Abstract
To investigate whether depression is a consequence of disturbed function in 5HT systems, neuroendocrine responses to infusions of the 5HT precursorl-tryptophan (LTP) were studied in patients and controls. After an overnight fast and 60 min bed rest, a solution of LTP (10 g/l) was infused intravenously to a dose of 100 mg/kg over 30 min. Circulating growth hormone (GH), prolactin (PRL), cortisol and tryptophan concentrations were followed from 60 min pre-infusion to 60 min post-infusion. GH responses were attenuated in 23 major depressives (DSM-III) compared with 22 controls and were almost absent in endogenous depressives (New-castle criteria). PRL responses were normal in depressives who had lost more than 3 kg body weight but attenuated in those who had not. GH and PRL responses did not correlate with each other. Reduced basal tryptophan concentrations and more rapid tryptophan clearance were observed in the depressives, but there were no correlations with GH or PRL responses. However, basal cortisol concentrations, which were raised in depressives with chronic psychosocial difficulties, were strongly and inversely predictive of PRL responses in depressives and controls. Blunted GH and PRL responses to LTP appear to be distinct abnormalities in depression which may relate to two processes; (1), an endogenous mechanism indicated by reduced GH responses, and (2), an impairment in 5HT systems, indicated by blunted PRL responses and perhaps caused by raised circulating cortisol or reduced tryptophan concentrations.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Anderson IM, Cowen PJ (1986) Clomipramine enhances prolactin and growth hormone responses inl-tryptophan. Psychopharmacology 89:131–133
Asberg M, Thonen P, Traskman L, Bertilsson L, Ringerger V (1976) ‘Serotonin depression’ a biochemical subgroup within the affective disorders. Science 191:478–480
Biegon A, Rainbow TC, McEwen BS (1985) Corticosterone modulation of neurotransmitter receptors in rat hippocampus: a quantitative autoradiographic study. Brain Res 332:309–314
Bourne HR, Bunney WE, Colburn RW, Davis JN, Shaw DM, Coppen A (1968) Noradrenaline, 5 hydroxytryptamine and 5-hydroxyindoleacetic acid in hindbrains of suicidal patients. Lancet II:805–808
Ceuleman DLS, Hoopenbrowers MLJA, Gelders YG, Reyntjens AJM (1985) The influence of ritanserin, a serotonin antagonist, in anxiety disorders; a double blind placebo-controlled study versus lorazepam. Pharmacol Psychiatry 18:303–305
Charig EM, Anderson IM, Robinson JM, Nutt DJ, Cowen PJ (1987)l-Tryptophan and prolactin release: evidence for interaction between 5-HT1 and 5-HT2 receptors. Hum Psychopharmacol 1:93–97
Charney DS, Heninger GR, Renhard JF, Sternberg DE, Hafstead KM (1982) Effect of intravenousl-tryptophan on prolactin and growth hormone and mood in healthy subjects. Psychopharmacology 77:217–222
Cooper SJ, Owen F, Chambers DR, Crow TJ, Johnson J, Poulter M (1986) Post-mortem neurochemical findings in suicide and depression: a study of the serotonergic system and imipramine binding in suicide victims. In: Deakin JFW (ed) The biology of depression. Gaskell, London, pp 53–70
Cowen PJ, Charig EM (1987) Neuroendocrine responses to tryptophan in major depression. Arch Gen Psychiatry 44:958–966
Cowen PJ, Parry-Billings M, Newsholme EA (1989) Decreased plasma tryptophan levels in major depression. J Affective Disord 16:27–31
Crow TJ, Cross AJ, Cooper SK et al. (1984) Neurotransmitter receptors and monoamine metabolites in the brains of patients with Alzheimer-type dementia and depression and suicides. Neuropharmacology 23:1561–1569
De Kloet ER, Sybesma H, Reul JMHM (1986) Selective control by corticosterone of serotonin receptor capacity in raphe-hippocampal system. Neuroendocrinology 42:513–522
De Montigny C, Aghajanian GK (1984) Tricyclic antidepressants: Long-term treatment increases responsivity of rat forebrain neurones to serotonin. Science 202:1303–1306
Deakin JFW (1983) Roles of serotonergic systems in escape, avoidance and other behaviours. In: Cooper SJ (ed) Theory in psychopharmacology, vol 2. Academic Press, London, pp 149–193
Deakin JFW (1989) Role of 5HT receptor subtypes in depression and anxiety. In: Archer T, Bevan P, Cools A (eds) Behavioural pharmacology of 5HT. Lawrence Erlbaum, New York (in press)
Deakin JFW, Pennell I (1986) 5HT receptor subtypes and depression. Psychopharmacology 89:S24
Deakin JFW, Wang M (1989) Role of 5HT2 receptors in anxiety and depression. In: Paoletti P, Vanhoutte PM (eds) Serotonin from cell biology to pharmacology and therapeutics. Kluwer, Dordrecht, Netherlands (in press)
Delgado PL, Charney DS, Price LH, Landis H, Heninger GR (1989) Neuroendocrine and behavioural effects of dietary tryptophan restriction in healthy subjects. Life Sci (in press)
