First-Episode Psychosis and Pre-Onset Cannabis Use

描述(申请人提供)：大麻在青春期和青春期的使用在美国非常普遍。越来越多的证据表明，与其他非法药物不同，青少年时期使用大麻可能是精神分裂症的一个原因风险因素，而大麻的使用会影响疾病的症状、病程和结果。拟议的研究试图澄清大麻使用对前驱症状(例如，功能下降、注意力不集中、易怒和精神错乱之前的睡眠障碍)、精神症状(即幻觉和妄想)开始时的年龄，以及精神分裂症阴性、认知、神经和阳性症状的性质的影响。这项研究还将确定以前描述的涉及儿茶酚-O-甲基转移酶(COMT)基因和发病前大麻使用的基因-环境相互作用是否会影响发病年龄和症状。这项研究涉及首发精神分裂症谱系障碍的住院患者，其中大多数是非裔美国人。考虑到各族裔群体之间持续存在的公认的医疗保健差距、非洲裔美国人在临床研究中的代表性不足、非裔美国人对精神卫生服务的利用不足以及这一群体中非常高的大麻使用率，这一群体具有特别重要的意义。这项研究的具体目的是：(1)通过研究(A)在发病前几年使用大麻的首发患者和未使用大麻的首发患者的首发症状开始年龄和(B)首发患者在发病前几年使用大麻和不使用大麻的患者的精神症状开始年龄，阐明大麻使用对疾病现象学(即症状、认知障碍、神经体征)的影响；(2)通过比较住院前使用大麻的首发患者和未使用大麻的患者的临床特征，研究大麻使用对疾病现象学(即症状、认知障碍、神经体征)的影响；(3)通过研究COMT Val158Met功能多态基因型、大麻使用及其交互作用对首发患者发病年龄和症状的影响，阐明特定的基因-环境交互作用对疾病发病和疾病现象学的影响。这项研究将使用对住院的首发患者进行广泛的横断面评估，其数据将得到来自家庭成员/告密者的信息的补充。将使用全面的心理测量学仪器来回顾评估过去的药物使用情况。公共卫生相关性：因为精神分裂症可能是一种毁灭性的疾病，努力更好地了解可改变的决定因素当然和结果是至关重要的。这项研究特别具有相关性和创新性的创新方面包括：(1)将测试与最近发现的特定基因-环境相互作用有关的重点假说；(2)依赖以非裔美国人为主的样本，尽管关键风险因素很普遍，但在精神病学研究中代表不足；(3)与未来通过减少特别高风险青少年的大麻使用来改善结果有关的预防影响；(4)彻底和仔细地衡量过去所有物质的使用，允许检查正在研究的关键变量之间的潜在相互作用，以及(5)在遗传分析中使用祖先信息标记来控制混杂和种群分层的潜在影响。

DESCRIPTION (provided by applicant): Cannabis use in adolescence and young adulthood is very common in the United States. Accumulating evidence suggests that, unlike other illicit drugs, cannabis used in adolescence may be a causal risk factor for schizophrenia, and cannabis use affects the symptoms, course, and outcomes of the illness. The proposed research seeks to clarify the impact of cannabis use on the age at onset of prodromal symptoms (e.g., decline in functioning, difficulties concentrating, irritability, and sleep disturbances that precede psychosis), the age at onset of psychotic symptoms (i.e., hallucinations and delusions), and the nature of negative, cognitive, neurological, and positive symptoms of schizophrenia. The study also will determine whether or not a previously characterized gene-environment interaction} involving the catechol-O-methyltransferase (COMT) gene and pre-onset cannabis use} influences onset ages and symptomatology. The study involves hospitalized patients with a first episode of a schizophrenia-spectrum disorder, most of whom are African American. This population is of particular relevance given well-recognized ongoing healthcare disparities across ethnic groups, under-representation of African Americans in clinical research, underuse of mental health services by African Americans, and very high rates of cannabis use in this population. The specific aims of the research are: (1) to clarify the effects of cannabis use on disease onset by studying (a) age at onset of prodromal symptoms and (b) age at onset of psychotic symptoms in first-episode patients who used cannabis in the years prior to onset as well as those who did not; (2) to study the impact of cannabis use on disease phenomenology (i.e., symptoms, cognitive deficits, neurological signs) by comparing the clinical characteristics of first-episode patients who used cannabis prior to hospitalization with those who did not; and (3) to elucidate the impact of a specific gene-environment interaction on disease onset and disease phenomenology by investigating the effects of the COMT Val158Met functional polymorphism genotype, cannabis use, and their interaction on onset ages and symptom profiles of first-episode patients. The research will be conducted using extensive cross-sectional assessments of hospitalized first-episode patients whose data will be supplemented by information from family members/informants. Thorough and psychometrically sound instruments will be used to retrospectively assess past substance use. PUBLIC HEALTH RELEVANCE: Because schizophrenia can be such a devastating illness, efforts to better understand modifiable determinants of course and outcomes are crucial. Innovative aspects of this research that make it especially relevant and innovative include: (1) testing of focused hypotheses will be tested related to a specific recently discovered gene-environment interaction, (2) reliance on a predominantly African American sample, a group that is under- represented in psychiatric research despite a high prevalence of key risk factors, (3) the preventive implications related to future potential enhancements of outcomes by reducing cannabis use among adolescents who are at especially high risk, (4) measurement of all past use of all substances thoroughly and carefully, allowing for examination of potential interactions among the key variables being studied, and (5) the use of Ancestry-Informative Markers in the genetic analysis to control for potential effects of admixture and population stratification.