Abstract
In a recent study (Tafet, Toister-Achituv, & Shinitzky, 2001), we demonstrated that cortisol induces an increase in the expression of the gene coding for the serotonin transporter, associated with a subsequent elevation in the uptake of serotonin. This stimulatory effect, produced upon incubation with cortisol in vitro, was observed in peripheral blood lymphocytes from normal subjects. In the present work we investigated the cortisol-induced increase in serotonin uptake in lymphocytes from hypercortisolemic patients, including subjects with major depressive disorder (n = 8), and subjects with generalized anxiety disorder (n = 12), in comparison with a control group of normal healthy subjects (n = 8). A significant increase in serotonin uptake (+37%+14, M + SD) was observed in the control group, whereas neither the generalized anxiety disorder nor the major depression group exhibited changes in serotonin uptake upon incubation with cortisol. It is likely that under chronic stress or depression, the capacity for increase in serotonin transporter has reached its limit due to the chronically elevated blood cortisol level. The physiological and diagnostic implications of this observation are discussed.
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Abramson, L. Y., Seligman, M., & Teasdale, L. D. (1978). Learned helplessness in humans: Critique and reformulation. Journal of Abnormal Psychology, 87, 49–78.
Akil, H. A., & Morano, M. I. (1995). Stress. In F. E. Bloom & D. J. Kupfer (Eds.), Psychopharmacology: The fourth generation of progress (pp. 773–785). New York: Raven.
Amara, S. G., & Kuhar, M. J. (1993). Neurotransmitter transporters: Recent progress. Annual Review of Neuroscience, 16, 73–93.
American Psychiatric Association (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author.
Axelrod, J., & Reisine, T. D. (1984). Stress hormones: Their interaction and regulation. Science, 224, 452–459.
Azmitia, E. C., & Whitaker-Azmitia, P. M. (1995). Anatomy, cell biology, and plasticity of the serotonergic system: Neuropsychopharmacological implications for the actions of psychotropic drugs. In F. E. Bloom & D. J. Kupfer (Eds.), Psychopharmacology: The fourth generation of progress (pp. 443–449). New York: Raven.
Barker, E. L., & Blakely, R. D. (1995). Norepinephrine and serotonin transporters: Molecular targets of antidepressant drugs. In F. E. Bloom & D. J. Kupfer (Eds.), Psychopharmacology: The fourth generation of progress (pp. 321–334). New York: Raven.
Beck, A. T., Rush, A. J., Shaw, B. F., & Emery, G. (1979). Cognitive therapy of depression. New York: Guilford.
Breier, A., Albus, M., Pickar, D., Zahn, T. P., Wolkowitz, O. M., & Paul, S. M. (1987). Controllable and uncontrollable stress in humans: Alterations in mood and neuroendocrine and psychophysiological function. American Journal of Psychiatry, 144, 1419–1425.
Chrousos, G. P., & Gold, P. W. (1992). The concepts of stress and stress system disorders. Journal of the American Medical Association, 267, 1244–1252.
Chrousos, G. P., & Gold, P. W. (1998). A healthy body in a healthy mind—and vice versa—the damaging power of “uncontrollable” stress. Journal of Clinical Endocrinology & Metabolism, 83, 1842–1845.
Croes, S., Merz, P., & Netter, P. (1993). Cortisol reaction in success and failure condition in endogenous depressed patients and controls. Psychoneuroendocrinology, 18, 23–35.
Dallman, M. F., Akana, S. F., Levin, N., Walker, C.-D., Bradbury, M. J., Suemaru, S., & Scribner, K. S. (1994). Corticosteroids and the control of function in the hypothalamo-pituitary-adrenal (HPA) axis. In E. R. de Kloet, E. C. Azmitia, & P.W. Landfield (Eds.), Brain corticosteroid receptors: Studies on the mechanism, function, and neurotoxicity of corticosteroid action (Annals of the New York Academy of Sciences, Vol. 746, pp. 22–33). New York: New York Academy of Sciences.
Deakin, J. F. W. (1991). Distinct roles of 5HT subsystems in panic, anxiety and depression. In G. Racagni, N. Brunello, & T. Fukuda (Eds.), Biological psychiatry (Vol. 1, pp. 305–307). Amsterdam: Elsevier.
Dinan, T. G. (1994). Glucocorticoids and the genesis of depressive illness: A psychobiological model. British Journal of Psychiatry, 164, 365–371.
Dolan, R. J., Calloway, S. P., Fonagy, P., De Souza, F. V. A., & Wakeling, A. (1985). Life events, depression and hypothalamic-pituitary-adrenal axis function. British Journal of Psychiatry, 147, 429–433.
Faraj, B. A., Olkowsky, Z. L., & Jackson, R. T. (1991). Binding of [3H]-dopamine to human lymphocytes: Possible relationship to neurotransmitter uptake sites. Pharmacology, 42, 135–141.
Faraj, B. A., Olkowsky, Z. L., & Jackson, R. T. (1994). Expression of a high-affinity serotonin transporter in human lymphocytes. International Journal of Immunopharmacology, 16, 561–567.
Faraj, B. A., Olkowsky, J. L., & Jackson, R. T. (1997). Prevalence of high serotonin uptake in lymphocytes of abstinent alcoholics. Biochemical Pharmacology, 53, 53–57.
First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (1997). Structured clinical interview for DSM-IV: Axis I Disorders. Clinician Version. Washington, DC: American Psychiatric Press.
Gold, P. W., Goodwin, F. K., & Chrousos, G. P. (1988a). Clinical and biochemical manifestations of depression: Relation to neurobiology of stress (Part I). New England Journal of Medicine, 319, 348–353.
