Cortical and Subcortical Neuroanatomical Signatures of Schizotypy in 3,004 Individuals Assessed in a Worldwide ENIGMA Study
Authors: Kirschner Matthias , Hodzic-Santor Benazir , Antoniades Mathilde , Nenadic Igor , Kircher Tilo , Krug Axel , Meller Tina , Grotegerd Dominik , Fornito Alex , Arnatkeviciute Aurina , Bellgrove Mark A , Tiego Jeggan , Dannlowski Udo , Koch Katharina , Hülsmann Carina , Kugel Harald , Enneking Verena , Klug Melissa , Leehr Elisabeth J. , Böhnlein Joscha , Gruber Marius , Mehler David , DeRosse Pamela , Moyett Ashley , Baune Bernhard T. , Green Melissa , Quidé Yann , Pantelis Christos , Chan Raymond , Wang Yi , Ettinger Ulrich , Debbané Martin , Derome Melodie , Gaser Christian , Besteher Bianca , Diederen Kelly , Spencer Tom J , Fletcher Paul , Rössler Wulf , Smigielski Lukasz , Kumari Veena , Premkumar Preethi , Park Haeme R. P. , Wiebels Kristina , Lemmers-Jansen Imke , Gilleen James , Allen Paul , Kozhuharova Petya , Marsman Jan-Bernard , Lebedeva Irina , Tomyshev Alexander , Mukhorina Anna , Kaiser Stefan , Fett Anne-Kathrin , Sommer Iris , Schuite-Koops Sanne , Paquola Casey , Larivière Sara , Bernhardt Boris , Dagher Alain , Grant Phillip , van Erp Theo G. M. , Turner Jessica A. , Thompson Paul M. , Aleman André , Modinos Gemma 
Published: April 2021

Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3,004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r=.07, pFDR=.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r=.33, pspin=.01), but not BD (r=.19, pspin=.16) or MDD (r=-.22, pspin=.10). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho=-.65, pspin=.01), BD (rho=-.63, pspin=.01), and MDD (rho=-.69, pspin=.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.