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Relationships between clinical effects and monoamine metabolites and amino acids in sulpiride-treated schizophrenic patients

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Abstract

Twenty-four acutely ill schizophrenic patients (DSM-III-R), 18–42 years old, were treated for 6 weeks with sulpiride. Sulpiride was administered in three different daily dosages (400, 800 or 1200 mg) according to a double dummy blind randomized administration schedule. The psychopathology of the patients was rated by the Comprehensive Psychopathological Rating Scale (CPRS) and the Nurse's Observation Scale for Inpatient Evaluation (NOSIE). The monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA), 4-hydroxy-3-methoxy-phenylglycol (HMPG) and the amino acids tyrosine, tryptophan, glutamate and glutamine were measured in serum before and once a week during sulpiride treatment. There were no significant correlations between the CPRS or the NOSIE morbidity scores and the biochemical measures before drug treatment. HVA levels were not correlated to rating scores during treatment, but after 6 weeks HVA had decreased significantly in the patients with a good response but not in the patients with a poor response. A negative relationship between 5-HIAA levels and depressive and negative symptoms was found. Nonresponders according to the subscale for depression had low 5-HIAA levels throughout the treatment. An increase of tryptophan was correlated to improvement in the early part of treatment. High levels of glutamate or glutamine were found in non-responders before treatment. During treatment an increase of the glutamate level was correlated to improvement. Low levels of glutamine were related to improvement according to global and NOSIE (total) rating scores. Peripheral biochemical measures may be a valuable tool in the study of pathophysiological mechanisms and treatment effects in patients with schizophrenia.

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References

  • Alfredsson G, Wiesel F-A (1989) Monoamine metabolites and amino acids in serum from schizophrenic patients before and during sulpiride treatment. Psychopharmacology 99:322–327

    Article  PubMed  Google Scholar 

  • Alfredsson G, Bjerkenstedt L, Edman G, Härnryd C, Oxenstierna G, Sedvall G, Wiesel F-A (1984) Relationships between drug concentrations in serum and CSF, clinical effects and monoaminergic variables in schizophrenic patients treated with sulpiride or chlorpromazine. Acta Psychiatr Scand [Suppl 311] 69:49–74

    Google Scholar 

  • Alfredsson G, Wiesel F-A, Lindberg M (1988a) Glutamate and glutamine in cerebrospinal fluid and serum from healthy volunteers — analytical aspects. J Chromatogr Biomed Appl 424:378–384

    Article  Google Scholar 

  • Alfredsson G, Wiesel F-A, Tylec A (1988b) Relationships between glutamate and monoamine metabolites in cerebrospinal fluid and serum. Biol Psychiatry 23:689–697

    Article  PubMed  Google Scholar 

  • Åsberg M, Träskman L, Thoren P (1976) 5-HIAA in the cerebrospinal fluid. Arch Gen Psychiatry 33:1193–1197

    PubMed  Google Scholar 

  • Åsberg M, Montgomery S, Perris C, Schalling D, Sedvall G (1978) CPRS — the psychopathological rating scale. Acta Psychiatr Scand [Suppl] 271:5–27

    Google Scholar 

  • Beck O, Hesselgren T (1980) Method for the determination of tryptophan in serum and cerebrospinal fluid. J Chromatogr Biomed Appl 181:100–102

    Article  Google Scholar 

  • Bjerkenstedt L, Edman G, Hagenfeldt L, Sedvall G, Wiesel F-A (1985) Plasma amino acids in relation to cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy controls. Br J Psychiatry 147:276–282

    PubMed  Google Scholar 

  • Borg J, Edström L, Bjerkenstedt L, Wiesel F-A, Farde L, Hagenfeldt L (1987) Muscle biopsy findings, conduction velocity and refractory period of single motor nerve fibres in schizophrenia. J Neurol Neurosurg Psychiatry 50:1655–1664

    PubMed  Google Scholar 

  • Bowers MB Jr, Swigar ME, Jatlow PI, Goicoechea N (1984) Plasma catecholamine metabolites and early response to haloperidol. J Clin Psychiatry 45:248–251

    PubMed  Google Scholar 

  • Bowers MB Jr, Swigar ME, Jatlow PI, Hoffman FJ, Giocoechea N (1986) Early neuroleptic response in psychotic men and women: correlation with plasma HVA and HMPG. Compr Psychiatry 27:181–185

