Dean Charles E
Tardive Dyskinesia Assessment Clinic, Minneapolis VA Medical Center, One Veterans Drive, Minneapolis Minnesota 55417, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2006 Mar;30(2):174-89. doi: 10.1016/j.pnpbp.2005.08.019. Epub 2005 Dec 22.
The increasingly wide-spread use of antipsychotics in both adults and children calls for a detailed examination of antipsychotic-associated neuronal changes in the brain, and whether these changes are toxic, therapeutic, or perhaps irrelevant to the outcome of major psychiatric disorders, especially schizophrenia. In this review we will examine the extensive evidence demonstrating both acute and longer-term antipsychotic-associated neurotoxicity and neuroplasticity, as well as the more specific cellular changes that appear to underlie these phenomena. These include changes in proteins affecting cell survival, impairment of the mitochondrial respiratory chain, increases in DNA fragmentation, injury to dendritic microtubules, increases in dopamine-generated reactive oxygen species, changes in cell morphology, and rapid induction of apoptosis. We shall also examine the correlation between these changes and alterations in gross brain structure. There appears to be a disjunction between the widespread cellular and gross structural brain changes in schizophrenia, and the duration of illness, expression of symptoms, and response to treatment. We shall explore possible explanations for this apparent paradox.
抗精神病药物在成人和儿童中的使用日益广泛，这就需要详细研究抗精神病药物相关的大脑神经元变化，以及这些变化是有毒性的、治疗性的，还是可能与主要精神疾病（尤其是精神分裂症）的预后无关。在这篇综述中，我们将研究大量证据，这些证据表明了抗精神病药物相关的急性和长期神经毒性及神经可塑性，以及似乎是这些现象基础的更具体的细胞变化。这些变化包括影响细胞存活的蛋白质变化、线粒体呼吸链损伤、DNA片段化增加、树突微管损伤、多巴胺产生的活性氧增加、细胞形态变化以及凋亡的快速诱导。我们还将研究这些变化与大脑总体结构改变之间的相关性。精神分裂症中广泛的细胞和大脑总体结构变化与病程、症状表达及治疗反应之间似乎存在脱节。我们将探讨这一明显矛盾的可能解释。
