Article
Author: van Erp, Theo G M ; Turner, Jessica A ; Iasevoli, Felice ; Einenkel, Karolin E ; Thomas-Odenthal, Florian ; Vallée, Corentin ; Passiatore, Roberta ; Rossell, Susan L ; Jo, Hang Joon ; Dazzan, Paola ; van Haren, Neeltje E M ; Homan, Stephanie ; Lella, Annalisa ; Carruthers, Sean ; Blasi, Giuseppe ; Sim, Kang ; Fuentes-Claramonte, Paola ; Chung, Young-Chul ; Sponheim, Scott R ; Lencer, Rebekka ; Kircher, Tilo ; Banaj, Nerisa ; Thomopoulos, Sophia I ; Vriend, Chris ; Stein, Frederike ; Cobia, Derin ; Vecchio, Daniela ; Michielse, Stijn ; Glahn, David C ; Gruber, Oliver ; Meinert, Susanne ; Saponaro, Alessandro ; Baeza, Inmaculada ; Ramsay, Ian S ; Slate, Rachael ; Bellantuono, Loredana ; Brosch, Katharina ; Rodrigue, Amanda L ; Antonucci, Linda A ; Cecere, Giacomo ; Sugranyes, Gisela ; Pontillo, Giuseppe ; Salvador, Raymond ; Ricci, Patrizia ; Calhoun, Vince D ; Pearlson, Godfrey D ; Omlor, Wolfgang ; Nenadić, Igor ; Altamura, Mario ; Fatjó-Vilas, Mar ; Karuk, Andriana ; Rootes-Murdy, Kelly ; Straube, Benjamin ; Van Rheenen, Tamsyn E ; Bertolino, Alessandro ; Hahn, Tim ; De la Serna, Elena ; Goldman, Aaron L ; Rampino, Antonio ; Wang, Lei ; Marcelis, Machteld ; Pergola, Giulio ; Homan, Philipp ; Preda, Adrian ; Dannlowski, Udo ; Piras, Fabrizio ; Odkhuu, Soyolsaikhan ; Selvaggi, Pierluigi ; Lee, Taeyoung ; Ciccarelli, Mariateresa ; Quidé, Yann ; Blangero, John ; Castro-Fornieles, Josefina ; Barendse, Marjolein E A ; Green, Melissa J ; Demro, Caroline ; Popolizio, Teresa ; Di Sciascio, Guido ; Hamers, Saskia ; Sumner, Phillip J ; Grotegerd, Dominik ; Thompson, Paul M ; Pomarol-Clotet, Edith
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.