Homovanillic acid in the cerebrospinal fluid: Patterns of response after four weeks of neuroleptic treatment

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      Lumbar cerebrospinal fluid (CSF) homovanillic acid (HVA) concentrations were measured before and after 4 weeks of neuroleptic treatment in schizophrenic (n = 15) and schizoaffective (n = 4) patients. Neuroleptic treatment induced a nonsignificant (17%) increase in CSF HVA group mean levels. For the total group, no correlations were found between pretreatment CSF HVA and clinical measures, or between changes in HVA and clinical response. An alternative interpretation was attempted by defining “tolerant” and “nontolerant” subgroups. A “tolerant” response was defined as a reduction in posttreatment HVA values below prettreatment levels, whereas a “nontolerant” response was characterized by posttreatment values above pretreatment levels. When thus defined, nontolerant patients had a significantly inferior clinical response to neuroleptics, in contrast to their tolerant counterparts. Further, although there was no difference in pretreatment CSF HVA values between these two groups, prettreatment clinical profiles did differ significantly. Also, in a retrospective analysis, nontolerant patients were found to have a significantly earlier age of illness onset, a greater number of prior psychiatric hospitalizations, and more time spent in psychiatric hospitals.


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        • Bacopoulos N.G.
        • Hattox S.E.
        • Roth R.H.
        Dihydroxyphenylacetic and homovanillic acid in rat plasma.
        Eur J Pharmacol. 1979; 56: 225-236
        • Bjerkenstedt L.
        • Gullberg B.
        • Harnryd C.
        • Sedvall G.
        Monoamine metabolite levels in cerebrospinal fluid of psychotic women treated with Melperone or thiothixene.
        Arch Psychiat Nervenkr. 1977; 224: 107-118
        • Biggio G.
        • Casu M.
        • Klimek V.
        • Gessa G.L.
        Dopamine synthesis: Tolerance to haloperidol and supersensitivity to apomorphine depend on presynaptic receptor.
        Adv Biochem Psychopharmacol. 1980; 24: 17-22
        • Blanc G.
        • Herve D.
        • Simon H.
        • et al.
        Response to stress of mesocortical frontal depletion in rats after long term isolation.
        Nature. 1980; 284: 265-267
        • Bowers M.G.
        Family history and CSF homovanillic acid patterns during neuroleptic treatment.
        Am J Psychiatry. 1984; 141: 296-298
        • Bowers M.B.
        • Heninger G.R.
        Cerebrospinal fluid homovanillic acid patterns during neuroleptic treatment.
        Psychiatry Res. 1981; 4: 285-290
        • Bowers M.G.
        • Rozitis A.
        Regional differences in homovanillic acid concentrations after acute and chronic administration of antipsychotic drugs.
        J Pharm Pharmacol. 1974; 26: 743-745
        • Bunney B.S.
        • Grace A.A.
        Acute and chronic haloperidol treatment: Comparison of effects on nigral dopaminergic activity.
        Life Sci. 1978; 23: 1715-1728
        • Carlsson M.
        • Carlsson A.
        Interactions between glutamatergic and monoaminergic systems within the basal ganglia: Implications for schizophrenia and Parkinson's disease.
        Trends Neurosci. 1990; 13: 276-372
        • Chiodo L.A.
        • Bannon M.J.
        • Grace A.A.
        • Roth R.H.
        Evidence for the absence of impulse-regulating somatodendritic and synthesis-modulating nerve terminal autoreceptors on subpopulations of mesocortical dopamine neurons.
        Neuroscience. 1984; 12: 1-16
        • Cooper S.J.
        • Leahey W.
        • King D.J.
        • et al.
        The relationship between clinical and biochemical changes following neuroleptic treatment in schizophrenia.
        Schizophr Res. 1990; 3: 261-267
        • Costall B.
        • Naylor R.J.
        • Marsden C.D.
        • Pycock C.J.
        Serotonergic modulation of the dopamine response from the nucleus accumbens.
        J Pharm Pharmacol. 1976; 28: 523-526
        • Csernansky J.G.
        • Murphy G.M.
        • Faustman W.O.
        Limbic/mesolimbic connections and the pathogenesis of Schizophrenia.
        Biol Psychiatry. 1991; 30: 383-400
        • Davidson M.
        • Davis K.L.
        A comparison of plasma homovanillic acid concentration in schizophrenic patients and normal controls.
        Arch Gen Psychiatry. 1988; 45: 561-563
        • Doran A.R.
        • Rubinow D.R.
        • Wolkowitz O.M.
        • Brier A.
        • Pickar D.
        Fluphenazine treatment reduces CSF Somatostatin in patients with Schizophrenia: Correlations with CSF HVA.
