This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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