    Article  PubMed  Google Scholar 

  • Chang W-H, Chen T-Y, Lee C-F, Hung J-C, Hu W-H, Yeh E-K (1988) Plasma homovanillic acid levels and subtyping of schizophrenia. Psychiatry Res 23:239–244

    Article  PubMed  Google Scholar 

  • Cheramy A, Romo R, Godeheu G, Baruch P, Glowinski J (1986) In vivo presynaptic control of dopamine release in the cat caudate nucleus-II. Facilitatory or inhibitory influence of L-glutamate. Neuroscience 19:1081–1090

    Article  PubMed  Google Scholar 

  • Davila R, Manero E, Zumarraga M, Andia I, Schweitzer JW, Friedhoff AJ (1988) Plasma homovanillic acid as a predictor of response to neuroleptics. Arch Gen Psychiatry 45:564–567

    PubMed  Google Scholar 

  • Fernström JD, Wurtman RJ (1971) Brain serotonin content: physiological dependence on plasma tryptophan levels. Science 173:149–152

    PubMed  Google Scholar 

  • Fonnum F (1984) Glutamate: a neurotransmitter in mammalian brain. J Neurochem 42:1–11

    PubMed  Google Scholar 

  • Hagenfeldt L, Venizelos N, Bjerkenstedt L, Wiesel F-A (1987) Decreased tyrosine transport in fibroblasts from schizophrenic patients. Life Sci 41:2749–2757

    Article  PubMed  Google Scholar 

  • Harris PQ, Brown SJ, Friedman MJ, Bacopoulos NG (1984) Plasma drug and homovanillic acid levels in psychotic patients receiving neuroleptics. Biol Psychiatry 19:849–860

    PubMed  Google Scholar 

  • Härnryd C, Bjerkenstedt L, Björk K, Gullberg B, Oxenstierna G, Sedvall G, Wiesel F-A, Wik G, Åberg-Wistedt A (1984) Clinical evaluation of sulpiride in schizophrenic patients — a double-blind comparison with chlorpromazine. Acta Psychiatr Scand [Suppl 311] 69:7–30

    Google Scholar 

  • Honigfeld G, Gillis RV, Klett CJ (1966) NOSIE — 30: A treatment — sensitive ward behaviour scale. Psychol Rep 19:180–182

    PubMed  Google Scholar 

  • Hunneman DH (1983) Mass fragmentographic determination of homovanilic and 4-hydroxy-3-methoxy mandelic acids in 50 µl plasma. Clin Chim Acta 135:169–174

    Article  PubMed  Google Scholar 

  • Ko GN, Jimerson DC, Richard JW, Bigelow LB (1988) Plasma-3-methoxy-4-hydroxyphenylglycol changes associated with clinical state and schizophrenic subtype. Arch Gen Psychiatry 45:842–846

    PubMed  Google Scholar 

  • Kopin IJ (1978) Measuring turnover of neurotransmitters in human brain. In: Lipton MA, Di Mascio A, Killam KF (eds) Psychopharmacology: a generation of progress. Raven Press, New York, pp 933–942

    Google Scholar 

  • Kopin IJ, Gordon EK, Jimerson DC, Polinsky RJ (1983) Relation between plasma and cerebrospinal fluid levels of 3-methoxy-4-hydroxyphenylglycol. Science 219:73–76

    PubMed  Google Scholar 

  • Kornhuber HH, Kornhuber I, Kim JS, Kornhuber ME (1984) Zur biochemischen Theorie der Schizophrenie (A biochemical theory of schizophrenia). Nervenarzt 55:602–606

    PubMed  Google Scholar 

  • Lindroth P, Mopper K (1979) High performance liquid chromatographic determination of subpicomole amounts of amino acids by precolumn fluorescence derviatization with ophthaldialdehyde. Anal Chem 51:1667–1674

    Article  Google Scholar 

  • Lloyd KJ, Farley IJ, Deck JHN, Hornykiewicz (1974) Serotonin and 5-hydroxyindoleacetic acid in discrete areas of the brain-stem of suicide victims and control patients. Adv Biochem Psychopharmacol 11:387–397

