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


CONCLUSIONS
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.
Marcelis
Machteld
M
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands. m.marcelis@sp.unimaas.nl
Suckling
John
J
Hofman
Paul
P
Woodruff
Peter
P
Bullmore
Ed
E
van Os
Jim
J
D000293:Adolescent; D000328:Adult; D003847:Deoxyglucose / Q000378:metabolism; D005260:Female; D006719:Homovanillic Acid / Q000097:blood*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D012559:Schizophrenia / Q000097:blood* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
D003847:Deoxyglucose; D006719:Homovanillic Acid