Reduced Brain Cannabinoid Receptor Availability in Schizophrenia.
Reduced Brain Cannabinoid Receptor Availability in Schizophrenia.
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DOI：
10.1016/j.biopsych.2015.08.021
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发表时间：
2016-06-15
影响因子：
10.6
通讯作者：
D'Souza DC
中科院分区：
文献类型：
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作者：
Ranganathan M;Cortes-Briones J;Radhakrishnan R;Thurnauer H;Planeta B;Skosnik P;Gao H;Labaree D;Neumeister A;Pittman B;Surti T;Huang Y;Carson RE;D'Souza DC
几条证据表明，在精神分裂症（SCZ）的内源性大麻素（eCB）系统中存在异常。然而，SCZ中eCB系统的体内测量有限。将25名男性SCZ受试者（SCZ）、18名接受抗精神病药物治疗的[SCZ-MED]和7名未接受抗精神病药物治疗的[SCZ-UNMED]）与18名年龄匹配的男性健康对照受试者（HC）进行比较。受试者在高分辨率研究断层扫描（HRRT）扫描仪上接受一次正电子发射断层扫描（PET），每次扫描均使用大麻素受体-1（CB 1 R）选择性放射性示踪剂[11 C]OMAR。使用PET数据的动力学建模确定局部分布容积（VT）值，作为CB 1 R可用性的度量。比较SCZ和HC之间平均复合[11 C]OMAR VT值的组间差异。还进行了15个脑区域内CB 1 R可用性的探索性比较。所有分析均为年龄和体重指数的协变量。SCZ显示复合[11 C]OMAR VT显著（p =0.02）低于HC（差异约12%，效应量d= 0.73）。[11 C]OMAR VT在杏仁核、尾状核、后扣带皮层、海马、下丘脑和小脑的SCZ中显著降低（所有ps <0.05）。HC> SCZ-MED>SCZ-UNMED的复合[11 C]OMAR VT更大。此外，HC> SCZ吸烟者（n=11）> SCZ非吸烟者（n=14）的复合[11 C]OMAR VT更大。与HC相比，男性SCZ中的CB 1 R可用性较低。此外，抗精神病药物和烟草使用可能会增加该人群中CB 1 R的可用性。该研究的结果提供了进一步的证据，支持eCB系统的改变可能有助于SCZ的病理生理学的假设。
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. Twenty five male SCZ subjects (SCZs), 18 antipsychotic treated [SCZ-MED] and 7 antipsychotic free [SCZ-UNMED]) were compared to 18 age- matched male healthy control subjects (HCs). Subjects underwent one Positron Emission Tomography (PET) scan each with the cannabinoid receptor-1 (CB1R) selective radiotracer [11C]OMAR on the High Resolution Research Tomography (HRRT) scanner. Regional volume of distribution (VT) values were determined using kinetic modeling of PET data as a measure of CB1R availability. Group differences in mean composite [11C]OMAR VT 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. SCZs showed significantly (p =0.02) lower composite [11C]OMAR VT relative to HCs (~12% difference, effect size d= 0.73). [11C]OMAR VT was significantly (all ps <0.05) lower in SCZs in the amygdala, caudate, posterior cingulate cortex, hippocampus, hypothalamus and insula. Composite [11C]OMAR VT was greater in HCs> SCZ-MED>SCZ-UNMED. Furthermore, composite [11C]OMAR VT was greater in HCs> SCZ smokers (n=11) > SCZ non-smokers (n=14). CB1R availability is lower in males SCZs compared to 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.