Cannabis and Schizophrenia

大麻和精神分裂症

基本信息

批准号：
7103049
负责人：
Sanjiv Kumra
金额：
$ 33.64万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
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

项目摘要

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提出，精神分裂症患者遗传了导致大脑结构偏差的基因；环境损害可能会加剧这些偏差。七项研究包括从基于人口的登记册或队列中抽取的明确样本，并使用大麻和成人精神病的前瞻性指标，报告称使用大麻会使后期精神分裂症的相对风险总体增加两倍。临床研究表明，非法药物的使用，特别是大麻的使用，常见于患有精神分裂症的青少年，并且与症状严重程度增加有关。这些数据表明，需要进行研究来了解大麻使用与精神病之间关联的机制。迄今为止，人们对于经常接触大麻对健康青少年或患有精神分裂症的青少年大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。大麻素 CB1 受体在出生后大脑发育期间的白质区域中丰富，并且白质在青春期持续发育，尤其是在额叶中。在本申请中，我们建议进行一项纵向研究，使用弥散张量成像（DTI）和体积分析来检查健康青少年和精神分裂症青少年反复接触大麻与额上回区域白质异常之间的关联。我们小组的初步 DTI 数据表明，大麻的使用与健康青少年额叶白质完整性降低（通过使用 DTI 的较低分数各向异性水平测量）相关。其次，在患有精神分裂症的青少年中，与精神分裂症或单独使用大麻相比，滥用大麻的合并症与额叶白质完整性的更大缺陷相关。在患有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（与精神分裂症相关的核心神经认知缺陷）显着相关。现在需要进一步的研究来证实这些初步发现。该提案的具体目的是：1）检查精神分裂症青少年和健康对照者反复接触大麻对额上回区域分数各向异性水平（FA）和脑白质体积的影响；2）关联研究结果从神经认知功能、临床症状和定量结构 MRI 异常的 DTI 研究中了解异常分数各向异性的相关性。一项积极的发现将有助于了解当前的精神分裂症神经发育模型，并指出可能防止疾病恶化的干预措施。