Dickinson SL, Kennett GA, Curzon G (1985) Reduced 5-hydroxy-tryptamine-dependent behaviour in rats following chronic corticosterone treatment. Brain Res 345:10–18
Dolan RJ, Calloway SP, Fonagy P, De Souza FVA, Wakeling A (1985) Life events, depression and hypothalamic-pituitary-adrenal axis function. Br J Psychiatry 147:429–433
Ferrier IN, McKeith IG, Cross AJ, Perry EK, Candy JM, Perry RH (1986) Post-mortem neurochemical studies in depression. Ann NY Acad Sci 487:128–142
Fuxe K, Ogren S, Agnati L, Gustafson JA, Jonsson G (1977) On the mechanism of action of the antidepressant drugs amitripty-line and nortriptyline. Evidence for 5-hydroxytryptamine receptor blocking activity. Neurosci Lett 6:339–343
Gjerris A, Sorensen AS, Rafaelsen OJ, Wederlin L, Alling G, Linnoila M (1987) 5HT and 5HT1AA in cerebrospinal fluid in depression. J Affective Disord 12:13–22
Goodwin FK, Post RM, Dunner DL, Fordon EK (1973) Cerebrospinal fluid amine metabolites in affective illness: the probenecid technique. Am J Psychiatry 130:73–79
Goodwin GM, Fairburn CG, Cowen PJ (1987a) Dieting changes serotonergic function in women not men: implications for the aetiology of anorexia nervosa? Psychol Med 17:839–842
Goodwin GM, Fairbairn CG, Cowen PJ (1987b) The effects of dieting and weight loss on neuroendocrine responses tol-tryptophan, clonidine and apomorphine in volunteers: important implications for neuroendocrine investigation in depression. Arch Gen Psychiatry 44:952–955
Guimaraes FS, Hellewell J, Wang M, Deakin JFW (1990) Sex difference in aversive classical conditioning and responsiveness to anxiolytic drugs in humans. Br J Clin Pharmacol (in press)
Heninger GR, Charney DS, Sternberge DE (1984) Serotonergic function in depression. Arch Gen Psychiatry 41:398–402
Joseph MH, Young SN, Curzon G (1976) The metabolism of a tryptophan load in rat brain and liver. The influence of hydrocortisone and allopurinol. Biochem Pharmacol 25:2599–2604
Kennett GA, Dickinson S, Curzon G (1985) Enhancement of some 5-HT-dependent behavioural responses following repeated immobilization in rats. Brain Res 330:253–263
Kennett GA, Dourish CT, Curzon G (1987) Antidepressant-like action of 5HT1 A agonists and conventional antidepressants in an animal model of depression. Eur J Pharmacol 134:265–274
Koyama T, Meltzer HY (1986) A biochemical and neuroendocrine study of the serotonergic system in depression. In: Hippius H et al. (eds) New results in depression research. Springer, Berlin Heidelberg New York, pp 169–188
Lopez-Ibor JJ Jr, Saiz-Ruiz J, Iglesias M (1988) The fenfluramine challenge test in the affective spectrum: a possible marker of endogeneity and severity. Pharmacopsychiatry 21:9–14
McCance SL, Cowen PJ, Waller H, Grahame-Smith DG (1988) The effect of metergoline on endocrine responses tol-tryptophan. J Psychopharmacol 2:90–94
Medical Research Council Clinical Psychiatry Committee (1965) Clinical trial of the treatment of depressive illness. Br Med J i:881–886
Mitchell P, Smythe G (1989) Hormonal responses to fenfluramine in depressed and control subjects. J Affective Disord (in press)
Mitchell PB, Bearn JHA, Corn TH, Checkley SA (1988) Growth hormone response to clonidine after recovery in patients with endogenous depression. Br J Psychiatry 152:34–38
Moller SE, de Beurs P, Timmerman L, Tan BK, Leijnse-Ybema HJ, Cohen Stuart MH, Hopfner Peterson HE (1986) Plasma tryptophan and tyrosine ratios to competing amino acids in relation to antidepressant response to citalopram and maprotiline. A preliminary study. Psychopharmacology 88:96–100
Nagayama H, Hingten JN, Aprison MH (1981) Postsynaptic action for four antidepressive drugs in an animal model of depression. Pharmacol Biochem Behav 15:215–230
Nausieda PA, Carvey PM, Weiner WJ (1982) Modification of central serotonergic and dopaminergic behaviours in the course of chronic corticosteroid administration. Eur J Pharmacol 78:335–343
Sjostrom R, Roos BE (1972) 5-Hydroxyindoleacetic acid and homovanillic acid in cerebrosopinal fluid in manic-depressive psychosis. Eur J Clin Pharmacol 4:170–176
Stanley M, Mann JJ (1983) Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet I:214–216
Tye NC, Everitt BJ, Ivensen SD (1977) 5-Hydroxytryptamine and punishment. Nature 268:741–743
Wilson CA, Hunter AJ (1985) Progesterone stimulates sexual behaviour in female rats by increasing 5HT activity on 5HT2 receptors. Brain Res 333:223–229
Wise CD, Berger BD, Stein L (1970) Serotonin: a possible mediator of behavioural suppression induced by anxiety. Dis Nerv Syst GWAN [Suppl] 3:34–37
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Deakin, J.F.W., Pennell, I., Upadhyaya, A.J. et al. A neuroendocrine study of 5HT function in depression: evidence for biological mechanisms of endogenous and psychosocial causation. Psychopharmacology 101, 85–92 (1990). https://doi.org/10.1007/BF02253723
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02253723