The use of antipsychotic medication to manage psychosis, principally in those with a diagnosis of schizophrenia or bipolar disorder, is well established. Antipsychotics are effective in normalizing positive symptoms of psychosis in the short term (delusions, hallucinations and disordered thought). Their long-term use is, however, associated with side effects, including several types of movement (extrapyramidal syndrome, dyskinesia, akathisia), metabolic and cardiac disorders. Furthermore, higher lifetime antipsychotic dose-years may be associated with poorer cognitive performance and blunted affect, although the mechanisms driving the latter associations are not well understood. In this article, we propose a novel model of the long-term effects of antipsychotic administration focusing on the changes in brain metabolic homeostasis induced by the medication. We propose here that the brain metabolic normalization, that occurs in parallel to the normalization of psychotic symptoms following antipsychotic treatment, may not ultimately be sustainable by the cerebral tissue of some patients; these patients may be characterized by already reduced oxidative metabolic capacity and this may push the brain into an unsustainable metabolic envelope resulting in tissue remodeling. To support this perspective, we will review the existing data on the brain metabolic trajectories of patients with a diagnosis of schizophrenia as indexed using available neuroimaging tools before and after use of medication. We will also consider data from pre-clinical studies to provide mechanistic support for our model.

中文翻译：

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使异常正常化：抗精神病药物是否会将皮质推入不可持续的代谢范围？


使用抗精神病药物来治疗精神病，尤其是诊断为精神分裂症或双相情感障碍的患者，已得到广泛认可。抗精神病药物可以在短期内有效地使精神病的阳性症状（妄想、幻觉和思维混乱）正常化。然而，长期使用它们会产生副作用，包括几种类型的运动（锥体外系综合征、运动障碍、静坐不能）、代谢和心脏疾病。此外，较高的终生抗精神病药物剂量年数可能与较差的认知能力和迟钝的情感有关，尽管驱动后者关联的机制尚不清楚。在本文中，我们提出了一种抗精神病药物长期影响的新模型，重点关注药物引起的大脑代谢稳态的变化。我们在此提出，与抗精神病药物治疗后精神病症状正常化同时发生的大脑代谢正常化可能最终无法由某些患者的脑组织维持；这些患者的特征可能是氧化代谢能力已经降低，这可能会将大脑推入不可持续的代谢范围，导致组织重塑。为了支持这一观点，我们将回顾关于被诊断为精神分裂症的患者的大脑代谢轨迹的现有数据，这些数据使用现有的神经影像工具在使用药物之前和之后进行索引。我们还将考虑临床前研究的数据，为我们的模型提供机制支持。