Koutsouleris Nikolaos, Buciuman Madalina-Octavia, Vetter Clara Sophie, Weyer Clara Francesca Charlotte, Zhutovsky Paul, Perdomo Santiago Tovar, Khuntia Adyasha, Milaneschi Yuri, Popovic David, Ruef Anne, Dwyer Dominic, Chisholm Katharine, Kambeitz Lana, Antonucci Linda, Ruhrmann Stephan, Kambeitz Joseph, Riecher-Rössler Anita, Upthegrove Rachel, Salokangas Raimo, Hietala Jarmo, Pantelis Christos, Lencer Rebekka, Meisenzahl Eva, Wood Stephen, Brambilla Paolo, Borgwardt Stefan, Bertolino Alessandro, Falkai Peter
Ludwig-Maximilians-University.
Amstedam Medical Center.
Res Sq. 2024 Mar 13:rs.3.rs-3949072. doi: 10.21203/rs.3.rs-3949072/v1.
Symptom heterogeneity characterizes psychotic disorders and hinders the delineation of underlying biomarkers. Here, we identify symptom-based subtypes of recent-onset psychosis (ROP) patients from the multi-center PRONIA (Personalized Prognostic Tools for Early Psychosis Management) database and explore their multimodal biological and functional signatures. We clustered N = 328 ROP patients based on their maximum factor scores in an exploratory factor analysis on the items. We assessed inter-subgroup differences and compared to N = 464 healthy control (HC) individuals regarding gray matter volume (GMV), neurocognition, polygenic risk scores, and longitudinal functioning trajectories. Finally, we evaluated factor stability at 9- and 18-month follow-ups. A 4-factor solution optimally explained symptom heterogeneity, showing moderate longitudinal stability. The ROP-MOTCOG () subgroup was characterized by GMV reductions within salience, control and default mode networks, predominantly throughout cingulate regions, relative to HC individuals, had the most impaired neurocognition and the highest genetic liability for schizophrenia. ROP-SOCWD () patients showed GMV reductions within medial fronto-temporal regions of the control, default mode, and salience networks, and had the lowest social functioning across time points. ROP-POS () evidenced GMV decreases in salience, limbic and frontal regions of the control and default mode networks. The ROP-AFF () subgroup showed GMV reductions in the salience, limbic, and posterior default-mode and control networks, thalamus and cerebellum. GMV reductions in fronto-temporal regions of the salience and control networks were shared across subgroups. Our results highlight the existence of behavioral subgroups with distinct neurobiological and functional profiles in early psychosis, emphasizing the need for refined symptom-based diagnosis and prognosis frameworks.
症状异质性是精神障碍的特征，阻碍了潜在生物标志物的识别。在此，我们从多中心PRONIA（早期精神病管理个性化预后工具）数据库中识别近期发病精神病（ROP）患者基于症状的亚型，并探索其多模态生物学和功能特征。我们在对这些项目的探索性因素分析中，根据N = 328名ROP患者的最大因素得分进行聚类。我们评估了亚组间差异，并与N = 464名健康对照（HC）个体在灰质体积（GMV）、神经认知、多基因风险评分和纵向功能轨迹方面进行了比较。最后，我们在9个月和18个月的随访中评估了因素稳定性。一个4因素解决方案最佳地解释了症状异质性，显示出适度的纵向稳定性。与HC个体相比，ROP-MOTCOG（）亚组的特征是在突显、控制和默认模式网络内的GMV减少，主要在整个扣带区域，神经认知受损最严重，精神分裂症的遗传易感性最高。ROP-SOCWD（）患者在控制、默认模式和突显网络的内侧额颞区域显示GMV减少，并且在各个时间点的社会功能最低。ROP-POS（）在控制和默认模式网络的突显、边缘和额叶区域显示GMV降低。ROP-AFF（）亚组在突显、边缘、后默认模式和控制网络、丘脑和小脑中显示GMV减少。突显和控制网络的额颞区域的GMV减少在各亚组中均有体现。我们的结果强调了早期精神病中存在具有不同神经生物学和功能特征的行为亚组，强调了基于症状的精细诊断和预后框架的必要性。
