Gil-Berrozpe Gustavo J, Segura Alex G, Sánchez-Torres Ana M, Amoretti Silvia, Giné-Servén Eloi, Vieta Eduard, Mezquida Gisela, Lobo Antonio, Gonzalez-Pinto Ana, Andreu-Bernabeu Alvaro, Roldán Alexandra, Forte Maria Florencia, Castro Josefina, Bergé Daniel, Rodríguez Natalia, Ballesteros Alejandro, Mas Sergi, Cuesta Manuel J, Bernardo Miquel
Servicio de Psiquiatría, Hospital Universitario de Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra, Pamplona, , IdiSNA, Spain.
Bipolar and Depressive Disorders Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
Eur Neuropsychopharmacol. 2025 Mar;92:52-61. doi: 10.1016/j.euroneuro.2024.12.002. Epub 2024 Dec 24.
Psychopathological manifestations and cognitive impairments are core features of psychotic disorders. Polygenic risk scores (PRS) offer insights into the relationships between genetic vulnerability, symptomatology, and cognitive impairments. This study used a network analysis to explore the connections between PRS, cognition, psychopathology, and overall functional outcomes in individuals experiencing a first episode of psychosis (FEP). The study sample comprised 132 patients with FEP. Genetic data were used to construct PRS for mental disorders and cognitive traits via PRS-continuous shrinkage. We conducted comprehensive clinical and neuropsychological assessments at 2 months post-diagnosis and again at a 2-year follow-up. A network analysis was performed to generate two distinct networks and their centrality indices, encompassing 19 variables across domains such as symptoms, cognition, functioning, and PRS. Variables were grouped within related domains, and stronger relationships were observed within domains than between them. PRS for schizophrenia showed weak negative associations with attention, working memory, and verbal memory, while PRS for cognitive performance showed weak positive associations with attention. Negative symptoms were negatively associated with functioning and verbal memory at both the 2-month and 2-year assessments, as well as with social cognition at 2 years. Poor functioning was moderately related to greater severity of Positive and Negative Syndrome Scale dimensions. This study identified pathways linking PRS, cognition, symptoms, and functioning, suggesting that genetic risk may serve as a marker of vulnerability and disorder progression. The findings also highlight the importance of considering genetic predispositions alongside clinical and cognitive factors to better understand the heterogeneity of psychotic disorders.
精神病理表现和认知障碍是精神障碍的核心特征。多基因风险评分（PRS）为了解遗传易感性、症状学和认知障碍之间的关系提供了见解。本研究采用网络分析来探索首次发作精神病（FEP）患者的PRS、认知、精神病理学和整体功能结局之间的联系。研究样本包括132名FEP患者。通过PRS连续收缩法，利用遗传数据构建精神障碍和认知特征的PRS。我们在诊断后2个月和2年随访时进行了全面的临床和神经心理学评估。进行网络分析以生成两个不同的网络及其中心性指数，涵盖症状、认知、功能和PRS等领域的19个变量。变量在相关领域内分组，观察到领域内的关系比领域间的关系更强。精神分裂症的PRS与注意力、工作记忆和言语记忆呈弱负相关，而认知表现的PRS与注意力呈弱正相关。在2个月和2年评估时，阴性症状与功能和言语记忆均呈负相关，在2年时与社会认知也呈负相关。功能不良与阳性和阴性症状量表维度的更高严重程度中度相关。本研究确定了连接PRS、认知、症状和功能的途径，表明遗传风险可能作为易感性和疾病进展的标志物。研究结果还强调了在临床和认知因素之外考虑遗传易感性对于更好理解精神障碍异质性的重要性。
