精神疾病个体化治疗的生物标志物。

Expert opinion on medical diagnostics Pub Date : 2013-09-01 Epub Date: 2013-07-22 DOI:10.1517/17530059.2013.821979
Gyorgy Bagdy, Gabriella Juhasz
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引用次数: 7

摘要

精神疾病的生物标志物研究被症状模式相关的诊断类别所延迟,这些诊断类别与生物学机制仅具有较远的相关性。在具有高遗传性的神经精神疾病(精神分裂症、自闭症、阿尔茨海默病)中,基因组研究通过增加病例对照研究的受试者数量,导致了显著的全基因组关联研究(GWAS)结果,从而为这些疾病的病因学提供了新的假设,并为新的治疗方法的研究提供了可能的目标。相比之下,在中度遗传性精神障碍(焦虑症、单极重度抑郁症)中,除了风险基因外,症状的发展更多地取决于特定环境风险因素的存在。因此,控制异质性,而不是简单地增加受试者数量,对于进一步显著的精神病学GWAS发现至关重要,这些发现保证了收集更详细的个体表型数据和有关先前环境暴露的信息。基因-基因相互作用(上位性)和中间表型或精神和躯体共病,通过在诊断类别中识别类似病例,可能进一步增加个体基因的普遍微弱作用,限制其作为生物标志物的用途。总之,我们认为,在给定的精神疾病中,适合识别生物学上更均匀的亚群的方法对于推进生物标志物研究是必要的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Biomarkers for personalised treatment in psychiatric diseases.

Biomarker research of psychiatric disorders is delayed by symptom pattern-related diagnostic categories that are only distantly associated with biological mechanisms. In neuropsychiatric disorders that have high heritability (schizophrenia, autism, Alzheimer's disease), genomic research led to significant genome-wide association study (GWAS) results by increasing the number of subjects in case-control studies, and thus provided new hypotheses regarding the aetiology of these disorders and possible targets for research of new treatment approaches. In contrast, in moderately heritable psychiatric disorders (anxiety disorders, unipolar major depression), the development of symptoms, in addition to risk genes, is more dependent on the presence of specific environmental risk factors. Thus, controlling for heterogeneity, and not simply increasing the number of subjects, is crucial for further significant psychiatric GWAS findings that warrant the collection of more detailed individual phenotypic data and information about relevant previous environmental exposures. Gene-gene interactions (epistasis) and intermediate phenotypes or psychiatric and somatic co-morbidities, by identifying similar cases within a diagnostic category, could further increase the generally weak effects of individual genes that limit their usefulness as biomarkers. In conclusion, we argue that methods that are suitable to identify biologically more homogeneous subgroups within a given psychiatric disorder are necessary to advance biomarker research.

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