Advertisement

Plasma neuropeptide-Y concentrations in humans exposed to military survival training

  • Charles A Morgan III
    Correspondence
    Address reprint requests to C.A. Morgan III, M.D., M.A., National Center for PTSD Anxiety Clinic, VA Connecticut Healthcare Systems, Psychiatry 116A, West Haven CT 06516
    Affiliations
    National Center for PTSD, VA Connecticut Healthcare Systems, West Haven, Connecticut, USA (CAM, SMS, SW, AR, DSC)

    Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA (CAM, SMS, SW, AR, DSC)

    JFK Special Warfare Training Center and School, Fort Bragg, North Carolina, USA (GH)
    Search for articles by this author
  • Sheila Wang
    Affiliations
    National Center for PTSD, VA Connecticut Healthcare Systems, West Haven, Connecticut, USA (CAM, SMS, SW, AR, DSC)

    Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA (CAM, SMS, SW, AR, DSC)
    Search for articles by this author
  • Steven M Southwick
    Affiliations
    National Center for PTSD, VA Connecticut Healthcare Systems, West Haven, Connecticut, USA (CAM, SMS, SW, AR, DSC)

    Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA (CAM, SMS, SW, AR, DSC)
    Search for articles by this author
  • Ann Rasmusson
    Affiliations
    National Center for PTSD, VA Connecticut Healthcare Systems, West Haven, Connecticut, USA (CAM, SMS, SW, AR, DSC)

    Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA (CAM, SMS, SW, AR, DSC)
    Search for articles by this author
  • Gary Hazlett
    Affiliations
    JFK Special Warfare Training Center and School, Fort Bragg, North Carolina, USA (GH)
    Search for articles by this author
  • Richard L Hauger
    Affiliations
    School of Medicine, University of California, San Diego, California, USA (RLH)
    Search for articles by this author
  • Dennis S Charney
    Affiliations
    National Center for PTSD, VA Connecticut Healthcare Systems, West Haven, Connecticut, USA (CAM, SMS, SW, AR, DSC)

    Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA (CAM, SMS, SW, AR, DSC)
    Search for articles by this author

      Abstract

      Background: Neuropeptide-Y (NPY) is present in extensive neuronal systems of the brain and is present in high concentrations in cell bodies and terminals in the amygdala. Preclinical studies have shown that injections of NPY into the central nucleus of the amygdala function as a central anxiolytic and buffer against the effects of stress. The objective of this study was to assess plasma NPY immunoreactivity in healthy soldiers participating in high intensity military training at the U.S. Army survival school. The Army survival school provides a means of observing individuals under high levels of physical, environmental, and psychological stress, and consequently is considered a reasonable analogue to stress incurred as a result of war or other catastrophic experiences.
      Methods: Plasma levels of NPY were assessed at baseline (prior to initiation of training), and 24 hours after the conclusion of survival training in 49 subjects, and at baseline and during the Prisoner of War (P.O.W.) experience (immediately after exposure to a military interrogation) in 21 additional subjects.
      Results: Plasma NPY levels were significantly increased compared to baseline following interrogations and were significantly higher in Special Forces soldiers, compared to non-Special Forces soldiers. NPY elicited by interrogation stress was significantly correlated to the subjects’ behavior during interrogations and tended to be negatively correlated to symptoms of reported dissociation. Twenty-four hours after the conclusion of survival training, NPY had returned to baseline in Special Forces soldiers, but remained significantly lower than baseline values in non–Special Forces soldiers. NPY was positively correlated with both cortisol and behavioral performance under stress. NPY was negatively related to psychological symptoms of dissociation.
      Conclusions: These results provide evidence that uncontrollable stress significantly increases plasma NPY in humans, and when extended, produces a significant depletion of plasma NPY. Stress-induced alterations of plasma NPY were significantly different in Special Forces soldiers compared to non–Special Forces soldiers. These data support the idea that NPY may be involved in the enhanced stress resilience seen in humans.

