PILOT STUDY OF MARIJUANA INDUCED DEPERSONALIZATION DISORDER

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个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，不一定是研究者的机构。 具体目标：确定大麻素受体基因CB 1/Cnr 1的突变可能与孤立摄入大麻后发展慢性人格解体的脆弱性有关。 人格解体障碍（DPD）是一种分离性障碍，其特征是突出的人格解体和经常的现实解体，没有临床记忆或身份改变。 人格解体是一种特殊类型的解离，涉及主观自我感知的破坏，表现为诸如感觉分离，机器人，身体外或与自我断开的症状。这种疾病的性别比例约为1：1，平均发病年龄约为16岁。 该过程通常是慢性的，并且经常是连续的。 情绪、焦虑和人格障碍常与DPD共病，但不能预测症状的严重程度。 这种疾病最常见的近端诱因是严重的压力、抑郁、恐慌、吸食大麻和致幻剂。 DPD还与更远的童年人际创伤有关，特别是情感虐待和忽视。 神经化学研究结果表明，可能涉及的多巴胺能，内源性阿片类药物，NMDA和大麻素途径。 人格解体也与自主神经功能减弱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联合皮层中代谢活动的广泛改变，以及对情绪刺激的前额叶过度激活和边缘系统抑制。 迄今为止，还没有确定的药物或心理治疗的障碍。 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，有时甚至是一次性使用大麻引发的。 这种描述和记录良好的现象高度暗示了这些个体中大麻素相关神经化学途径的遗传脆弱性。 因此，这项试点研究的目标是探索这一假设，通过证明进行研究的可行性，并为未来的拨款申请产生初步的遗传学发现。

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.