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

ABSTRACT: 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 (? 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.

SUBMITTER: Walton E

PROVIDER: S-EPMC5826665 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

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

Psychological medicine 20170526 1

<h4>Background</h4>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 symp ...[more]

PMID: 28545597

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Project description:BACKGROUND:The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS:The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS:Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS:The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.

Dataset Information

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

Publications

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

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