PILOT STUDY OF MARIJUANA INDUCED DEPERSONALIZATION DISORDER

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。特定目的：鉴定大麻素受体基因CB1/Cnr1突变可能与孤立摄入大麻后发生慢性人格解体的易感性相关。人格解体障碍（Depersonalization disorder， DPD）是一种分离性障碍，其特征是严重的人格解体和现实感丧失，没有临床记忆或身份改变。人格解体是一种特殊类型的分离，涉及主观自我感知的破坏，表现为感觉分离、机械、灵魂出窍或与自我脱节等症状。该疾病的性别比例约为1:1，平均发病年龄约为16岁。这个过程通常是慢性的，经常是连续的。情绪，焦虑和人格障碍通常与DPD共病，但没有预测症状的严重程度。最常见的近端诱发因素是严重的压力、抑郁、恐慌、大麻和致幻剂摄入。DPD还与更多的童年远端人际创伤有关，特别是情感虐待和忽视。神经化学研究结果表明可能涉及血清素能、内源性阿片、NMDA和大麻素途径。去人格化也与自主神经钝化和对地塞米松抑制的抵抗有关。DPD的脑成像研究揭示了感觉关联皮层代谢活动的广泛改变，以及前额叶过度激活和边缘抑制对情绪刺激的反应。到目前为止，还没有确定的药物或心理治疗方法来治疗这种疾病。值得注意的是，在10- 20%的DPD患者中，持续数月、数年或数十年的慢性人格解体最初是由偶尔使用，有时甚至是一次性使用大麻引发的。这种被充分描述和记录的现象高度暗示了大麻素相关神经化学途径在这些个体中的遗传脆弱性。因此，这项试点研究的目标是通过证明进行研究的可行性和为未来的拨款提交提供初步的遗传学发现来探索这一假设。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aim: To identify mutations of the cannabinoid receptor gene CB1/Cnr1 that may be associated with the vulnerability towards developing chronic depersonalization after the isolated ingestion of marijuana. Depersonalization disorder (DPD) is a dissociative disorder characterized by prominent depersonalization and often derealization, without clinical memory or identity alterations. Depersonalization is a particular type of dissociation that involves a disruption of subjective self-perceptions, manifested in symptoms such as feeling detached, robotic, out-of-body, or otherwise disconnected from one's self. The disorder has an approximately 1:1 gender ratio with mean onset around 16 years of age. The course is typically chronic and often continuous. Mood, anxiety and personality disorders are often comorbid with DPD but none predict symptom severity. The most common proximal precipitants of the disorder are severe stress, depression, panic, marijuana and hallucinogen ingestion. DPD has also been associated with more distal childhood interpersonal trauma, in particular emotional abuse and neglect. Neurochemical findings have suggested possible involvement of serotonergic, endogenous opioid, NMDA and cannabinoid pathways. Depersonalization has also been associated with autonomic blunting and resistance to dexamethasone suppression. Brain imaging studies in DPD have revealed widespread alterations in metabolic activity in the sensory association cortex, as well as prefrontal hyperactivation and limbic inhibition in response to emotional stimuli. To date there are no established pharmacological or psychotherapeutic treatments for the disorder. In a notable minority of 10-20 % of individuals with DPD, chronic depersonalization lasting for months, years or decades is initially triggered by the sporadic, sometimes even one-time use, of marijuana. This well-described and documented phenomenon is highly suggestive of a genetic vulnerability in cannabinoid-related neurochemical pathways in such individuals. The goal, therefore, of this pilot study is to explore this hypothesis, by demonstrating feasibility to conduct the study and generating preliminary genetics findings for future grant submission.