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Letter

Acetylcholinesterase inhibition and Gulf War illnesses: Conclusions are not supported by independent reviews of the same evidence

Dan Blazer, Gregory C. Gray, Matthew Hotopf, Gary Macfarlane, Malcolm Sim, Tyler C. Smith, and Simon Wessely
PNAS April 29, 2008 105 (17) E20; first published April 23, 2008; https://doi.org/10.1073/pnas.0802669105
Dan Blazer
*Gibbons Professor of Psychiatry, Duke University Medical Center, Durham, NC 27710;
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Gregory C. Gray
†Center for Emerging Infectious Diseases and Department of Epidemiology and International Programs, University of Iowa College of Public Health, Iowa City, IA 52242;
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Matthew Hotopf
‡Department of Psychological Medicine, Institute of Psychiatry, King's College London, London SE5 9RJ, United Kingdom;
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Gary Macfarlane
§Epidemiology Group, Department of Public Health, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom;
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Malcolm Sim
¶Centre for Occupational and Environmental Health, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne VIC 3004, Australia;
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Tyler C. Smith
‖Department of Defense Center for Deployment Health Research Naval Health Research Center, San Diego, CA 92186; and
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Simon Wessely
**Department of Psychological Medicine, King's Centre for Military Health Research, King's College London, London SE5 9RJ, United Kingdom
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  • For correspondence: s.wessely@iop.kcl.ac.uk

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  • Correction for Golomb, “Reply to Blazer et al.: Flawed challenges to ‘Acetylcholinesterase inhibitors and Gulf War illnesses’,”
    - Nov 10, 2008
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To the Editor: Golomb (1) concludes that there is strong evidence that exposure to acetylcholinesterase inhibitors [e.g., nerve agents, pyridostigmine bromide (PB), and pesticides] caused illness in 1991 Gulf War veterans (GWVs). We neither agree with her interpretation of the literature, including our own work, nor her conclusions, and believe she has neglected research that does not support her views.

The reported increase in extra cases of ALS in U.S. GWVs reported in one paper is an important part of her argument, and she makes inferences about possible links between ALS and acetylcholinesterase inhibitors. However, the excess was small, there was a strong possibility that cases were overascertained among GWVs, and the control sample had an unusually low incidence of ALS (2, 3). There is no increase in deaths from neurological causes in GWVs. The increase in ALS is in veterans of wars not associated with anticholinesterases, which is evidence against, not in favor, of her hypothesis.

Golomb does not mention the numerous large, representative, controlled, investigations of Gulf veterans, all of which concluded that there was no evidence of damage to the peripheral nervous system that could be accounted for by exposure to organophosphate-containing compounds (e.g., ref. 4).

Golomb quotes extensively many of our papers that have identified associations between neurological symptoms and self-reported exposure to pesticides, PB, and nerve gas but, unlike the original authors, does not pay any attention to recall bias.

Finally, Golomb ignores a series of authoritative and extensive reports, such as those produced by the prestigious and independent Institute of Medicine (5, 6) and others, which have undertaken scholarly reviews of the same literature and come to very different conclusions.

Footnotes

  • ↵††To whom correspondence should be addressed. E-mail: s.wessely{at}iop.kcl.ac.uk
  • Author contributions: D.B., G.C.G., M.H., G.M., M.S., T.C.S., and S.W. wrote the paper.

  • Conflict of interest statement: S.W. is an unpaid Civilian Advisor in Psychiatry to the British Army. D.B. cochaired the Institute of Medicine (IOM) Committee on “Gulf War Veterans: Measuring Health” and serves on the Defense Health Board.

  • © 2008 by The National Academy of Sciences of the USA

References

  1. ↵
    1. Golomb BA
    (2008) Acetylcholinesterase inhibitors and Gulf War illnesses. Proc Natl Acad Sci USA 105:4295–4300.
    .
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Rose M
    (2003) Gulf war service an uncertain trigger for ALS. Neurology 61:730–731.
    .
    OpenUrlFREE Full Text
  3. ↵
    1. Armon C
    (2007) Occurrence of amyotrophic lateral sclerosis among Gulf War Veterans. Neurology 68:1083.
    .
    OpenUrlFREE Full Text
  4. ↵
    1. Sharief M,
    2. et al.
    (2002) Neurophysiologic evaluation of neuromuscular symptoms in UK Gulf War veterans: A controlled study. Neurology 59:1518–1525.
    .
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Institute of Medicine
    (2000) Depleted Uranium, Sarin, Pyridostigmine Bromide, Vaccines (Natl Acad Sci, Washington), Vol 1.
    .
  6. ↵
    1. Committee on Gulf War and Health
    (2004) Gulf War and Health: Updated Literature Review of Sarin (Natl Acad Sci, Washington).
    .
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Acetylcholinesterase inhibition and Gulf War illnesses: Conclusions are not supported by independent reviews of the same evidence
Dan Blazer, Gregory C. Gray, Matthew Hotopf, Gary Macfarlane, Malcolm Sim, Tyler C. Smith, Simon Wessely
Proceedings of the National Academy of Sciences Apr 2008, 105 (17) E20; DOI: 10.1073/pnas.0802669105

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Acetylcholinesterase inhibition and Gulf War illnesses: Conclusions are not supported by independent reviews of the same evidence
Dan Blazer, Gregory C. Gray, Matthew Hotopf, Gary Macfarlane, Malcolm Sim, Tyler C. Smith, Simon Wessely
Proceedings of the National Academy of Sciences Apr 2008, 105 (17) E20; DOI: 10.1073/pnas.0802669105
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