Summary
In order to delineate putatively coexisting dysregulations between sympathoadrenal system and hypothalamic-pituitary-adrenal (HPA)-axis during depression, the authors measured the following: the pre and postdexamethasone (1mg) 24 hr urine excretion of noradrenaline, dopamine, adrenaline, 3-methoxy-4-hydroxyphenylglycol (MHPG), free cortisol (UFC), and plasma cortisol. Melancholic patients were characterized by a significantly higher excretion of noradrenaline, dopamine and adrenaline, combined with significantly increased UFC, postdexamethasone plasma cortisol, and UFC values. We found significant and positive correlations between UFC on the one hand, and the 24 hr urine excretion of noradrenaline, dopamine, and adrenaline, on the other. By the same token, we established significant relationships between the 24 hr urine excretion of those catecholamines and the postdexamethasone UFC and plasma cortisol values. Cortisol nonsuppressors exhibited a significantly higher excretion of noradrenaline, dopamine and adrenaline, as compared with cortisol suppressors. Dexamethasone administration did not have a significant effect on the urinary output of noradrenaline, dopamine, adrenaline or MHPG.
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References
Agren H (1982) Depressive symptom patterns and urinary MHPG excretion. Psychiatry Res 6: 184–196
Al-Damluji S (1988) Adrenergic mechanisms in the control of corticotropin secretion. J Endocrinol 119: 5–14
American Psychiatric Association (1980) Diagnostic and statistical manual of mental disorders, 3rd edn. American Psychiatric Association, Washington D.C.
Axelrod J (1977) Catecholamines, effects of ACTH and adrenal corticoids. Ann NY Acad Sci 297: 275–283
Axelrod J, Reisine T (1984) Stress hormones: their interaction and regulation. Science 224: 452–459
Banki C, Bissette G, Arato M, O'Connor L, Nemeroff C (1987) CSF corticotropin-releasing factor-like immunoreactivity in depression and schizophrenia. Am J Psychiatry 144: 873–877
Berger M, Doerr P, Lund R, Bronisch T, von Zerssen D (1982) Neuroendocrinological and neurophysiological studies in major depressive disorders: are there biological markers for the endogenous subtype? Biol Psychiatry 17: 1217–1242
Blombery PA, Kopin IJ, Gordon EK, Markey SP, Ebert MH (1980) Conversion of MHPG to vanillylmandelic acid. Arch Gen Psychiatry 37: 1095–1098
Brown WA, Shuey I (1980) Response to dexamethasone and subtype of depression. Arch Gen Psychiatry 37: 747–751
Carroll BJ, Curtis GC, Mendels J (1976) Neuroendocrine regulation in depression. II. Discrimination of depressed from non-depressed patients. Arch Gen Psychiatry 33: 1051–1058
Carroll BJ (1980) Clinical application of neuroendocrine research in depression. In: van Praag MH, Lader MH, Rafaelsen OJ, Sachar EJ (eds) Handbook of biological psychiatry, part III. Brain mechanisms and abnormal behaviour — genetics and neuroendocrinology. Marcel Dekker, New York, pp 179–193
Carroll BJ (1982) The dexamethasone suppression test for melancholia. Br J Psychiatry 140: 292–304
Chernow B, O'Brian JT (1984) Overview of catecholamines in selected endocrine systems. In: Ziegler MG, Lake CR (eds) Norepinephrine, frontiers of clinical neuroscience, vol 2. Williams and Wilkins, Baltimore London, pp 439–449
Coppen A, Abou-Saleh M, Milln P, Metcalfe M, Harwood J, Bailey J (1983) Dexamethasone suppression test in depression and other psychiatric illness. Br J Psychiatry 142: 498–504
Davis KL, Hollister LE, Mathé AA, Davis BM, Rothpearl AB, Faull KF, Hsich JYK, Barchas JD, Berger PA (1981) Neuroendocrine and neurochemical measurements in depression. Am J Psychiatry 138: 1555–1562
de Villiers A, Russell V, Carsters M, Aalbers C, Gagiano C, Charlton D, Taljaard J (1987) Noradrenergic function and hypothalamic-pituitary-adrenal axis activity in unipolar major depressive disorder. Psychiatr Res 22: 127–140
