■严重精神疾病(SMI)症状的治疗,特别是精神分裂症的阴性症状和认知功能障碍,仍然是一个未满足的主要需求。有充分的证据表明,SMI具有很强的遗传背景,并且具有多种生物学改变的特征,包括大脑回路和连通性受到干扰,神经元兴奋抑制失调,多巴胺能和谷氨酸能途径受到干扰,和部分失调的炎症过程。失调的信号通路相互联系的方式在很大程度上仍然未知,部分原因是缺乏对综合生物材料的特征明确的临床研究。此外,治疗精神分裂症等SMI的药物的开发受到使用可操作的基于症状的聚类进行诊断的限制.
■根据研究领域标准倡议,临床深层表型(CDP)研究使用多模式方法,通过使用标准化的神经认知评估进行广泛的跨诊断临床表征来揭示临床相关精神分裂症亚组的神经生物学基础,多模态神经成像,电生理评估,视网膜检查,以及基于组学的血液和脑脊液分析。此外,为了弥合生物精神病学中的翻译鸿沟,这项研究包括对人类诱导的多能干细胞的体外研究,可以从参与者的子集获得。
■这里,我们报告了这种多式联运方法的可行性,已在CDP队列的第一批参与者中成功启动;迄今为止,该队列包括超过194名SMI患者和187名年龄和性别匹配的健康对照.此外,我们描述了应用研究模式和研究目标。
■识别患者的交叉诊断和诊断特异性生物型信息亚组以及这些亚组的翻译解剖可能有助于通过人工智能支持的定制干预措施和治疗为精准医学铺平道路。这个目标在精神病学中尤为重要,一个迫切需要创新的领域,因为特定的症状领域,如阴性症状和认知功能障碍,和治疗抵抗症状一般仍然难以治疗。
UNASSIGNED: Treatment of severe mental illness (SMI) symptoms, especially negative symptoms and cognitive dysfunction in schizophrenia, remains a major unmet need. There is good evidence that SMIs have a strong genetic background and are characterized by multiple biological alterations, including disturbed brain circuits and connectivity, dysregulated neuronal excitation-inhibition, disturbed dopaminergic and glutamatergic pathways, and partially dysregulated inflammatory processes. The ways in which the dysregulated signaling pathways are interconnected remains largely unknown, in part because well-characterized clinical studies on comprehensive biomaterial are lacking. Furthermore, the development of drugs to treat SMIs such as schizophrenia is limited by the use of operationalized symptom-based clusters for diagnosis.
UNASSIGNED: In line with the Research Domain Criteria initiative, the Clinical Deep Phenotyping (CDP)
study is using a multimodal approach to reveal the neurobiological underpinnings of clinically relevant schizophrenia subgroups by performing broad transdiagnostic clinical characterization with standardized neurocognitive assessments, multimodal neuroimaging, electrophysiological assessments, retinal investigations, and omics-based analyzes of blood and cerebrospinal fluid. Moreover, to bridge the translational gap in biological psychiatry the
study includes in vitro investigations on human-induced pluripotent stem cells, which are available from a subset of participants.
UNASSIGNED: Here, we report on the feasibility of this multimodal approach, which has been successfully initiated in the first participants in the CDP cohort; to date, the cohort comprises over 194 individuals with SMI and 187 age and gender matched healthy controls. In addition, we describe the applied research modalities and
study objectives.
UNASSIGNED: The identification of cross-diagnostic and diagnosis-specific biotype-informed subgroups of patients and the translational dissection of those subgroups may help to pave the way toward precision medicine with artificial intelligence-supported tailored interventions and treatment. This aim is particularly important in psychiatry, a field where innovation is urgently needed because specific symptom domains, such as negative symptoms and cognitive dysfunction, and treatment-resistant symptoms in general are still difficult to treat.