Thalamocortical Structural Covariation Networks Are Related to Familial Risk for Schizophrenia in the Context of Lower Nuclei Volume Estimates in Patients: An ENIGMA Study

Authors

Annalisa Lella
Linda A. Antonucci
Roberta Passiatore
Loredana Bellantuono
Pierluigi Selvaggi
Teresa Popolizio
Guido Di Sciascio
Alessandro Saponaro
Patrizia Ricci
John Blangero, The University of Texas Rio Grande ValleyFollow

Document Type

Article

Publication Date

11-2025

Abstract

Background

Structural brain differences in the thalamus and the cortex have been widely reported in schizophrenia (SCZ) relative to neurotypical control individuals (NCs). Most previous studies examined the thalamusas a whole as a single region of interest. In addition, findings in individuals at familial high risk for SCZ (FHRs) remain inconclusive. Here, we investigated whether local and network-wide thalamic-related structural alterations vary as a function of familial risk for SCZ.

Methods

Structural magnetic resonance imaging scans were obtained from 5197 participants (NC, n = 3409; FHR, n = 257; SCZ, n = 1531) across 32 cross-sectional samples within the ENIGMA (Enhancing Neuro ImagingGenetics through Meta Analysis) Consortium. Random-effects meta-analyses and network analyses were conducted on 1) local thalamic alterations (volume estimates of 7 thalamic subdivisions) and 2) network-wide thalamic alterations (thickness and surface-related thalamocortical/corticocortical covariation patterns) across groups (NC, FHR, SCZ).

Results

Individuals with SCZ showed significantly lower gray matter volume estimates in the anterior, pulvinar, medial, posterior, and ventral thalamic subdivisions compared with NCs (false discovery rate–corrected q [qFDR] < .05). FHRs did not differ from NCs. At the network-wide level, thalamocortical covariations discriminated FHRs from NCs (qFDR < .05), with FHRs showing intermediate covariation between individuals with SCZ and NCs. Corticocortical covariation patterns revealed that individuals with SCZ and FHRs shared similarly disconnected clustering configurations, distinct from NCs (qFDR < .05).

Conclusions

Results revealed lower thalamic volume estimates in individuals with SCZ but not in FHRs, hence yielding no evidence of a familial risk trait, whereas thalamocortical and corticocortical covariation estimates were associated with familial risk for SCZ. These findings suggest that, once the thalamus is parsed into subdivisions, network-wide thalamocortical features may identify trait-dependent, neurobiological correlates of genetic risk for SCZ.

Comments

Copyright 2025 Society of Biological Psychiatry. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/

Recommended Citation

Lella, A., Antonucci, L. A., Passiatore, R., Bellantuono, L., Selvaggi, P., Popolizio, T., Di Sciascio, G., Saponaro, A., Ricci, P., Altamura, M., Blasi, G., Rampino, A., Vriend, C., Calhoun, V. D., Rootes-Murdy, K., Goldman, A. L., Baeza, I., Castro-Fornieles, J., Sugranyes, G., … Pergola, G. (2025). Thalamocortical Structural Covariation Networks Are Related to Familial Risk for Schizophrenia in the Context of Lower Nuclei Volume Estimates in Patients: An ENIGMA Study. Biological Psychiatry, 98(9), 698–711. https://doi.org/10.1016/j.biopsych.2025.03.027

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Publication Title

Biological Psychiatry

DOI

10.1016/j.biopsych.2025.03.027

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics