A Diagnosis and Biotype Comparison across the Psychosis Spectrum: Investigating Volume and Shape Amygdala-Hippocampal Differences from the B-SNIP Study

Objective: Brain-based Biotypes for psychotic disorders have been developed as part of the B-SNIP consortium to create neurobiologically distinct subgroups within idiopathic psychosis, independent from traditional phenomenological diagnostic methods. In the current study, we aimed to validate the Biotype model by assessing differences in volume and shape of the amygdala and hippocampus contrasting traditional clinical diagnoses with Biotype classification. Methods: A total of 811 participants from 6 sites were included: Probands with schizophrenia (n = 199), schizoaffective disorder (n = 122), psychotic bipolar disorder with psychosis (n = 160), and healthy controls (n = 330). Biotype classification, previously developed using cognitive and electrophysiological data and K-means clustering, was used to categorize psychosis probands into 3 Biotypes, with Biotype-1 (B-1) showing reduced neural salience and severe cognitive impairment. MAGeT-Brain segmentation was used to determine amygdala and hippocampal volumetric data and shape deformations. Results: When using Biotype classification, B-1 showed the strongest reductions in amygdala-hippocampal volume and the most widespread shape abnormalities. Using clinical diagnosis, probands with schizophrenia and schizoaffective disorder showed the most significant reductions of amygdala and hippocampal volumes and the most abnormal hippocampal shape compared with healthy controls. Biotype classification provided the strongest neuroanatomical differences compared with conventional DSM diagnoses, with the best discrimination seen using bilateral amygdala and right hippocampal volumes in B-1. Conclusion: These findings characterize amygdala and hippocampal volumetric and shape abnormalities across the psychosis spectrum. Grouping individuals by Biotype showed greater between-group discrimination, suggesting a promising approach and a favorable target for characterizing biological heterogeneity across the psychosis spectrum.