First-Episode Psychosis and Pre-Onset Cannabis Use

描述（由申请人提供）：在美国，青少年和青年吸食大麻是非常普遍的。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因果风险因素，使用大麻会影响这种疾病的症状、病程和结果。拟议的研究旨在澄清大麻使用对出现前驱症状（如功能下降、注意力难以集中、易怒和精神病前的睡眠障碍）的年龄、出现精神病症状（如幻觉和妄想）的年龄的影响，以及精神分裂症的阴性、认知、神经和阳性症状的性质。该研究还将确定先前描述的涉及儿茶酚-o -甲基转移酶（COMT）基因和发病前使用大麻的基因-环境相互作用是否会影响发病年龄和症状。该研究涉及首次出现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。鉴于公认的种族群体之间持续存在的医疗保健差异，非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，以及该人群中大麻使用率非常高，这一人群具有特别的相关性。该研究的具体目的是：(1)通过研究(a)在发病前几年使用大麻和未使用大麻的首次发作患者的前驱症状发病年龄和(b)精神病症状发病年龄，澄清使用大麻对疾病发病的影响；(2)通过比较住院前使用大麻和未使用大麻的首发患者的临床特征，研究大麻使用对疾病现象学（即症状、认知缺陷、神经体征）的影响；(3)通过研究COMT Val158Met功能多态性基因型、大麻使用及其相互作用对首发患者发病年龄和症状特征的影响，阐明特定基因-环境相互作用对疾病发病和疾病现象学的影响。本研究将对住院首发患者进行广泛的横断面评估，其数据将由家庭成员/举报人提供的信息补充。彻底和心理测量健全的工具将用于回顾性评估过去的药物使用。公共卫生相关性：由于精神分裂症可能是一种毁灭性的疾病，因此更好地了解可改变的决定因素和结果的努力至关重要。本研究的创新方面使其特别具有相关性和创新性，包括：(1)重点假设的测试将与最近发现的特定基因-环境相互作用有关，(2)主要依赖于非裔美国人样本，尽管关键风险因素普遍存在，但在精神病学研究中代表性不足的群体，(3)通过减少高风险青少年中大麻的使用，与未来潜在的增强结果有关的预防意义。(4)彻底而仔细地测量所有物质的所有过去使用情况，允许检查所研究的关键变量之间的潜在相互作用；(5)在遗传分析中使用祖先信息标记，以控制混合和群体分层的潜在影响。

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.