Abnormal brain response to cholinergic challenge in chronic encephalopathy from the 1991 Gulf War

Haley, Robert W.; Spence, Jeffrey S.; Carmack, Patrick S.; Gunst, Richard F.; Schucany, William R.; Petty, Frederick; Devous, Michael D.; Bonte, Frederick J.; Trivedi, Madhukar H.

doi:10.1016/j.pscychresns.2008.05.004

« Previous Next »Psychiatry Research: Neuroimaging
Volume 171, Issue 3 , Pages 207-220, 31 March 2009

Abnormal brain response to cholinergic challenge in chronic encephalopathy from the 1991 Gulf War

Robert W. Haley
- Epidemiology Division, Departments of Internal Medicine and Clinical Science, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Corresponding author. Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard., Dallas, TX 75390-8874, USA. Tel.: +1 214 648 3075; fax: +1 214 648 7558.
Jeffrey S. Spence
- Epidemiology Division, Departments of Internal Medicine and Clinical Science, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Statistical Science, Southern Methodist University, Dallas, TX, USA
Patrick S. Carmack
- Epidemiology Division, Departments of Internal Medicine and Clinical Science, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Statistical Science, Southern Methodist University, Dallas, TX, USA
Richard F. Gunst
- Department of Statistical Science, Southern Methodist University, Dallas, TX, USA
William R. Schucany
- Department of Statistical Science, Southern Methodist University, Dallas, TX, USA
Frederick Petty
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
- US Department of Veterans Affairs Medical Center, Dallas, TX, USA
Michael D. Devous Sr.
- Nuclear Medicine Center, Department of Radiology, University of Texas Southwestern Medical, Center, Dallas, TX, USA
Frederick J. Bonte
- Nuclear Medicine Center, Department of Radiology, University of Texas Southwestern Medical, Center, Dallas, TX, USA
Madhukar H. Trivedi
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA

Received 11 May 2007; received in revised form 10 April 2008; accepted 6 May 2008.

Abstract

Several case definitions of chronic illness in veterans of the 1991 Persian Gulf War have been linked epidemiologically with environmental exposure to cholinesterase-inhibiting chemicals, which cause chronic changes in cholinergic receptors in animal models. Twenty-one chronically ill Gulf War veterans (5 with symptom complex 1, 11 with complex 2, and 5 with complex 3) and 17 age-, sex- and education-matched controls, underwent an 99mTc-HMPAO-SPECT brain scan following infusion of saline and >48 h later a second scan following infusion of physostigmine in saline. From each SPECT image mean normalized regional cerebral blood flow (nrCBF) from 39 small blocks of correlated voxels were extracted with geostatistical spatial modeling from eight deep gray matter structures in each hemisphere. Baseline nrCBF in symptom complex 2 was lower than controls throughout deep structures. The change in nrCBF after physostigmine (challenge minus baseline) was negative in complexes 1 and 3 and controls but positive in complex 2 in some structures. Since effects were opposite in different groups, no finding typified the entire patient sample. A hold-out discriminant model of nrCBF from 17 deep brain blocks predicted membership in the clinical groups with sensitivity of 0.95 and specificity of 0.82. Gulf War-associated chronic encephalopathy in a subset of veterans may be due to neuronal dysfunction, including abnormal cholinergic response, in deep brain structures.