Forte M Florencia, Clougher Derek, Segura Àlex G, Mezquida Gisela, Sánchez-Torres Ana Maria, Vieta Eduard, Garriga Marina, Lobo Antonio, González-Pinto Ana M, Diaz-Caneja Covadonga M, Roldan Alexandra, Martínez-Arán Anabel, de la Serna Elena, Mané Anna, Mas Sergi, Torrent Carla, Allot Kelly, Bernardo Miquel, Amoretti Silvia
Bipolar and Depressive Disorders Unit, Hospital Clinic of Barcelona, Institute of Neurosciences, IDIBAPS, Barcelona, Catalonia, Spain.
University of Barcelona, Barcelona, Catalonia, Spain.
Acta Psychiatr Scand. 2024 Dec 25;151(5):600-12. doi: 10.1111/acps.13779.
Studies have shown associations between polygenic risk scores for educational attainment (PRS), cognitive reserve (CR), cognition, negative symptoms (NS), and psychosocial functioning in first-episode psychosis (FEP). However, their specific interactions remain unclear. This study aimed to investigate the mediating roles of CR, cognition, and NS in the relationship between PRS and psychosocial functioning one year after a FEP. Additionally, we sought to explore the impact of two NS subtypes on this relationship: diminished Expression (EXP-NS) and Motivation and Pleasure (MAP-NS).
A total of 138 FEP participants, predominantly male (70%), with a mean age of 24.77 years (SD = 5.29), underwent genetic, clinical, and cognitive assessments two months after study enrollment. Functioning evaluation followed at one-year follow-up. To investigate the mediating role of CR, cognition, and NS in the relationship between PRS and functioning, a serial mediation model was employed. Two further mediation models were tested to explore the differential impact of EXP-NS and MAP-NS. Mediation analysis was performed using the PROCESS macro version 4.1 within SPSS version 26.
The serial mediation model revealed a causal chain for PRS > CR > cognition > NS > Functioning (β = -3.08, 95%CI [-5.73, -0.43], p = 0.023). When differentiating by type of NS, only EXP-NS were significantly associated in the casual chain (β = -0.17, 95% CI [-0.39, -0.01], p < 0.05).
CR, cognition and NS -specifically EXP-NS- mediate the association between PRS and psychosocial functioning at one-year follow-up in FEP patients. These results highlight the potential for personalized interventions based on genetic predisposition.
研究表明，教育成就多基因风险评分（PRS）、认知储备（CR）、认知、阴性症状（NS）与首发精神病（FEP）患者的心理社会功能之间存在关联。然而，它们之间的具体相互作用尚不清楚。本研究旨在调查FEP发病一年后，CR、认知和NS在PRS与心理社会功能关系中的中介作用。此外，我们试图探讨两种NS亚型对这种关系的影响：表达减退型（EXP-NS）和动机与快感缺乏型（MAP-NS）。
共有138名FEP参与者，以男性为主（70%），平均年龄24.77岁（标准差=5.29），在入组研究两个月后接受了基因、临床和认知评估。在一年随访时进行功能评估。为了研究CR、认知和NS在PRS与功能关系中的中介作用，采用了系列中介模型。还测试了另外两个中介模型，以探讨EXP-NS和MAP-NS的不同影响。使用SPSS 26版本中的PROCESS宏版本4.1进行中介分析。
系列中介模型揭示了一条因果链：PRS＞CR＞认知＞NS＞功能（β=-3.08，95%置信区间[-5.73，-0.43]，p=0.023）。按NS类型进行区分时，只有EXP-NS在因果链中显著相关（β=-0.17，95%置信区间[-0.39，-0.01]，p＜0.05）。
在FEP患者发病一年后的随访中，CR、认知以及特定的EXP-NS介导了PRS与心理社会功能之间的关联。这些结果凸显了基于遗传易感性进行个性化干预的潜力。
