Mátyás Trixler
PTE AOK Pszichiátriai és Pszichoterápiás Klinika, Pécs.
Psychiatr Hung. 2006;21(6):404-12.
The author reviews relevant data on the neuropathology and molecular genetics of schizophrenia. Anatomical alterations are localized mainly in the hippocampus, dorsal thalamus and dorsolateral prefrontal cortex, and involve the morphology and molecular structure of the neurons and synapses. Several susceptibility genes [including COMT, dysbindin, neuregulin, DISCI, RGS4, GRM3, G72, PPP3CC, CHRNA7, PRODH2, Aktl, 5qGABA(A)] having physiological function in the brain have been identified and this supports the view of schizophrenia as a disorder of cerebral synaptic function. NMDA receptor-mediated glutamate transmission may be particularly involved, but disturbances of dopamine and GABA signalling seem to be linked as well. Based on recent data, an agreement is emerging between the roles of the genes on the molecular and synaptic levels and the understanding of the disorder at the neural systems level.
作者回顾了关于精神分裂症神经病理学和分子遗传学的相关数据。解剖学改变主要定位于海马体、背侧丘脑和背外侧前额叶皮层，涉及神经元和突触的形态及分子结构。已鉴定出多个在大脑中具有生理功能的易感基因[包括儿茶酚-O-甲基转移酶（COMT）、失调素、神经调节蛋白、精神分裂症相关断裂基因1（DISCI）、RGS4、代谢型谷氨酸受体3（GRM3）、G72、蛋白磷酸酶3催化亚基γ（PPP3CC）、α7烟碱型乙酰胆碱受体（CHRNA7）、脯氨酸脱氢酶2（PRODH2）、蛋白激酶B（Aktl）、5qγ-氨基丁酸A受体（5qGABA(A)）]，这支持了精神分裂症是一种大脑突触功能障碍的观点。N-甲基-D-天冬氨酸（NMDA）受体介导的谷氨酸传递可能尤其受到影响，但多巴胺和γ-氨基丁酸（GABA）信号传导的紊乱似乎也有关联。基于最近的数据，在基因在分子和突触水平的作用与对该疾病在神经系统水平的理解之间正逐渐达成共识。
