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Effect of acute tryptophan depletion on CO2-induced anxiety in patients with panic disorder and normal volunteers

  • H. E. J. Miller (a1), J. F. W. Deakin (a2) and I. M. Anderson (a2)
Extract
Background

Uncertainties remain about the role of serotonin in the aetiology and treatment of panic disorder.

Aims

To investigate the effect of reducing brain serotonin function on anxiety at rest, and following 5% CO2 provocation in normal controls and patients with panic disorder.

Method

Twenty drug-free patients with DSM–III–R panic disorder and 19 controls received a tryptophan-free amino acid drink on one occasion and a control drink on the other in a double-blind, balanced protocol. 5% CO2 was given as a panic challenge after 270 minutes.

Results

Plasma tryptophan fell by more than 80% both patients and controls after the tryptophan-free drink. Tryptophan depletion did not alter resting anxiety. In patients alone, tryptophan depletion caused a greater anxiogenic response and an increased rate of panic attacks (9 v. 2, P<0.05) after 5% CO2 challenge. No normal volunteers panicked.

Conclusions

Serotonin may directly modulate panic anxiety in patients with panic disorder. This may underlie the efficacy of serotonergic antidepressants in treating panic disorder.

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Copyright
Corresponding author
Dr I. M. Anderson, University of Manchester Department of Psychiatry, Room 9809, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK. Tel: 0161 276 5396; Fax: 0161 273 2135; e-mail: ian.anderson@man.ac.uk
Footnotes
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Previously presented at the Annual Meeting of the British Association for Psychopharmacology in association with the British Neuropsychiatry Association, 16–19 July 1995, Cambridge.

Declaration of interest

This study was supported by an MRC project grant.

