Cannabis and Schizophrenia

大麻和精神分裂症

• 批准号: 7582328
• 负责人: Sanjiv Kumra
• 金额: $ 32.66万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-07 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7582328
• 关键词: 17 year old; Accounting; Adolescence; Adolescent; Adult; Affect; Age; Alcohol or Other Drugs use; Anatomy; Anisotropy; Area; Biological Neural Networks; Brain; CNR1 gene; Cannabis; Clinical; Clinical Data; Clinical Research; Comorbidity; Counseling; Cross-Sectional Studies; Data; Development; Diffusion Magnetic Resonance Imaging; Doctor of Medicine; Environmental Risk Factor; Epidemiologic Studies; Exposure to; Figs - dietary; Foundations; Functional disorder; Genes; Imaging Techniques; Impairment; Individual; Inherited; Intervention; Ligands; Longitudinal Studies; Magnetic Resonance Imaging; Maintenance; Marijuana Smoking; Measures; Memory impairment; Modeling; Myelin; Neurocognitive; Neurocognitive Deficit; Pathology; Play; Psychotic Disorders; Recurrence; Relative Risks; Reporting; Research; Research Personnel; Role; Sampling; Schizophrenia; Severities; Short-Term Memory; Structure of superior frontal gyrus; Study models; Symptoms; Syndrome; Work; age group; age related; animal data; base; biological research; brain volume; cannabinoid receptor; cohort; early onset; effective intervention; follow-up; frontal lobe; healthy volunteer; neurodevelopment; performance tests; population based; postnatal; prevent; prospective; repaired; social implication; white matter

DESCRIPTION (provided by applicant): Neurodevelopmental models of the pathology of schizophrenia propose that individuals with schizophrenia inherit genes that cause structural brain deviations; these deviations may be compounded by environmental insults. Seven studies that included a well-defined sample drawn from population-based registers or cohorts and used prospective measures of cannabis and adult psychosis have reported that cannabis use confers an overall twofold increase in the relative risk for later schizophrenia. Clinical studies indicate that illicit substance use, particularly cannabis use, occurs commonly in adolescents with schizophrenia and is associated with increased symptom severity. These data suggest that research is needed to understand the mechanisms underlying the association between cannabis use and psychosis. To date, little is known about the impact of recurrent exposure to cannabis on brain anatomy in either healthy adolescents or adolescents with schizophrenia. There is increasing evidence that schizophrenia has a white matter component. Cannabinoid CB1 receptors are abundant in white matter areas during postnatal brain development and there is ongoing development of white matter, especially in the frontal lobes, during adolescence. In this application, we propose to conduct a longitudinal study to examine the association between repeated exposure to cannabis and white matter abnormalities in the superior frontal gyrus region in healthy adolescents and adolescents with schizophrenia using both diffusion tensor imaging (DTI) and volumetric analysis. Preliminary DTI data from our group indicate that cannabis use is associated with reduced frontal white matter integrity (as measured by lower fractional anisotropy levels using DTI) in healthy adolescents. Second, in adolescents with schizophrenia, comorbidity of cannabis misuse was associated with greater deficits in frontal white matter integrity than what was observed in schizophrenia or cannabis use alone. In adolescents with schizophrenia, decreased fractional anisotropy levels were significantly correlated with attentional impairments, a core neurocognitive deficit associated with schizophrenia. Further studies are now needed to confirm these initial findings. The specific aims of this proposal are to: 1) examine the impact of repeated exposure to cannabis in adolescents with schizophrenia and healthy controls on fractional anisotropy levels (FA) and volume of brain white matter in the superior frontal gyrus region and 2) correlate findings from DTI studies with neurocognitive functions, clinical symptoms and quantitative structural MRI abnormalities to understand the correlates of abnormal fractional anisotropy. A positive finding would help inform current neurodevelopmental models of schizophrenia and point to an intervention that might prevent worsening of the illness.

描述（由申请人提供）：精神分裂症病理学的神经发育模型表明，精神分裂症的个体继承了引起结构性脑偏差的基因；这些偏差可能会受到环境侮辱的加剧。七项研究包括从基于人群的登记册或队列中得出明确的样本，并使用了前瞻性衡量大麻和成人精神病的方法，报告说，大麻的使用赋予了后来精神分裂症的相对风险的总体增加。临床研究表明，非法药物使用，尤其是大麻使用，通常发生在精神分裂症的青少年中，并且与症状严重程度增加有关。这些数据表明，需要进行研究以了解大麻使用与精神病之间关联的基础机制。迄今为止，对健康青少年或精神分裂症的青少年反复暴露对大麻的反复暴露对脑解剖结构的影响知之甚少。越来越多的证据表明精神分裂症具有白质成分。在产后脑发育期间，白质区域中大麻素CB1受体很丰富，并且在青春期期间，白质的发育持续发展，尤其是在额叶。在此应用中，我们建议进行一项纵向研究，以检查健康青少年和精神分裂症青少年使用扩散tensor成像（DTI）和体积分析的精神分裂症的上额回区域中反复接触大麻和白质异常之间的关联。来自我们组的初步DTI数据表明，在健康青少年中，大麻的使用与降低的额叶白质完整性（通过使用DTI的较低分数各向异性水平来衡量）有关。其次，在精神分裂症的青少年中，滥用大麻的合并症与额叶白质完整性的缺陷相比，比单独使用或大麻的使用比单独观察到的更大。在精神分裂症的青少年中，分数各向异性水平降低与注意力障碍显着相关，这是与精神分裂症相关的核心神经认知缺陷。现在需要进一步的研究来确认这些初步发现。该提案的具体目的是：1）检查精神分裂症的青少年反复暴露对大麻的影响对分数各向异性水平（FA）（FA）和上额回回和2的脑白质的体积和2的影响，与DTI研究的发现与DTI研究的发现与临床识别型，临床识别的症状，临床上的MRM MRI MRI MRI MRI MRI MRI MRI MRI MRI相关。异常分数各向异性。一个积极的发现将有助于为当前的精神分裂症神经发育模型提供信息，并指出一种干预措施可能会阻止疾病恶化。