Twitchell G R, Hanna G L, Cook E H, Stoltenberg S F, Fitzgerald And H E, Zucker R A
Integrated Substance Abuse Programs (GRT), University of California, Los Angeles, California 90025, USA.
Alcohol Clin Exp Res. 2001 Jul;25(7):953-9.
Serotonergic (5-HT) dysfunction has been implicated in the etiology of both behavioral disinhibition (BD) and negative affect (NA). This work extends our previous finding of relationships between whole blood 5-HT and both BD and NA in pubescent, but not prepubescent, children of alcoholics and continues examination of a hypothesized role of 5-HT dysfunction in alcoholism risk. The long and short (L and S) variants of the 5-HT transporter gene-linked polymorphic region (5-HTTLPR) are responsible for differing transcriptional efficiencies in 5-HT uptake. Although associations have been found between the SS 5-HTTLPR genotype and severe alcoholism and neuroticism, recent reports describe relationships between the LL genotype and both low level of response to alcohol and alcoholism diagnosis and a predominance of the LL genotype in early-onset alcoholics.
This report is from an ongoing prospective study of the development of risk for alcoholism and other problematic outcomes in a sample of families classified by father's alcoholism subtype. This study examines relationships between 5-HTTLPR genotype and both child BD (Child Behavior Checklist Aggressive Behavior) and NA (Child Behavior Checklist Anxious/Depressed) in offspring from 47 families.
Results showed significantly higher levels of BD and NA in the 16 children with the LL genotype than the 46 SS or SL children.
Behaviors of undercontrol, which occur at increased rates in children of alcoholics, may be genetically influenced through the regulation of the 5-HT transporter. Due to the small sample size and the preliminary nature of our findings, replication is necessary.
血清素能(5-羟色胺,5-HT)功能障碍与行为抑制(BD)和消极情绪(NA)的病因学均有关联。这项研究扩展了我们之前的发现,即全血5-HT水平与青春期而非青春期前的酗酒者子女的BD和NA之间存在关联,并继续探讨5-HT功能障碍在酒精成瘾风险中所假定的作用。5-羟色胺转运体基因连锁多态性区域(5-HTTLPR)的长、短(L和S)变体导致5-HT摄取的转录效率不同。尽管已发现SS型5-HTTLPR基因型与严重酒精成瘾及神经质之间存在关联,但最近的报告描述了LL基因型与对酒精的低反应水平及酒精成瘾诊断之间的关系,以及LL基因型在早发性酒精成瘾者中的优势。
本报告来自一项正在进行的前瞻性研究,该研究对一个按父亲酒精成瘾亚型分类的家庭样本中酒精成瘾及其他问题结果的风险发展情况进行研究。本研究调查了47个家庭后代中5-HTTLPR基因型与儿童BD(儿童行为量表攻击性行为)和NA(儿童行为量表焦虑/抑郁)之间的关系。
结果显示,16名LL基因型儿童的BD和NA水平显著高于46名SS或SL基因型儿童。
在酗酒者子女中发生率增加的行为失控可能通过5-羟色胺转运体的调节受到遗传影响。由于样本量小且我们的发现具有初步性质,因此有必要进行重复研究。