Biological Prediction of Psychosis Susceptibility among Adolescent Cannabis Users

描述（由申请人提供）：人们早就知道大麻可引起急性精神病发作，最近的流行病学研究表明，青少年频繁使用大麻可导致急性精神分裂症样障碍，其本身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。因此，在那些受影响的人身上，一定有某种机制导致了精神病的发展。如果大麻被用于具有精神分裂症遗传易感性的个体，它可能与遗传机制相互作用，引发后来发展为精神分裂症的精神病。因此，本提案的主要目的将是确定精神分裂症家族史在一级亲属对大麻使用者随后的精神分裂症发展的影响。这个问题将通过评估连续在使用大麻后首次出现精神病发作的青少年患者和在纽约市两家大型精神病急诊室住院的非使用大麻后出现精神病发作的类似患者来进行检查。将这些人的家族史与从未有过精神病发作的青少年大麻使用者进行比较，并将年龄、性别和社会阶层与非大麻使用者相匹配。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，特别是精神分裂症的诊断。所有使用大麻的受试者和不使用大麻的精神病患者将在首次发作后进行两年的诊断随访评估，以确定这些受试者中谁会发展为精神分裂症。将探讨精神分裂症遗传风险对大麻使用者精神分裂症发展的影响。这项研究将有助于我们科学地理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。

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.