Dillon WR, Goldstein M (1984) Linear structural relations (Lisrel). In: Multivariate analyses: methods and applications. Wiley, New York, pp 430–439
Edwards DJ, Spiker DG, Neil JF, Kupfer DJ, Rizk M (1980) MHPG excretion in depression. Psychiatry Res 2: 295–305
Essler M, Turbott J, Schwarz R, Leonard P, Bobik A, Skews H, Jackman G (1982) The peripheral kinetics of norepinephrine in depressive illness. Arch Gen Psychiatry 39: 295–300
Evans DL, Burnett GB, Nemeroff CB (1983) The dexamethasone suppression test in the clinical setting. Am J Psychiatry 140: 586–589
Feinberg M, Carroll BJ (1984) Biological “markers” for endogenous depression. Arch Gen Psychiatry 41: 1080–1085
Filser JG, Muller WE, Beckmann H (1986) Should plasma or urinary MHPG be measured in psychiatric research? A critical comment. Br J Psychiatry 148: 95–97
Garfinkel PE, Warsch JJ, Stancer HC (1979) Depression: new evidence in support of biological differentiation. Am J Psychiatry 136: 535–539
Garvey MJ, Hollon S, Evans M, DeRubeis RJ, Tuason VB (1988) The association of MHPG to dexamethasone suppression test status. Psychiatry Res 24: 223–230
Goodwin FD, Post RM (1975) Studies of amine metabolites in affective illness and in schizophrenia, a comparative analysis. In: Freedman DX (ed) Biology of the major psychoses. Raven Press, New York, pp 299–332
Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23: 56–61
Jimerson DC, Insel TR, Reus VI, Kopin IJ (1983) Increased plasma MHPG in dexamethasone resistant depressed patients. Arch Gen Psychiatry 40: 173–176
Kelner K, Pollard H (1985) Glucocorticoid receptors and regulation of phenylethanolamineN-methyltransferase activity in cultured chromaffm cells. J Neurosci 5: 2161–2168
Kopin IJ, Jimerson DC, Markey SP, Ebert MH, Polinsky RJ (1984) Disposition and metabolism of MHPG in humans: application to studies in depression. Pharmacopsychiatry 17: 3–8
Koslow SH, Maas JW, Bowden CL, Davis JM, Hanin I, Javaid J (1983) CSF and urinary biogenic amines and metabolites in depression and mania: a controlled, univariate analysis. Arch Gen Psychiatry 40: 999–1010
Lake CR, Chernow B, Feuerstein G, Goldstein DS, Ziegler MG (1984) The sympathetic nervous system in man: its evaluation and the measurement of plasma NE. In: Ziegler MG, Lake CR (eds) Norepinephrine, frontiers of clinical neuroscience, vol 2. Williams and Wilkins, Baltimore London, pp 1–26
Linnoila M, Karoum F, Potter WZ (1982) High correlation of norepinephrine and its major metabolite excretion ranges. Arch Gen Psychiatry 39: 521–523
Loo H, Poirier M-F, Dennis T, Benkelfat C, Vanelle JM, Gay C, Galinowski A, Askienazy S, Scatton B (1988) Lack of correlation between DST results and urinary MHPG in depressed patients. J Neural Transm 72: 121–130
Maas JW, Dekirmerjian H, DeLeon-Jones F (1973) The identification of depressed patients who have a disorder of norepinephrine metabolism and/or disposition. In: Usdin E, Synden S (eds) Frontiers in catecholamine research. Pergamon Press, New York, pp 1091–1096
Maas JW, Leckmann JF (1983) Relationships between central nervous system noradrenergic function and plasma and urinary MHPG and other norepinephrine metabolites. In: Maas J (ed) MHPG: basic mechanisms and psychopathology. Academic Press, New York, pp 33–34
Maas JW, Koslow SH, Davis J, Katz M, Frazer A, Bowden CL, Berman N, Gibbons R, Stokes P, Landis H (1987) Catecholamine metabolism and disposition in healthy and depressed subjects. Arch Gen Psychiatry 44: 337–344
Maes M, De Ruyter M, Hobin P, Suy E (1986a) The dexamethasone suppression test, the Hamilton depression rating scale and the DSM-III depression categories. J Affect Disord 10: 207–214
