Biological Prediction of Psychosis Susceptibility among Adolescent Cannabis Users

描述(申请人提供)：长期以来，人们都知道大麻会导致急性精神病发作，最近的流行病学研究表明，青少年经常使用大麻可能会导致急性分裂样障碍，本身就会发展为慢性精神分裂症。然而，大多数吸食大麻的人不会患上精神病。因此，在那些受影响的人中，一定有某种机制支撑着精神病的发展。如果对精神分裂症有遗传易感性的人使用大麻，它可能会与遗传机制相互作用，引发精神病，然后发展为精神分裂症。因此，这项提议的主要目的将是确定精神分裂症的一级亲属家族史对大麻吸毒者随后精神分裂症发展的影响。这一问题将通过评估连续的青少年患者和类似的患者进行评估，这些患者在吸食大麻后首次出现精神症状，而在纽约市两个大型精神科急诊室入院的患者没有因吸食大麻而出现精神症状。这些人将有他们的家族史，而青少年吸食大麻的人从未发生过精神病发作，年龄、性别和社会阶层与对照组的非大麻相匹配。所有有精神症状的一级亲属都将接受面谈，以确定DSM-IV的诊断，特别是精神分裂症。所有使用大麻的受试者和使用精神病患者的非大麻受试者将在第一次发作后进行为期两年的诊断跟踪评估，以确定这些受试者中谁会患上精神分裂症。将探索精神分裂症的遗传风险对吸食大麻者精神分裂症发展的影响。这项研究将有助于我们科学地了解大麻与精神分裂症的关系，并最终对具有高遗传风险的青少年大麻使用者的早期治疗策略产生影响。 项目简介：大麻滥用是一个主要的公共卫生问题，特别是在年轻人中。最近，公众对大麻使用与慢性致残性精神障碍--精神分裂症--之间的联系一直很感兴趣。一些研究人员认为，大麻会以某种方式损害大脑，导致精神分裂症，而另一些人则不会。这项拟议的项目将对经常使用大麻的人进行评估，以确定是否只有具有精神分裂症遗传易感性的人才会产生大麻的不利影响。如果我们正确地认为，大麻导致精神分裂症需要精神分裂症的基因，这项研究的一个含义将是，大麻本身并不直接导致精神分裂症，但它可能会通过某种方式与易感基因相互作用，对遗传精神分裂症的人产生不利影响。这项研究的另一个含义是，应该强烈警告有精神分裂症家族史的人不要使用大麻，如果他们在青少年时期使用大麻，则应密切观察他们是否有不良的精神症状。

DESCRIPTION (provided by applicant): It has long been known that cannabis can cause an acute psychotic episode and recent epidemiologic studies suggest that frequent cannabis use in adolescents can lead to an acute schizophreniform disorder that by itself develops into chronic schizophrenia. However, the majority of individuals who use cannabis do not develop a psychosis. Thus, some mechanism must underlie the development of psychosis in those that are affected. If cannabis is used in individuals with a genetic susceptibility for schizophrenia, it may interact with the genetic mechanism to initiate a psychosis that later develops into schizophrenia. Thus, the primary aim of this proposal will be to determine the effect of family history of schizophrenia in a first degree relative on subsequent development of schizophrenia in cannabis users. This issue will be examined by evaluating consecutive adolescent patients with a first psychotic episode subsequent to cannabis use and similar patients with an episode not subsequent to cannabis use that are admitted to two large NYC psychiatric emergency rooms. These individuals will have their family histories compared with adolescent cannabis users who never had a psychotic episode, and age, sex, and social class matched non-cannabis using controls. All available first-degree relatives with psychiatric symptoms will be interviewed to determine DSM-IV diagnoses, particularly of schizophrenia. All cannabis using subjects and non-cannabis using psychotic individuals will have a diagnostic follow-up evaluation for two years subsequent to the first episode to determine who among these subjects develops schizophrenia. The effect of genetic risk for schizophrenia on the development of schizophrenia in those with cannabis use will be explored. This study will aid in our scientific understanding of the relationship of cannabis to schizophrenia and ultimately have implications for early treatment strategies in adolescent cannabis users who are at high genetic risk for the disorder. Project Narrative: Cannabis abuse is a major public health problem, particularly in young adults. Recently there has been public interest in the connection between cannabis use and later development of the chronic disabling psychiatric disorder, schizophrenia. Some researchers believe that cannabis can damage the brain in some way to cause schizophrenia, while others do not. This proposed project will evaluate people who frequently use cannabis to determine whether only people who have a genetic vulnerability for schizophrenia will have this adverse effect of cannabis. If we are correct that genes for schizophrenia are needed for cannabis to lead to schizophrenia, one implication of this study will be that cannabis alone does not directly cause schizophrenia, but it may have an adverse effect on people who have inherited schizophrenia by interacting with the vulnerability genes in some way. Another implication of this study would be that people who have a family history of schizophrenia should be strongly cautioned from using cannabis and if they do as adolescents, be observed closely for adverse psychotic symptoms.