Wiggins Jillian Lee, Brotman Melissa A, Adleman Nancy E, Kim Pilyoung, Wambach Caroline G, Reynolds Richard C, Chen Gang, Towbin Kenneth, Pine Daniel S, Leibenluft Ellen
Emotion and Development Branch, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD; San Diego State University and San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology.
Emotion and Development Branch, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD.
J Am Acad Child Adolesc Psychiatry. 2017 Jan;56(1):67-78. doi: 10.1016/j.jaac.2016.10.009. Epub 2016 Nov 2.
Bipolar disorder (BD) is highly heritable. Neuroimaging studies comparing unaffected youth at high familial risk for BD (i.e., those with a first-degree relative with the disorder; termed "high-risk" [HR]) to "low-risk" (LR) youth (i.e., those without a first-degree relative with BD) and to patients with BD may help identify potential brain-based markers associated with risk (i.e., regions where HR+BD≠LR), resilience (HR≠BD+LR), or illness (BD≠HR+LR).
During functional magnetic resonance imaging (fMRI), 99 youths (i.e., adolescents and young adults) aged 9.8 to 24.8 years (36 BD, 22 HR, 41 LR) performed a task probing face emotion labeling, previously shown to be impaired behaviorally in youth with BD and HR youth.
We found three patterns of results. Candidate risk endophenotypes (i.e., where BD and HR shared deficits) included dysfunction in higher-order face processing regions (e.g., middle temporal gyrus, dorsolateral prefrontal cortex). Candidate resilience markers and disorder sequelae (where HR and BD, respectively, show unique alterations relative to the other two groups) included different patterns of neural responses across other regions mediating face processing (e.g., fusiform), executive function (e.g., inferior frontal gyrus), and social cognition (e.g., default network, superior temporal sulcus, temporo-parietal junction).
If replicated in longitudinal studies and with additional populations, neural patterns suggesting risk endophenotypes could be used to identify individuals at risk for BD who may benefit from prevention measures. Moreover, information about risk and resilience markers could be used to develop novel treatments that recruit neural markers of resilience and attenuate neural patterns associated with risk. Clinical trial registration information-Studies of Brain Function and Course of Illness in Pediatric Bipolar Disorder and Child and Adolescent Bipolar Disorder Brain Imaging and Treatment Study; http://clinicaltrials.gov/; NCT00025935 and NCT00006177.
双相情感障碍（BD）具有高度遗传性。神经影像学研究将双相情感障碍高家族风险的未患病青年（即有该疾病一级亲属的青年；称为“高风险”[HR]）与“低风险”（LR）青年（即无双相情感障碍一级亲属的青年）以及双相情感障碍患者进行比较，可能有助于识别与风险（即HR + BD ≠ LR的区域）、恢复力（HR ≠ BD + LR）或疾病（BD ≠ HR + LR）相关的潜在脑标志物。
在功能磁共振成像（fMRI）期间，99名年龄在9.8至24.8岁的青年（即青少年和青年成年人）（36名双相情感障碍患者、22名高风险青年、41名低风险青年）执行了一项探测面部情绪标签的任务，此前已证明该任务在双相情感障碍青年和高风险青年中存在行为障碍。
我们发现了三种结果模式。候选风险内表型（即双相情感障碍患者和高风险青年共有的缺陷）包括高阶面部加工区域（如颞中回、背外侧前额叶皮质）功能障碍。候选恢复力标志物和疾病后遗症（分别为高风险青年和双相情感障碍患者相对于其他两组表现出独特改变的情况）包括在介导面部加工（如梭状回）、执行功能（如额下回）和社会认知（如默认网络、颞上沟、颞顶联合区）的其他区域的不同神经反应模式。
如果在纵向研究和其他人群中得到重复验证，提示风险内表型的神经模式可用于识别可能从预防措施中受益的双相情感障碍风险个体。此外，关于风险和恢复力标志物的信息可用于开发新的治疗方法，这些方法利用恢复力的神经标志物并减弱与风险相关的神经模式。临床试验注册信息 - 儿童双相情感障碍的脑功能与病程研究以及儿童和青少年双相情感障碍脑成像与治疗研究；http://clinicaltrials.gov/；NCT00025935和NCT00006177。
