Convergent Evidence from Multimodal Imaging Reveals Amygdala Abnormalities in Schizophrenic Patients and Their First-Degree Relatives

BackgroundShared neuropathological features between schizophrenic patients and their first-degree relatives have potential as indicators of genetic vulnerability to schizophrenia. We sought to explore genetic influences on brain morphology and function in schizophrenic patients and their relatives. MethodsUsing a multimodal imaging strategy, we studied 33 schizophrenic patients, 55 of their unaffected parents, 30 healthy controls for patients, and 29 healthy controls for parents with voxel-based morphometry of structural MRI scans and functional connectivity analysis of resting-state functional MRI data. ResultsSchizophrenic patients showed widespread gray matter reductions in the bilateral frontal cortices, bilateral insulae, bilateral occipital cortices, left amygdala and right thalamus, whereas their parents showed more localized reductions in the left amygdala, left thalamus and right orbitofrontal cortex. Patients and their parents shared gray matter loss in the left amygdala. Further investigation of the resting-state functional connectivity of the amygdala in the patients showed abnormal functional connectivity with the bilateral orbitofrontal cortices, bilateral precunei, bilateral dorsolateral frontal cortices and right insula. Their parents showed slightly less, but similar changes in the pattern in the amygdala connectivity. Co-occurrences of abnormal connectivity of the left amygdala with the left orbitofrontal cortex, right dorsolateral frontal cortex and right precuneus were observed in schizophrenic patients and their parents. ConclusionsOur findings suggest a potential genetic influence on structural and functional abnormalities of the amygdala in schizophrenia. Such information could help future efforts to identify the endophenotypes that characterize the complex disorder of schizophrenia.研究背景：精神分裂症患者与其一级亲属共有的神经病理特征，有望作为精神分裂症遗传易感性的指示指标。本研究旨在探讨精神分裂症患者及其亲属的脑形态与功能所受的遗传影响。 研究方法：本研究采用多模态成像策略，对33名精神分裂症患者、55名患者的未受累父母、30名与患者组匹配的健康对照以及29名与父母组匹配的健康对照，开展结构磁共振成像（structural MRI）的基于体素的形态测量学（voxel-based morphometry, VBM）分析，以及静息态功能磁共振成像（resting-state functional MRI）的功能连接分析。 研究结果：精神分裂症患者双侧额叶皮层、双侧脑岛、双侧枕叶皮层、左侧杏仁核及右侧丘脑均出现广泛的灰质体积减少；而其父母仅在左侧杏仁核、左侧丘脑及右侧眶额皮层出现更局限的灰质减少。患者与父母共有的灰质丢失区域为左侧杏仁核。进一步对患者的杏仁核静息态功能连接进行分析发现，其与双侧眶额皮层、双侧楔前叶、双侧背外侧额叶皮层及右侧脑岛的功能连接存在异常。其父母的杏仁核连接模式虽改变程度较轻，但与患者存在相似的变化趋势。精神分裂症患者与其父母均观察到左侧杏仁核与左侧眶额皮层、右侧背外侧额叶皮层及右侧楔前叶的功能连接异常共存现象。 研究结论：本研究结果表明，遗传因素可能对精神分裂症患者杏仁核的结构与功能异常存在潜在影响。该发现可为未来识别表征精神分裂症这一复杂疾病的内表型（endophenotype）提供助力。