基于神经影像指标的早发精神分裂症早期识别与发展轨迹研究

Compared with adult-onset schizophrenia, early-onset schizophrenia (EOS) is characteristic of more significant prodromal neurodevelopmental abnormalities, more severe genetic burden and worse outcome of prognosis. Furthermore, a large portion of the EOS patients have been in the state of ultra high risk (UHR) for psychosis before onset of the illness. However, the features of brain structure and function of EOS and its dynamic changes are still unclear. Based on prior research progress in EOS and normal brain development as well as our preliminary work, we proposed that children and adolescents with UHR may demonstrate distinct neuroimaging patterns associated with transition to schizophrenia, EOS may exhibit altered patterns of neural circuits and neurodevelopment. We plan to perform the following work: 1) collecting clinical and other phenotypic data as well as multimodal magnetic resonance imaging (MRI) data from children and adolescents with UHR, first-episode and chronic patients with EOS as well as healthy controls; 2) following up the first-episode patients with EOS and individuals with UHR for 8 weeks and 1 year respectively, collecting the above measurements again; 3) comparing the MRI measurements among the groups, correlating them with the phenotypic information; 4) comparing the MRI measurements between baseline and follow-up in the first-episode EOS group and UHR group respectively, comparing brain structural and functional differences among subgroups of UHR individuals transiting to schizophrenia and those who do not transit to schizophrenia. With the above work, we attempt to explore the characteristics and developmental trajectories of EOS and its influence factors. This research will not only shed light on exploration of the neural basis of EOS, but also provide new theoretical evidence for early identification, prediction of response to antipsychotics and prognosis, as well as individualized intervention for EOS.

较成年患者而言，早发精神分裂症表现为更显著的前驱期神经发育异常、更严重的家族遗传负担，长期预后更差，多数患儿起病前已处于超高危风险状态，但其脑结构功能模态和动态变化特点尚不明确。基于现有研究进展、本课题组前期工作及正常人脑发展研究现状，我们假设：精神病超高危风险儿童青少年存在与临床转归相关的特异性神经影像指标；早发精神分裂症存在特异性脑结构功能改变；随年龄增长及病程发展，早发精神分裂症表现为特定的脑发展轨迹。本研究拟纳入精神病超高危风险状态儿童青少年、首发和长病程的早发精神分裂症患者及健康对照人群，收集上述研究对象基线和追踪后的神经影像及临床表型、神经认知、社会心理指标，探索早发精神分裂症的脑结构功能特点、动态发展变化趋势及其影响因素，寻找有助于早发精神分裂症早期识别、疗效预测、预后判断的客观指标，为其早期、个体化干预提供理论依据。

早发精神分裂症患者较成年起病者表现为更显著的前驱期神经发育异常和不良预后，多数患儿起病前已处于超高危风险状态。本项目纳入了精神病超高危状态人群、首发和长病程的早发精神分裂症患者及健康对照，拟探讨上述人群的神经影像表型特点，以期寻找有助于早发精神分裂症早期识别、预后判断相关的客观指标。本项目主要发现：（1）首发的早发精神分裂症患者左侧伏隔核与右侧颞上回、左侧顶上回功能连接增强，右侧伏隔核与左侧枕中回功能连接增强；（2）首发的早发精神分裂症患者较超高危患者及对照组均表现为双侧壳核静息状态局部一致性（regional homogeneity,ReHo）增高；（3）健康对照、精神病超高危患者、精神分裂症患者三组被试的额中回ReHo值呈下降趋势；（4）精神病超高危患者较健康对照表现为右侧小脑、左侧海马/海马旁回ReHo值增高，右侧额中回、右侧额上回ReHo值降低；（5）长病程精神分裂症患者较首发患者及精神病超高危人群均表现为右侧顶下小叶/颞上回及左侧额中回ReHo值升高，左侧中央后回ReHo值降低。上述结果提示：（1）早发精神分裂症存在奖赏与动机环路关键节点（伏隔核）与感觉运动整合、认知加工相关脑区（颞叶、顶叶、枕叶）间功能联系的失衡；（2）壳核功能异常增高可能是精神分裂症发病的特异性指标；（3）额上回功能异常可能是出现精神病风险、进而罹患精神分裂症的早期识别指标；（4）精神病超高危患者存在额叶-边缘-小脑环路功能异常；（5）顶叶、颞叶交界区及额中回功能异常可能与精神分裂症慢性化过程相关。本项目初步发现了精神病超高危状态人群及早发精神分裂症特异性的脑功能特点，以及随疾病发展的脑功能变化模式，相关结果有待在更大样本量及追踪研究、多指标分析中加以验证。