relative to the CC genotype group. Those carrying the TPH2 rs4290270 A allele reported higher 'good effect' and lower 'depressed' effect relative to the TT genotype group. Those carrying the SLC6A4 5-HTTLPR S' allele reported greater 'desire' and 'access' compared with the L'L' genotype group.
These findings indicate that TPH1, TPH2, and SLC6A4 variants moderate the subjective effects of cocaine in non-treatment-seeking cocaine-dependent participants.
本研究调查了色氨酸羟化酶（TPH）1、TPH2和溶质载体家族6成员4（SLC6A4）的变体对可卡因主观效应的调节作用。
未寻求治疗的可卡因依赖个体（N = 66）以随机顺序静脉注射生理盐水和可卡因（40毫克）。参与者使用视觉模拟量表自我报告可卡因的主观效应，从注射生理盐水或可卡因前15分钟开始，直至输注后20分钟。视觉模拟量表的自我报告评分范围为0（无效应）至100（最大效应）。对参与者进行TPH1 rs1799913、TPH2 rs4290270和SLC6A4 5-羟色胺转运体相关多态性区域（5-HTTLPR）变体的基因分型。采用重复测量协方差分析来检验主观效应得分随时间的变化，同时控制群体结构。
携带TPH1 rs1799913 A等位基因的参与者相对于CC基因型组，在“兴奋”和“欲求”方面对可卡因的主观反应更强。携带TPH2 rs4290270 A等位基因的参与者相对于TT基因型组，“良好效应”更高，“抑郁效应”更低。携带SLC6A4 5-HTTLPR S'等位基因的参与者与L'L'基因型组相比，“欲望”和“欲求”更强。
这些发现表明，TPH1、TPH2和SLC6A4变体在未寻求治疗的可卡因依赖参与者中调节可卡因的主观效应。
