School of Psychiatry, University of New South Wales, Randwick, Australia (Roberts, Ridgway, Leung, Mitchell); Department of Clinical Neurosciences, University of Cambridge, and Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, U.K. (Perry); Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, U.K. (Perry); QIMR Berghofer Medical Research Institute, Brisbane, Australia (Perry, Breakspear); School of Psychology, College of Science, and Discipline of Psychiatry, College of Health and Medicine, University of Newcastle, Newcastle, Australia (Campbell, Breakspear); Neuroscience Research Australia, Randwick, Australia (Lenroot); University of New Mexico, Albuquerque (Lenroot).
Am J Psychiatry. 2022 May;179(5):350-361. doi: 10.1176/appi.ajp.21010047. Epub 2022 Mar 28.
Recent studies of patients with bipolar disorder or at high genetic risk reveal structural dysconnections among key brain networks supporting cognitive and affective processes. Understanding the longitudinal trajectories of these networks across the peak age range of bipolar disorder onset could inform mechanisms of illness onset or resilience.
Longitudinal diffusion-weighted MRI and phenotypic data were acquired at baseline and after 2 years in 183 individuals ages 12-30 years in two cohorts: 97 unaffected individuals with a first-degree relative with bipolar disorder (the high-risk group) and 86 individuals with no family history of mental illness (the control group). Whole-brain structural networks were derived using tractography, and longitudinal changes in these networks were studied using network-based statistics and mixed linear models.
Both groups showed widespread longitudinal changes, comprising both increases and decreases in structural connectivity, consistent with a shared neurodevelopmental process. On top of these shared changes, high-risk participants showed weakening of connectivity in a network encompassing the left inferior and middle frontal areas, left striatal and thalamic structures, the left fusiform, and right parietal and occipital regions. Connections among these regions strengthened in the control group, whereas they weakened in the high-risk group, shifting toward a cohort with established bipolar disorder. There was marginal evidence for even greater network weakening in those who had their first manic or hypomanic episode before follow-up.
Neurodevelopment from adolescence into early adulthood is associated with a substantial reorganization of structural brain networks. Differences in these maturational processes occur in a multisystem network in individuals at high genetic risk of bipolar disorder. This may represent a novel candidate to understand resilience and predict conversion to bipolar disorder.
最近对双相情感障碍患者或遗传风险较高的患者的研究揭示了支持认知和情感过程的关键大脑网络之间的结构连接中断。了解这些网络在双相情感障碍发病高峰期的纵向轨迹，可以为发病机制或恢复能力提供信息。
在两个队列中，对 183 名年龄在 12-30 岁的个体，在基线时和 2 年后，分别采集了纵向弥散加权 MRI 和表型数据：一个队列由 97 名无家族精神病史的个体组成（高风险组），其一级亲属有双相情感障碍；另一个队列由 86 名个体组成（对照组），其一级亲属无精神病史。使用轨迹追踪法得出全脑结构网络，并用基于网络的统计学和混合线性模型研究这些网络的纵向变化。
两组均表现出广泛的纵向变化，包括结构连接的增加和减少，这与共同的神经发育过程一致。在这些共同变化的基础上，高风险组的一个包括左侧额中回和额下回、左侧纹状体和丘脑结构、左侧梭状回以及右侧顶叶和枕叶区域的网络的连接强度减弱。对照组中这些区域的连接增强，而高风险组中这些区域的连接减弱，向已确诊为双相情感障碍的队列转移。在随访前有首次躁狂或轻躁狂发作的患者中，网络进一步减弱的证据更为充分。
从青春期到成年早期的神经发育与结构大脑网络的大量重组有关。在遗传上易患双相情感障碍的个体中，这些成熟过程的差异发生在一个多系统网络中。这可能代表了一种新的候选物，可用于理解恢复能力和预测双相情感障碍的转化。