Footnotes
References
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American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM–III–R). Washington, DC: APA.
Armitage, P. & Berry, G. (1987) Statistical Methods in Medical Research (2nd edn). Oxford: Blackwell Scientific Publications.
Aronson, S. C., Black, J. E., McDougle, C. J., et al (1995) Serotonergic mechanisms of cocaine effects in humans. Psychopharmacology, 119, 179185.
Barr, L. C., Goodman, W. K., McDougle, C. J., et al (1994) Tryptophan depletion in patients with obsessive-compulsive disorder who respond to serotonin reuptake inhibitors. Archives of General Psychiatry, 51, 309317.
Beck, A. T., Ward, C. H., Mendelson, M., et al (1961) An inventory for measuring depression. Archives of General Psychiatry, 4, 561567.
Benkelfat, C., Ellenbogen, M. A., Dean, P., et al (1994) Mood-lowering effect of tryptophan depletion: enhanced susceptibility in young men at genetic risk for major affective disorders. Archives of General Psychiatry, 51, 687697.
Benkelfat, C., Seletti, B., Palmour, R. M., et al (1995) Tryptophan depletion in stable lithium-treated patients with bipolar disorder in remission. Archives of General Psychiatry, 52, 154155.
Bertani, A., Perna, G., Arancio, C., et al (1997) Pharmacological effect of imipramine, paroxetine, and sertraline on 35% carbon dioxide hypersensitivity in panic patients: a double-blind, random, placebo-controlled study. Journal of Clinical Psychopharmacology, 17, 97101.
Carpenter, L. L., Anderson, G. M., Pelton, G. H., et al (1998) Tryptophan depletion during continuous CSF sampling in healthy human subjects. Neuropsychopharmacology, 19, 2635.
Carr, D. B., Sheehan, D. V., Surman, O. S., et al (1986) Neuroendocrine correlates of lactate-induced anxiety and their response to chronic alprazolam therapy. American Journal of Psychiatry, 143, 483494.
Charney, D. S., Woods, S. W., Goodman, W. K., et al (1987) Serotonin function in anxiety. II. Effects of the serotonin agonist MCPP in panic disorder patients and healthy subjects. Psychopharmacology, 92, 1424.
Clark, D. M. (1986) A cognitive approach to panic. Behaviour Research and Therapy, 24, 461470.
Coplan, J. D., Gorman, J. M. & Klein, D. F. (1992) Serotonin related functions in panic-anxiety: a critical overview. Neuropsychopharmacology, 6, 189200.
Deakin, J. F. W. & Graeff, F. G. (1991) 5-HT and mechanisms of defence. Journal of Psychopharmacology, 5, 305315.
Deakin, J. F. W., Graeff, F. G. & Guimaraes, F. S. (1992) 5-HT receptor subtypes and the modulation of aversion. In Central Serotonin Receptors and Psychotropic Drugs (ed. Marsden, C. A. & Heal, D. J.), pp. 147174. Oxford: Blackwell Scientific Publications.
Deakin, J. F. W., Guimaraes, F. S. & Graeff, F. G. (1994) Testing 5HT theories of anxiety in normal volunteers. In Strategies for Studying Brain Disorders. Volume I. Depressive, Anxiety and Drug Abuse Disorders (ed. Palomo, T. & Archer, T.), pp. 211238. London: Farrand Press.
Delgado, P. L., Charney, D. S., Price, L. H., et al (1990) Serotonin function and the mechanism of antidepressant action: reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. Archives of General Psychiatry, 47, 411418.
Delgado, P. L., Price, L. H., Miller, H. L., et al (1994) Serotonin and the neurobiology of depression: effects of tryptophan depletion in drug-free depressed patients. Archives of General Psychiatry, 51, 865874.
Dillon, D. J., Gorman, J. M., Liebowitz, M. R., et al (1987) Measurement of lactate-induced panic and anxiety. Psychiatry Research, 20, 97105.
Dratcu, L. & Bond, A. (1993) Audit: referrals for panic disorder to a clinical psychopharmacology research unit. Psychiatric Bulletin, 17, 416417.
Goddard, A. W., Sholomskas, D. E., Walton, K. E., et al (1994) Effects of tryptophan depletion in panic disorder. Biological Psychiatry, 36, 775777.
Goddard, A. W., Charney, D. S., Germine, M., et al (1995) Effects of tryptophan depletion on responses to yohimbine in healthy human subjects. Biological Psychiatry, 38, 7486.
Gorman, J. M., Fyer, M. R., Goetz, R., et al (1988) Ventilatory physiology of patients with panic disorder. Archives of General Psychiatry, 45, 3139.
Gorman, J. M., Browne, S. T., Papp, L. A., et al (1997) Effect of antipanic treatment on response to carbon dioxide. Biological Psychiatry, 42, 982991.
Gray, J. A. (1987) The Psychology of Fear and Stress (2nd edn). Cambridge: Cambridge University Press.
Hamilton, M. (1960) A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry, 23, 5663.
Hamilton, M. (1969) Diagnosis and ratings of anxiety. British Journal of Psychiatry, 3, 7679.
Kent, J. M., Coplan, J. D., Martinez, J., et al (1996) Ventilatory effects of tryptophan depletion in panic disorder: a preliminary report. Psychiatry Research, 64, 8390.
Klaassen, T., Klumperbeek, J., Deutz, N. E. P., et al (1998) Effects of tryptophan depletion on anxiety and on panic provoked by carbon dioxide challenge. Psychiatry Research, 77, 167174.
Klein, D. F. (1993) False suffocation alarms, spontaneous panics, and related conditions. Archives of General Psychiatry, 50, 306317.
Koszycki, D., Zacharko, R. M., Le Melledo, J.-M., et al (1996) Effect of acute tryptophan depletion on behavioural, cardiovascular, and hormonal sensitivity to cholecystokinin-tetrapeptide challenge in healthy volunteers. Biological Psychiatry, 40, 648655.
McNair, D. M., Lorr, M. & Droppelman, L. F. (1971) Manual for the Profile of Mood States. San Diego, CA: Educational and Industrial Testing Service.
Menkes, D. B., Coates, D. C. & Fawcett, J. P. (1994) Acute tryptophan depletion aggravates premenstrual syndrome. Journal of Affective Disorders, 32, 3744.
Mortimore, C., Connell, J. & Van, F. (1997) Acute tryptophan depletion in healthy human subjects: effects on two anxiety paradigms. Journal of Psychopharmacology, 11 (suppl.), A26.
Nishizawa, S., Benkelfat, C., Young, S. N., et al (1997) Differences between males and females in rates of serotonin synthesis in human brain. Proceedings of the National Academy of Sciences (United States of America), 94, 53085313.
Oldman, A. D., Walsh, A. E. S., Salkovskis, P., et al (1994) Effect of acute tryptophan depletion on mood and appetite in healthy female volunteers. Journal of Psychopharmacology, 8, 813.
Olson, E. B., Dempsey, J. A. & McCrimmon, D. R. (1979) Serotonin and the control of ventilation in awake rats. Journal of Clinical Investigation, 64, 689693.
Perna, G., Cocchi, S., Bertani, A., et al (1995) Sensitivity to 35% CO2 in healthy first-degree relatives of patients with panic disorder. American Journal of Psychiatry, 152, 623625.
Ramos, R. T., Gentil, V. & Gorenstein, C. (1993) Clomipramine and initial worsening in panic disorder: beyond the ‘jitteriness syndrome’. Journal of Psychopharmacology, 7, 265269.
Reilly, J. G., McTavish, S. F. B. & Young, A. H. (1997) Rapid depletion of plasma tryptophan: a review of studies and experimental methodology. Journal of Psychopharmacology, 11, 381392.
Roth, W. T., Margraf, J., Ehlers, A., et al (1992) Stress test reactivity in panic disorder. Archives of General Psychiatry, 49, 301310.
Sanderson, W. C. & Wetzler, S. (1990) Five percent carbon dioxide challenge: valid analogue and marker of panic disorder? Biological Psychiatry, 27, 689701.
Sanderson, W. C., Rapee, R. M. & Barlow, D. H. (1989) The influence of an illusion of control on panic attacks induced via inhalation of 5.5% carbon dioxide-enriched air. Archives of General Psychiatry, 46, 157162.
Smith, K. A., Fairburn, C. G. & Cowen, P. J. (1997) Relapse of depression after rapid depletion of tryptophan. Lancet, 349, 915919.
Spielberger, C. D., Gorsuch, R. L. & Lushese, R. E. (1979) Manual for the State–Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists Press.
Spitzer, R. L., Williams, J. B., Gibbon, M., et al (1990a) Structured Clinical Interview for DSM–III–R–Patient Edition (SCID–P, Version 1.0). Washington, DC: American Psychiatric Press.
Spitzer, R. L., Williams, J. B., Gibbon, M., et al (1990b) Structured Clinical Interview for DSM–III–R–Nonpatient Edition (SCID–NP, Version 1.0). Washington, DC: American Psychiatric Press.
Targum, S. D. & Marshall, L. E. (1989) Fenfluramine provocation of anxiety in patients with panic disorder. Psychiatry Research, 28, 295306.
Weltzin, T. E., Fernstrom, J. D., McConaha, C., et al (1994) Acute tryptophan depletion in bulimia: effects on large neutral amino acids. Biological Psychiatry, 35, 388397.
Young, S. N., Smith, S. E., Pihl, R., et al (1985) Tryptophan depletion causes a rapid lowering of mood in normal males. Psychopharmacology, 87, 173177.
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Effect of acute tryptophan depletion on CO2-induced anxiety in patients with panic disorder and normal volunteers

  • H. E. J. Miller (a1), J. F. W. Deakin (a2) and I. M. Anderson (a2)
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