Longitudinal neuroimaging and neurocognitive assessment of risk and protective factors across the schizophrenia spectrum

项目总结 分裂型人格障碍(SPD)与精神分裂症(SZ)相似，但数量较少，程度较轻 异常，因此代表了一个重要但未被充分研究的中间SZ谱表型。 对SPD异常的检查将提供有关病因、遗传学、治疗和风险的信息。 与精神病有关的因素。尽管SPD患者表现出明显的颞叶 类似于SZ的异常，我们假设 额叶(例如，背外侧前额叶皮质)可以保护这些人免受坦率的精神病和 严重的社会和认知缺陷通常在深圳观察到。研究SPD是一种强大的抗精神病药物 在深圳观察到的用药和住院混淆并不存在。此外，也没有研究 检查SZ谱中的神经生物学变化，该谱结合了SPD患者 这里提出的纵向设计。这一新的方法将有助于理清潜在的风险和保护 SZ谱系中的精神病因素。这是第一次利用多模式磁共振成像进行纵向研究。 和研究领域标准(RDoC)方法在SZ谱系障碍中识别异常神经 从健康对照组(HCS)到SPD再到SZ的连续回路，并检查这些指标的变化 与症状严重程度、神经认知和功能结果的损害有关。我们建议 研究了三组(每组80人)的人口统计匹配和严格诊断的个人(18岁- 40)：HCS(无轴心I或人格障碍)，未服药的SPD患者(无轴心I障碍)，以及 基线、9个月和18个月随访的早发性(患病头2年)SZ患者。措施评估 额叶和颞叶的完整性包括多模式磁共振成像(结构MRI、DTI、静息状态fMRI和 基于任务的功能磁共振成像，采用非语言事件相关工作记忆任务；基线和18个月)和 神经心理评估(所有三个时间点)。我们将利用动态因果模型来测试 相互竞争的神经生物学模型涉及SZ频谱中异常的额颞部连接和 集成多模式神经成像、神经认知和临床评估的机器学习方法 数据。本研究的主要目的有三：(1)研究额-颞叶/环路的纵向运动过程 应用多模式磁共振成像研究SZ谱的异常；(2)研究SZ谱的纵向过程 SZ谱中的神经认知、临床和功能结果；(3)决定哪种因素或组合 的因素来区分SZ谱中的群体，以识别那些与罹患和 使用机器学习保护SZ。

PROJECT SUMMARY Schizotypal personality disorder (SPD) is similar to schizophrenia (SZ), but with fewer and attenuated abnormalities, thus representing an important yet understudied intermediate SZ-spectrum phenotype. Examination of abnormalities in SPD will provide information regarding etiology, genetics, treatment and risk factors associated with psychosis. Although individuals with SPD demonstrate marked temporal lobe abnormalities that resemble SZ, we hypothesize that relative “sparing” or “functional enhancement” in the frontal lobes (e.g., dorsolateral prefrontal cortex), may protect these individuals from frank psychosis and the severe social and cognitive deficits typically observed in SZ. Studying SPD is powerful as antipsychotic medication and hospitalization confounds observed in SZ are not present. Moreover, there is no study examining neurobiological changes in the SZ-spectrum that incorporates individuals with SPD using a longitudinal design as proposed here. This novel approach will help disentangle potential risk and protective factors for psychosis in the SZ spectrum. This is the first longitudinal study to utilize multimodal MR imaging and Research Domain Criteria (RDoC) approaches in SZ-spectrum disorders to identify aberrant neural circuitry along a continuum from healthy controls (HCs) to SPD to SZ and examine changes in these measures in relationship to impairments in symptom severity, neurocognition and functional outcome. We propose studying three groups (80 in each) of demographically matched and rigorously diagnosed individuals (age 18- 40): HCs (no Axis I or personality disorder), unmedicated individuals with SPD (and no Axis I disorder), and early-onset (first 2 years of illness) SZ patients at baseline, 9-, and 18-month follow-up. Measures assessing frontal and temporal lobe integrity include multimodal MR imaging (structural MRI, DTI, resting-state fMRI, and task-based fMRI with a nonverbal event related working-memory task; baseline and 18-months) and neuropsychological assessment (all three timepoints). We will utilize dynamic causal modeling to test competing neurobiological models involving abnormal frontotemporal connectivity in the SZ-spectrum and machine learning approaches to integrate multimodal neuroimaging, neurocognitive, and clinical assessment data. We focus on three specific aims: (1) Investigate the longitudinal course of frontal-temporal lobe/circuitry abnormalities in the SZ-spectrum using multimodal MR imaging; (2) Investigate the longitudinal course of neurocognition, clinical, and functional outcome in the SZ spectrum; (3) Determine which factor or combination of factors differentiate groups in the SZ-spectrum to identify those that are associated with risk for and protection from SZ using machine learning.