      Keywords

      To read this article in full you will need to make a payment

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Allen R.
        • Boublik J.
        • Hauger R.
        • Scott H.
        • Rivier J.
        • Brown M.
        Neuropeptide Y radio-immunoassay.
        Clin Exp Pharmacol Physiol. 1991; 18: 825-833
        • Bremner J.D.
        • Krystal J.H.
        • Putnam F.W.
        • Southwick S.M.
        • Marmar C.
        • Charney D.S.
        • et al.
        Measurement of dissociative states with the Clinician-Administered Dissociative States Scale (CADSS).
        J Traumatic Stress. 1998; 11: 125-136
        • Britten K.T.
        • Southerland S.
        • Van Uden E.
        • Kirby D.
        • Rivier J.
        • Koob G.
        Anxiolytic activity of NPY receptor agaonists in the conflict test.
        Psychopharmacol. 1997; 132: 6-13
        • Broqua P.
        • Wettstein J.G.
        • Rocher M.N.
        • Gauthier-Martin B.
        • Junien J.L.
        Behavioral effects of neuropeptide Y receptor agonists in the elevated plus-maze and fear-potentiated startle procedures.
        Behav Pharmacol. 1995; 6: 215-222
        • Chatterton Jr, R.T.
        • Vogelson K.M.
        • Lu Y.C.
        • Hudgens G.A.
        Hormonal responses to psychological stress in men preparing for skydiving.
        J Clinical Endocrinol Metab. 1997; 82: 2503-2509
        • Corder R.
        • Castagne V.
        • Rivet J.-M.
        • Mormede P.
        • Gaillard R.C.
        Central and peripheral effects of repeated stress and high NaCl diet on neuropeptide Y.
        Physiol Behav. 1992; 52: 205-210
        • Dotsch J.
        • Adelmann M.
        • Englaro P.
        • Dotsch A.
        • Hanze J.
        • Blum W.F.
        • et al.
        Relation of leptin and neuropeptide Y in human blood and cerebrospinal fluid.
        J Neurol Sci. 1997; 151: 185-188
        • Ehlers C.L.
        • Somes C.
        • Siefritz E.
        • Rivier J.E.
        CRF/NPY interactions.
        Depression Anxiety. 1997; 6: 1-9
        • Flood J.F.
        • Baker M.L.
        • Hernandez E.N.
        • Morley J.E.
        Modulation of memory processing by neuropeptide Y varies with brain injection site.
        Brain Res. 1989; 503: 73-82
        • Heilig M.
        • Koob G.F.
        • Britton K.T.
        Anxiolytic-like effect of neuropeptide Y (NPY), but not other peptides, in an operant conflict test.
        Reg Peptides. 1992; 41: 65-69
        • Heilig M.
        • Murrison R.
        Intracerebroventricular neuropeptide Y protects against stress-induced gastric erosions in the rat.
        Eur J Pharmacol. 1987; 137: 127-129
        • Heilig M.
        • McLeod S.
        • Brot M.
        • Heinrichs S.C.
        • Menzaghi F.
        • Koob G.F.
        • et al.
        Anxiolytic-like action of neuropeptide Y.
        Neuropsychopharmacology. 1993; 98: 357-363
        • Heilig M.
        • Widerlov E.
        Neuropeptide Y.
        Acta Psychiatr Scand. 1990; 82: 95-114
        • Illes P.
        • Regenold J.
        Interaction between neuropeptide Y and noradrenaline on central catecholamine neurons.
        Nature. 1990; 334: 62-63
        • Jahng J.W.
        • Houpt T.A.
        • Joh T.H.
        • Wessel T.C.
        Expression of catecholamine-synthesizing enzymes, peptidylglycine α-amidating monooxygenase, and neuropeptide Y mRNA in the rat adrenal medulla after acute systemic nicotine.
        J Molec Neurosci. 1997; 7: 45-52
        • Kaijser L.
        • Pernow J.
        • Berglund B.
        • Lundberg J.M.
        Neuropeptide Y is released together with noradrenaline from the human heart during exercise and hypoxia.
        Clin Physiol. 1990; 10: 179-188
        • Kaye W.H.
        • Berrettini W.
        • Gwirtsman H.
        • George D.T.
        Altered cerebrospinal fluid neuropeptide Y and peptide YY immunoreactivity in anorexia and bulimia nervosa.
        Arch Gen Psychiatry. 1990; 47: 548-556
        • Kopin I.J.
        • Gordon E.K.
        • Jimerson D.C.
        • Polinski R.J.
