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Open Access Publications from the University of California

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

  • Author(s): Walton, E
  • Hibar, DP
  • van Erp, TGM
  • Potkin, SG
  • Roiz-Santiañez, R
  • Crespo-Facorro, B
  • Suarez-Pinilla, P
  • van Haren, NEM
  • de Zwarte, SMC
  • Kahn, RS
  • Cahn, W
  • Doan, NT
  • Jørgensen, KN
  • Gurholt, TP
  • Agartz, I
  • Andreassen, OA
  • Westlye, LT
  • Melle, I
  • Berg, AO
  • Morch-Johnsen, L
  • Færden, A
  • Flyckt, L
  • Fatouros-Bergman, H
  • Karolinska Schizophrenia Project Consortium (KaSP)
  • Jönsson, EG
  • Hashimoto, R
  • Yamamori, H
  • Fukunaga, M
  • Jahanshad, N
  • De Rossi, P
  • Piras, F
  • Banaj, N
  • Spalletta, G
  • Gur, RE
  • Gur, RC
  • Wolf, DH
  • Satterthwaite, TD
  • Beard, LM
  • Sommer, IE
  • Koops, S
  • Gruber, O
  • Richter, A
  • Krämer, B
  • Kelly, S
  • Donohoe, G
  • McDonald, C
  • Cannon, DM
  • Corvin, A
  • Gill, M
  • Di Giorgio, A
  • Bertolino, A
  • Lawrie, S
  • Nickson, T
  • Whalley, HC
  • Neilson, E
  • Calhoun, VD
  • Thompson, PM
  • Turner, JA
  • Ehrlich, S
  • et al.

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.

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