Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Mol Psychiatry. 2020 Apr;25(4):863-872. doi: 10.1038/s41380-018-0269-0. Epub 2018 Oct 3.
Although schizophrenia is considered a brain disorder, the role of brain organization for symptomatic improvement remains inadequately defined. We investigated the relationship between baseline brain morphology, resting-state network connectivity and clinical response after 24-weeks of antipsychotic treatment in patients with schizophrenia (n = 95) using integrated multivariate analyses. There was no significant association between clinical response and measures of cortical thickness (r = 0.37, p = 0.98) and subcortical volume (r = 0.56, p = 0.15). By contrast, we identified a strong mode of covariation linking functional network connectivity to clinical response (r = 0.70; p = 0.04), and particularly to improvement in positive (weight = 0.62) and anxious/depressive symptoms (weight = 0.49). Higher internal cohesiveness of the default mode network was the single most important positive predictor. Key negative predictors involved the functional cohesiveness of central executive subnetworks anchored in the frontoparietal cortices and subcortical regions (including the thalamus and striatum) and the inter-network integration between the default mode and sensorimotor networks. The present findings establish links between clinical response and the functional organization of brain networks involved both in perception and in spontaneous and goal-directed cognition, thereby advancing our understanding of the pathophysiology of schizophrenia.
尽管精神分裂症被认为是一种脑部疾病，但大脑组织结构与症状改善之间的关系仍未得到充分定义。我们使用综合多元分析方法，研究了 95 例精神分裂症患者的基线大脑形态、静息态网络连接与抗精神病治疗 24 周后的临床反应之间的关系。临床反应与皮质厚度（r=0.37，p=0.98）和皮质下体积（r=0.56，p=0.15）之间无显著相关性。相比之下，我们发现了一种将功能网络连接与临床反应联系起来的强模式（r=0.70；p=0.04），特别是与阳性症状（权重=0.62）和焦虑/抑郁症状（权重=0.49）的改善有关。默认模式网络的内部一致性是最重要的阳性预测指标。关键的阴性预测指标涉及到以额顶叶皮层和皮质下区域（包括丘脑和纹状体）为锚点的中央执行子网的功能一致性，以及默认模式网络和感觉运动网络之间的网络间整合。这些发现确立了临床反应与涉及感知、自发和目标导向认知的大脑网络功能组织之间的联系，从而加深了我们对精神分裂症病理生理学的理解。
