Batalla Albert, Soriano-Mas Carles, López-Solà Marina, Torrens Marta, Crippa José A, Bhattacharyya Sagnik, Blanco-Hinojo Laura, Fagundo Ana B, Harrison Ben J, Nogué Santiago, de la Torre Rafael, Farré Magí, Pujol Jesús, Martín-Santos Rocío
Department of Psychiatry, Clinical Institute of Neuroscience, Hospital Clínic, IDIBAPS, CIBERSAM, Spain; Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Spain.
Addict Biol. 2014 Jul;19(4):722-32. doi: 10.1111/adb.12027. Epub 2013 Jan 14.
Neuroimaging studies have shown that chronic consumption of cannabis may result in alterations in brain morphology. Recent work focusing on the relationship between brain structure and the catechol-O-methyltransferase (COMT) gene polymorphism suggests that functional COMT variants may affect brain volume in healthy individuals and in schizophrenia patients. We measured the influence of COMT genotype on the volume of four key regions: the prefrontal cortex, neostriatum (caudate-putamen), anterior cingulate cortex and hippocampus-amygdala complex, in chronic early-onset cannabis users and healthy control subjects. We selected 29 chronic cannabis users who began using cannabis before 16 years of age and matched them to 28 healthy volunteers in terms of age, educational level and IQ. Participants were male, Caucasians aged between 18 and 30 years. All were assessed by a structured psychiatric interview (PRISM) to exclude any lifetime Axis-I disorder according to Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition. COMT genotyping was performed and structural magnetic resonance imaging data was analyzed by voxel-based morphometry. The results showed that the COMT polymorphism influenced the volume of the bilateral ventral caudate nucleus in both groups, but in an opposite direction: more copies of val allele led to lesser volume in chronic cannabis users and more volume in controls. The opposite pattern was found in left amygdala. There were no effects of COMT genotype on volumes of the whole brain or the other selected regions. Our findings support recent reports of neuroanatomical changes associated with cannabis use and, for the first time, reveal that these changes may be influenced by the COMT genotype.
神经影像学研究表明,长期吸食大麻可能导致大脑形态改变。最近一项关注脑结构与儿茶酚-O-甲基转移酶(COMT)基因多态性之间关系的研究表明,功能性COMT变体可能会影响健康个体和精神分裂症患者的脑容量。我们测量了COMT基因型对四个关键区域体积的影响:前额叶皮质、新纹状体(尾状核-壳核)、前扣带回皮质和海马-杏仁核复合体,研究对象为慢性早发性大麻使用者和健康对照者。我们选取了29名在16岁之前开始吸食大麻的慢性大麻使用者,并将他们与28名健康志愿者在年龄、教育水平和智商方面进行匹配。参与者均为18至30岁的白人男性。所有参与者均通过结构化精神病学访谈(PRISM)进行评估,以排除根据《精神疾病诊断与统计手册(第四版)》诊断的任何终生轴I障碍。进行了COMT基因分型,并通过基于体素的形态学分析对结构磁共振成像数据进行了分析。结果表明,COMT多态性对两组双侧腹侧尾状核的体积均有影响,但方向相反:缬氨酸等位基因拷贝数越多,慢性大麻使用者的脑体积越小,而对照组的脑体积越大。在左侧杏仁核中发现了相反的模式。COMT基因型对全脑或其他选定区域的体积没有影响。我们的研究结果支持了最近关于大麻使用相关神经解剖学变化的报道,并首次揭示这些变化可能受COMT基因型的影响。