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

The Apulian Network on Risk for Psychosis

doi:10.1016/j.biopsych.2025.03.027

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

The Apulian Network on Risk for Psychosis

Department of Medicine

University of Bari
Johns Hopkins University
National Institute for Nuclear Physics
Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
San Giovanni Rotondo
Department of Mental Health
Barletta-Andria-Trani
University of Foggia
Amsterdam University Medical Centers
Amsterdam UMC
Georgia Institute of Technology
University of Barcelona
Centro de Investigación Biomédica En Red de Salud Mental
Sisters Hospitallers Research Foundation
Boston Children's Hospital
Harvard University
Institute of Living
University of Texas Rio Grande Valley
Ohio State University
Kyungpook National University
Hanyang University
Heidelberg University
Hannover Medical School
University of California at Irvine
Jeonbuk National University
King's College London
South London and Maudsley NHS Foundation Trust
Maastricht University
University of Marburg
Feinstein Institutes for Medical Research
Swinburne University of Technology
University of Melbourne

Research output: Contribution to journal › Journal article › peer-review

3 Scopus citations

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 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.

Original language	English
Pages (from-to)	698-711
Number of pages	14
Journal	Biological Psychiatry
Volume	98
Issue number	9
DOIs	https://doi.org/10.1016/j.biopsych.2025.03.027
State	Published - 2025.11.1

Keywords

Familial high risk for schizophrenia
Meta-analyses
Morphometric measures
Structural neuroimaging
Thalamic subdivisions
Thalamocortical networks

Quacquarelli Symonds(QS) Subject Topics

Medicine

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10.1016/j.biopsych.2025.03.027

Cite this

@article{21cb183583f94ae29779f9bbc5bc3834,

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

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 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 [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.",

keywords = "Familial high risk for schizophrenia, Meta-analyses, Morphometric measures, Structural neuroimaging, Thalamic subdivisions, Thalamocortical networks",

author = "\{The Apulian Network on Risk for Psychosis\} and Annalisa Lella and Antonucci, \{Linda A.\} and Roberta Passiatore and Loredana Bellantuono and Pierluigi Selvaggi and Teresa Popolizio and \{Di Sciascio\}, Guido and Alessandro Saponaro and Patrizia Ricci and Mario Altamura and Giuseppe Blasi and Antonio Rampino and Chris Vriend and Calhoun, \{Vince D.\} and Kelly Rootes-Murdy and Goldman, \{Aaron L.\} and Inmaculada Baeza and Josefina Castro-Fornieles and Gisela Sugranyes and \{De la Serna\}, Elena and Edith Pomarol-Clotet and Mar Fatj{\'o}-Vilas and Raymond Salvador and Andriana Karuk and Paola Fuentes-Claramonte and Glahn, \{David C.\} and Rodrigue, \{Amanda L.\} and John Blangero and Lei Wang and Taeyoung Lee and Einenkel, \{Karolin E.\} and Saskia Hamers and Oliver Gruber and Adrian Preda and Chung, \{Young Chul\} and Soyolsaikhan Odkhuu and Corentin Vall{\'e}e and Paola Dazzan and Machteld Marcelis and Stijn Michielse and Katharina Brosch and Frederike Stein and Igor Nenadi{\'c} and Benjamin Straube and Florian Thomas-Odenthal and Tilo Kircher and Sean Carruthers and Rossell, \{Susan L.\} and Sumner, \{Phillip J.\} and \{Van Rheenen\}, \{Tamsyn E.\}",

note = "Publisher Copyright: {\textcopyright} 2025 Society of Biological Psychiatry",

year = "2025",

month = nov,

day = "1",

doi = "10.1016/j.biopsych.2025.03.027",

language = "English",

volume = "98",

pages = "698--711",

journal = "Biological Psychiatry",

issn = "0006-3223",

number = "9",

}

TY - JOUR

T1 - Thalamocortical Structural Covariation Networks Are Related to Familial Risk for Schizophrenia in the Context of Lower Nuclei Volume Estimates in Patients

T2 - An ENIGMA Study

AU - The Apulian Network on Risk for Psychosis

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 - Nenadić, 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.

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 [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.

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 [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.

KW - Familial high risk for schizophrenia

KW - Meta-analyses

KW - Morphometric measures

KW - Structural neuroimaging

KW - Thalamic subdivisions

KW - Thalamocortical networks

UR - https://www.scopus.com/pages/publications/105010213509

U2 - 10.1016/j.biopsych.2025.03.027

DO - 10.1016/j.biopsych.2025.03.027

M3 - Journal article

C2 - 40345610

AN - SCOPUS:105010213509

SN - 0006-3223

VL - 98

SP - 698

EP - 711

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 9

ER -

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

Abstract

Keywords

Quacquarelli Symonds(QS) Subject Topics

Access to Document

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