Lin Bei, Li Xian-Bin, Ruan Sen, Wu Yu-Xin, Zhang Chao-Yue, Wang Chuan-Yue, Wang Lu-Bin
The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, 100850, China.
The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, China.
Schizophrenia (Heidelb). 2022 Jun 4;8(1):55. doi: 10.1038/s41537-022-00261-9.
High-risk populations of schizophrenia can be mainly identified as genetic high-risk based on putative endophenotypes or ultra-high-risk (UHR) based on clinically manifested symptoms. Previous studies have consistently shown brain structural abnormalities in both genetic high-risk and UHR individuals. In this study, we aimed to disentangle the convergent and divergent pattern of gray matter alterations between UHR and unaffected first-degree relatives from genetic high-risk individuals. We used structural MRI scans and voxel-based morphometry method to examine gray matter volume (GMV) differences among 23 UHR subjects meeting the Structured Interview for Prodromal Syndromes (SIPS) criteria, 18 unaffected first-degree relatives (UFDR), 26 first-episode schizophrenia patients (FES) and 54 healthy controls (CN). We found that a number of brain regions exhibited a monotonically decreasing trend of GMV from CN to UFDR to UHR to FES. Compared with CN, the UHR subjects showed significant decreases of GMV similar to the patients in the inferior temporal gyrus, fusiform gyrus, middle occipital gyrus, insula, and limbic regions. Moreover, the UHR transformed subgroup had significantly lower GMV than UHR non-transformed subgroup in the right inferior temporal/fusiform gyrus. On the other hand, the UFDR subjects only showed significant GMV decreases in the inferior temporal gyrus and fusiform. Moreover, we found GMV in the occipital lobe was negatively correlated with the UHR subjects' composite positive symptom of SIPS, and GMV in the cerebellum was positively correlated with FES subjects' symptom severity. Our results suggest that GMV deficits and regional dysfunction are evident prior to the onset of psychosis and are more prominent in the UHR than the UFDR individuals.
精神分裂症的高危人群主要可基于假定的内表型被确定为遗传高危人群，或基于临床表现症状被确定为超高危（UHR）人群。以往研究一致表明，遗传高危人群和超高危人群均存在脑结构异常。在本研究中，我们旨在厘清超高危人群与遗传高危个体的未患病一级亲属之间灰质改变的趋同和差异模式。我们使用结构磁共振成像扫描和基于体素的形态测量方法，检查了23名符合前驱综合征结构化访谈（SIPS）标准的超高危受试者、18名未患病一级亲属（UFDR）、26名首发精神分裂症患者（FES）和54名健康对照（CN）之间的灰质体积（GMV）差异。我们发现，从健康对照到未患病一级亲属，再到超高危人群，最后到首发精神分裂症患者，多个脑区的灰质体积呈现出单调递减趋势。与健康对照相比，超高危受试者在颞下回、梭状回、枕中回、脑岛和边缘区域的灰质体积显著减少，与患者相似。此外，超高危转化亚组在右侧颞下回/梭状回的灰质体积显著低于未转化亚组。另一方面，未患病一级亲属仅在颞下回和梭状回表现出显著的灰质体积减少。此外，我们发现枕叶的灰质体积与超高危受试者的SIPS综合阳性症状呈负相关，小脑的灰质体积与首发精神分裂症患者的症状严重程度呈正相关。我们的结果表明，灰质体积缺陷和区域功能障碍在精神病发作之前就很明显，并且在超高危人群中比未患病一级亲属更为突出。
