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Brain mechanisms associated with depressive relapse and associated cognitive impairment following acute tryptophan depletion

Published online by Cambridge University Press:  03 January 2018

Katharine A. Smith
Affiliation:
University Department of Psychiatry, Warneford Hospital, Oxford
John S. Morris
Affiliation:
Wellcome Department; of Cognitive Neurology, London
Karl J. Fristdn
Affiliation:
Wellcome Department; of Cognitive Neurology, London
Philip J. Cowen
Affiliation:
University Department of Psychiatry, VVarneford Hospital, Oxford
Raymond J. Dolan*
Affiliation:
Wellcome Department of Cognitive Neurology, London
*
Professor R. J. Dolan, Wellcome Department of Cognitive Neurology, Queen Square, London WCIN 3BG

Abstract

Background

Acute tryptophan depletion lowers brain serotonin synthesis and results in a transient, but striking, clinical relapse in recovered depressed patients.

Aims

To identify brain regions which change their activity as an acute depressive relapse evolves and to determine how pathological mood might modulate neural activity during a cognitive task.

Method

We used H215O positron-emission tomography (PET) to study eight recovered depressed men after tryptophan depletion and after a control procedure. During both PET scan sessions, subjects performed a paced verbal fluency task which alternated with a control verbal repetition task.

Results

Increasing levels of depression after tryptophan depletion were associated with diminished neural activity in the ventral anterior cingulate, orbitofrontal cortex and caudate nucleus regions. In addition, depressive relapse attenuated cognitive task-related activation in the anterior cingulate cortex.

Conclusions

Our data indicate that changes in neural activity in distinct brain regions mediate the clinical phenomena of depression and depression-related cognitive impairment following acute tryptophan depletion. These changes could be associated with the widespread distribution of serotonin neurons in brain pathways associated with the expression of affect and cognitive performance.

Type
Papers
Copyright
Copyright © 1999 The Royal College of Psychiatrists 

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Footnotes

Declaration of interest

This study was supported by the Wellcome Trust.

References

American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM-III-R). Washington. DC: APA.Google Scholar
Baker, S. C., Frith, C. D. & Dolan, R. J. (1997) The interaction between mood and cognitive function studied with PET. Psychological Medicine, 27, 565578.Google Scholar
Bremner, J. D., Lnnis, R. B., Salomon, R. M., at al (1997) Positron emission tomography measurement of cerebral metabolic correlates of tryptophan depletion-induced depressive relapse. Archives of General Psychiotry 54, 364374.CrossRefGoogle ScholarPubMed
Cudennec, A., Bonvento, G., Duverger, D., et al (1993) Effects of dorsal raphe nucleus stimulation on cerebral blood flow and flow-metabolism coupling in the conscious rat. Neuroscience, 55, 385401.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Devinsky, O., Morrell, M. J. & Vogt, B. A. (1995) Contributions of anterior cingulate to behaviour. Brain, 118, 279306.Google Scholar
Drevets, W. C., Price, J. L., Simpson, J. R., et al (1997) Subgenual prefrontal cortex abnormalities in mood disorders. Nature, 386, 824827.CrossRefGoogle ScholarPubMed
Ebert, D. & Ebmeier, K. P. (1996) The role of the cingulate gyrus in depression: from functional anatomy to neurochemistry. Biological Psychiatry 39, 10441050.Google Scholar
Frank, E., Prion, R. F., Jarrett, R. B., et al (1991) Conceptualization and rationale for consensus definitions in major depressive disorder. Archives of General Psychiatry 48, 851855.Google Scholar
Friston, K. J., Ashburner, J., Pollne, J.-P., et al (1995a) Spatial registration and normalization of images. Human Brain Mapping, 3, 165189.Google Scholar
Friston, K. J., Holmes, A. P., Worsley, K. J., et al (1995b) Statistical parametric maps in functional imaging: a general linear approach. Human Brain Mopping, 2, 189210.CrossRefGoogle Scholar
Goodwin, G. M. (1996) Functional imaging, affective disorder and dementia. British Medical Bulletin, 52, 495512.CrossRefGoogle ScholarPubMed
Hamilton, M. (1960) A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry, 23 5662.Google Scholar
Kunishio, K. & Haber, S. N. (1994) Primate cingulostriatal projection: limbic striatal versus sensorimotor striatal input. Journal of Comparative Neurology, 350, 337356.Google Scholar
Nishizawa, S., Benkelfat, C., Young, S. N., et al (1997) Differences between males and females in rates of serotonin synthesis in the human brain. Proceedings of the National Academy of Sciences, 94, 53085313.CrossRefGoogle Scholar
Rolis, E. T., Hornak, J., Wade, D., et al (1994) Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage. Journal of Neurology, Neurosurgery and Psychiatry, 57, 15181524.CrossRefGoogle Scholar
Smith, K. A. & Cowen, P. J. (1997) Serotonin and depression. in Depression: Neurobiological, Psychopathological and Therapeutic Advances (eds Honig, A., Ansseau, M. & van Praag, H.), pp. 129146. London: John Wiley & Sons.Google Scholar
Smith, K. A., Fairburn, C. G. & Cowen, P. J. (1997) Release of depression after rapid depletion of tryptophan. Lancet, 349, 915919.Google Scholar
Spitzer, R. L., Williams, J. B. W., Gibbon, M., et al (1990) Structured Clinical Interview for DSM-III-R. Washington, DC: American Psychiatric Press.Google Scholar
Talairach, J. & Tournoux, P. (1988) Co-Planar Stereotaxic Atlas of the Human Brain. New York: Threme Medical Publishers.Google Scholar
Trichard, C., Martinot, J. L., Alagille, M., et al (1995) Time course of prefrontal tobe dysfunction in severely depressed in-patients: a longitudinal neuropsychological study. Psychological Medicine, 25, 7985.CrossRefGoogle Scholar
Young, S. N., Smith, S. E., Pihl, R. O., et al (1985) Tryptophan depletion causes a rapid lowering of mood in normal males. Psychopharmacology, 87, 173177.Google Scholar
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