Evidence that brain tissue volumes are associated with HVA reactivity to metabolic stress in schizophrenia

Marcelis, Machteld; Suckling, John; Hofman, Paul; Woodruff, Peter; Bullmore, Ed; van Os, Jim

doi:10.1016/j.schres.2006.05.001

« Previous Next »Schizophrenia Research
Volume 86, Issue 1 , Pages 45-53, September 2006

Evidence that brain tissue volumes are associated with HVA reactivity to metabolic stress in schizophrenia

Machteld Marcelis
- Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, PO Box 616 (VIJV1), 6200 MD Maastricht, The Netherlands
- Corresponding author. Tel.: +31 43 3688679/666; fax: +31 43 3688689.
John Suckling
- Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
Paul Hofman
- Department of Radiology, University Hospital Maastricht, Maastricht, The Netherlands
Peter Woodruff
- Department of Psychiatry, Sheffield Cognition and Neuroimaging Laboratory, Academic Clinical Psychiatry, University of Sheffield, The Longley Centre, Norwood Grange Drive, Sheffield, S5 7JT, UK
Ed Bullmore
- Department of Psychiatry, University of Cambridge, UK
Jim van Os
- Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, PO Box 616 (VIJV1), 6200 MD Maastricht, The Netherlands
- Division of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK

Received 27 July 2005; received in revised form 1 May 2006; accepted 2 May 2006.

Abstract

Background

Although liability to psychosis is thought to have its origins in cerebral alterations, expressed as cerebral grey and white matter loss, less is known about the degree to which such vulnerabilities impact on functional parameters, in particular altered stress reactivity. Breier et al. [Breier, A., Davis, O.R., Buchanan, R.W., Moricle, L.A., Munson, R.C., 1993b. Effects of metabolic perturbation on plasma homovanillic acid in schizophrenia. Relationship to prefrontal cortex volume. Arch. Gen. Psychiatry 50(7), 541–550] reported that lower prefrontal cortex volume was associated with altered metabolic stress response, but this finding has never been replicated.

Methods

Thirty-one patients with psychosis underwent structural magnetic resonance imaging scanning and a metabolic stress paradigm (glucoprivic 2-deoxyglucose (2DG) condition versus placebo condition) that yielded information on plasma homovanillic acid (HVA) reactivity. Total cerebral tissue volumes were derived from automated segmentation procedures. Associations between metabolic stress and tissue volumes (as well as their interactions) on the one hand, and plasma HVA level on the other, were investigated using multilevel random regression techniques.

Results

Analysis revealed a significant increase in plasma HVA over time in the 2DG condition. The increase in HVA in the stress condition was stronger in patients with lower grey and white matter volumes. There was no significant interaction between metabolic stress and CSF volume.

Conclusion

Lower grey and white matter volumes in schizophrenia are associated with a dysregulated dopaminergic/noradrenergic mediated stress response. These findings may support the hypothesis that alterations in cortico-subcortical connections affect psychosis susceptibility through an altered stress response.

Keywords: Schizophrenia, Brain alteration, Magnetic resonance imaging, Metabolic stress, Homovanillic acid, Dopamine