Anterior Hippocampal-Cortical Functional Connectivity Distinguishes Antipsychotic Naive First-Episode Psychosis Patients From Controls and May Predict Response to Second-Generation Antipsychotic Treatment
Anterior Hippocampal-Cortical Functional Connectivity Distinguishes Antipsychotic Naive First-Episode Psychosis Patients From Controls and May Predict Response to Second-Generation Antipsychotic Treatment
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DOI：
10.1093/schbul/sbz076
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发表时间：
2020-05-01
影响因子：
6.6
通讯作者：
Goff, Donald C.
中科院分区：
文献类型：
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作者：
Blessing, Esther M.;Murty, Vishnu P.;Goff, Donald C.
背景：一致的证据表明前海马与精神分裂症的近端病理生理学有关。尽管静息态功能连接（FC）有望表征前海马回路异常及其与治疗反应的关系，但该技术尚未以区分前海马和后海马的方式用于首发精神病（FEP）患者。方法：我们使用双重回归的掩蔽海马组独立成分分析来对比健康对照（HC）和未接受抗精神病药物的 FEP 患者（N = 61,36 名女性）之间的次区域海马全脑 FC。在 FEP 患者的子样本（N = 27，其中 15 名女性）中，我们在第二代抗精神病药物治疗 8 周后重复了这一分析，并探讨了基线 FC 是否可以使用随机森林预测治疗反应。结果：相对于 HC，未经治疗的 FEP 受试者在左前内侧海马和皮质区域（包括前扣带回和岛叶皮质）之间表现出可重复的较低 FC（P < .05，已校正）。治疗后 FEP 患者的前内侧海马 FC 增加 (P < .005)，与 HC 不再有差异。随机森林分析显示基线前内侧海马 FC 具有四个脑区，即岛盖皮层、额上回、中央前回和中央后回，预测治疗反应（曲线下面积 = 0.95）。结论：初次使用抗精神病药物的 FEP 与先前与精神分裂症有关的前海马区和皮质区之间的 FC 较低有关。初步分析表明，基于海马 FC 的随机森林模型可以预测 FEP 患者的治疗反应，因此可能成为治疗开发的有用生物标志物。
Background: Converging evidence implicates the anterior hippocampus in the proximal pathophysiology of schizophrenia. Although resting state functional connectivity (FC) holds promise for characterizing anterior hippocampal circuit abnormalities and their relationship to treatment response, this technique has not yet been used in first-episode psychosis (FEP) patients in a manner that distinguishes the anterior from posterior hippocampus. Methods: We used masked-hippocampal-group-independent component analysis with dual regression to contrast subregional hippocampal-whole brain FC between healthy controls (HCs) and antipsychotic naive FEP patients (N= 61,36 female). In a subsample of FEP patients (N = 27, 15 female), we repeated this analysis following 8 weeks of second-generation antipsychotic treatment and explored whether baseline FC predicted treatment response using random forest. Results: Relative to HC, untreated FEP subjects displayed reproducibly lower FC between the left anteromedial hippocampus and cortical regions including the anterior cingulate and insular cortex (P < .05, corrected). Anteromedial hippocampal FC increased in FEP patients following treatment (P < .005), and no longer differed from HC. Random forest analysis showed baseline anteromedial hippocampal FC with four brain regions, namely the insular-opercular cortex, superior frontal gyrus, precentral gyrus, and postcentral gyrus predicted treatment response (area under the curve = 0.95). Conclusions: Antipsychotic naive FEP is associated with lower FC between the anterior hippocampus and cortical regions previously implicated in schizophrenia. Preliminary analysis suggests that random forest models based on hippocampal FC may predict treatment response in FEP patients, and hence could be a useful biomarker for treatment development.