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

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 thalamus as 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 Imaging Genetics 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 [q_FDR] < .05). FHRs did not differ from NCs. At the network-wide level, thalamocortical covariations discriminated FHRs from NCs (q_FDR < .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 (q_FDR < .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.