A Cross-Sectional and Longitudinal Magnetic Resonance Imaging Study of Cingulate Gyrus Gray Matter Volume Abnormalities in First-Episode Schizophrenia and First-Episode Affective Psychosis
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CONTEXT: Previous magnetic resonance imaging (MRI) findings have demonstrated psychopathological symptom-related smaller gray matter volumes in various cingulate gyrus subregions in schizophrenia and bipolar disorder. However, it is unclear whether these gray matter abnormalities show a subregional specificity to either disorder and whether they show postonset progression. OBJECTIVE: To determine whether there are initial and progressive gray matter volume deficits in cingulate gyrus subregions in patients with first-episode schizophrenia (FESZ) and patients with first-episode affective psychosis (FEAFF, mainly manic) and their specificity to FESZ or FEAFF. DESIGN: A naturalistic cross-sectional study at first hospitalization for psychosis and a longitudinal follow-up approximately 1(1/2) years later. SETTING AND PARTICIPANTS: Patients were from a private psychiatric hospital. Thirty-nine patients with FESZ and 41 with FEAFF at first hospitalization for psychosis and 40 healthy control subjects (HCs) recruited from the community underwent high-spatial-resolution MRI, with follow-up scans in 17 FESZ patients, 18 FEAFF patients, and 18 HCs. Individual subjects were matched for age, sex, parental socioeconomic status, and handedness. MAIN OUTCOME MEASURES: Cingulate gyrus gray matter volumes in 3 anterior subregions (subgenual, affective, and cognitive) and 1 posterior subregion, and whether there was a paracingulate sulcus. RESULTS: At first hospitalization, patients with FESZ showed significantly smaller left subgenual (P = .03), left (P = .03) and right (P = .005) affective, right cognitive (P = .04), and right posterior (P = .003) cingulate gyrus gray matter subregions compared with HCs. Moreover, at the 1(1/2)-year follow-up, patients with FESZ showed progressive gray matter volume decreases in the subgenual (P = .002), affective (P < .001), cognitive (P < .001), and posterior (P = .02) cingulate subregions compared with HCs. In contrast, patients with FEAFF showed only initial (left, P < .001; right, P = .002) and progressive subgenual subregion abnormalities (P < .001). Finally, patients with FESZ showed a less asymmetric paracingulate pattern than HCs (P = .02). CONCLUSIONS: Patients with FEAFF and FESZ showed differences in initial gray matter volumes and in their progression. Initial and progressive changes in patients with FEAFF were confined to the subgenual cingulate, a region strongly associated with affective disorder, whereas patients with FESZ evinced widespread initial and progressively smaller volumes.
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Gray matter volume loss is observed in widespread areas of the frontal/prefrontal regions in psychosis, including middle frontal gyrus, inferior frontal regions, anterior cingulate, and orbitofrontal and dorsolateral prefrontal cortices.
“Gray matter volume loss is observed in widespread areas of the frontal/prefrontal regions in psychosis, including middle frontal gyrus, inferior frontal regions, anterior cingulate, and orbitofrontal and dorsolateral prefrontal cortices [74-77] .”
From The traumagenic neurodevelopmental model of psychosis revisited (2014) · cites this paper as [75]
The Comment section (page unavailable) reports anterior cingulate gray matter volume deficits in first-episode schizophrenia and affective psychosis, and mentions prefrontal volume deficits in previous studies. It does not substantiate the claim's full list of regions: middle and inferior frontal gyri, orbitofrontal cortex, and dorsolateral prefrontal cortex. (LLM, conf=0.88)
Experimental — accuracy not yet measuredA longitudinal study has shown progression of the abnormality in subjects with psychotic mood disorders.
“Nevertheless, a longitudinal study also has shown progression of the abnormality in subjects with psychotic mood disorders (Koo et al, 2008).”
From Neurocircuitry of Mood Disorders (2010) · cites this paper as Koo et al, 2008
Depressed patients show reductions in cortical volume and thickness in several frontal cortex regions, most reliably in PFo area 11, sulcal area 47, and subgenual frontal cortex.
“Furthermore, reductions of cortical volume and thickness occur in several parts of the frontal cortex in depressed patients, with the most reliable and best characterized of these abnormalities occurring in PFo area 11 (44), the sulcal part of area 47 (45, 46), and the subgenual frontal cortex (47–50).”
From Localization of Dysfunction in Major Depressive Disorder: Prefrontal Cortex and Amygdala (2011) · cites this paper as [50]
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Transdiagnostic neuroimaging in psychiatry: a review
Mitelman, S. A. (2019) · Psychiatry Research · doi:10.1016/j.psychres.2019.01.026 · Cited by 50 · see citing works
Chaves, C., Marque, C. R., Maia-de-Oliveira, J. P., Wichert-Ana, L., Ferrari, T. B., Santos, A. C., Araújo, D., Machado-de-Sousa, J. P., Bressan, R. A., Elkis, H., et al. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2014.11.031 · Cited by 41 · see citing works
- Authors
- Koo, M.-S., Levitt, J. J., Salisbury, D. F., Nakamura, M., Shenton, M. E., & McCarley, R. W.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2008-07-07
- Volume
- 65
- Issue
- 7
- Pages
- 746
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC2793338
- OpenAlex
- W2149425620
- Cited by
- 175
- References
- 71
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 11 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 12 · 2014: 10 · 2013: 18 · 2012: 19
- FWCI
- 14.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institute of Mental Health (R01MH058704, R01 MH40799, P50MH080272, R01MH052807, K02MH001110, R01MH050740, R01MH040799, R01MH 50747, R01 MH 58704, K02MH 01110)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- cingulate gyrus, gray matter volume, first-episode schizophrenia, manic episodes, subgenual cingulate, posterior cingulate cortex, paracingulate sulcus, gray matter atrophy, longitudinal progression, bipolar disorder, psychosis spectrum disorders, neuroimaging biomarkers
- MeSH terms
- Adolescent, Adult, Cross-Sectional Studies, Female, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Brief Psychiatric Rating Scale, Psychotic Disorders, Schizophrenia, Severity of Illness Index, Mood Disorders, Diagnostic and Statistical Manual of Mental Disorders
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