Tanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Drug Dev Res. 2021 Aug;82(5):678-684. doi: 10.1002/ddr.21681. Epub 2020 May 11.
Tardive dyskinesia (TD) is a potentially irreversible movement disorder observed following long-term antipsychotic exposure. Its cause is unknown; however, a genetic component has been supported by studies of affected families. Dysbindin-1, encoded by the dystrobrevin-binding protein 1 DTNBP1 gene, has been associated with schizophrenia and is potentially involved in dopamine neurotransmission through its regulation of dopamine release and dopamine D2 receptor recycling, making it a candidate for investigation in TD. We investigated common variants across the DTNBP1 gene in our schizophrenia/patients with schizoaffective disorder of European ancestry. We found a number of DTNBP1 three-marker haplotypes to be associated with TD occurrence and TD severity (p < 0.05). These preliminary findings, if replicated in larger independent samples, would suggest that drugs targeting dysbindin-1 may be an option in the prevention and treatment of TD.
迟发性运动障碍（TD）是一种潜在的不可逆运动障碍，发生于长期使用抗精神病药物之后。其病因不明；然而，受影响家族的研究支持存在遗传因素。由肌联蛋白结合蛋白 1（DTNBP1）基因编码的 dysbindin-1 与精神分裂症有关，并且可能通过调节多巴胺释放和多巴胺 D2 受体再循环参与多巴胺神经传递，使其成为 TD 研究的候选基因。我们在欧洲血统的精神分裂症/精神分裂情感障碍患者中研究了 DTNBP1 基因中的常见变异。我们发现多个 DTNBP1 三标记单倍型与 TD 发生和 TD 严重程度相关（p < 0.05）。如果在更大的独立样本中得到复制，这些初步发现表明，针对 dysbindin-1 的药物可能是预防和治疗 TD 的一种选择。
