Kimel Family Translational Imaging Genetics Research Laboratory, The Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada.
Campbell Family Mental Health Research Institute, The Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada.
Neuropsychopharmacology. 2019 Aug;44(9):1649-1658. doi: 10.1038/s41386-019-0408-6. Epub 2019 May 6.
Structural and functional cortico-striatal-thalamic-cortical (CSTC) circuit abnormalities have been observed in schizophrenia and the clinical high-risk state. However, this circuit is sexually dimorphic and changes across neurodevelopment. We examined effects of sex and age on structural and functional properties of the CSTC circuit in a large sample of youth with and without psychosis spectrum symptoms (PSS) from the Philadelphia Neurodevelopmental Cohort. T1-weighted and resting-state functional MRI scans were collected on a 3T Siemens scanner, in addition to participants' cognitive and psychopathology data. After quality control, the total sample (aged 11-21) was n = 1095 (males = 485, females = 610). Structural subdivisions of the striatum and thalamus were identified using the MAGeT Brain segmentation tool. Functional seeds were segmented based on brain network connectivity. Interaction effects among PSS group, sex, and age on striatum, thalamus, and subdivision volumes were examined. A similar model was used to test effects on functional connectivity of the CSTC circuit. A sex by PSS group interaction was identified, whereby PSS males had higher volumes and PSS females had lower volumes in striatal and thalamic subdivisions. Reduced functional striato-cortical connectivity was found in PSS youth, primarily driven by males, whereby younger male PSS youth also exhibited thalamo-cortical hypo-connectivity (compared to non-PSS youth), vs. striato-cortical hyper-connectivity in older male PSS youth (compared to non-PSS youth). Youth with PSS demonstrate sex and age-dependent differences in striatal and thalamic subdivision structure and functional connectivity. Further efforts at biomarker discovery and early therapeutic intervention targeting the CSTC circuit in psychosis should consider effects of sex and age.
结构和功能皮质纹状体丘脑皮质（CSTC）回路异常已在精神分裂症和临床高风险状态中观察到。然而，该回路存在性别二态性，并在神经发育过程中发生变化。我们在费城神经发育队列中，对有和没有精神病谱症状（PSS）的大量青年进行了研究，检查了性别和年龄对 CSTC 回路的结构和功能特性的影响。除了参与者的认知和精神病理学数据外，还在 3T 西门子扫描仪上采集了 T1 加权和静息状态功能磁共振成像扫描。经过质量控制，总样本（年龄 11-21 岁）n=1095（男性=485，女性=610）。使用 MAGeT Brain 分割工具识别纹状体和丘脑的结构细分。根据脑网络连接性分割功能种子。检验 PSS 组、性别和年龄对纹状体、丘脑和细分体积的交互作用。使用类似的模型检验 CSTC 回路功能连接的影响。确定了 PSS 组、性别和年龄之间的交互作用，即 PSS 男性的纹状体和丘脑细分体积较高，而 PSS 女性的纹状体和丘脑细分体积较低。发现 PSS 年轻人的纹状体皮质功能连接减少，主要是男性，年轻男性 PSS 年轻人还表现出丘脑皮质连接不足（与非 PSS 年轻人相比），而年长男性 PSS 年轻人表现出纹状体皮质连接过度（与非 PSS 年轻人相比）。患有 PSS 的年轻人在纹状体和丘脑细分结构和功能连接方面表现出性别和年龄依赖性差异。在精神病 CSTC 回路的生物标志物发现和早期治疗干预方面，应进一步考虑性别和年龄的影响。
