Orbitofrontal volume deficit in schizophrenia and thought disorder
Open accessAbstract
Orbitofrontal Cortex (OFC) structural abnormality in schizophrenia has not been well characterized, probably due to marked anatomical variability and lack of consistent definitions. We previously reported OFC sulcogyral pattern alteration and its associations with social disturbance in schizophrenia, but OFC volume associations with psychopathology and cognition have not been investigated. We compared chronically treated schizophrenia patients with healthy control (HC) subjects, using a novel, reliable parcellation of OFC subregions and their association with cognition, especially the Iowa Gambling Task (IGT), and with schizophrenic psychopathology including thought disorder. Twenty-four patients with schizophrenia and 25 age-matched HC subjects underwent MRI. OFC Regions of Interest (ROI) were manually delineated according to anatomical boundaries: Gyrus Rectus (GR); Middle Orbital Gyrus (MiOG); and Lateral Orbital Gyrus (LOG). The OFC sulcogyral pattern was also classified. Additionally, MiOG probability maps were created and compared between groups in a voxel-wise manner. Both groups underwent cognitive evaluations using the IGT, Wisconsin Card Sorting Test, and Trail Making Test (TMT). An 11% bilaterally smaller MiOG volume was observed in schizophrenia, compared with HC (F(1,47) = 17.4, P = 0.0001). GR and LOG did not differ, although GR showed a rightward asymmetry in both groups (F(1,47) = 19.2, P < 0.0001). The smaller MiOG volume was independent of the OFC sulcogyral pattern, which differed in schizophrenia and HC (chi2 = 12.49, P = 0.002). A comparison of MiOG probability maps suggested that the anterior heteromodal region was more affected in the schizophrenia group than the posterior paralimbic region. In the schizophrenia group, a smaller left MiOG was strongly associated with worse 'positive formal thought disorder' (r = -0.638, P = 0.001), and a smaller right MiOG with a longer duration of the illness (r = -0.618, P = 0.002). While schizophrenics showed poorer performance than HC in the IGT, performance was not correlated with OFC volume. However, within the HC group, the larger the right hemisphere MiOG volume, the better the performance in the IGT (r = 0.541, P = 0.005), and the larger the left hemisphere volume, the faster the switching attention performance for the TMT, Trails B (r = -0.608, P = 0.003). The present study, applying a new anatomical parcellation method, demonstrated a subregion-specific OFC grey matter volume deficit in patients with schizophrenia, which was independent of OFC sulcogyral pattern. This volume deficit was associated with a longer duration of illness and greater formal thought disorder. In HC the finding of a quantitative association between OFC volume and IGT performance constitutes, to our knowledge, the first report of this association.
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These alterations contribute to predictive impairments as well as to negative and positive psychotic symptoms.
“These alterations contribute to predictive impairments as well as to negative and positive psychotic symptoms (Baar ´ e et al., 1999; Gur et al., 2000; Nakamura et al., 2008; Onitsuka et al., 2004; Sun et al., 2009; Wible, 2012).”
From Predictive coding in neuropsychiatric disorders: a systematic transdiagnostic review. (2025) · cites this paper as Nakamura et al., 2008
The Patient group results link smaller left orbitofrontal volume to more severe positive formal thought disorder, and the Discussion reports earlier studies linking orbitofrontal volume to negative symptoms (page numbers unavailable in our copy). But this study found no correlation between orbitofrontal volume and cognitive performance in patients; it does not establish that the alterations cause predictive impairments or either symptom category. (LLM, conf=0.86)
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“These alterations contribute to predictive impairments as well as to negative and positive psychotic symptoms (Baar ´ e et al., 1999; Gur et al., 2000; Nakamura et al., 2008; Onitsuka et al., 2004; Sun et al., 2009; Wible, 2012).”
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- Authors
- Nakamura, M., Nestor, P. G., Levitt, J. J., Cohen, A. S., Kawashima, T., Shenton, M. E., & McCarley, R. W.
- Affiliations
- VA Boston Healthcare System (US)
- Brigham and Women's Hospital (US)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-12-03
- Volume
- 131
- Issue
- 1
- Pages
- 180-195
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC2773826
- OpenAlex
- W2145308745
- Cited by
- 186
- References
- 71
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 7 · 2023: 5 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 9 · 2018: 14 · 2017: 9 · 2016: 7 · 2015: 14 · 2014: 15 · 2013: 13 · 2012: 13
- FWCI
- 6.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- U.S. Department of Veterans Affairs
- National Institute of Mental Health (R01 MH40799, K02MH001110, R01MH040799, R01MH 50747, K02MH 01110)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- schizophrenia, orbitofrontal cortex, gyrus rectus, thought disorder, formal thought disorder, Iowa Gambling Task, decision-making, cognitive function, hemispheric lateralization, disease duration, Wisconsin Card Sorting Test, Trail Making Test
- MeSH terms
- Adult, Brain Mapping, Choice Behavior, Female, Frontal Lobe, Gambling, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Schizophrenia, Schizophrenic Psychology, Time Factors
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