Psychiatry Research
Volume 157, Issue 1 , Pages 123-129 , 15 January 2008

Decreased cerebrospinal fluid concentrations of substance P in treatment-resistant depression and lack of alteration after acute adjunct vagus nerve stimulation therapy

  • Linda L. Carpenter

      Affiliations

    • Mood Disorders Research Program, Butler Hospital, Brown University, Providence, RI, USA
    • Corresponding Author InformationCorresponding author. Butler Hospital, 345 Blackstone Blvd., Providence, RI 02906, USA. Tel.: +1 401 455 6349; fax: +1 401 455 6534.
  • ,
  • Lily Bayat

      Affiliations

    • Mood Disorders Research Program, Butler Hospital, Brown University, Providence, RI, USA
  • ,
  • Francisco Moreno

      Affiliations

    • Department of Psychiatry, University of Arizona Health Sciences Center, Tucson, AZ, USA
  • ,
  • Mitchel A. Kling

      Affiliations

    • Departments of Psychiatry and Medicine, University of Maryland School of Medicine and Baltimore VA Medical Center, Baltimore, MD, USA
  • ,
  • Lawrence H. Price

      Affiliations

    • Mood Disorders Research Program, Butler Hospital, Brown University, Providence, RI, USA
  • ,
  • Audrey R. Tyrka

      Affiliations

    • Mood Disorders Research Program, Butler Hospital, Brown University, Providence, RI, USA
  • ,
  • Becky Kinkead

      Affiliations

    • Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
  • ,
  • Michael J. Owens

      Affiliations

    • Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
  • ,
  • Charles B. Nemeroff

      Affiliations

    • Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

Received 14 February 2006 ,Revised 9 April 2007 ,Accepted 16 April 2007.

