Hippocampus in the symptom architecture of schizophrenia spectrum disorders: A network analysis approach

Hippocampal volume reductions are among the most robust neuroanatomical findings in schizophrenia spectrum disorders (SSD). However, how these structural alterations relate to core functional domains such as cognition, sensorimotor functioning, and impulsivity remains largely unclear. To address this gap, we applied network analysis to elucidate the complex interplay between hippocampal volume, cognition, neurological soft signs (NSS) and impulsivity, while controlling for overall psychopathology and global functional status.

We included 204 SSD individuals (mean age: 38.00 years; 80 females) from two separate in-house cohorts, who underwent structural 3 T magnetic resonance imaging (MRI). Hippocampal volumes were automatically segmented using FreeSurfer version 7.3.2. Assessments included the Brief Cognitive Assessment Tool for Schizophrenia (B-CATS), the Heidelberg Neurological Soft Signs (NSS) scale, the Barratt Impulsiveness Scale (BIS-11), the Positive and Negative Syndrome Scale (PANSS), and the Global Assessment of Functioning (GAF).

Total hippocampal volume was negatively associated with PANSS (edge weight [ew] = -0.08), reversed GAF scores (ew = -0.04) and B-CATS (ew = -0.03), but showed no association with BIS-11 or NSS scores. Hippocampal body volume was negatively associated with PANSS (ew = -0.08), B-CATS (ew = -0.03), NSS (ew = -0.03) and reversed GAF (ew = -0.02) scores.

This is the first study that incorporated structural MRI-derived volume measures into a network analysis framework to model the interplay between hippocampus, cognitive symptoms, NSS, impulsivity, psychopathology and global functioning in SSD. Our findings indicated that hippocampal volume is more strongly linked to cognition, psychopathology and global functioning than to impulsivity or NSS.