Thalamo-cortical structural co-variation networks are related to familial risk for schizophrenia in the context of lower nuclei volume estimates in patients: an ENIGMA study
Child And Adolescent Mental Health
Thalamo-cortical structural co-variation networks are related to familial risk for schizophrenia in the context of lower nuclei volume estimates in patients: an ENIGMA study
Child And Adolescent Mental Health

Thalamo-cortical structural co-variation networks are related to familial risk for schizophrenia in the context of lower nuclei volume estimates in patients: an ENIGMA study

Biol Psychiatry. 2025 May 7:S0006-3223(25)01178-3. doi: 10.1016/j.biopsych.2025.03.027. Online ahead of print.

ABSTRACT

BACKGROUND: Structural brain differences in the thalamus and the cortex have been widely reported in schizophrenia (SCZ) relative to neurotypical controls (NC). Most prior studies examined the thalamus as a whole, single region-of-interest. Additionally, findings in individuals at familial high-risk for schizophrenia (FHR) remain inconclusive. Here, we investigated whether local and network-wide thalamic-related structural alterations vary as a function of familial risk for schizophrenia.

METHODS: Structural MRI scans were obtained from 5,197 participants (3,409 NC, 257 FHR, 1,531 SCZ) across 32 cross-sectional samples within the ENIGMA Consortium. Random-effects meta-analyses, and network analyses were conducted on (i) local thalamic alterations (volume estimates of seven thalamic subdivisions), and (ii) network-wide thalamic alterations (thickness and surface-related thalamo-cortical/cortico-cortical co-variation 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 to NC (qFDR<0.05). FHR did not differ from NC. At the network-wide level, thalamo-cortical co-variations discriminated FHR from NC (qFDR<0.05), with FHR showing intermediate co-variation between SCZ and NC. Cortico-cortical co-variation patterns revealed that SCZ and FHR shared similarly disconnected clustering configurations, distinct from NC (qFDR<0.05).

CONCLUSIONS: Results revealed lower thalamic volume estimates in SCZ but not in FHR, hence yielding no evidence of a familial risk trait, whereas thalamo-cortical and cortico-cortical co-variation estimates were associated with familial risk for SCZ These findings suggest that, once the thalamus is parsed into subdivisions, network-wide thalamo-cortical features may identify trait-dependent, neurobiological correlates of genetic risk for SCZ.

PMID:40345610 | DOI:10.1016/j.biopsych.2025.03.027