References 

  1. Aguiar MS, Brandao ML. Effects of microinjections of the neuropeptide substance P in the dorsal periaqueductal gray on the behaviour of rats in the plus-maze test. Physiology and Behavior. 1996;60:1183–1186
  2. Arai H, Emson PC. Regional distribution of neuropeptide K and other tachykinins (neurokinin A, neurokinin B and substance P) in rat central nervous system. Brain Research. 1986;399:240–249
  3. Berrettini WH, Rubinow DR, Nurnberger JI, Simmons-Alling S, Post RM, Gershon ES. CSF substance P immunoreactivity in affective disorders. Biological Psychiatry. 1985;20:965–970
  4. Bondy B, Baghai TC, Minov C, Schule C, Schwarz MJ, Zwanzger P, et al. Substance P serum levels are increased in major depression: preliminary results. Biological Psychiatry. 2003;53:538–542
  5. Carpenter LL, Moreno FA, Kling MA, Anderson GM, Regenold WT, Labiner DM, et al. Effect of vagus nerve stimulation on cerebrospinal fluid monoamine metabolites, norepinephrine, and gamma-aminobutyric acid concentrations in depressed patients. Biological Psychiatry. 2004;56:418–426
  6. Commons KG, Connolley KR, Valentino RJ. A neurochemically distinct dorsal raphe-limbic circuit with a potential role in affective disorders. Neuropsychopharmacology. 2003;28:206–215
  7. Culman J, Unger T. Central tachykinins: mediators of defence reaction and stress reactions. Canadian Journal of Physiology and Pharmacology. 1995;73:885–891
  8. De Felipe C, Herrero JF, O'Brien JA, Palmer JA, Doyle CA, Smith AJ, et al. Altered nociception, analgesia and aggression in mice lacking the receptor for substance P. Nature. 1998;392:394–397
  9. Deuschle M, Sander P, Herpfer I, Fiebich BL, Heuser I, Lieb K. Substance P in serum and cerebrospinal fluid of depressed patients: no effect of antidepressant treatment. Psychiatry Research. 2005;136:1–6
  10. Ebner K, Rupniak NM, Saria A, Singewald N. Substance P in the medial amygdala: emotional stress-sensitive release and modulation of anxiety-related behavior in rats. Proceedings of the National Academy of Sciences of the United States of America. 2004;101:4280–4285
  11. Elliott PJ. Place aversion induced by the substance P analogue, dimethyl-C7, is not state dependent: implication of substance P in aversion. Experimental Brain Research. 1988;73:354–356
  12. Freed AL, Audus KL, Lunte SM. Investigation of substance P transport across the blood–brain barrier. Peptides. 2002;23:157–165
  13. George MS, Rush AJ, Marangell LB, Sackeim HA, Brannan SK, Davis SM, et al. A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression. Biological Psychiatry. 2005;58:364–373
  14. Geracioti TD, Carpenter LL, Owens MJ, Baker DG, Ekhator NN, Horn PS, et al. Elevated cerebrospinal fluid substance P concentrations in post-traumatic stress disorder and major depression. American Journal of Psychiatry. 2006;163:637–643
  15. Guest PC, Knowles MR, Molon-Noblot S, Salim K, Smith D, Murray F, et al. Mechanisms of action of the antidepressants fluoxetine and the substance P antagonist L-000760735 are associated with altered neurofilaments and synaptic remodeling. Brain Research. 2004;1002:1–10
  16. Haddjeri N, Blier P. Sustained blockade of neurokinin-1 receptors enhances serotonin neurotransmission. Biological Psychiatry. 2001;50:191–199
  17. Hamilton M. A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry. 1960;23:56–62
  18. Harrison S, Geppetti P. Substance p. International Journal of Biochemistry and Cell Biology. 2001;33:555–576
  19. Henry TR. Therapeutic mechanisms of vagus nerve stimulation. Neurology. 2002;59:S3–S14
  20. Hokfelt T, Pernow B, Wahren J. Substance P: a pioneer amongst neuropeptides. Journal of Internal Medicine. 2001;249:27–40
  21. Hwang BH, Katner J, Iyengar S. Corticotropin-releasing factor mRNA and substance P receptor binding in the paraventricular hypothalamic nucleus, central nucleus of the amygdala, and locus coeruleus of Sprague–Dawley rats following restraint-induced stress. Journal of Molecular Neuroscience. 2005;25:239–250
  22. Jessop DS, Renshaw D, Larsen PJ, Chowdrey HS, Harbuz MS. Substance P is involved in terminating the hypothalamo–pituitary–adrenal axis response to acute stress through centrally located neurokinin-1 receptors. Stress. 2000;3:209–220
  23. Landgraf R, Klauschenz E, Bienert M, Ermisch A, Oehme P. Some observations indicating a low brain uptake of [3H]Nle11-Substance P. Pharmazie. 1983;38:108–110
  24. Lejeune F, Gobert A, Millan MJ. The selective neurokinin (NK)(1) antagonist, GR205,171, stereospecifically enhances mesocortical dopaminergic transmission in the rat: a combined dialysis and electrophysiological study. Brain Research. 2002;935:134–139
  25. Lieb K, Walden J, Grunze H, Fiebich BL, Berger M, Normann C. Serum levels of substance P and response to antidepressant pharmacotherapy. Pharmacopsychiatry. 2004;37:238–239
  26. Mantyh PW, Hunt SP, Maggio JE. Substance P receptors: localization by light microscopic autoradiography in rat brain using [3H]SP as the radioligand. Brain Research. 1984;307:147–165
  27. Martensson B, Nyberg S, Toresson G, Brodin E, Bertilsson L. Fluoxetine treatment of depression. Clinical effects, drug concentrations and monoamine metabolites and N-terminally extended substance P in cerebrospinal fluid. Acta Psychiatrica Scandinavica. 1989;79:586–596
  28. McLean S. Do substance P and the NK1 receptor have a role in depression and anxiety?. Current Pharmaceutical Design. 2005;11:1529–1547
  29. Millan MJ, Lejeune F, De Nanteuil G, Gobert A. Selective blockade of neurokinin (NK)(1) receptors facilitates the activity of adrenergic pathways projecting to frontal cortex and dorsal hippocampus in rats. Journal of Neurochemistry. 2001;76:1949–1954
  30. O'Keane V, Dinan TG, Scott L, Corcoran C. Changes in hypothalamic–pituitary–adrenal axis measures after vagus nerve stimulation therapy in chronic depression. Biological Psychiatry. 2005;58:963–968
  31. Ohayon MM. Specific characteristics of the pain/depression association in the general population. Journal of Clinical Psychiatry. 2004;65(Suppl 12):5–9
  32. Ohayon MM, Schatzberg AF. Using chronic pain to predict depressive morbidity in the general population. Archives of General Psychiatry. 2003;60:39–47
  33. Pernow B. Studies on substance P; purification, occurrence and biological actions. Acta Physiologica Scandinavica. Supplementum. 1953;29:1–89
  34. Rimon R, Le Greves P, Nyberg F, Heikkila L, Salmela L, Terenius L. Elevation of substance P-like peptides in the CSF of psychiatric patients. Biological Psychiatry. 1984;19:509–516
  35. Rush AJ, Marangell LB, Sackeim HA, George MS, Brannan SK, Davis SM, et al. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biological Psychiatry. 2005;58:347–354
  36. Santarelli L, Saxe MD. Substance P antagonists: meet the new drugs, same as the old drugs? Insights from transgenic animal models. CNS Spectrums. 2003;8:589–596
  37. Santarelli L, Gobbi G, Debs PC, Sibille ET, Blier P, Hen R, et al. Genetic and pharmacological disruption of neurokinin 1 receptor function decreases anxiety-related behaviors and increases serotonergic function. Proceedings of the National Academy of Sciences of the United States of America. 2001;98:1912–1917
  38. Shirayama Y, Mitsushio H, Takashima M, Ichikawa H, Takahashi K. Reduction of substance P after chronic antidepressants treatment in the striatum, substantia nigra and amygdala of the rat. Brain Research. 1996;739:70–78
  39. Stout SC, Owens MJ, Nemeroff CB. Neurokinin(1) receptor antagonists as potential antidepressants. Annual Review of Pharmacology and Toxicology. 2001;41:877–906
  40. Teixeira RM, Santos AR, Ribeiro SJ, Calixto JB, Rae GA, De Lima TC. Effects of central administration of tachykinin receptor agonists and antagonists on plus-maze behavior in mice. European Journal of Pharmacology. 1996;311:7–14
  41. von Euler US, Gaddum JH. An unidentified depressor substance in certain tissue extracts. Journal of Physiology. 1931;72:74–78

 This study was funded by Cyberonics, the manufacturer of the vagus nerve stimulation device. Drs. Linda Carpenter, Francisco Moreno, Mitchel Kling, Lawrence Price, and Charles Nemeroff have received consultant and/or lecture honoraria payments from Cyberonics.

PII: S0165-1781(07)00124-2

doi: 10.1016/j.psychres.2007.04.016

Psychiatry Research
Volume 157, Issue 1 , Pages 123-129 , 15 January 2008