Maes M, De Ruyter M, Suy E (1986b) The importance of creatinine flow, age and 24 hr urinary output in the interpretation of the MHPG flow. J Affect Disord 10: 221–225
Maes M, De Ruyter M, Suy E (1987a) Cortisol response to dexamethasone and noradrenergic function in depression. Acta Psychiatr Scand 75: 171–175
Maes M, De Ruyter M, Suy E (1987b) Prediction of subtype and severity of depression by means of dexamethasone suppression test, L-tryptophan/competing amino acid ratio and MHPG excretion. Biol Psychiatry 22: 177–186
Maes M, Vandevelde R, Suy E (1989) Influences on cortisol and noradrenergic turnover of healthy controls and depressed patients during L-tryptophan loading. J Affect Disord 17: 173–182
Maes M (1990a) The interrelationships between the pre and postdexamethasone plasma cortisol values, urinary free cortisol, dexamethasone levels, age and DSM-III classification: results of pathway analysis. In: Ansseau M (ed) Biological markers of depression: state of the art. Elsevier, Amsterdam (in press)
Maes M, Jacobs M-P, Suy E, Leclercq C, Christiaens F, Raus J (1990b) An augmented escape of β-endorphins to suppression by dexamethasone in severely depressed patients. J Affect Disord 18: 149–156
Maes M, Schotte C, Martin M, Vandewoude M, Blockx P (1990c) A revised interpretation of the postdexamethasone ACTH and cortisol data in unipolar depressed females. Psychiatry Res 34: 109–127
Maes M, Vandewoude M, Schotte C, Martin M, Blockx P (1990d) Positive relationship between the catecholaminergic turnover and the DST results in depression. Psychol Med 20: 493–499
Markey K, Towle A, Sze P (1982) Glucocorticoid influence on tyrosine hydroxylase activity in mouse locus coeruleus during postnatal development. Endocrinology 111: 1519–1523
Mazure CM, Bowers MB Jr, Hoffman F Jr, Miller KB, Nelson JC (1987) Plasma catecholamine metabolites in subtypes of major depression. Biol Psychiatry 22: 1469–1472
Moleman P, Borstrok JJM (1982) Analysis of 3-methoxy-4-hydroxyphenylglycol by highperformance liquid chromatography and electrochemical detection. J Chromatogr 227: 391–405
Mueller RA, Thoenen H, Axelrod J (1970) Effect of pituitary and ACTH on the maintenance of basal tyrosine hydroxylase activity in the rat adrenal gland. Endocrinology 86: 751–755
Nemeroff CB, Widerlow E, Bissette G, Walleus H, Karlsson I, Eklund K, Kiets CD, Loosen PT, Vale W (1984) Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 226: 1342–1344
Plotsky PM, Cunningham ET Jr, Widmaier EP (1989) Catecholaminergic modulation of corticotropin-releasing factor and adrenocorticotropin secretion. Endocr Rev 4: 437–458
Rivier C, Vale W (1985) Effects of corticotropin-releasing factor, neurohypophyseal peptides, and catecholamines on pituitary function. Fed Proc 44: 189–196
Rosenbaum AH, Maruta T, Schatzberg AF, Orsulak PJ, Jiang N-S, Cole JO, Schildkraut JJ (1983) Toward a biochemical classification of depressive disorders, VII. Urinary free cortisol and urinary MHPG in depression. Am J Psychiatry 140: 314–318
Roy A, Pickar D, Linnoila M, Potter W (1985) Plasma norepinephrine in affective disorders: relationship to melancholia. Arch Gen Psychiatry 42: 1181–1185
Roy A, Jimerson D, Pickar D (1986) Plasma 3-methoxy-4-hydroxyphenylethyleneglycol in depressive disorders. Am J Psychiatry 143: 846–851
Roy A, Pickar D, De Jong J, Karoum F, Linnoila M (1988) Norepinephrine and its metabolites in cerebrospinal fluid, plasma and urine. Arch Gen Psychiatry 45: 849–857
Rubin AL, Price LH, Charney DS, Henninger GR (1985) Noradrenergic function and the cortisol response to dexamethasone in depression. Psychiatry Res 15: 5–15
Rubinow DR, Post RM, Gold PW, Ballenger JC, Wolff EA (1984) In: Post RM, Ballenger JC (eds) Neurobiology of mood disorders, frontiers of clinical neuroscience, vol 1. Williams and Wilkins, Baltimore, pp 271–289
