Reduced Brain Cannabinoid Receptor Availability in Schizophrenia

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• 作者：Mohini Ranganathan^a ; ^b ; ^c ; ^{mohini.ranganathan@yale.edu" class="auth_mail" title="E-mail the corresponding author} ; Jose Cortes-Briones^a ; ^b ; ^c ; Rajiv Radhakrishnan^a ; ^b ; ^c ; Halle Thurnauer^a ; ^b ; ^c ; Beata Planeta^b ; ^c ; ^d ; Patrick Skosnik^a ; ^b ; ^c ; Hong Gao^d ; David Labaree^d ; Alexander Neumeister^e ; Brian Pittman^b ; ^c ; ^d ; Toral Surti^c ; Yiyun Huang^d ; Richard E. Carson^d ; Deepak Cyril D&rsquo ; Souza^a ; ^b ; ^c
• 关键词：Antipsychotics ; Cannabinoid ; CB1R ; OMAR ; Schizophrenia ; Smoking
• 刊名：Biological Psychiatry
• 出版年：2016
• 出版时间：15 June 2016
• 年：2016
• 卷：79
• 期：12
• 页码：997-1005
• 全文大小：726 K

文摘

Several lines of evidence suggest the presence of abnormalities in the endocannabinoid (eCB) system in schizophrenia (SCZ). However, there are limited in vivo measures of the eCB system in SCZ.

Methods

Twenty five male SCZ subjects (SCZs) (18 antipsychotic treated and 7 antipsychotic free) were compared with 18 age-matched male healthy control subjects (HCs). Subjects underwent one positron emission tomography scan each with the cannabinoid receptor-1 (CB₁R) selective radiotracer [¹¹C]OMAR on the high resolution research tomography scanner. Regional volume of distribution (V_T) values were determined using kinetic modeling of positron emission tomography data as a measure of CB₁R availability. Group differences in mean composite [¹¹C]OMAR V_T values were compared between SCZs and HCs. Exploratory comparisons of CB₁R availability within 15 brain regions were also conducted. All analyses were covaried for age and body mass index.

Results

SCZs showed significantly (p = .02) lower composite [¹¹C]OMAR V_T relative to HCs (~12% difference, effect size d = .73). [¹¹C]OMAR V_T was significantly (all ps < .05) lower in SCZs in the amygdala, caudate, posterior cingulate cortex, hippocampus, hypothalamus, and insula. Composite [11]OMAR VT was HCs > antipsychotic treated SZCs > antipsychotic free SZCs. Furthermore, composite [¹¹C]OMAR V_T was greater in HCs than SCZ smokers (n = 11) and SCZ nonsmokers (n = 14).

Conclusions

CB₁R availability is lower in male SCZ subjects compared with HCs. Furthermore, antipsychotics and tobacco use may increase CB₁R availability in this population. The findings of the study provide further evidence supporting the hypothesis that alterations in the eCB system might contribute to the pathophysiology of SCZ.