Original Articles| Volume 46, ISSUE 9, P1253-1258, November 01, 1999

Plasma norepinephrine and prediction of outcome in major depressive disorder


      Background: Several epidemiologic and clinical factors have been shown to predict long term outcome in major depressive disorder (MDD). The value of biological predictors has not been extensively studied. This study examined whether plasma norepinephrine may be useful in predicting outcome in MDD.
      Methods: Forty patients were followed up 8 years after an index major depressive episode. Three outcome variables were assessed: time to first recurrence (the primary outcome measure), the Lee and Murray criteria and the Depression Outcome Scale (DOS). The results were examined against plasma norepinephrine value, at the index episode, using survival analysis and linear regression.
      Results: High plasma norepinephrine at the index episode was positively and significantly associated with time to first recurrence for patients with nonpsychotic MDD (n = 31, χ2 = 8.38, on 1 df, p < .01). Similarly, plasma norepinephrine was significantly associated with good global outcome, both using Lee and Murray criteria (n = 34, adjusted R2 = .24, p < .01) and DOS criteria (n = 31, adjusted R2 = .17, p < .01) for this group of patients. In contrast, plasma norepinephrine was not significantly related to outcome for MDD with psychotic features.
      Conclusions: Plasma norepinephrine at index episode seems to be a predictor of outcome in MDD.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. American Psychiatric Association (1987): Diagnostic and Statistical Manual of Mental Disorders, 3rd ed rev. (DSM IIIR) Washington, DC: American Psychiatric Press.

        • Brugha T.S
        • Bebbington P.E
        • MacCarthy B
        • Sturt E
        • Wykes T
        Antidepressants may not assist recovery in practice.
        Acta Psychiatr Scand. 1992; 86: 5-11
        • Cooper S.J
        • Kelly J.K
        • King D.J
        Adrenergic receptors in depression.
        Br J Psychiatry. 1985; 147: 23-29
        • Cooper S.J
        • Kelly C.B
        • King D.J
        5-Hydroxyindoleacetic acid in cerebrospinal fluid and prediction of suicidal behaviour in schizophrenia.
        Lancet. 1992; 340: 940-941
        • Cox D
        Regression models and life tables.
        J R Stat Soc. 1972; 34: 187-202
        • Esler M
        • Turbott J
        • Schwarz R
        • et al.
        The peripheral kinetics of norepinephrine in depressive illness.
        Arch Gen Psychiatry. 1982; 39: 295-300
        • Esler M.D
        • Lambert G.W
        • Ferrier C
        • et al.
        Central nervous system noradrenergic control of sympathetic outflow, in normotensive and hypertensive humans.
        Clin Exp Hypertens. 1995; 17: 409-423
      2. First MB, Spitzer RL, Gibbon RL, Williams JB (1996): User’s Guide for the Structured Clinical Interview DSM-IV Disorders-Patient Edition (SCID-I/P, Version 2.0) Biometric Research Department, New York State Psychiatric Institute, 722 West 168th Street, New York.

