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Psychopharmacology

, Volume 87, Issue 4, pp 442–448 | Cite as

MHPG excretion in endogenous depression: Relationship to clinical state and the effects of ECT

  • M. H. Joseph
  • D. Risby
  • T. J. Crow
  • J. F. W. Deakin
  • Eve C. Johnstone
  • P. Lawler
Original Investigations

Abstract

In a group of 70 patients with endogenous depression entering a controlled trial of real versus sham ECT, urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion was significantly reduced by comparison with previously studied groups of control subjects, of acute and chronic schizophrenic patients and of anxious patients. However, urinary MHPG was unrelated to severity of depression, or to the presence of delusions, retardation or agitation. MHPG excretion did not predict clinical outcome, or the response to ECT. Urinary MHPG content at trial entry was unrelated to past tricyclic antidepressant or benzodiazepine medication, although an influence of the latter on the findings cannot be excluded, since all patients received benzodiazepine (nitrazepam) night sedation during the trial.

During the 4-week trial MHPG excretion remained low and did not increase in relation to change in clinical state, although there was a small but significant increase in patients who received real ECT. The findings confirm that urinary MHPG excretion is reduced in depression, but establish that such reductions are not state dependent. Since the increase in MHPG excretion with ECT is not related to changes in clinical state, the former presumably does not reflect the mechanism of action of ECT.

Key words

3-methoxy-4-hydroxyphenylglycol (MHPG) Electro convulsive therapy (ECT) Endogenous depression Clinical trial Clinical response Urinary excretion 

