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Psychol Med. 2018 Jan;48(1):82-94. doi: 10.1017/S0033291717001283. Epub 2017 May 26.

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

Author information

1
Department of Psychology,Georgia State University,Atlanta, GA 30302,USA.
2
Imaging Genetics Center,Mark and Mary Stevens Institute for Neuroimaging & Informatics,University of Southern California,Marina del Rey, CA,USA.
3
Department of Psychiatry and Human Behavior,University of California,Irvine,California.
4
Department of Psychiatry,University Hospital Marqués de Valdecilla,School of Medicine,University of Cantabria-IDIVAL,Avda. Valdecilla s/n, 39008,Santander,Spain.
5
Department of Psychiatry,Brain Center Rudolf Magnus,University Medical Center Utrecht,Utrecht,The Netherlands.
6
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction,University of Oslo,P.O. Box 4956 Nydalen, 0424 Oslo,Norway.
7
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction,Oslo University Hospital,P.O. Box 4956 Nydalen, 0424, Oslo,Norway.
8
Division of Mental Health and Addiction,Oslo University Hospital,P.O. Box 4956 Nydalen, 0424, Oslo,Norway.
9
Department of Clinical Neuroscience,Karolinska Institutet, Centre for Psychiatry Research,Norra Stationsgatan 69, 113 64 Stockholm,Sweden.
10
Molecular Research Center for Children's Mental Development,United Graduate School of Child Development,Osaka University,D3, 2-2, Yamadaoka, Suita, Osaka, 565-0871,Japan.
11
Department of Psychiatry,Osaka University Graduate School of Medicine D3,2-2, Yamadaoka, Suita, Osaka, 565-0871,Japan.
12
Division of Cerebral Integration,National Institute for Physiological Sciences,38 Nishigonaka Myodaiji,Okazaki, Aichi, 444-8585,Japan.
13
NESMOS Department (Neurosciences, Mental Health and Sensory Functions),School of Medicine and Psychology, Sapienza University,Rome,Italy.
14
Department of Clinical and Behavioural Neurology,IRCCS Santa Lucia Foundation,00179, Rome,Italy.
15
Brain Behavior Laboratory,University of Pennsylvania,Philadelphia, PA 19104,USA.
16
Department of Psychiatry and Psychotherapy,Center for Translational Research in Systems Neuroscience and Psychiatry,University Medical Center Göttingen,Von-Siebold-Str. 5, 37075 Göttingen,Germany.
17
Centre for Neuroimaging and Cognitive Genomics (NICOG), NCBES Galway Neuroscience Centre, National University of Ireland Galway,Galway,Ireland.
18
Trinity College,Dublin,Ireland.
19
Section of Psychiatry and Psychology, IRCCS Casa Sollievo della Sofferenza,S.G. Rotondo (FG), 71013,Italy.
20
Psychiatric Neuroscience Group,University of Bari 'Aldo Moro',Bari, 70124,Italy.
21
Division of Psychiatry,University of Edinburgh,Royal Edinburgh Hospital,Morningside, Edinburgh, EH10 5HF,UK.
22
The Mind Research Network,Albuquerque, NM 87106,USA.
23
Department of Psychology and Neuroscience Institute,Georgia State University,Atlanta, GA 30302,USA.
24
Division of Psychological and Social Medicine and Developmental Neurosciences,Faculty of Medicine,Technische Universität Dresden,Fetscherstr. 74, 01307 Dresden,Germany.

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 (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.

KEYWORDS:

Cortical thickness; ENIGMA; FreeSurfer; MRI; PANSS; SANS; medial orbitofrontal cortex; negative symptoms; schizophrenia

PMID:
28545597
PMCID:
PMC5826665
[Available on 2019-01-01]
DOI:
10.1017/S0033291717001283
[Indexed for MEDLINE]
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