The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder
The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder
复制标题
DOI：
10.1016/j.biopsych.2019.03.985
复制
发表时间：
2019-10-01
影响因子：
10.6
通讯作者：
van Haren, Neeltje E. M.
中科院分区：
文献类型：
--
作者：
de Zwarte, Sonja M. C.;Brouwer, Rachel M.;van Haren, Neeltje E. M.
背景：精神分裂症和双相情感障碍有共同的遗传倾向，并且两种疾病都有一些共同的脑结构异常。精神分裂症患者的一级亲属（FDRS-SZ）表现出与患者相似的大脑异常，尽管效应量较小。双相情感障碍患者（FDRS-BD）一级亲属的影像学表现在过去一直不一致，但最近的研究报告与对照组相比，区域性更大的体积。我们对6008名个体的整体和皮层下大脑测量进行了荟萃分析（1228例FDRs-SZ，852例FDRs-BD，2246例对照受试者，1016例精神分裂症患者，666例双相情感障碍患者）来自34个精神分裂症和/或双相情感障碍家族队列，采用标准化方法。结果：FDRS-BD组的颅内容积明显大于对照组（d =+10.16，q <0.05），而FDRS-SZ组的丘脑容积小于对照组（d =-0.12，q <0.05）。ICV解释了FDR-BD中脑测量的放大。在FDRS-SZ中，校正ICV后，全脑、皮质灰质、大脑白色物质、小脑灰质和白色物质以及丘脑体积显著较小;皮质较薄（d <-0.09，q <0.05校正）;第三脑室较大（d =+0.15，q <0.05校正）。调查结果没有解释的精神病理学的亲属或对照subjects.CONCLUSIONS：尽管共享的遗传倾向，FDRS-SZ和FDRS-BD表现出不同的模式的结构性脑异常，特别是在ICV的发散效应。这可能意味着导致精神分裂症或双相情感障碍患者大脑异常的神经发育轨迹是不同的。
BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects.METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects.RESULTS: FDRs-BD had significantly larger ICV (d = +10.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects.CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.