Mapping brain-behavior space relationships along the psychosis spectrum.
Mapping brain-behavior space relationships along the psychosis spectrum.
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DOI：
10.7554/elife.66968
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发表时间：
2021-07-20
期刊：
影响因子：
7.7
通讯作者：
Anticevic A
中科院分区：
文献类型：
--
作者：
Ji JL;Helmer M;Fonteneau C;Burt JB;Tamayo Z;Demšar J;Adkinson BD;Savić A;Preller KH;Moujaes F;Vollenweider FX;Martin WJ;Repovš G;Cho YT;Pittenger C;Murray JD;Anticevic A
在推进有效的精神疾病患者特异性治疗方面的困难突出了需要在神经和症状变异之间建立稳定的神经生物学基础映射。这种差距在精神病谱系障碍（PSD）中尤其严重。在这里，在436名跨越几种诊断的PSD患者的样本中，我们推导并复制了一个跨越标志性精神病理症状和认知缺陷的维度降低的症状空间。这些症状轴依次映射到不同的、可复制的大脑地图上。关键的是，我们发现多元脑行为映射技术（例如典型相关分析）在当前的样本量下不能产生稳定的结果。然而，我们表明单变量脑行为空间（BBS）可以解决稳定的个性化预测。最后，我们展示了一个原理证明框架，通过5 -羟色胺和谷氨酸受体的操作以及来自Allen人类大脑图谱的神经基因表达图，将个性化BBS指标与分子靶标联系起来。总的来说，这些结果突出了一个稳定的、数据驱动的跨PSD的BBS映射，它提供了一个可操作的路径，可以迭代优化个性化的临床生物标志物终点。
Difficulties in advancing effective patient-specific therapies for psychiatric disorders highlight a need to develop a stable neurobiologically grounded mapping between neural and symptom variation. This gap is particularly acute for psychosis-spectrum disorders (PSD). Here, in a sample of 436 PSD patients spanning several diagnoses, we derived and replicated a dimensionality-reduced symptom space across hallmark psychopathology symptoms and cognitive deficits. In turn, these symptom axes mapped onto distinct, reproducible brain maps. Critically, we found that multivariate brain-behavior mapping techniques (e.g. canonical correlation analysis) do not produce stable results with current sample sizes. However, we show that a univariate brain-behavioral space (BBS) can resolve stable individualized prediction. Finally, we show a proof-of-principle framework for relating personalized BBS metrics with molecular targets via serotonin and glutamate receptor manipulations and neural gene expression maps derived from the Allen Human Brain Atlas. Collectively, these results highlight a stable and data-driven BBS mapping across PSD, which offers an actionable path that can be iteratively optimized for personalized clinical biomarker endpoints.