Okada Naohiro, Fukunaga Masaki, Miura Kenichiro, Nemoto Kiyotaka, Matsumoto Junya, Hashimoto Naoki, Kiyota Masahiro, Morita Kentaro, Koshiyama Daisuke, Ohi Kazutaka, Takahashi Tsutomu, Koeda Michihiko, Yamamori Hidenaga, Fujimoto Michiko, Yasuda Yuka, Hasegawa Naomi, Narita Hisashi, Yokoyama Satoshi, Mishima Ryo, Kawashima Takahiko, Kobayashi Yuko, Sasabayashi Daiki, Harada Kenichiro, Yamamoto Maeri, Hirano Yoji, Itahashi Takashi, Nakataki Masahito, Hashimoto Ryu-Ichiro, Tha Khin K, Koike Shinsuke, Matsubara Toshio, Okada Go, van Erp Theo G M, Jahanshad Neda, Yoshimura Reiji, Abe Osamu, Onitsuka Toshiaki, Watanabe Yoshiyuki, Matsuo Koji, Yamasue Hidenori, Okamoto Yasumasa, Suzuki Michio, Turner Jessica A, Thompson Paul M, Ozaki Norio, Kasai Kiyoto, Hashimoto Ryota
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
The International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo Institutes for Advanced Study (UTIAS), Tokyo, Japan.
Mol Psychiatry. 2023 Dec;28(12):5206-5216. doi: 10.1038/s41380-023-02141-9. Epub 2023 Aug 4.
Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.
在实际的精神科环境中，依据当前基于症状和体征的诊断系统进行鉴别诊断有时会很困难。人们期望能创建一种使用客观生物标志物的新型诊断系统。神经影像学研究及其他研究报告称，皮层下脑结构是各种心理行为功能的枢纽，然而，目前尚无基于神经影像学数据的临床标准能够克服当前诊断系统的局限性，而这些标准应能反映认知/社会功能。在进行主要分析之前，我们对5,604名受试者（3,078名对照者和2,526名患者）的T1加权图像进行了一项关于精神分裂症、双相情感障碍、重度抑郁症和自闭症谱系障碍患者皮层下体积及侧化改变的大规模多中心研究。我们发现，精神分裂症、双相情感障碍和重度抑郁症患者的侧脑室体积更大，精神分裂症和双相情感障碍患者的海马体体积更小，精神分裂症患者的杏仁核、丘脑和伏隔核体积有特异性减小，而尾状核、壳核和苍白球体积增大。此外，我们特别观察到，精神分裂症患者苍白球体积的侧化出现向左改变。此外，作为我们的主要目标，我们根据皮层下体积对这5,604名受试者进行了聚类，并探讨了数据驱动的聚类结果是否能够解释亚组中的认知/社会功能。我们展示了一种四种生物类型的分类，即边缘区域极度（脑生物类型[BB]1）和中度较小（BB2）、基底神经节较大（BB3）以及体积正常（BB4），它们与认知/社会功能相关。具体而言，BB1和BB2 - 3分别与严重和轻度认知/社会损害相关，而BB4的特征是认知/社会功能正常。我们的研究结果可能会促使未来创建基于生物数据的新型精神科诊断标准，有望用于预测或治疗选择。
