Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, Canada.
Institute of Medical Science, University of Toronto, Toronto, Canada.
World J Biol Psychiatry. 2021 Jul;22(6):399-427. doi: 10.1080/15622975.2020.1834619. Epub 2020 Nov 12.
Startle response is an objective physiological measure integral to the human defense system and a promising target for endophenotype investigations of anxiety. Given the alterations in startle reactivity observed among anxiety and related disorders, we searched for genetic variants associated with startle reactivity as they may be further involved in pathological anxiety risk.
A systematic literature review was performed to identify genetic variants associated with startle reactivity in humans, specifically baseline and fear- or anxiety-potentiated startle.
The polymorphisms Val66Met (rs6265) from brain-derived neurotrophic factor (), Val158Met (rs4680) from catechol-O-methyltransferase (), and the serotonin transporter-linked polymorphic region (5-HTTLPR) from the serotonin transporter gene () were most commonly studied in human startle. In addition, several other genetic variants have also been identified as potential candidates that warrant further research, especially given their novelty in in the context of anxiety.
Similar to psychiatric genetic studies, the studies on startle reactivity primarily focus on candidate genes and are plagued by non-replication. Startle reactivity is a promising endophenotype that requires concerted efforts to collect uniformly assessed, large, well-powered samples and hypothesis-free genome-wide strategies. To further support startle as an endophenotype for anxiety, this review suggests advanced genetic strategies for startle research.
惊跳反应是人类防御系统的一个客观生理指标，也是焦虑相关表型研究的一个有前途的靶点。鉴于在焦虑和相关障碍中观察到的惊跳反应改变，我们寻找与惊跳反应相关的遗传变异，因为它们可能进一步涉及病理性焦虑风险。
系统地进行文献检索，以确定与人类惊跳反应相关的遗传变异，特别是基线和恐惧或焦虑增强的惊跳反应。
脑源性神经营养因子（）中的 Val66Met（rs6265）、儿茶酚-O-甲基转移酶（）中的 Val158Met（rs4680）和 5-羟色胺转运体基因（）中的 5-羟色胺转运体连接多态性区域（5-HTTLPR）是人类惊跳中最常研究的多态性。此外，还确定了其他一些遗传变异作为潜在的候选者，需要进一步研究，特别是考虑到它们在焦虑背景下的新颖性。
与精神科遗传研究类似，惊跳反应的研究主要集中在候选基因上，并受到非复制的困扰。惊跳反应是一个很有前途的内表型，需要共同努力收集统一评估、大型、强大的样本和无假设的全基因组策略。为了进一步支持惊跳反应作为焦虑的内表型，本综述提出了惊跳反应研究的高级遗传策略。
