Mathalon Daniel H, Ford Judith M
Psychiatry Service, San Francisco VA Medical Center San Francisco, CA, USA.
Front Hum Neurosci. 2012 May 25;6:136. doi: 10.3389/fnhum.2012.00136. eCollection 2012.
In the last half-century, human neuroscience methods provided a way to study schizophrenia in vivo, and established that it is associated with subtle abnormalities in brain structure and function. However, efforts to understand the neurobiological bases of the clinical symptoms that the diagnosis is based on have been largely unsuccessful. In this paper, we provide an overview of the conceptual and methodological obstacles that undermine efforts to link the severity of specific symptoms to specific neurobiological measures. These obstacles include small samples, questionable reliability and validity of measurements, medication confounds, failure to distinguish state and trait effects, correlation-causation ambiguity, and the absence of compelling animal models of specific symptoms to test mechanistic hypotheses derived from brain-symptom correlations. We conclude with recommendations to promote progress in establishing brain-symptom relationships.
在过去的半个世纪里，人类神经科学方法为体内研究精神分裂症提供了一种途径，并证实它与大脑结构和功能的细微异常有关。然而，在理解诊断所依据的临床症状的神经生物学基础方面所做的努力大多没有成功。在本文中，我们概述了一些概念和方法上的障碍，这些障碍破坏了将特定症状的严重程度与特定神经生物学测量联系起来的努力。这些障碍包括样本量小、测量的可靠性和有效性存疑、药物混淆、未能区分状态和特质效应、相关因果关系不明确，以及缺乏用于检验从脑症状相关性得出的机制假说的特定症状的令人信服的动物模型。我们最后提出了一些建议，以促进在建立脑症状关系方面取得进展。
