Decreased choline and creatine concentrations in centrum semiovale in patients with generalized anxiety disorder: Relationship to IQ and early trauma
Abstract
We have demonstrated, using proton magnetic resonance spectroscopy imaging ((1)H-MRSI), elevations of N-acetyl-aspartate/creatine (NAA/CR) in right dorsolateral prefrontal cortex (DLPFC) in patients with generalized anxiety disorder (GAD) in comparison to healthy volunteers. A recent study indicates that the volume of prefrontal cortical white matter may be disproportionately increased in man in comparison to other primate species, with evolutionary implications. We therefore re-analyzed the identical scans with a specific focus on the centrum semiovale (CSO) as a representative region of interest of cerebral white matter. The central hypothesis was, in accordance with our gray matter findings, that patients with GAD, in comparison to healthy controls, would exhibit either an increase in NAA in CSO, or alternatively demonstrate reductions in concentrations of choline (CHO)-containing compounds and/or creatine+phosphocreatine (CR). MRSI scans that were obtained from an earlier [Mathew, S.J., Mao, X., Coplan, J.D., Smith, E.L., Sackeim, H.A., Gorman, J.M., Shungu, D.C., 2004. Dorsolateral prefrontal cortical pathology in generalized anxiety disorder: a proton magnetic resonance spectroscopic imaging study. American Journal of Psychiatry 161, 1119-1121] sample of 15 patients with GAD [6 with early trauma (ET)] and 15 healthy age- and sex-matched volunteers were analyzed further for CSO metabolite alterations. Self-reported worry was scored using the Penn State Worry Questionnaire (PSWQ) and intelligence was assessed using the Wechsler Abbreviated Scale of Intelligence (WASI). Serial multislice/multivoxel MRSI scans had been performed on a 1.5-T MRI. Using absolute quantification methods for metabolite concentrations, we examined NAA, CHO and CR. GAD patients without ET exhibited bilaterally decreased concentrations of CHO and CR in CSO in comparison to healthy volunteers, whereas GAD patients with ET were indistinguishable from controls. In patients with GAD, high IQ was paired with greater worry, whereas in healthy volunteers, high IQ was associated with less worry. In all subjects, IQ inversely predicted left and right CSO CHO concentrations, independent of age, sex, group assignment and PSWQ scores. The CSO may therefore represent a neural substrate that exhibits reductions in CHO and CR metabolite concentrations that are inversely associated with GAD symptomatology and, in the case of CHO, with intelligence. These conclusions are deemed preliminary due to small sample size, with further study of cerebral WM in anxiety disorders suggested.
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A decrease in choline and creatine levels is found in the left hippocampus and centrum semiovale in human adults with anxiety disorder.
“A decrease in choline and creatine levels is also found in the left hippocampus and centrum semiovale in human adults with anxiety disorder [101, 102].”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [101]
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Self-citation
- Authors
- Coplan, J. D., Mathew, S. J., Mao, X., Smith, E. L. P., Hof, P. R., Coplan, P. M., Rosenblum, L. A., Gorman, J. M., & Shungu, D. C.
- Affiliations
- State University of New York (US)
- Icahn School of Medicine at Mount Sinai (US)
- Cornell University (US)
- International Partnership for Microbicides (US)
- Corresponding author
- Coplan, Jeremy D.
- ORCID
- Venue
- Psychiatry Research: Neuroimaging
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 147
- Issue
- 1
- Pages
- 27-39
- ISSN
- 0925-4927 (ISSN-L)
- OpenAlex
- W2054154633
- Cited by
- 45
- References
- 46
- Citations by year
- 2025: 5 · 2024: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 2 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 4 · 2013: 1 · 2012: 5
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychiatry Research Neuroimaging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (K23MH069656, T32MH15144, T32MH015144)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- generalized anxiety disorder, centrum semiovale, choline, creatine, N-acetylaspartate, white matter, early trauma, intelligence, worry, dorsolateral prefrontal cortex, proton magnetic resonance spectroscopic imaging, metabolite concentrations, Penn State Worry Questionnaire, WASI
- MeSH terms
- Adult, Anxiety Disorders, Choline, Cognition Disorders, Creatine, Frontal Lobe, Humans, Functional Laterality, Magnetic Resonance Spectroscopy, Phosphocreatine, Protons, Surveys and Questionnaires, Regression Analysis, Stress Disorders, Post-Traumatic, Time Factors, Wechsler Scales, Body Mass Index, Prosencephalon
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