Cortical Morphology Differences in Subjects at Increased Vulnerability for Developing a Psychotic Disorder: A Comparison between Subjects with Ultra-High Risk and 22q11.2 Deletion Syndrome

Introduction
Subjects with 22q11.2 deletion syndrome (22q11DS) and subjects with ultra-high risk for psychosis (UHR) share a risk of approximately 30% to develop a psychotic disorder. Studying these groups helps identify biological markers of pathophysiological processes involved in the development of psychosis. Total cortical surface area (cSA), total cortical grey matter volume (cGMV), cortical thickness (CT), and local gyrification index (LGI) of the cortical structure have a distinct neurodevelopmental origin making them important target markers to study in relation to the development of psychosis.
Materials and Methods
Structural T1-weighted high resolution images were acquired using a 3 Tesla Intera MRI system in 18 UHR subjects, 18 22q11DS subjects, and 24 matched healthy control (HC) subjects. Total cSA, total cGMV, mean CT, and regional vertex-wise differences in CT and LGI were assessed using FreeSurfer software. The Positive and Negative Syndrome Scale was used to assess psychotic symptom severity in UHR and 22q11DS subjects at time of scanning.
Results
22q11DS subjects had lower total cSA and total cGMV compared to UHR and HC subjects. The 22q11DS subjects showed bilateral lower LGI in the i) prefrontal cortex, ii) precuneus, iii) precentral gyrus and iv) cuneus compared to UHR subjects. Additionally, lower LGI was found in the left i) fusiform gyrus and right i) pars opercularis, ii) superior, and iii) inferior temporal gyrus in 22q11DS subjects compared to HC. In comparison to 22q11DS subjects, the UHR subjects had lower CT of the insula. For both risk groups, positive symptom severity was negatively correlated to rostral middle frontal gyrus CT.
Conclusion
A shared negative correlation between positive symptom severity and rostral middle frontal gyrus CT in UHR and 22q11DS may be related to their increased vulnerability to develop a psychotic disorder. 22q11DS subjects were characterised by widespread lower degree of cortical gyrification linked to early and postnatal neurodevelopmental pathology. No implications for early neurodevelopmental pathology were found for the UHR subjects, although they did have distinctively lower insula CT which may have arisen from defective pruning processes during adolescence. Implications of these findings in relation to development of psychotic disorders are in need of further investigation in longitudinal studies.

引言
携带22q11.2缺失综合征（22q11.2 deletion syndrome, 22q11DS）的受试者与精神病超高风险（ultra-high risk for psychosis, UHR）人群，发展为精神病性障碍的风险均约为30%。对这两类人群开展研究，有助于识别参与精神病性障碍发病的病理生理过程的生物标志物。皮层结构的总皮层表面积（total cortical surface area, cSA）、总皮层灰质体积（total cortical grey matter volume, cGMV）、皮层厚度（cortical thickness, CT）以及局部回指数（local gyrification index, LGI）具有明确的神经发育起源，因此是研究精神病性障碍发病机制的重要靶标标志物。

材料与方法
本研究采用3特斯拉Intera磁共振成像（MRI）系统，对18名UHR受试者、18名22q11DS受试者以及24名匹配的健康对照（healthy control, HC）受试者采集结构T1加权高分辨率图像。使用FreeSurfer软件评估总cSA、总cGMV、平均CT以及CT和LGI的区域顶点差异。在扫描时，采用阳性与阴性症状量表评估UHR受试者与22q11DS受试者的精神病性症状严重程度。

结果
相较于UHR受试者与健康对照受试者，22q11DS受试者的总cSA与总cGMV水平更低。与UHR受试者相比，22q11DS受试者在以下脑区出现双侧LGI降低：i）前额叶皮层、ii）楔前叶、iii）中央前回以及iv）楔叶。此外，相较于健康对照受试者，22q11DS受试者还在左侧i）梭状回以及右侧i）额下回岛盖部、ii）颞上回和iii）颞下回出现LGI降低。与22q11DS受试者相比，UHR受试者的岛叶CT水平更低。在两类高风险人群中，阳性症状严重程度均与额中回喙部CT呈负相关。

结论
UHR受试者与22q11DS受试者中，阳性症状严重程度与额中回喙部CT均呈负相关，这或许与二者罹患精神病性障碍的易感性升高有关。22q11DS受试者以广泛的皮层回化程度降低为特征，该改变与产前及产后神经发育病理密切相关。未发现UHR受试者存在与早期神经发育病理相关的影像学特征，但UHR受试者的岛叶CT显著降低，这可能源于青春期的突触修剪过程异常。上述发现与精神病性障碍发病的关联，尚需通过纵向研究开展进一步探索。