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References

  1. Beckmann H, Goodwin FK (1975) Antidepressant response to tricyclics and urinary MHPG in unipolar patients. Arch Gen Psychiatry 32:17–21Google Scholar
  2. Blomberg PA, Kopin IJ, Gordon EK, Mackey SP, Ebert MH (1980) Conversion of MHPG to vanillylmandelic acid; implications for the importance of urinary MHPG. Arch Gen Psychiatry 37:1095–1098Google Scholar
  3. Bond PA, Jenner FA, Sampson G (1972) Daily variations of the urine content of 3-methoxy-4-hydroxyphenylglycol in two manic depressive patients. Psychol Med 2:81–85Google Scholar
  4. Bonsnes RW, Taussky HH (1945) The colorimetric determination of creatinine by the Jaffe reaction. J Biol Chem 158:581–591Google Scholar
  5. Carney MWP, Roth M, Garside RF (1965) The diagnosis of depressive syndromes and the prediction of ECT response. Br J Psychiatry 111:659–674Google Scholar
  6. Charney DS, Heninger GR, Sternberg DE, Landis DH (1982) Abrupt discontinuation of tricyclic antidepressant drugs; evidence for noradrenergic hyperactivity Br J Psychiatry 141:377–386Google Scholar
  7. Charney DS, Heninger GR Redmond DE (1983) Yohimbine induced anxiety and increased noradrenergic function in humans: effects of diazepam and clonidine. Life Sci 33:19–29Google Scholar
  8. Charney DS, Menkes DB, Heninger GR (1981) Receptor sensitivity and the mechanism of action of antidepressant treatment. Arch Gen Psychiatry 38:1160–1180Google Scholar
  9. Cobbin DM, Requin-Blow B, Williams LR, Williams WO (1979) Urinary MHPG levels and tricyclic antidepressant drug selection. Arch Gen Psychiatry 36:1111–1115Google Scholar
  10. Coppen A, Rama Rao VA, Ruthven CRJ, Goodwin BL, Sandler M (1979) Urinary 4-hydroxy-3-methoxyphenylglycol is not a predictor for clinical response to amitriptyline in depressive illness. Psychopharmacology 64:95–97Google Scholar
  11. CRC (Clinical Research Centre) Division of Psychiatry (1984) The Northwick Park ECT trial; predictors of response to real and simulated ECT. Br J Psychiatry 144:227–237Google Scholar
  12. Cross AJ, Crow TJ, Johnson JA, Joseph MH, Perry EK, Perry RH, Blessed G, Tomlinson BE (1983) Monoamine metabolism in senile dementia of Alzheimer type. J Neurol Sci 60:383–392Google Scholar
  13. Crow TJ, Cross AJ, Cooper S, Deakin JFW, Ferrier IN, Johnson JA, Joseph MH, Owen F, Poulter M Lofthouse R, Corsellis JAN, Chambers DR, Blessed G, Perry EK, Perry RH, Tomlinson BE (1984) Neurotransmitter receptors and monoamine metabolites in the brains of patients with Alzheimer-type dementia and depression and suicides. Neuropharmacology 23:1561–1569Google Scholar
  14. Deakin JFW, Crow TJ, Johnstone EC, Frith CD, Lawler P, Macmillan JF, McPherson K, Owens DCG, Price JS, Stevens M (1981) A trial of real versus simulated electroconvulsive therapy in 70 depressed patients. Adv Biol Psychiatr 7:187–197Google Scholar
  15. De Leon-Jones F, Maas JW, Dekirmenjian H, Fawcett JA (1973) Urinary catecholamine metabolites during behavioural changes in a patient with manic-depressive cycles. Science 179:300–302Google Scholar
  16. Edwards DJ, Spiker DG, Neil JF, Kupfer DJ, Rizk M (1980) MHPG excretion in depression. Psychiatr Res 2:295–305Google Scholar
  17. Feighner JP, Robins E, Guze SB, Woodruff A, Winokur G, Munoz R (1972) Diagnostic criteria for use in psychiatric research. Arch Gen Psychiatry 26:57–63Google Scholar
  18. Gaertner HJ, Kreuter F, Sharek G, Wiatr G, Breyer-Pfaff U (1982) Do urinary MHPG and plasma drug levels correlate with response to amitriptyline therapy? Psychopharmacology 76:236–239Google Scholar
  19. Garfinkel PE, Warsh JJ, Stancer HC, Godse DD (1977) CNS monoamine metabolism in bipolar affective disorder. Arch Gen Psychiatry 34:735–739Google Scholar
  20. Goodwin FK, Potter WZ (1979) Norepinephrine metabolite studies in affective illness In: Usdin E, Kopin IJ, Barchas J (eds) Catecholamines: Basic and clinical frontiers, vol 2. Pergamon Press, New York, 1863–1865Google Scholar
  21. Greenspan K, Schildkraut JJ, Gordon EK, Baer L, Aronoff MJ, Durell J (1970) Catecholamine metabolism in affective disorders III. J Psychiatr Res 7:171–183Google Scholar
  22. Hamilton M (1967) Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6:278–296Google Scholar
  23. Heninger GR, Charney DS (1983) Letter. Arch Gen Psychiatry 40:467Google Scholar
  24. Hollister LE, Davis KL, Berger PA (1980) Subtypes of depression based on excretion of MHPG and response to nortriptyline. Arch Gen Psychiatry 37:1107–1110Google Scholar
  25. Hossman V, Maling TJB, Hamilton CA, Reid JL, Dollery CT (1980) Sedative and cardiovascular effects of clonidine and nitrazepam. Clin Pharmacol Ther 28:167–176Google Scholar
  26. Johnstone EC, Deakin JFW, Lawler P, Frith CD, Stevens M, McPherson K, Crow TJ (1980) The Northwick Park ECT Trial. Lancet ii:1317–1320Google Scholar
  27. Joseph MH, Baker HF, Crow TJ, Johnstone EC (1976) Determination of 3-methoxy-4-hydroxyphenylglycol conjugates in urine; application to the study of central noradrenaline metabolism in unmedicated chronic schizophrenic patients. Psychopharmacology 51:47–51Google Scholar
