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Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study

Kirschner, M., Hodzic-Santor, B., Antoniades, M., Nenadic, I., Kircher, T., Krug, A., Meller, T., Grotegerd, D., Fornito, A., Arnatkeviciute, A., Bellgrove, M. A., Tiego, J., Dannlowski, U., Koch, K., Hülsmann, C., Kugel, H., Enneking, V., Klug, M., Leehr, E. J., Böhnlein, J., Gruber, M., Nehler, D., DeRosse, P., Moyett, A., Baune, B. T., Green, M., Quidé, Y., Pantelis, C., Chan, R., Wang, Y., Ettinger, U., Debbané, M., Derome, M., Gaser, C., Besteher, B., Diederen, K., Spencer, T. J., Fletcher, P., Rössler, W., Smigielski, L., Kumari, V., Premkumar, P., Park, H. R. P., Wiebels, K., Lemmers-Jansen, I., Gilleen, J., Allen, P., Kozhuharova, P., Marsman, J-B., Lebedeva, I., Tomyshev, A., Mukhorina, A., Kaiser, S., Fett, A-K. ORCID: 0000-0003-0282-273X, Sommer, I., Schuite-Koops, S., Paquola, C., Larivière, S., Bernhardt, B., Dagher, A., Grant, P., van Erp, T. G. M., Turner, J. A., Thompson, P. M., Aleman, A. and Modinos, G. (2021). Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study. Molecular Psychiatry, doi: 10.1038/s41380-021-01359-9

Abstract

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 3004 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 = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = −0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = −0.690, pspin = 0.006), BD (rho = −0.672, pspin = 0.009), and MDD (rho = −0.692, pspin = 0.004). 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.

Publication Type: Article
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Publisher Keywords: Psychology, Schizophrenia
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Departments: School of Arts & Social Sciences > Psychology
Date available in CRO: 28 Oct 2021 11:29
Date deposited: 28 October 2021
Date of acceptance: 8 October 2021
Date of first online publication: 27 October 2021
URI: https://openaccess.city.ac.uk/id/eprint/26953
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