Grey and white matter differences in brain energy metabolism in first episode schizophrenia: 31P-MRS chemical shift imaging at 4 Tesla

Jensen, J. Eric; Miller, Jodi; Williamson, Peter C.; Neufeld, Richard W.J.; Menon, Ravi S.; Malla, Ashok; Manchanda, Rahul; Schaefer, Betsy; Densmore, Maria; Drost, Dick J.

doi:10.1016/j.pscychresns.2005.11.004

« Previous Next »Psychiatry Research: Neuroimaging
Volume 146, Issue 2 , Pages 127-135, 31 March 2006

Grey and white matter differences in brain energy metabolism in first episode schizophrenia: ³¹P-MRS chemical shift imaging at 4 Tesla

J. Eric Jensen
- Brain Imaging Center, McLean Hospital, Belmont, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
- Corresponding author. Room 208, Brain Imaging Center, McLean Hospital, 115 Mill Street, Belmont, MA 02478-9106, USA. Tel.: +1 617 855 3366; fax: +1 617 855 2770.
Jodi Miller
- Department of Medical Biophysics, University of Western Ontario, Canada
- Diagnostic Radiology and Nuclear Medicine, St. Joseph's Health Care, London, Ontario, Canada
Peter C. Williamson
- Department of Medical Biophysics, University of Western Ontario, Canada
- Department of Psychiatry, University of Western Ontario, Canada
Richard W.J. Neufeld
- Department of Psychology, University of Western Ontario, Canada
Ravi S. Menon
- Department of Medical Biophysics, University of Western Ontario, Canada
- Laboratory for Magnetic Resonance Imaging Research, Robarts Research Institute, London, Ontario, Canada
Ashok Malla
- Douglas Hospital, McGill University, Montreal, Quebec, Canada
Rahul Manchanda
- Department of Psychiatry, University of Western Ontario, Canada
Betsy Schaefer
- Department of Psychiatry, University of Western Ontario, Canada
Maria Densmore
- Diagnostic Radiology and Nuclear Medicine, St. Joseph's Health Care, London, Ontario, Canada
Dick J. Drost
- Department of Medical Biophysics, University of Western Ontario, Canada
- Department of Psychiatry, University of Western Ontario, Canada
- Diagnostic Radiology and Nuclear Medicine, St. Joseph's Health Care, London, Ontario, Canada

Received 6 July 2005; received in revised form 20 October 2005; accepted 28 November 2005.

Abstract

Altered high energy and membrane metabolism, measured with phosphorus magnetic resonance spectroscopy (³¹P-MRS), has been inconsistently reported in schizophrenic patients in several anatomical brain regions implicated in the pathophysiology of this illness, with little attention to the effects of brain tissue type on the results. Tissue regression analysis correlates brain tissue type to measured metabolite levels, allowing for the extraction of “pure” estimated grey and white matter compartment metabolite levels. We use this tissue analysis technique on a clinical dataset of first episode schizophrenic patients and matched controls to investigate the effect of brain tissue specificity on altered energy and membrane metabolism. In vivo brain spectra from two regions, (a) the fronto-temporal-striatal region and (b) the frontal-lobes, were analyzed from 12 first episode schizophrenic patients and 11 matched controls from a ³¹P chemical shift imaging (CSI) study at 4 Tesla (T) field strength. Tissue regression analyses using voxels from each region were performed relating metabolite levels to tissue content, examining phosphorus metabolite levels in grey and white matter compartments. Compared with controls, the first episode schizophrenic patient group showed significantly increased adenosine triphosphate levels (B-ATP) in white matter and decreased B-ATP levels in grey matter in the fronto-temporal-striatal region. No significant metabolite level differences were found in grey or white matter compartments in the frontal cortex. Tissue regression analysis reveals grey and white matter specific aberrations in high-energy phosphates in first episode schizophrenia. Although past studies report inconsistent regional differences in high-energy phosphate levels in schizophrenia, the present analysis suggests more widespread differences that seem to be strongly related to tissue type. Our data suggest that differences in grey and white matter tissue content between past studies may account for some of the variance in the literature.

Keywords: Brain, Chemical-shift imaging, Magnetic resonance spectroscopy, Energy metabolism, Phospholipids, Schizophrenia