Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium

E. Walton, D. P. Hibar, Karolinska Schizophrenia Project Consortium (KaSP), T. G.M. Van Erp, S. G. Potkin, R. Roiz-Santiañez, B. Crespo-Facorro, P. Suarez-Pinilla, University Medical Utrecht, S. M.C. De Zwarte, R. S. Kahn, W. Cahn, N. T. Doan, K. N. Jorgensen, T. P. Gurholt, I. Agartz, O. A. Andreassen, L. T. Westlye, I. Melle, A. O. BergL. Morch-Johnsen, A. Færden, L. Flyckt, H. Fatouros-Bergman, E. G. Jönsson, R. Hashimoto, H. Yamamori, M. Fukunaga, N. Jahanshad, P. De Rossi, F. Piras, N. Banaj, G. Spalletta, R. E. Gur, R. C. Gur, D. H. Wolf, T. D. Satterthwaite, L. M. Beard, I. E. Sommer, S. Koops, O. Gruber, A. Richter, B. Krämer, S. Kelly, G. Donohoe, C. McDonald, D. M. Cannon, A. Corvin, M. Gill, A. Di Giorgio, J. A. Turner

Research output: Contribution to journalArticleAcademicpeer-review

79 Citations (Scopus)


Background Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. Methods This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). Results Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. Conclusions Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

Original languageEnglish
Pages (from-to)82-94
Number of pages13
JournalPsychological Medicine
Issue number1
Publication statusPublished - 1 Jan 2018
Externally publishedYes

Bibliographical note

Funding Information:
ENIGMA was supported in part by a Consortium grant (U54 EB020403 to PMT) from the NIH Institutes contributing to the Big Data to Knowledge (BD2K) Initiative, including the NIBIB and NCI. The authors would also like to express their gratitude for the personal support from the Deutsche Forschungsgemeinschaft (Research Fellowship to E.W.; Wa 3635/1–1). For additional support, see online Supplementary Section 3.

Publisher Copyright:
© 2017 Cambridge University Press.


Dive into the research topics of 'Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium'. Together they form a unique fingerprint.

Cite this