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 - 2025/5/7
Y1 - 2025/5/7
N2 - 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 (q <0.05). FHR did not differ from NC. At the network-wide level, thalamo-cortical co-variations discriminated FHR from NC (q <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 (q <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.
AB - 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 (q <0.05). FHR did not differ from NC. At the network-wide level, thalamo-cortical co-variations discriminated FHR from NC (q <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 (q <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.
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
JO - Biological Psychiatry
JF - Biological Psychiatry
ER -