Schatzberg A, Rothschild A, Langlais P, Lervinger J, Schildkraut J, Cole J (1987) Psychotic and nonpsychotic depressions. II. Platelet MAO activity, plasma catecholamines, cortisol and specific symptoms. Psychiatry Res 20: 155–164
Schildkraut JJ (1982a) The biochemical discrimination of subtypes of depressive disorders: an outline of our studies on norepinephrine metabolism and psychoactive drugs in endogenous depressions since 1967. Pharmacopsychiatry 5: 121–127
Schildkraut JJ, Orsulak PJ, Schatzberg AF, Cole JO, Rosenbaum AH (1982b) Biochemical discrimination of subgroups of depressive disorders based on differences in catecholamine metabolism. In: Harrin I, Usdin E (eds) Biological markers in psychiatry and neurology. Pergamon Press, New York, pp 23–33
Sheperd DM, West GB (1951) Noradrenaline and the suprarenal medulla. Br J Pharmacol 6: 665–674
Spark RF, Connolly PB, Gluckin DS, White R, Sacks B, Landsberg L (1979) ACTH secretion from a functioning pheochromocytoma. N Engl J Med 301: 416–418
Spitzer RL, Williams JBW, Gibbon M (1985) Structured clinical interview for DSM-III patient version. Biometrics Research Department, New York State Psychiatric Institute
Stene M, Panagiotis N, Tuck ML, Sowers JR, Mayes D, Berg G (1980) Plasma norepinephrine levels are influenced by sodium intake, glucocorticoid administration and circadian changes in normal man. J Clin Endocrinol Metab 51: 1340–1345
Sternbach HA, Extein I, Sweeney DR, Gold MS, Pottash ALC (1983) Cortisol secretion and urinary MHPG in unipolar depression. Int J Psychiatr Med 13: 261–266
Stokes PE, Frazer A, Casper R (1981) Unexpected neuroendocrinetransmitter relationships. Psychopharmacol Bull 17: 72–75
Stokes PE, Stoll PM, Koslow SH, Maas JW, Davis JM, Swann AC, Robins E (1984) Pretreatment DST and hypothalamic-pituitary-adrenocortical function in depressed patients and comparison groups. Arch Gen Psychiatry 41: 257–267
Stokes P, Maas J, Davis J, Koslow S, Casper R, Stoll P (1987) Biogenic amine and metabolite levels in depressed patients with high vs normal hypothalamic-pituitary-adrenocortical activity. Am J Psychiatry 144: 868–872
Valentino R, Foote S, Aston-Jones G (1983) Corticotropin-releasing factor activates noradrenergic neurons of the locus coeruleus. Brain Res 270: 363–367
Van Loon GR (1985) Brain opioid peptide regulation of catecholamine secretion. In: BenJonathan N, Bahr JM, Weiner RI (eds) Catecholamines as hormone regulators. Raven Press, New York, pp 223–236
Warsh JJ, Hasey G, Cooke R, Stancer HC, Persad E, Jorna T, Godse DD (1985) Elevated 3, 4-dihydroxyphenyl ethyleneglycol (DHPG) excretion in dexamethasone resistant depressed patients. Progr Neuropsychopharmacol Biol Psychiatry 9: 661–664
Williams JBW, Spitzer RL (1982) Research diagnostic criteria and DSM-III: an annotated comparison. Arch Gen Psychiatry 39: 1283–1289
Wolkowitz OM, Doran AR, Breier A, Roy A, Jimerson DC (1987) The effects of dexamethasone on plasma homovanillic acid and 3-methoxy-4-hydroxyphenylglycol; evidence for abnormal corticosteroid-catecholamine interactions in major depression. Arch Gen Psychiatry 44: 782–789
Wurtman RJ, Axelrod J (1966) Control of enzymatic synthesis of adrenaline in the adrenal medulla by adrenal cortical steroids. J Biol Chem 241: 2301–2305
Zhou D, Shen Y, Shu L, Loo H (1987) Dexamethasone suppression test and urinary MHPG-SO4 determination in depressive disorder. Biol Psychiatry 22: 883–891
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Maes, M., Minner, B., Suy, E. et al. Coexisting dysregulations of both the sympathoadrenal system and hypothalamic-pituitary-adrenal-axis in melancholia. J. Neural Transmission 85, 195–210 (1991). https://doi.org/10.1007/BF01244945
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DOI: https://doi.org/10.1007/BF01244945