Longitudinal clinical outcomes based on cognitive and hippocampal clusters of first episode psychosis

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.