    PubMed  Google Scholar 

  • Maas JW, Hattox SE, Greene NM, Landis DH (1980) Estimates of dopamine and serotonin synthesis by the awake human brain. J Neurochem 34:1547

    PubMed  Google Scholar 

  • Möller SE (1985) Tryptophan to competing amino acids ratio in depressive disorder: relation to efficacy of antidepressive treatments. Acta Psychiatr Scand [Suppl 325] 72:1–31

    PubMed  Google Scholar 

  • Montgomery SA, Åsberg M (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry 134:382–389

    PubMed  Google Scholar 

  • Munro HN (1979) Factors in the regulation of glutamate metabolism. In: Filer LJ Jr, Gorattini S, Kare MR, Reynolds WA, Wurtman RJ (eds) Glutamic acid: advances in biochemistry and physiology. Raven Press, New York, pp 55–68

    Google Scholar 

  • Perry TL, Hansen S (1969) Technical pitfalls leading to errors in the quantitation of plasma amino acids. Clin Chim Acta 25:53–58

    Article  PubMed  Google Scholar 

  • Pickar D, Labarca R, Linnoila M, Roy A, Hommer D, Everett D, Paul S (1984) Neuroleptic-induced decrease in plasma homovanillic acid and antipsychotic activity in schizophrenic patients. Science 32:521–542

    Google Scholar 

  • Roberts PJ, McBean GJ, Sharif NA, Thomas EM (1982) Striatal glutamatergic function: modifications following specific lesions. Brain Res 235:83–91

    Article  PubMed  Google Scholar 

  • Sedvall G, Wode-Helgodt B (1980) Aberrant monoamine metabolite levels in CSF and family history of schizophrenia. Arch Gen Psychiatry 37:1113–1116

    PubMed  Google Scholar 

  • Sedvall G, Alfredsson G, Bjerkenstedt L, Eneroth P, Fyrö B, Härnryd C, Swahn C-G, Wiesel F-A, Wode-Helgodt B (1975) Selective effects of psychoactive drugs on levels of monoamine metabolites and prolactin in cerebrospinal fluid of psychiatric patients. In: Proceedings of the Sixth International Congress of Pharmacology 3:255–267

    Google Scholar 

  • Sjöquist B, Lindström B, Änggård E (1975) Mass fragmentographic determination of 4-hydroxy-3-methoxyphenylglucol (HMPG) in urine, cerebrospinal fluid, plasma and tissues using a deuterium-labelled internal standard. J Chromatogr 105:309–316

    Article  PubMed  Google Scholar 

  • Spitzer RL, Williams JBW (1987) Diagnostic and statistical manual of mental disorders, DSM-III-R. Am Psychiatr Assoc, Washington DC

    Google Scholar 

  • Swahn C-G, Sandgärde B, Wiesel F-A, Sedvall G (1976) Simultaneous determination of the three major monoamine metabolites in brain tissue and body fluids by a mass fragmentographic method. Psychopharmacology 48:147–152

    Article  PubMed  Google Scholar 

  • Wiesel F-A, Alfredsson G, Jönsson E (1989a) Dose-finding and serum concentrations of neuroleptics in the treatment of schizophrenic patients. In: Dahl SG, Gram LF (eds) Clinical pharmacology in psychiatry. (Psychopharmacology Series 7). Springer, Berlin Heidelberg, pp 302–310

    Google Scholar 

  • Wiesel F-A, Halldin C, Blomquist G, Sjögren I, Stone-Elander S, Bjerkenstedt L, Hagenfeldt L, Venizelos N (1989b) The influx of tyrosine across the blood-brain barrier in healthy volunteers and schizophrenic patients. J Cereb Blood Flow Metab [suppl 1] 9:65

    PubMed  Google Scholar 

  • Wode-Helgodt B, Fyrö, B, Gullberg, B, Sedvall G (1977) Effects of chlorpromazine treatment on monoamine metabolite levels in cerebrospinal fluid of psychotic patients. Acta Psychiatr Scand 56:129–142

    PubMed  Google Scholar 

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Alfredsson, G., Wiesel, FA. Relationships between clinical effects and monoamine metabolites and amino acids in sulpiride-treated schizophrenic patients. Psychopharmacology 101, 324–331 (1990). https://doi.org/10.1007/BF02244049

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  • DOI: https://doi.org/10.1007/BF02244049

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