Giuliani Luigi, Sanmarchi Francesco, Mucci Armida, Rucci Paola, Caporusso Edoardo, Bucci Paola, Giordano Giulia M, Amore Mario, Rocca Paola, Rossi Alessandro, Bertolino Alessandro, Galderisi Silvana, Maj Mario
Department of Psychiatry, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Schizophrenia (Heidelb). 2025 Jan 3;11(1):1. doi: 10.1038/s41537-024-00545-2.
The present study aimed to investigate the causal relationships among cognitive impairment, psychopathology, and real-life functioning in a large sample of people with schizophrenia, using a data-driven causal discovery procedure based on partial ancestral graphs (PAGs). This method may provide additional insights for the identification of potential therapeutic targets to promote recovery in people with chronic schizophrenia. State-of-the-art instruments were used to assess the study variables. Two PAGs were generated at baseline and after 4 years of follow-up to model the nature of the causal relationships linking psychopathology, cognition, and functioning. The study sample was composed of more than 600 clinically stable patients with schizophrenia at two time points. The PAGs model indicated that working memory impairment is the first ancestor of the causal links, influencing all the other neurocognitive domains, social cognition, and functional capacity, which in turn affects everyday life functioning. From this domain of functioning a causal link is directed to disorganization and positive symptoms, and another to work skills and interpersonal relationships domains; the latter had a direct link to asociality and the other domains of negative symptoms. The structure of the PAGs did not differ significantly between baseline and follow-up, indicating the stability of the causal relationship model investigated cross-sectionally at both time points. The role of working memory impairment in the pathways to functional outcomes in schizophrenia highlights the importance of implementing integrated pharmacological and cognitive remediation interventions targeting neurocognition. The impact of everyday life and interpersonal functioning on the clinical presentation of schizophrenia suggests that integrated and personalized treatments, promoting relevant skills to improve these functional outcomes, may have a beneficial impact on clinical outcomes.
本研究旨在使用基于部分祖先图（PAG）的数据驱动因果发现程序，调查大量精神分裂症患者样本中认知障碍、精神病理学和现实生活功能之间的因果关系。这种方法可能为识别潜在治疗靶点以促进慢性精神分裂症患者康复提供更多见解。使用了最先进的工具来评估研究变量。在基线和4年随访后生成了两个PAG，以模拟连接精神病理学、认知和功能的因果关系的性质。研究样本由两个时间点的600多名临床稳定的精神分裂症患者组成。PAG模型表明，工作记忆损害是因果联系的首要祖先，影响所有其他神经认知领域、社会认知和功能能力，而这反过来又影响日常生活功能。从这个功能领域出发，一条因果联系指向紊乱和阳性症状，另一条指向工作技能和人际关系领域；后者与社交障碍和其他阴性症状领域有直接联系。PAG的结构在基线和随访之间没有显著差异，表明在两个时间点进行横断面研究的因果关系模型具有稳定性。工作记忆损害在精神分裂症功能结局途径中的作用突出了实施针对神经认知的综合药物和认知补救干预措施的重要性。日常生活和人际功能对精神分裂症临床表现的影响表明，促进相关技能以改善这些功能结局的综合和个性化治疗可能对临床结局产生有益影响。