        Biol Psychiatry. 1989; 25: 431-439
        • Endicott J.
        • Spitzer R.L.
        • Fleiss J.L.
        • Cohen J.
        The global assessment scale.
        Arch Gen Psychiat. 1976; 33: 766-771
        • Faull K.
        • Anderson P.J.
        • Barchas J.D.
        • Berger P.D.
        Selected ion monitoring assay for biogenic amine metabolites and probenecid in human lumbar cerebrospinal fluid.
        Chromatogr. 1979; 163: 337-349
        • Folstein M.F.
        • Folstein S.E.
        • McHugh P.R.
        “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician.
        J Psychiatry Res. 1975; 12: 189-198
        • Harnryd C.
        • Bjerkendstedt L.
        • Gullberg B.
        • Oxenstierna G.
        • Sedvall G.
        • Wiesel F.A.
        Time course for effects of sulpiride and chlorpromazine on monoamine metabolite and prolactin levels in CSF from schizophrenic patients.
        Acta Psychiat Scand Suppl. 1984; 311: 75-92
        • Jones G.H.
        • Hernandez T.D.
        • Marsden C.
        • Robbins T.W.
        Enhanced striatal response to d-amphetamine as revealed by intracerebral dialysis following social isolation in rats.
        Br J Pharmacol. 1988; 94: 349-350
        • Joseph M.H.
        • Frith D.
        • Waddington J.L.
        Dopaminergic mechanisms and cognitive deficit in schizophrenia.
        Psychopharmacology. 1979; 63: 273-280
        • Karoum F.
        • Karson C.N.
        • Bigelow L.B.
        • et al.
        Preliminary evidence of reduced combined output of dopamine and its metabolites in chronic schizophrenia.
        Arch Gen Psychiatry. 1987; 44: 604-607
        • Lerner P.
        • Nose P.
        • Gordon E.K.
        • Lovenberg W.
        Haloperidol effect of long term treatment on rat striatal dopamine synthesis and turnover.
        Science. 1977; 197: 181-183
        • Meltzer H.Y.
        The role of serotonin in the action of atypical antipsychotic drugs.
        Psychiat Ann. 1990; 20: 571-578
        • Nicolaou N.M.
        • Garcia-Munoz
        • Arbuthrott G.W.
        Interactions between serotonergic and dopaminergic systems in rat brain demonstrated by small unilateral lesions of the raphe nuclei.
        Eur J Pharmacol. 1979; 57: 295-305
        • Overall J.E.
        • Gorham D.R.
        The brief psychiatric rating scale.
        Psychol Reports. 1962; 10: 799-812
        • Post R.M.
        • Fink E.
        • Carpenter Jr., W.T.
        • Goodwin F.K.
        Cerebrospinal fluid amine metabolites in acute schizophrenia.
        Arch Gen Psychiatry. 1975; 32: 1063-1069
        • Post R.M.
        • Goodwin F.K.
        Time dependent effects of Phenothiazines on Dopamine Turnover in psychiatric patients.
        Science. 1975; 190: 488-499
        • Pycock C.J.
        • Kerwin R.W.
        • Carter C.J.
        Effect of lesion of cortical dopamine terminals on subcortical dopamine receptors in rats.
        Nature. 1980; 286: 74-77
        • Roth R.H.
        • Bacopoulos N.G.
        • Bustos G.
        • Redmond E.
        Antipsychotic drugs: Differential effects on dopamine neurons following chronic administration in human and nonhuman primates.
        Adv Biochem Psychopharmacol. 1980; 24: 513-520
        • Sanberg P.R.
        • Bunsey M.D.
        • Giordano M.
        • et al.
        The catalepsy test: Its ups and downs.
        Behav Neurosci. 1988; 102: 748-759
        • Sedval G.
        • Bjerkenstedt L.
        • Lindstrom L.
        • Wode-Helgodt B.
        Clinical assessment of dopamine receptor blockade.
        Life Sci. 1978; 23: 425-430
        • Sharma R.
        • Javaid J.I.
        • Janicak P.G.
        • et al.
        Plasma and CSF HVA before and after pharmacological treatment.
        Psychiatry Res. 1989; 28: 97-104
        • White F.J.
        • Wang R.Y.
        Comparison of the effects of chronic haloperidol treatment on A9 and A10 dopamine neurons in the rat.
        Life Sci. 1983; 32: 983-993
        • Wode-Helgodt B.
        • Fyro B.
        • Gullberg B.
        • Sedvall G.
        Effect of chlorpromazine treatment on monoamine metabolite levels in cerebrospinal fluid of psychotic patients.
        Acta Psychiatr Scand. 1979; 56: 129-142