87 - Morphological Changes in Subcortical Brain Structures and Associated Genetic Risk of Schizophrenia

Poster Board Number: 87
There are separate poster presentation times for odd and even posters.
Odd poster #s – first hour
Even poster #s – second hour

Abstract Body : Introduction & Objective: Schizophrenia is a psychiatric disorder with polygenic and neurodevelopmental etiological roots. Subtle anatomical brain changes have been reported in clinical samples, including gray matter reductions widespread over the brain. Several studies have also shown the influence of the genetic burden on schizophrenia in global and cortical brain structural measures. However, such effects remain unexplored in subcortical structures, leading to non-consistent conclusions. Geometric Morphometrics (GM) provides a robust methodology that goes beyond the typical brain volumetric approaches to detect more detailed size and shape dysmorphologies. Morphometric features can be later combined with genetic data to improve the description and analysis of anatomical changes associated with the disease. We hypothesized that patients and healthy individuals will show differences in the volume and shape of subcortical structures, and that these changes will be modulated by the genetic load for schizophrenia.

Materials and Methods: Head structural Magnetic Resonance Images (MRI) and genetic samples were obtained from 90 patients with schizophrenia (SZ) and 47 healthy controls (HC) of European ancestry. Subcortical structures were segmented from the MRIs using FSL FIRST, and volumetric differences between HC and SZ were evaluated with a regression model, accounting for sex and age as covariates. A set of 60 3D landmarks was registered over the hippocampus, and Generalized Procrustes Analysis was performed to compare with high precision the hippocampal shape between SZ and HC. The Polygenic Risk Score of SZ (PRS-SZ) was estimated using the PRS-CS Auto method and the latest GWAS of schizophrenia as reference (PGC-2022). Linear regressions were performed to assess the influence of PRS on the volume of subcortical regions and the hippocampal shape.

Results: The putamen (p=0.002), pallidum (p=0.015) and caudate (p=0.018) showed a significant volume reduction in SZ. The hippocampus shape was significantly different in SZ as compared to HC (p=0.012), presenting anterior and posterior bending that leads to a more concave hippocampal shape. Patients with SZ showed higher PRS-SZ scores than HC (t=-7.654, p< 0.001), and higher PRS were associated with smaller amygdala volumes in both SZ and HC (β=-0.244, p=0.027). However, no significant associations were detected between the hippocampus shape and PRS, either in SZ or HC.

Conclusion and Significance: Our results showed volume reductions in several subcortical brain structures, in line with previously published data. In addition, our shape analysis based on landmarking and geometric morphometrics extends current findings from the ENIGMA Consortium, further characterizing hippocampal dysmorphologies in schizophrenia. Finally, we replicated in our sample the role of PRS as a vulnerability marker, and showed its effect on modulating the amygdala’s volume. Our approach suggests the potential of future studies combining volumetric, shape and genetic data, to improve our understanding of the etiological and neurobiological basis of schizophrenia.