        Relation between plasma and cerebrospinal fluid levels of 3-methoxy-4-hydroxyphenethylenneglycol.
        Science. 1983; 219: 73-75
        • Leedy M.G.
        • Wilson M.S.
        Testosterone and cortisol levels in crewman of U.S. Air Force fighter and cargo planes.
        Psychosomat Med. 1985; 47: 333-338
        • Leino T.
        • Leppaluoto J.
        • Huttunen P.
        • Ruokonen A.
        • Kuronen P.
        Neuroendocrine responses to real and simulated BA Hawk MK 51 flight.
        Aviation Space Environ Med. 1995; 66: 108-113
        • Lundberg J.M.
        • Martinsson A.
        • Hemsen A.
        • Theodorsson-Norheim E.
        • Svedenhag J.
        • Ekblom B.
        • Hjemdahl P.
        Co-release of neuropeptide Y and catecholamines during physical exercise in man.
        Biochem Biophys Res Commun. 1985; 133: 30-36
        • Morris M.J.
        • Russell A.E.
        • Kapoor V.
        • Elliott J.M.
        • West M.J.
        • Wing L.M.H.
        • et al.
        Increases in plasma neuropeptide Y concentrations during sympathetic activation in man.
        J Auton Nerv System. 1986; 17: 143-149
        • Nakajima M.
        • Inui A.
        • Teranishi A.
        • Miura M.
        • Hirosue Y.
        • Okita M.
        • et al.
        Effects of pancreatic polypeptide family peptides on feeding and learning behavior in mice.
        J Pharmacol Exp Ther. 1994; 268: 1010-1014
        • Opstad P.K.
        Androgenic hormones during prolonged physical stress, sleep and energy deficiency.
        J Clin Endocrinol Metab. 1992; 74: 1176-1183
        • Parker L.
        • Eugene J.
        • Farber D.
        • Lifrak E.
        • Lai M.
        • Juler G.
        Dissociation of adrenal androgen and cortisol levels in acute stress.
        Horm Metab Res. 1985; 17: 209-212
        • Pernow J.
        • Lundberg J.M.
        • Kaijser L.
        • Hjemdahl P.
        • Theodorsson-Norhem E.
        • Martinsson A.
        • et al.
        Plasma neuropeptide Y-like immunoreactivity and catecholamines during various degrees of sympathetic activation in man.
        Clin Physiol. 1986; 6: 561-578
        • Rasmusson A.M.
        • Southwick S.M.
        • Hauger R.L.
        • Charney D.S.
        Plasma neuropeptide Y (NPY) increases in humans in response to the α-2 antatgonist yohimbine.
        Neuropsychopharmacol. 1998; 19: 95-98
        • Rasmusson A.M.
        • Hauger R.L.
        • Morgan III, C.A.
        • Bremner J.D.
        • Charney D.S.
        • Southwick S.M.
        Low baseline and yohimbine-stimulated plasma neuropeptide Y (NPY) levels in combat-related PTSD.
        Biol Psychiatry. 2000; 47: 526-539
        • Stanley B.G.
        • Leibowitz S.F.
        Neuropeptide Y injected in a paraventricular hypothalamus.
        Proc Natl Acad Sci U S A. 1985; 82: 3940-3943
        • Torda T.
        • Cruciani R.A.
        • Saavedra J.
        Localization of neuropeptide Y binding sites in the zona glomerulosa of the bovine adrenal gland.
        Neuroendocrinol. 1988; 48: 207-210
        • Wahlestedt C.
        • Reis D.J.
        Neuropeptide Y-related peptides and their receptors.
        Ann Rev Pharmacol Toxicol. 1993; 32: 309-352
        • Wahlestedt C.
        • Pich E.
        • Koob G.F.
        • Yee F.
        • Heilig M.
        Modulation of anxiety and neuropeptide Y-Y1 receptors by antisense oligodeoxynucleotides.
        Science. 1993; 259: 528-530
        • Widdowson P.S.
        • Ordway G.A.
        • Halaris A.E.
        Reduced neuropeptide Y concentrations in suicide brain.
        J Neurochem. 1992; 59: 73-80
        • Widerlov D.
        • Lindstrom L.H.
        • Wahlestedt C.
        • Ekman R.
        Neuropeptide Y and peptide YY as possible cerebrospinal markers for major depression and schizophrenia, respectively.
        J Psychiatr Res. 1988; 22: 69-79
        • Zukowska-Grojec Z.
        • Pruszczyk P.
        • Colton C.
        • Yao J.
        • Shen G.H.
        • Myers A.K.
        • et al.
        Mitogenic effect of neuropeptide Y in rat vascular smooth muscled cells.
        Peptides. 1993; 14: 263-268