Eyal Asor, Dorit Ben-Shachar, Laboratory of Psychobiology, Department of Psychiatry, Rambam Medical Center and B. Rappaport Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Technion, PO Box 9649, Haifa 31096, Israel.
World J Psychiatry. 2012 Dec 22;2(6):124-33. doi: 10.5498/wjp.v2.i6.124.
Schizophrenia is a severe mental disorder, characterized by behavioral, emotional and cognitive disturbances, which commonly follows a chronic course. Diagnostic accuracy, management plans, treatment evaluation and prognosis are dependent on relatively subjective assessments. Despite extensive research and improvement in imaging technology, as well as modern genetic and molecular methodologies, the biological basis of this disease is still unclear. Therefore, there is a need for objective and valid biological markers. Platelets have often been used as a model in neurobiological research. The accessibility of platelets and their similarities with neurons turns them into an attractive candidate to search for biological markers for diagnosis and for unraveling pathophysiological processes relevant to the etiology of brain disorders, including schizophrenia. The present review addresses the main changes in platelet physiology observed in schizophrenia and its response to antipsychotic medication. We summarize numerous studies demonstrating impaired metabolism, uptake and receptor kinetics of schizophrenia-relevant neurotransmitters, abnormalities in membrane derived phospholipids and polyunsaturated fatty acids, as well as dysfunctions in the mitochondria. These changes fit with the various hypotheses raised for the etiology of schizophrenia, including the dopamine-glutamate hypothesis, the autoimmune hypothesis, the polyunsaturated fatty acid hypothesis and the impaired energy metabolism hypothesis. Despite extensive research in platelets, no conclusive reliable biomarker has been identified yet. This review suggests that the clinical heterogeneity and the biological complexity of schizophrenia lead to the inevitable conclusion that biomarkers will be identified only for subgroups characterized according to the different diagnostic criteria. Moreover, any biomarker would have to be an array of interrelated factors or even a set of several such arrays.
精神分裂症是一种严重的精神障碍,其特征为行为、情感和认知障碍,通常呈慢性病程。诊断准确性、管理计划、治疗评估和预后都依赖于相对主观的评估。尽管影像学技术的广泛研究和改进,以及现代遗传和分子方法学的发展,这种疾病的生物学基础仍不清楚。因此,需要客观和有效的生物学标志物。血小板经常被用作神经生物学研究的模型。血小板的可及性及其与神经元的相似性使它们成为寻找生物标志物的有吸引力的候选物,可用于诊断和阐明与脑疾病病因学相关的病理生理过程,包括精神分裂症。本综述介绍了精神分裂症中观察到的血小板生理学的主要变化及其对抗精神病药物的反应。我们总结了许多研究,这些研究表明精神分裂症相关神经递质的代谢、摄取和受体动力学受损,膜衍生磷脂和多不饱和脂肪酸异常,以及线粒体功能障碍。这些变化与精神分裂症病因学提出的各种假说相符,包括多巴胺-谷氨酸假说、自身免疫假说、多不饱和脂肪酸假说和能量代谢受损假说。尽管在血小板中进行了广泛的研究,但尚未确定明确可靠的生物标志物。本综述表明,精神分裂症的临床异质性和生物学复杂性不可避免地得出结论,即只有根据不同的诊断标准对亚组进行特征描述,才能确定生物标志物。此外,任何生物标志物都将是相互关联的因素数组,甚至是几个这样数组的集合。