First-Episode Psychosis and Pre-Onset Cannabis Use

首发精神病和发作前吸食大麻

• 批准号: 8322750
• 负责人: NEELY A MYERS
• 金额: $ 34.84万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-05 至 2013-11-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8322750
• 关键词: 12 year old; 14 year old; Address; Admixture; Adolescence; Adolescent; Affect; African American; Age; Age of Onset; Alcohol or Other Drugs use; Alcohols; Attention; Auditory; Cannabis; Catechol O-Methyltransferase; Characteristics; Clinical; Clinical Research; Cognitive; Cognitive deficits; Data; Delusions; Disease; Environment; Ethnic group; Family; Family member; Future; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genotype; Hallucinations; Health; Healthcare; Heterogeneity; High Prevalence; Hospitalization; Illicit Drugs; Knowledge; Measurement; Mediating; Memory; Mental Health Services; Methyltransferase Gene; Nature; Neurobiology; Neurologic; Onset of illness; Outcome; Patients; Pattern; Pharmaceutical Preparations; Population; Preventive; Psychotic Disorders; Recommendation; Recording of previous events; Reliance; Research; Risk; Risk Factors; Role; Sampling; Schizoaffective Disorders; Schizophrenia; Schizophreniform Disorder; Short-Term Memory; Sleep disturbances; Specific qualifier value; Stratification; Symptoms; Syndrome; Testing; United States; executive function; first episode psychosis; functional decline; gene discovery; gene environment interaction; genetic analysis; high risk; informant; innovation; instrument; sex; sound; valylvaline; young adult

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.

描述（由申请人提供）：在美国，青少年和年轻人使用大麻非常普遍。越来越多的证据表明，与其他非法药物不同，青少年使用大麻可能是精神分裂症的一个因果风险因素，大麻的使用会影响疾病的症状、病程和结果。拟议的研究旨在澄清大麻使用对前驱症状发作年龄的影响（例如，功能下降、难以集中注意力、易怒和精神病之前的睡眠障碍），精神病症状发作时的年龄（即，幻觉和妄想），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表征的涉及儿茶酚-O-甲基转移酶（COMT）基因和发作前大麻使用的基因-环境相互作用是否影响发作年龄和麻醉学。这项研究涉及精神分裂症谱系障碍首次发作的住院患者，其中大多数是非洲裔美国人。考虑到种族群体之间公认的持续医疗保健差异，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。研究的具体目的是：（1）通过研究在发病前几年使用大麻以及未使用大麻的首次发病患者的（a）前驱症状发作时的年龄和（B）精神病症状发作时的年龄，澄清大麻使用对疾病发作的影响;（2）研究大麻使用对疾病现象学的影响（即，症状，认知缺陷，神经体征），通过比较住院前使用大麻的首次发作患者与未使用大麻的患者的临床特征;和（3）通过研究COMT Val 158 Met功能多态性基因型、大麻使用以及它们对首发患者发病年龄和症状特征的相互作用。本研究将对住院的首次发作患者进行广泛的横断面评估，其数据将由家庭成员/知情人的信息补充。将使用彻底和心理测量健全的仪器来回顾性评估过去的物质使用情况。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，因此更好地理解过程和结果的可改变决定因素的努力至关重要。这项研究的创新方面使其特别相关和创新，包括：（1）将对与最近发现的特定基因-环境相互作用相关的重点假设进行检验，（2）依赖于主要为非洲裔美国人的样本，尽管关键风险因素的流行率很高，但该群体在精神病学研究中的代表性不足，（3）通过减少高危青少年中大麻的使用，与未来潜在的结果增强有关的预防意义，（4）彻底和仔细地测量所有物质的所有过去使用情况，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合和群体分层的潜在影响。

项目成果

Life and treatment goals of individuals hospitalized for first-episode nonaffective psychosis.

• DOI: 10.1016/j.psychres.2011.05.039
• 发表时间: 2011-10-30
• 期刊: PSYCHIATRY RESEARCH
• 影响因子: 11.3
• 作者: Ramsay, Claire E.;Broussard, Beth;Goulding, Sandra M.;Cristofaro, Sarah;Hall, Dustin;Kaslow, Nadine J.;Killackey, Eoin;Penn, David;Compton, Michael T.
• 通讯作者: Compton, Michael T.

Early signs, diagnosis and therapeutics of the prodromal phase of schizophrenia and related psychotic disorders.

• DOI: 10.1586/ern.10.93
• 发表时间: 2010-08
• 期刊: Expert review of neurotherapeutics
• 影响因子: 4.3
• 作者: Larson MK;Walker EF;Compton MT
• 通讯作者: Compton MT

Similarities and Differences in Associations Between Duration of Untreated Psychosis (DUP) and Demographic, Premorbid, and Symptom Severity Measures in Two Samples of First-Episode Psychosis Patients from Mexico and the United States.

• DOI: 10.1007/s11126-020-09736-3
• 发表时间: 2020-09
• 期刊: The Psychiatric quarterly
• 作者: Fresan A;Apiquian R;Robles-García R;Zarate CT;Balducci PM;Broussard B;Wan CR;Compton MT
• 通讯作者: Compton MT

Demographic, socio-environmental, and substance-related predictors of duration of untreated psychosis (DUP).

• DOI: 10.1016/j.schres.2013.05.011
• 发表时间: 2013-08
• 期刊: Schizophrenia research
• 影响因子: 4.5
• 作者: Broussard B;Kelley ME;Wan CR;Cristofaro SL;Crisafio A;Haggard PJ;Myers NL;Reed T;Compton MT
• 通讯作者: Compton MT

Associations between duration of untreated psychosis and domains of positive and negative symptoms.

• DOI: 10.1111/eip.12256
• 发表时间: 2017-10
• 期刊: Early intervention in psychiatry
• 影响因子: 2
• 作者: Birnbaum ML;Wan CR;Broussard B;Compton MT
• 通讯作者: Compton MT