This Article  • References  • Full text PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Social Bookmarking   What's this?

Relationship to Prefrontal Cortex Volume

Alan Breier, MD; Orlando R. Davis, MD; Robert W. Buchanan, MD; Lea Ann Moricle, MD; Robert C. Munson

Arch Gen Psychiatry. 1993;50(7):541-550.

Abstract
Objective
Several recent hypotheses suggest that deficits in normal prefrontal cortical inhibition of subcortical dopamine activity result in dysregulated dopamine function and may contribute to the pathophysiology of schizophrenia. These effects seem to be more consistently demonstrable during stressful perturbation of the dopamine system, as opposed to during the resting state. We have developed a novel paradigm involving infusion of the glucose analog, 2-deoxyglucose (2DG), to examine the effects of perturbation on the dopamine metabolite, plasma homovanillic acid (HVA), in schizophrenics and healthy controls.

Design
Pharmacologic doses of 2DG (50 mg/kg) and placebo were infused in a double-blind manner. 2-Deoxyglucoseinduced effects on plasma HVA were related to magnetic reasonance imaging-derived prefrontal cortex volumes.

Subjects
Schizophrenic outpatients (N=18) and healthy volunteers (N=11) participated in the study.

Results
Schizophrenic patients, as compared with controls, had significantly greater 2DG-induced plasma HVA elevations. These effects were observed in subgroups of neuroleptic-free and neuroleptic-treated patients. Other neuroendocrine (plasma cortisol), physiologic (heart rate, diastolic blood pressure, temperature) and behavioral (selfratings of stress, fatigue) variables were significantly effected by 2DG but did not differentiate schizophrenics and controls suggesting that the effects on plasma HVA may be relatively specific. Magnetic resonance imagingderived volumes of the prefrontal cortex were significantly and inversely correlated to 2DG-related peak changes in plasma HVA levels in the schizophrenics.

Conclusion
These data support the hypothesis that schizophrenia is associated with abnormal regulation of dopamine and that this deficit may be related to reduced frontal cortical inhibitory influences.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Psychosocial Stress and Psychosis. A Review of the Neurobiological Mechanisms and the Evidence for Gene-Stress Interaction
van Winkel et al.
Schizophr Bull 2008;34:1095-1105.
ABSTRACT | FULL TEXT  

The Pathophysiology of Schizophrenia Disorders: Perspectives From the Spectrum
Siever and Davis
Am. J. Psychiatry 2004;161:398-413.
ABSTRACT | FULL TEXT  

Effects of Acute Metabolic Stress on the Peripheral Vasopressinergic System in Schizophrenia
Elman et al.
J Psychopharmacol 2003;17:317-323.
ABSTRACT  

Disturbed Gyrification of the Prefrontal Region in Male Schizophrenic Patients: A Morphometric Postmortem Study
Vogeley et al.
Am. J. Psychiatry 2000;157:34-39.
ABSTRACT | FULL TEXT