        • Frank E
        • Prien R.F
        • Jarrett R.B
        • et al.
        Conceptualization and rationale for consensus definitions of terms in major depressive disorder.
        Arch Gen Psychiatry. 1991; 48: 851-855
        • Hamilton M
        Development of a rating scale for primary depressive illness.
        Br J Soc Clin Psychiatry. 1959; 6: 278-296
        • Harris E.C
        • Barraclough B
        Excess mortality of mental disorder.
        Br J Psychiatry. 1998; 173: 11-53
        • Horwath E
        • Weissman M.M
        Epidemiology of depression and anxiety.
        in: Tsuang M.T Tohen M Zahner G.P Textbook in Psychiatric Epidemiology. Wiley, New York1995: 317-344
        • Johnson J
        • Horwath E
        • Weissman M.M
        The validity of major depression with psychotic features based on a community study.
        Arch Gen Psychiatry. 1991; 48: 1075-1081
        • Keller M.B
        • Lavori P.W
        • Lewis C.E
        • Klerman G.L
        Predictors of relapse in major depressive disorder.
        JAMA. 1988; 250: 3299-3304
        • Keller M.B
        • Lavori P.W
        • Mueller T.I
        • et al.
        Time to recovery, chronicity and levels of psychopathology in major depression.
        Arch Gen Psychiatry. 1992; 40: 809-816
        • Kelly C.B
        • Cooper S.J
        Plasma norepinephrine response to electroconvulsive therapy in depressive illness.
        Br J Psychiatry. 1997; 171: 182-186
        • Kelly C.B
        • Cooper S.J
        Plasma norepinephrine response to a cold pressor test in subtypes of depressive illness.
        Psychiatric Res. 1998; 81: 39-50
        • Kelly C.B
        • Cooper S.J
        Differences and variability in plasma norepinephrine between depressive and anxiety disorders.
        J Psychopharmacol. 1998; 12: 161-167
        • Lee A.S
        • Murray R.M
        The long-term outcome of Maudsley depressives.
        Br J Psychiatry. 1988; 153: 741-751
        • Lester D
        The concentration of neurotransmitter metabolites in the cerebrospinal fluid of suicidal individuals.
        Pharmacopsychiatry. 1995; 28: 45-50
        • Lykouras L
        • Markianos M
        • Hatzimanolis J
        • Mallaras D
        • Stefanis C
        Biogenic amine metabolites in delusional depression and melancholia subtypes of depression.
        Prog Neuropsychopharmacol Biol Psychiatry. 1994; 18: 1261-1271
        • Mann J.J
        • Malone K.M
        CSF amines and higher-lethality suicide attempts in depressed inpatients.
        Biol Psychiatry. 1997; 41: 162-171
        • Maj M
        • Veltro F
        • Pirozzi R
        • Labrace S
        • Magliano L
        Pattern of recurrence after recovery from an episode of major depression.
        Am J Psychiatry. 1992; 149: 795-800
        • Mueller T.I
        • Lavori P.W
        • Keller M.B
        • et al.
        Prognostic effect of the variable course of alcoholism in the 10-year course of depression.
        Am J Psychiatry. 1994; 151: 700-706
        • Murray C.J
        • Lopez A.D
        Global mortality, disability, and the contribution of risk factors.
        Lancet. 1997; 349: 1436-1442
        • Roy A
        • Pickar D
        • Linnoila M
        • Potter W.Z
        Plasma norepinephrine levels in affective disorder.
        Arch Gen Psychiatry. 1985; 42: 1181-1185
        • Roy A
        • Pickar D
        • Dejarg J
        • Karoum F
        • Linnoila M
        Norepinephrine and its metabolites in cerebrospinal fluid, plasma and urine.
        Arch Gen Psychiatry. 1988; 45: 849-857
        • Roy A
        • De Jong J
        • Linnoila M
        Cerebrospinal fluid monoamine metabolites and suicidal behaviour in depressed patients.
        Arch Gen Psychiatry. 1989; 46: 609-612
        • Schatzberg A.F
        • Rothschild A.J
        Psychotic major depres-sion.
        Am J Psychiatry. 1992; 149: 733-745
        • Sekunda S.K
        • Cross C
        • Koslow S
        • Katz M.M
        • Kocsis J.H
        • Maas J.W
        Studies of amine metabolites in depressed patients.
        Ann NY Acad Sci. 1992; 3: 231-241
        • Solomon D.A
        • Keller M.B
        • Leon E.C
        • et al.
        Recovery from major depression.
        Arch Gen Psychiatry. 1997; 54: 1001-1006
        • Surtees P.G
        • Backley C
        Future imperfect; the long-term outcome of depression.
        Br J Psychiatry. 1994; 164: 327-341
        • Werstiuk E.S
        • Coote M
        • Griffith L
        • Shannon H
        • Steiner M
        Effects of electroconvulsive therapy on peripheral adrenoreceptors, norepinephrine, MHPG and cortisol in depressed patients.
        Br J Psychiatry. 1996; 169: 758-765
        • Wyatt R.J
        • Portnoy B
        • Kupfer D.J
        • Engelman K
        Resting plasma catecholamine concentrations in patients with depression and anxiety.
        Arch Gen Psychiatry. 1971; 24: 65-70
        • Ziegler M.G
        • Lake C.R
        • Wood J.H
        • Brooks B.R
        • Ebert M.H
        Relationship between norepinephrine in blood and cerebrospinal fluid in the presence of a blood-cerebrospinal fluid barrier for norepinephrine.
        J Neurochem. 1977; 28: 677-679