Decreased choline and creatine concentrations in centrum semiovale in patients with generalized anxiety disorder: Relationship to IQ and early trauma

Coplan, Jeremy D.; Mathew, Sanjay J.; Mao, Xiangling; Smith, Eric L.P.; Hof, Patrick R.; Coplan, Paul M.; Rosenblum, Leonard A.; Gorman, Jack M.; Shungu, Dikoma C.

doi:10.1016/j.pscychresns.2005.12.011

« Previous Next »Psychiatry Research: Neuroimaging
Volume 147, Issue 1 , Pages 27-39, 30 June 2006

Decreased choline and creatine concentrations in centrum semiovale in patients with generalized anxiety disorder: Relationship to IQ and early trauma☆

Jeremy D. Coplan
- Department of Psychiatry, Division of Neuropsychopharmacology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY, 11023, USA
- Department of Biological Psychiatry, New York State Psychiatric Institute, Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA
- Corresponding author. Tel.: +1 718 270 2023; fax: +1 718 270 8826.
Sanjay J. Mathew
- Department of Psychiatry (SJM, JGM) and Department of Neuroscience (PRH), Mount Sinai School of Medicine, New York, NY, USA
Xiangling Mao
- Departments of Radiology, Psychiatry and Biophysics, Weill Medical College of Cornell University, New York, NY, USA
Eric L.P. Smith
- Department of Psychiatry, Division of Neuropsychopharmacology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY, 11023, USA
Patrick R. Hof
- Department of Psychiatry (SJM, JGM) and Department of Neuroscience (PRH), Mount Sinai School of Medicine, New York, NY, USA
Paul M. Coplan
- International Partnership for Microbicides, Silver Spring, MD, USA
Leonard A. Rosenblum
- Department of Psychiatry, Division of Neuropsychopharmacology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY, 11023, USA
Jack M. Gorman
- Department of Psychiatry (SJM, JGM) and Department of Neuroscience (PRH), Mount Sinai School of Medicine, New York, NY, USA
Dikoma C. Shungu
- Departments of Radiology, Psychiatry and Biophysics, Weill Medical College of Cornell University, New York, NY, USA

Received 17 July 2005; received in revised form 12 December 2005; accepted 29 December 2005.

Abstract

We have demonstrated, using proton magnetic resonance spectroscopy imaging (¹H-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.