Department of Psychiatry, Melbourne Brain Centre, The University of Melbourne Parkville, VIC, Australia.
Front Cell Neurosci. 2013 Jun 26;7:95. doi: 10.3389/fncel.2013.00095. eCollection 2013.
Post-mortem brain investigations of schizophrenia have generated swathes of data in the last few decades implicating candidate genes and protein. However, the relation of these findings to peripheral biomarker indicators and symptomatology remain to be elucidated. While biomarkers for disease do not have to be involved with underlying pathophysiology and may be largely indicative of diagnosis or prognosis, the ideal may be a biomarker that is involved in underlying disease processes and which is therefore more likely to change with progression of the illness as well as potentially being more responsive to treatment. One of the main difficulties in conducting biomarker investigations for major psychiatric disorders is the relative inconsistency in clinical diagnoses between disorders such as bipolar and schizophrenia. This has led some researchers to investigate biomarkers associated with core symptoms of these disorders, such as psychosis. The aim of this review is to evaluate the contribution of post-mortem brain investigations to elucidating the pathophysiology pathways involved in schizophrenia and psychosis, with an emphasis on major neurotransmitter systems that have been implicated. This data will then be compared to functional neuroimaging findings as well as findings from blood based gene expression investigations in schizophrenia in order to highlight the relative overlap in pathological processes between these different modalities used to elucidate pathogenesis of schizophrenia. In addition we will cover some recent and exciting findings demonstrating microRNA (miRNA) dysregulation in both the blood and the brain in patients with schizophrenia. These changes are pertinent to the topic due to their known role in post-transcriptional modification of gene expression with the potential to contribute or underlie gene expression changes observed in schizophrenia. Finally, we will discuss how post-mortem studies may aid future biomarker investigations.
在过去的几十年中，对精神分裂症的死后大脑研究产生了大量数据，这些数据暗示了候选基因和蛋白质的存在。然而，这些发现与外周生物标志物指标和症状之间的关系仍有待阐明。虽然疾病的生物标志物不一定与潜在的病理生理学有关，并且可能主要表明诊断或预后，但理想的情况是与潜在疾病过程有关的生物标志物，因此随着疾病的进展更有可能发生变化，并且可能对治疗更敏感。在进行重大精神疾病的生物标志物研究时，主要困难之一是双相情感障碍和精神分裂症等疾病之间的临床诊断相对不一致。这导致一些研究人员研究与这些疾病的核心症状（如精神病）相关的生物标志物。本综述的目的是评估死后大脑研究对阐明精神分裂症和精神病涉及的病理生理学途径的贡献，重点是涉及的主要神经递质系统。然后，将这些数据与功能神经影像学发现以及精神分裂症中基于血液的基因表达研究的发现进行比较，以突出这些用于阐明精神分裂症发病机制的不同方式之间的病理过程的相对重叠。此外，我们将介绍一些最近令人兴奋的发现，这些发现表明精神分裂症患者的血液和大脑中存在 microRNA（miRNA）失调。这些变化与该主题相关，因为它们在基因表达的转录后修饰中具有已知的作用，有可能导致或导致精神分裂症中观察到的基因表达变化。最后，我们将讨论死后研究如何有助于未来的生物标志物研究。
