Biological Prediction of Psychosis Susceptibility among Adolescent Cannabis Users

描述（由申请人提供）：长期以来，人们都知道大麻的使用会导致某些个体的急性精神病发作，最近的流行病学研究表明，青少年频繁使用大麻可能会导致急性精神病，其本身会发展为慢性精神分裂症。然而，大多数使用大麻的人不会患上精神病或精神分裂症。因此，在那些受影响的人中，精神分裂症的发展必须有一些额外的机制。如果大麻的使用可以与疾病的潜在遗传基础相互作用，那么精神分裂症患者的大脑结构特征的变化将出现在那些后来发展为精神分裂症的大麻使用者身上。大脑的变化可能代表了精神分裂症的遗传脆弱性，并预测谁会患上这种疾病。因此，该提案的目标#1（主要目标）是确定颞叶和额叶及其白色物质连接的大脑结构异常是否会预测大麻使用者患上精神分裂症。为了实现这一目标，我们将评估连续入院的第一次精神病发作后，大麻使用承认两个大型纽约市精神病急诊室。这些患者将与从未发生过精神病发作的青少年大麻使用者进行比较，并与年龄，性别和社会阶层匹配的非大麻使用者进行对照。脑结构异常的存在，特别是慢性精神分裂症患者的特征将通过MRI扫描确定。所有使用大麻的受试者将在第一次精神病发作后一年和两年进行诊断性随访评估，以确定谁被诊断为精神分裂症，或者最初的非精神病个体是否仍然没有精神分裂症。该提案的目的#2是检查大麻使用者首次精神分裂样精神病的大脑异常是否与精神分裂症的遗传风险增加有关。这将通过从可靠的家庭线人处获得家庭信息来实现。这项研究最终将对精神病遗传风险高的青少年大麻使用者的早期治疗策略产生影响，并通过对大麻使用后患有急性精神病的个体进行MRI评估，提出早期生物学预警信号。

DESCRIPTION (provided by applicant): It has long been known that cannabis use can cause an acute psychotic episode in some individuals and recent epidemiologic studies suggest that frequent cannabis use in adolescents may lead to an acute psychosis that by itself develops into chronic schizophrenia. However, the majority of individuals who use cannabis do not develop a psychosis or schizophrenia. Thus, some additional mechanism must underlie the development of schizophrenia in those that are affected. If cannabis use can interact with an underlying genetic basis for the illness, changes in brain structure characteristic of patients with schizophrenia will be seen in those cannabis users who later develop schizophrenia. The brain changes may represent the genetic vulnerability for schizophrenia and be predictive of who develops the illness. Thus, Aim #1 (primary aim) of this proposal is to determine whether brain structural deviances in temporal and frontal lobes and their white matter connections will predict which cannabis users develop schizophrenia. To accomplish this we will evaluate consecutive admissions with a first psychotic episode subsequent to cannabis use admitted to two large NYC psychiatric emergency rooms. These patients will be compared with adolescent cannabis users who never had a psychotic episode, and age, sex, and social class matched non-cannabis using controls. The presence of brain structural anomalies, particularly those characteristic of patients with chronic schizophrenia psychoses will be determined by MRI scans. All cannabis using subjects will have a diagnostic follow-up evaluation one and two years subsequent to the first psychotic episode to determine who developed a diagnosis of schizophrenia or whether the initially non-psychotic individuals remained symptom-free. Aim #2 of this proposal is to examine whether brain abnormalities among cannabis users with a first schizophrenic-like psychosis are associated with increased genetic risk for schizophrenia. This will be achieved by obtaining family information from reliable family informants. This study will ultimately have implications for early treatment strategies in adolescent cannabis users who are at high genetic-risk for psychosis and suggest early biological warning signs through MRI evaluations of individuals who have an acute psychosis following cannabis use.