Sankar Anjali, Scheinost Dustin, Goldman Danielle A, Drachman Rebecca, Colic Lejla, Villa Luca M, Kim Jihoon A, Gonzalez Yarani, Marcelo Imani, Shinomiya Mei, Pittman Brian, Lacadie Cheryl M, Oquendo Maria A, Constable R Todd, Blumberg Hilary P
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.
Transl Psychiatry. 2022 Jan 10;12(1):7. doi: 10.1038/s41398-021-01767-z.
Brain targets to lower the high risk of suicide in Bipolar Disorder (BD) are needed. Neuroimaging studies employing analyses dependent on regional assumptions could miss hubs of dysfunction critical to the pathophysiology of suicide behaviors and their prevention. This study applied intrinsic connectivity distribution (ICD), a whole brain graph-theoretical approach, to identify hubs of functional connectivity (FC) disturbances associated with suicide attempts in BD. ICD, from functional magnetic resonance imaging data acquired while performing a task involving implicit emotion regulation processes important in BD and suicide behaviors, was compared across 40 adults with BD with prior suicide attempts (SAs), 49 with BD with no prior attempts (NSAs) and 51 healthy volunteers (HVs). Areas of significant group differences were used as seeds to identify regional FC differences and explore associations with suicide risk-related measures. ICD was significantly lower in SAs than in NSAs and HVs in bilateral ventromedial prefrontal cortex (vmPFC) and right anterior insula (RaIns). Seed connectivity revealed altered FC from vmPFC to bilateral anteromedial orbitofrontal cortex, left ventrolateral PFC (vlPFC) and cerebellum, and from RaIns to right vlPFC and temporopolar cortices. VmPFC and RaIns ICD were negatively associated with suicidal ideation severity, and vmPFC ICD with hopelessness and attempt lethality severity. The findings suggest that SAs with BD have vmPFC and RaIns hubs of dysfunction associated with altered FC to other ventral frontal, temporopolar and cerebellar cortices, and with suicidal ideation, hopelessness, and attempt lethality. These hubs may be targets for novel therapeutics to reduce suicide risk in BD.
降低双相情感障碍（BD）自杀高风险的大脑靶点是必要的。采用依赖区域假设分析的神经影像学研究可能会遗漏对自杀行为病理生理学及其预防至关重要的功能障碍枢纽。本研究应用内在连接分布（ICD），一种全脑图谱理论方法，来识别与BD自杀未遂相关的功能连接（FC）紊乱枢纽。从在执行一项涉及BD和自杀行为中重要的内隐情绪调节过程的任务时获取的功能磁共振成像数据中得出的ICD，在40名有过自杀未遂（SA）的BD成年患者、49名无自杀未遂（NSA）的BD患者和51名健康志愿者（HV）中进行了比较。显著组间差异的区域被用作种子，以识别区域FC差异并探索与自杀风险相关测量指标的关联。在双侧腹内侧前额叶皮层（vmPFC）和右侧前岛叶（RaIns），SA组的ICD显著低于NSA组和HV组。种子连接显示从vmPFC到双侧眶额内侧皮层、左侧腹外侧前额叶皮层（vlPFC）和小脑，以及从RaIns到右侧vlPFC和颞极皮层的FC发生改变。VmPFC和RaIns的ICD与自杀观念严重程度呈负相关，vmPFC的ICD与绝望感和自杀未遂致死严重程度呈负相关。研究结果表明，BD伴SA患者具有vmPFC和RaIns功能障碍枢纽，这些枢纽与到其他腹侧额叶、颞极和小脑皮层的FC改变有关，也与自杀观念、绝望感和自杀未遂致死率有关。这些枢纽可能是降低BD自杀风险的新型治疗靶点。
