TY - JOUR
T1 - Thalamo-cortical structural co-variation networks are related to familial risk for schizophrenia in the context of lower nuclei volume estimates in patients
T2 - an ENIGMA study
AU - Lella, Annalisa
AU - Antonucci, Linda A
AU - Passiatore, Roberta
AU - Bellantuono, Loredana
AU - Selvaggi, Pierluigi
AU - Popolizio, Teresa
AU - Di Sciascio, Guido
AU - Saponaro, Alessandro
AU - Ricci, Patrizia
AU - Altamura, Mario
AU - Blasi, Giuseppe
AU - Rampino, Antonio
AU - Vriend, Chris
AU - Calhoun, Vince D
AU - Rootes-Murdy, Kelly
AU - Goldman, Aaron L
AU - Baeza, Inmaculada
AU - Castro-Fornieles, Josefina
AU - Sugranyes, Gisela
AU - De la Serna, Elena
AU - Pomarol-Clotet, Edith
AU - Fatjó-Vilas, Mar
AU - Salvador, Raymond
AU - Karuk, Andriana
AU - Fuentes-Claramonte, Paola
AU - Glahn, David C
AU - Rodrigue, Amanda L
AU - Blangero, John
AU - Wang, Lei
AU - Lee, Taeyoung
AU - Einenkel, Karolin E
AU - Hamers, Saskia
AU - Gruber, Oliver
AU - Preda, Adrian
AU - Chung, Young-Chul
AU - Odkhuu, Soyolsaikhan
AU - Vallée, Corentin
AU - Dazzan, Paola
AU - Marcelis, Machteld
AU - Michielse, Stijn
AU - Brosch, Katharina
AU - Stein, Frederike
AU - Nenadic, Igor
AU - Straube, Benjamin
AU - Thomas-Odenthal, Florian
AU - Kircher, Tilo
AU - Carruthers, Sean
AU - Rossell, Susan L
AU - Sumner, Phillip J
AU - Van Rheenen, Tamsyn E
AU - Apulian Network on Risk for Psychosis
PY - 2025/11/1
Y1 - 2025/11/1
N2 - 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.
AB - 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.
KW - Familial high risk for schizophrenia
KW - meta-analyses
KW - morphometric measures
KW - structural neuroimaging
KW - thalamic subdivisions
KW - thalamo-cortical networks
U2 - 10.1016/j.biopsych.2025.03.027
DO - 10.1016/j.biopsych.2025.03.027
M3 - Article
SN - 0006-3223
VL - 98
SP - 698
EP - 711
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 9
ER -