Palomo Tomas, Kostrzewa Richard M, Beninger Richard J, Archer Trevor
Psychiatry Service, 12 de Octubre, University Hospital, Madrid 28041, Spain.
Neurotox Res. 2007 Jul;12(1):29-42. doi: 10.1007/BF03033899.
Genetic factors underlying alcoholism, substance abuse, antisocial and violent behaviour, psychosis, schizophrenia and psychopathy are emerging to implicate dopaminergic and cannabinoid, but also monoaminergic and glutamatergic systems through the maze of promoter genes and polymorphisms. Candidate gene association studies suggest the involvement of a range of genes in different disorders of CNS structure and function. Indices of comorbidity both complicate the array of gene-involvement and provide a substrate of hazardous interactivity. The putative role of the serotonin transporter gene in affective-dissociative spectrum disorders presents both plausible genetic variation and complication of comorbidity The position of genetic variation is further complicated through ethnic, contextual and social factors that provide geometric progressions in the comordity already underlying diagnostic obstacles. The concept of shared biological susceptibility to two or more disorder conditions of comorbidity seems a recurring observation, e.g., bipolar disorder with alcoholism or schizophrenia with alcohol/substance abuse or diabetes with schizopsychotic disorder. Several lines of evidence seem to suggest that the factors influencing variation in one set of symptoms and those affecting one or more disorders are observed to a marked extent which ought to facilitate the search for susceptibility genes in comorbid brain disorders. Identification of regional genetic factors is awaited for a more compelling outline that ought eventually to lead to greater efficacy of symptom-disorder arrangements and an augmentation of current pharmacological treatment therapies.
酗酒、药物滥用、反社会和暴力行为、精神病、精神分裂症及精神变态背后的遗传因素正逐渐显现,表明多巴胺能和大麻素系统,以及单胺能和谷氨酸能系统通过启动子基因和多态性的迷宫而受到牵连。候选基因关联研究表明一系列基因参与了中枢神经系统结构和功能的不同紊乱。共病指数既使基因参与的情况变得复杂,又提供了有害相互作用的基础。血清素转运体基因在情感解离谱系障碍中的假定作用既呈现出合理的基因变异,又存在共病的复杂性。基因变异的情况因种族、背景和社会因素而进一步复杂化,这些因素在已经构成诊断障碍的共病中呈几何级数增长。对两种或更多共病状况具有共同生物易感性的概念似乎是一个反复出现的观察结果,例如,双相情感障碍与酗酒,或精神分裂症与酒精/药物滥用,或糖尿病与精神分裂症性障碍。几条证据线索似乎表明,在很大程度上观察到了影响一组症状变异的因素以及影响一种或多种疾病的因素,这应该有助于在共病脑部疾病中寻找易感基因。期待确定区域遗传因素,以获得更具说服力的概述,最终应该会提高症状-疾病安排的疗效,并增强当前的药物治疗方法。