Kraguljac Nina Vanessa, Lahti Adrienne Carol
Neuroimaging and Translational Research Laboratory, Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, United States.
Front Psychiatry. 2021 Mar 11;12:613764. doi: 10.3389/fpsyt.2021.613764. eCollection 2021.
Schizophrenia is a complex neuropsychiatric disorder with a diverse clinical phenotype that has a substantial personal and public health burden. To advance the mechanistic understanding of the illness, neuroimaging can be utilized to capture different aspects of brain pathology , including brain structural integrity deficits, functional dysconnectivity, and altered neurotransmitter systems. In this review, we consider a number of key scientific questions relevant in the context of neuroimaging studies aimed at unraveling the pathophysiology of schizophrenia and take the opportunity to reflect on our progress toward advancing the mechanistic understanding of the illness. Our data is congruent with the idea that the brain is fundamentally affected in the illness, where widespread structural gray and white matter involvement, functionally abnormal cortical and subcortical information processing, and neurometabolic dysregulation are present in patients. Importantly, certain brain circuits appear preferentially affected and subtle abnormalities are already evident in first episode psychosis patients. We also demonstrated that brain circuitry alterations are clinically relevant by showing that these pathological signatures can be leveraged for predicting subsequent response to antipsychotic treatment. Interestingly, dopamine D2 receptor blockers alleviate neural abnormalities to some extent. Taken together, it is highly unlikely that the pathogenesis of schizophrenia is uniform, it is more plausible that there may be multiple different etiologies that converge to the behavioral phenotype of schizophrenia. Our data underscore that mechanistically oriented neuroimaging studies must take non-specific factors such as antipsychotic drug exposure or illness chronicity into consideration when interpreting disease signatures, as a clear characterization of primary pathophysiological processes is an imperative prerequisite for rational drug development and for alleviating disease burden in our patients.
精神分裂症是一种复杂的神经精神障碍，具有多样的临床表型，给个人和公共卫生带来了沉重负担。为了深入了解该疾病的发病机制，可以利用神经影像学来捕捉脑病理学的不同方面，包括脑结构完整性缺陷、功能连接障碍以及神经递质系统改变。在这篇综述中，我们思考了一些与神经影像学研究相关的关键科学问题，这些研究旨在揭示精神分裂症的病理生理学，并借此反思我们在推进对该疾病发病机制理解方面所取得的进展。我们的数据与以下观点一致：在该疾病中大脑受到根本性影响，患者存在广泛的灰质和白质结构受累、皮质和皮质下信息处理功能异常以及神经代谢失调。重要的是，某些脑回路似乎受到优先影响，且在首发精神病患者中已经明显存在细微异常。我们还通过表明这些病理特征可用于预测抗精神病治疗的后续反应，证明了脑回路改变与临床相关。有趣的是，多巴胺D2受体阻滞剂在一定程度上可缓解神经异常。综上所述，精神分裂症的发病机制极不可能是单一的，更有可能的是存在多种不同病因，它们共同导致了精神分裂症的行为表型。我们的数据强调，在解释疾病特征时，以机制为导向的神经影像学研究必须考虑抗精神病药物暴露或疾病慢性化等非特异性因素，因为明确原发性病理生理过程是合理药物开发和减轻患者疾病负担的必要前提。