Gold, P. W., Goodwin, F. K., & Chrousos, G. P. (1988b). Clinical and biochemical manifestations of depression: Relation to neurobiology of stress (Part II). New England Journal of Medicine, 319, 413–420.
Grodzicki, J., Pardo, M., Schved, G., Schlosberg, A., Fuchs, S., & Kanety, H. (1990). Differences in 3H-spiperone binding to peripheral blood lymphocytes from neuroleptic responsive and non-responsive schizophrenic patients. Biological Psychiatry, 27, 1327–1330.
Halbach, M., & Henning, U. (1989). Abnormal glucocorticoid dependent increase of spiperone binding sites on lymphocytes from schizophrenics in vitro. Pharmacopsychiatry, 22, 168–173.
Halbreich, U., Asnis, G. M., Schindledecker, R., Zumoff, B., & Swami Nathan, R. (1985). Cortisol secretion in endogenous depression: I. Basal plasma levels. Archives of General Psychiatry, 42, 904–908.
Hamilton, M. (1959). The assessment of anxiety states by rating. British Journal of Medical Psychology, 32, 50.
Hamilton, M. (1960). A rating scale for depression. Journal of Neurology, Neurosurgery, & Psychiatry, 23, 56–62.
Henninger, G. R. (1995). The role of serotonin in clinical disorders. In F. E. Bloom & D. J. Kupfer (Eds.), Psychopharmacology: The fourth generation of progress (pp. 471–482). New York: Raven.
Henry, J. P. (1992). Biological basis of the stress response. Integrative Physiology & Behavioral Science, 27, 66–83.
Hoffman, B. J., Mezey, E., & Brownstein, M. J. (1991). Cloning of a serotonin transporter affected by antidepressants. Science, 254, 579–580.
Kanner, B. I., & Schuldiner, S. (1987). Mechanism of transport and storage of neurotransmitters. CRC Critical Reviews in Biochemistry, 22, 1–38.
Keller-Wood, M. E., & Dallmam, M. F. (1984). Corticosteroid inhibition of ACTH secretion. Endocrine Reviews, 5, 1–24.
Lazarus, R. S. (1996). Psychological stress and the coping process. New York: McGraw-Hill.
Lazarus, R. S., & Folkman, S. (1984). Stress, appraisal and coping. New York: Springer-Verlag.
Maes, M., & Meltzer, H. Y. (1995). The serotonin hypothesis of major depression. In F. E. Bloom & D. J. Kupfer (Eds.), Psychopharmacology: The fourth generation of progress (pp. 933–943). New York: Raven.
McEwen, B. S. (1998). Protective and damaging effects of stress mediators. New England Journal of Medicine, 338, 171–179.
McEwen, B. S., Davis, P. G., & Parsons, B. (1979). The brain as a target for steroid hormone action. Annual Review of Neuroscience, 2, 65–112.
Meltzer, H. Y., & Lowy, M. T. (1987). The serotonin hypothesis of depression. In H. Meltzer (Ed.), Psychopharmacology: The third generation of progress (pp. 513–526). New York: Raven.
Munck, A., Guyre, P. M., & Holbrook, N. J. (1984). Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocrine Reviews, 5, 25–55.
Ottenweller, J. E., Natelson, B. H., Pitman, D. L., & Drastal, S. D. (1989). Adrenocortical and behavioral responses to repeated stressors: Toward an animal model of chronic stress and stress-related mental illness. Biological Psychiatry, 26, 829–841.
Peeters, B. W. M. M., & Broekkamp, C. L. E. (1994). Involvement of corticosteroids in the processing of stressful life-events: A possible implication for the development of depression. Journal of Steroid Biochemistry & Molecular Biology, 49, 417–427.
Post, J. M. (1992). Transduction of psychosocial stress into the neurobiology of recurrent affective disorders. American Journal of Psychiatry, 149, 999–1010.
Reichel, R. R., & Jacob, S. T. (1993). Control of gene expression by lipophilic hormones. Federation of American Societies for Experimental Biology Journal, 7, 427–436.
Reus, V. I., Wolkowitz, O. W., & Frederick, S. (1997). Antiglucocorticoid treatments in psychiatry. Psychoneuroendocrinology, 22 (Suppl. 1), S121-S124.
Sapse, A. (1997). Cortisol, high cortisol diseases and anticortisol therapy. Psychoneuroendocrinology, 22 (Suppl. 1), S3-S10.
Smelik, P. G. (1987). Adaptation and brain function. Progress in Brain Research, 72, 3–9.
Tafet, G. E., Toister-Achituv, M., & Shinitzky, M. (2001). Enhancement of serotonin uptake by cortisol: A possible link between stress and depression. Cognitive, Affective, & Behavioral Neuroscience, 1, 96–104.
Thakore, J. H., & Dinan, T. (1995). Cortisol synthesis inhibition: A new treatment strategy for the climical and endocrine manifestations of depression. Biological Psychiatry, 37, 364–368.
Wolkowitz, O. M., Reus, V. I., Manfredi, F., Ingbar, J., Brizendine, L., & Weingartner, H. (1993). Ketoconazole administration in hypercortisolemic depression. American Journal of Psychiatry, 150, 810–812.
Zigmond, A. S., & Snaith, R. P. (1983). The hospital anxiety and depression scale. Acta Psychiatrica Scandinavica, 67, 361–370.
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Tafet, G.E., Idoyaga-Vargas, V.P., Abulafia, D.P. et al. Correlation between cortisol level and serotonin uptake in patients with chronic stress and depression. Cognitive, Affective, & Behavioral Neuroscience 1, 388–393 (2001). https://doi.org/10.3758/CABN.1.4.388
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DOI: https://doi.org/10.3758/CABN.1.4.388