Ronat Lucas A, Raucher-Chéné Delphine, Lavigne Katie M, Chakravarty Mallar, Joober Ridha, Malla Ashok, Shah Jai, Lepage Martin
Department of Psychiatry, McGill University, Montreal, QC, Canada; Douglas Research Centre, McGill University, Montreal, QC, Canada.
Department of Psychiatry, McGill University, Montreal, QC, Canada; Computional Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, QC H4H 1R3, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada; Department of Biological and Biomedical Engineering, McGill University, Montreal, QC H3A 0G4, Canada.
Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jun 20;139:111392. doi: 10.1016/j.pnpbp.2025.111392. Epub 2025 May 2.
In first episode psychosis (FEP), cognitive impairments are core features contributing to clinical and functional heterogeneity. Significant impairment indicates greater clinical severity throughout the course of the illness, particularly for negative symptoms. Hippocampal volume is smaller in FEP than in healthy controls (notably subfields like Cornu Ammonis 1-3 and subiculum), and is related to cognitive impairments and negative symptoms. The aim of this study was to compare the clinical and functional trajectories of FEP subgroups as a function of cognitive performance and hippocampal volumes.
One hundred FEP patients and sixty healthy controls initially assessed using the CogState research battery, underwent 3 T MRI to extract hippocampal subfields and adjacent structures using the MAGeT brain algorithm. Clinical assessments were carried out for negative (Motivational and Pleasure - MAP, and diminished expression - EXP) and depressive symptoms, and global functioning. Measurements were taken at 4 time points (3, 9, 15, 21 months following program entry). Based on available first timepoint standardized cognitive and hippocampal features, using healthy controls as reference, clusters were determined by a hierarchical ascending classification. Their clinical and functional longitudinal trajectories were analyzed using linear mixed-effects models.
Three baseline clusters were revealed: normal-range hippocampal volume with low attention, working and verbal memory (FEP 0), small hippocampus with low verbal memory and social cognition (FEP 1), and large hippocampus with low verbal memory (FEP 2). At baseline, the clusters did not differ on symptoms severity and global functioning. Longitudinally, MAP, EXP and depressive symptoms decreased over time in FEP 0. Global functioning improved in FEP 0 and FEP 1, while FEP 2 was clinically and functionally stable over time. Longitudinal inter-group comparisons did not yield any significant differences.
The clusters were dissociated between hippocampus and cognition, but their trajectories suggest the importance of hippocampal integrity in the clinical and/or functional outcome. Future studies are needed to understand intervention efficiency depending on hippocampal integrity.
在首发精神病（FEP）中，认知障碍是导致临床和功能异质性的核心特征。显著的认知障碍表明在疾病的整个过程中临床严重程度更高，尤其是对于阴性症状而言。FEP患者的海马体积比健康对照者小（特别是海马1-3区和海马下托等亚区），并且与认知障碍和阴性症状有关。本研究的目的是比较FEP亚组的临床和功能轨迹与认知表现及海马体积的关系。
100名FEP患者和60名健康对照者最初使用CogState研究电池进行评估，然后接受3T磁共振成像（MRI），使用MAGeT脑算法提取海马亚区和相邻结构。对阴性症状（动机和愉悦感-MAP，以及表情减少-EXP）、抑郁症状和整体功能进行临床评估。在4个时间点（入组后3、9、15、21个月）进行测量。基于首次测量时可用的标准化认知和海马特征，以健康对照者作为参照，通过分层升序分类确定分组。使用线性混合效应模型分析其临床和功能纵向轨迹。
揭示了三个基线分组：海马体积在正常范围但注意力、工作记忆和言语记忆较低的分组（FEP 0），海马较小且言语记忆和社会认知较低的分组（FEP 1），以及海马较大但言语记忆较低的分组（FEP 2）。在基线时，各分组在症状严重程度和整体功能方面没有差异。纵向来看，FEP 0组的MAP、EXP和抑郁症状随时间下降。FEP 0组和FEP 1组的整体功能有所改善，而FEP 2组在临床和功能上随时间保持稳定。纵向组间比较未产生任何显著差异。
这些分组在海马和认知之间存在分离，但它们的轨迹表明海马完整性在临床和/或功能结局中的重要性。需要进一步的研究来了解取决于海马完整性的干预效果。
