Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy; School of Medicine, Vita -Salute San Raffaele University, Milan, Italy.
Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jun 8;92:363-368. doi: 10.1016/j.pnpbp.2019.02.009. Epub 2019 Feb 18.
Cognitive impairments are considered core features of schizophrenia and are recognized as the most important predictors of functional outcome and quality of life. A better study of the mechanisms underlying the cognition is of extreme relevance. Literature has shown that several genetic and environmental factors affect cognitive performance. In particular, the interaction between Catechol-O-Methyltransferase (COMT) gene and cannabis use has gained increasing attention in the past years. Based on these premises, the present study, aimed to analyze the interplay between cannabis use and COMT polymorphism on cognitive performance in a sample of 135 patients with chronic schizophrenia. Patients were assessed for neurocognitive measures with a broad battery, genotyped for COMT Val158Met polymorphism from peripheral blood sample, and evaluated with a semi-structured interview in order to establish the history of cannabis abuse. Results showed a significant interaction effect between COMT polymorphism and cannabis use on verbal fluency and speed of processing. The analysis revealed significant differences between subjects COMT Val/Val homozygous and Met carriers with history of cannabis use, with a better performance on both tasks among the Met carriers group. These data are in line with literature on healthy subjects that suggests a more detrimental effect of cannabis among subjects with Val/Val genotype. In conclusions, results highlight the need to better disentangle the biological pathways in which cannabis use and COMT are converging, as possible treatment targets, as well as the importance to assess these factors in clinical to optimize individualized interventions.
认知障碍被认为是精神分裂症的核心特征，被认为是预测功能结果和生活质量的最重要因素。更好地研究认知背后的机制具有极端重要性。文献表明，有几个遗传和环境因素会影响认知表现。特别是，儿茶酚-O-甲基转移酶 (COMT) 基因与大麻使用之间的相互作用在过去几年中引起了越来越多的关注。基于这些前提，本研究旨在分析大麻使用和 COMT 多态性对 135 名慢性精神分裂症患者样本认知表现的相互作用。通过广泛的测试对患者进行神经认知评估，从外周血样中对 COMT Val158Met 多态性进行基因分型，并通过半结构化访谈对患者进行评估，以确定大麻滥用史。结果显示，COMT 多态性和大麻使用之间存在显著的相互作用效应，对词语流畅性和处理速度有影响。分析显示，在有大麻使用史的受试者中，COMT Val/Val 纯合子和 Met 携带者之间存在显著差异，Met 携带者组在这两个任务上的表现均更好。这些数据与针对健康受试者的文献一致，表明 Val/Val 基因型的受试者中，大麻的影响更为不利。总之，结果强调了需要更好地阐明大麻使用和 COMT 相互作用的生物学途径，将其作为可能的治疗靶点，并在临床中评估这些因素，以优化个体化干预。