  28. Joseph MH, Baker HF, Johnstone EC, Crow TJ (1979) 3-methoxy-4-hydroxyphenylglycol excretion in acutely schizophrenic patients studied during a controlled trial of the isomers of flupenthixol. Psychopharmacology 64:35–40Google Scholar
  29. Koslow SH, Maas JW, Bowden CL, Davis JM, Hanin I, Javaid J (1983) CSF and urinary biogenic amines and metabolites in depression and mania. Arch Gen Psychiatry 40:999–1010Google Scholar
  30. Linnoila M, Karoum F, Calil HM, Kopin IJ, Potter WZ (1982) Alteration of norepinephrine metabolism with desipramine and zimelidine in depressed patients. Arch Gen Psychiatry 39:1025–1028Google Scholar
  31. Linnoila M, Karoum F, Miller T, Potter WZ (1983a) Reliability of urinary monoamine and metabolite output measures in depressed patients. Am J Psychiatry 140:1055–1057Google Scholar
  32. Linnoila M, Karoum F, Rosenthal N, Potter WZ (1983b) Electroconvulsive treatment and lithium carbonate: their effects on noradrenaline metabolism in patients with primary major depression. Arch Gen Psychiatry 40:677–680Google Scholar
  33. Maas JW (1975) Biogenic amines and depression. Arch Gen Psychiatry 32:1357–1361Google Scholar
  34. Maas JW, Fawcett J, Dekirmenjian H (1968) 3-methoxy-4-hydroxy-phenylglycol (MHPG) excretion in depressive states. Arch Gen Psychiatry 19:129–134Google Scholar
  35. Maas JW, Fawcett JA, Dekirmenjian H (1972) Catecholamine metabolism, depressive illness and drug response. Arch Gen Psychiatry 26:252–262Google Scholar
  36. Maas JW, Hattox SE, Greene NM, Landis DH (1979) 3-methoxy-4-hydroxyphenethyleneglycol production by human brain in vivo. Science 205:1025–1027Google Scholar
  37. Maas JW, Kocsis JH, Bowden CL, Davis JM, Redmond DE, Hanin I, Robins E (1982) Pre-treatment neurotransmitter metabolites and response to imipramine or amitriptyline treatment. Psychol Med 12:37–43Google Scholar
  38. Mardh G, Sjoquist B, Anggard E (1981) Norepinephrine metabolism in man using deuterium labelling: the conversion of 4-hydroxy-3-methoxyphenylglycol to 4-hydroxy-3-methoxymandelic acid. J Neurochem 36:1181–1185Google Scholar
  39. Mardh G, Sjoquist B, Anggard E (1983) Norepinephrine metabolism in humans studied by deuterium labelling: turnover of 4-hydroxy-3-methoxyphenylglycol. J Neurochem 41:246–250Google Scholar
  40. Medical Research Council (1965) Clinical trial of the treatment of depressive illness. Br Med J i:881–886Google Scholar
  41. Modai I, Apter A, Golomb M, Wijsenbeck H (1979) Response to amitriptyline and urinary MHPG in bipolar depressive patients. Neuropsychobiology 5:181–184Google Scholar
  42. Petursson H, Bond PA, Smith B, Lader MH (1983) Monoamine metabolism during chronic benzodiazepine treatment and with-drawal. Biol Psychiatry 18:207–213Google Scholar
  43. Pickar D, Sweeney DR, Maas JW, Heninger GR (1978) Primary affective disorder, clinical state change, and MHPG excretion. Arch Gen Psychiatry 35:1378–1383Google Scholar
  44. Post RM, Stoddard FJ, Gillin JC, Buchsbaum MS, Runkle DC, Black KE, Bunney WE Jr (1977) Alterations in motor activity, sleep and biochemistry in a cycling manic depressive patient. Arch Gen Psychiatry 34:470–477Google Scholar
  45. Riederer P, Birkmayer W, Seeman D, Wuketich S (1980) 4-hydroxy-3-methoxyphenylglycol as an index of brain noradrenaline turnover in endogenous depression. Acta Psychiatr Scand Suppl 280:251–257Google Scholar
  46. Rosenbaum AH, Schatzberg AF, Maruta T, Orsulak PJ, Cole JO, Grab EL, Schildraut JJ (1980) MHPG as a predictor of antidepressant response to imipramine and maprotiline. Am J Psychiatry 137:1090–1092Google Scholar
  47. Shaw DM, O'Keeffe R, MacSweeney DA, Brooksbank BWL, Noguera R, Coppen A (1973) 3-methoxy-4-hydroxyphenylglycol in depression. Psychol Med 3:333–336Google Scholar
  48. Spiker DG, Edwards D, Hanin I, Neil JF, Kupfer DJ (1980) Urinary MHPG and clinical response to amitriptyline. Am J Psychiatry 137:1183–1187Google Scholar
  49. Sweeney D, Nelson C, Bowers M, Maas J, Heninger G (1978) Delusional versus non-delusional depression: neurochemical differences. Lancet ii:100–101Google Scholar
  50. Taube SL, Kirstein LS, Sweeney DR, Heninger GR Maas LW (1978) Urinary 3-methoxy-4-hydroxyphenylglycol and psychiatric diagnosis. Am J Psychiatry 135:78–82Google Scholar
  51. Vestergaard P, Leverett R (1958) Constancy of urinary creatinine excretion. J Lab Clin Med 51:211–218Google Scholar
  52. Wing JK, Cooper JE, Sartorius N (1974) The measurement and classification of psychiatric syndromes. Cambridge University PressGoogle Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • M. H. Joseph
    • 1
  • D. Risby
    • 1
  • T. J. Crow
    • 1
  • J. F. W. Deakin
    • 1
  • Eve C. Johnstone
    • 1
  • P. Lawler
    • 2
  1. 1.Division of PsychiatryMRC Clinical Research CentreHarrowUK
  2. 2.Division of AnaesthesiaMRC Clinical Research CentreHarrowUK

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