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New dopaminergic and non-dopaminergic theories in schizophrenia and their therapeutic impact

Published online by Cambridge University Press:  18 September 2015

Extract

The dopamine (DA) hypothesis of schizophrenia, postulating that schizophrenia is characterized by increased dopamine function, has been the most influential theory on the pathogenesis of schizophrenia. It has recently been revised based on the appreciation that the core symptoms of schizophrenia may not be the positive (psychotic) symptoms, but rather the negative symptoms and the cognitive deficits found in schizophrenic patients. This revision has prompted the hypothesis that schizophrenia is characterized by both decreased prefrontal dopamine activity (causing deficit symptoms) and increased dopamine activity in mesolimbic dopamine neurons (causing positive symptoms).

Notwithstanding this revision of a role for dopamine in schizophrenia, it has become increasingly evident that dysfunction of other monoaminergic systems may be as important in contributing to the pathophysiology of schizophrenia. Specifically, the putative role of serotonin (5-hydroxytryptamine, 5-HT) in schizophrenia is gaining considerable attention. Several observations, such as the ability of the 5-HT antagonist, ritanserin, to alleviate schizophrenic symptoms and, when added to haloperidol (Haldol®), to decrease its extrapyramidal side-effects (EPS), have stimulated studies into a role of 5-HT in schizophrenia. The finding that clozapine (Leponex®), clinically superior to conventional neuroleptics, is a weak DA2 antagonist but a potent 5-HT1c and 5-HT2 antagonist has further stimulated 5-HT-related research in schizophrenia.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1997

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References

Literature

1.Matthyse, S. Antipsychotic drug actions: a clue to the neuropathology of schizophrenia? Fed Proc 1973;32:200–5.Google Scholar
2.Davis, KL, Kahn, RS, Ko, G, et al.Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiat 1991; 148:1474–86.Google ScholarPubMed
3.Kane, J, Honigfeld, G, Singer, J, et al.Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlo-rpromazine. Arch gen Psychiat 1988; 45: 789–96.CrossRefGoogle Scholar
4.Canton, H, Verriele, L, Colpaert, FC. Binding of typical and atypical antipsychotics to 5HTlc and 5HT2 sites: clozapine potently interacts with 5 HTlc sites. Eur J Pharmacol 1990;191:93–6.CrossRefGoogle Scholar
5.Meltzer, HY. Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology 1989;99:S18–27.CrossRefGoogle ScholarPubMed
6.Tork, I. Anatomy of the serotonergic system. Ann N Y Acad Sci 1990;600:934.CrossRefGoogle ScholarPubMed
7.Kelland, MD, Freeman, AS, Chiodo, LA. Serotonergic afferent regulation of the basic physiology and pharmacological responsiveness of nigrostriatal dopamine neurons. J Pharmacol exp Ther 1990;253:803–11.Google ScholarPubMed
8.Bowers, MB. Family history and CSF homovanillic acid pattern during neuroleptic treatment. Am J Psychiat 1984;141:296–8.Google ScholarPubMed
9.Pickar, D, Labarca, R, Doran, AR, et al.Longitudinal measurement of plasma homovanillic acid levels in schizophrenic patients. Correlation with psychosis and response to neuroleptic treatment. Arch gen Psychiat 1986;43:669–76.CrossRefGoogle ScholarPubMed
10.Davila, R, Manero, E, Zumarraga, M, et al.Plasma homovanillic acid as a predictor of response to neuroleptics. Arch gen Psychiat 1988;45:564–7.CrossRefGoogle ScholarPubMed
11.Wolkowitz, OM, Breier, A, Doran, A, et al.Alprazolam augmentation of the antipsychotic effects of fluphenazine in schizophrenic patients. Preliminary results [see comments]. Arch gen Psychiat 1988;45:664–71.CrossRefGoogle ScholarPubMed
12.Bowers, MB, Swigar, ME, Jatlow, PI, et al.Plasma catecholomine metabolites and treatment response at neuroleptic steady state. Biol Psychiat 1989;25:734–8.CrossRefGoogle ScholarPubMed
13.Sharma, R, Javaid, IJ, Janicak, P, et al.Plasma and CSF HVA before and after pharmacological treatment. Psychiat Res 1989;28:97104.CrossRefGoogle ScholarPubMed
14.Chang, WH, Chen, TY, Lin, SK, et al.Plasma catecholamine metabolites in schizophrenia: evidence for the two-subtype concept. Biol Psychiat 1990;27:510–8.CrossRefGoogle ScholarPubMed
15.Davidson, M, Losonczy, MF, Mohs, RC, et al.Effects of debrisoquin and haloperidol on plasma homovanillic acid concentration in schizophrenic patients. Neuropsychopharmacol 1987;1:1723.CrossRefGoogle ScholarPubMed
16.Davidson, M, Kahn, RS, Knott, P, et al.Effects of neuroleptic treatment on symptoms of schizophrenia and plasma homovanillic acid concentrations. Arch gen Psychiat 1991;48:910–3.CrossRefGoogle ScholarPubMed
17.Pickar, D, Owen, RR, Litman, RE, et al.Clinical and biologic response to clozapine in patients with schizophrenia. Arch gen Psychiat 1992;49:345–53.CrossRefGoogle ScholarPubMed
18.Bowers, M, Swigar, ME, Jatlow, PI, et al.Early neuroleptic response: Clinical profiles and catecholamine metabolites. J clin Psychopharmacol 1987;7:83–6.CrossRefGoogle ScholarPubMed
19.Van Putten, T, Marder, S, Aravagiri, M, et al.Plasma homovanillic acid as a predictor of response to fluphenazine treatment. Psychopharmacol Bull 1989;1:8991.Google Scholar
20.Javaid, JI, Sharma, RP, Janicak, PG, et al.Plasma HVA in psychiatric patients: longitudinal studies. Psychopharmacol Bull 1990;26: 361–5.Google ScholarPubMed
21.Mazure, CM, Nelson, CJ, Jatlow, PI, et al.Plasma free homovanillic acid as a predictor of clinical response in acute psychosis. Biol Psychiat 1991;30:475–82.CrossRefGoogle ScholarPubMed
22.Pickar, D, Labarca, R, Linnoila, M, et al.Neuroleptic induced decrease in plasma homovanillic acid and antipsychotic activity in schizophrenia. Science 1984;225:954–7.CrossRefGoogle Scholar
23.Davis, KL, Davidson, M, Mohs, RC, et al.Plasma homovanillic acid concentration and the severity of schizophrenic. Science 1985;227: 1601–2.CrossRefGoogle ScholarPubMed
24.Davidson, M, Davis, KL. A comparison of plasma homovanillic acid concentrations in schizophrenic patients and normal controls. Arch gen Psychiat 1988;45:561–3.CrossRefGoogle ScholarPubMed
25.Kirch, DG, Jaskiw, G, Linnoila, M, et al.Plasma amine metabolites before and after withdrawal from neuroleptic treatment in chronic schizophrenic inpatients. Psychiat Res 1988;25:233–42.CrossRefGoogle ScholarPubMed
26.Maas, JW, Contreras, SA, Seleshi, E, et al.Dopamine metabolism and disposition in schizophrenic patients. Studies using debriso-quin. Arch gen Psychiat 1988;45:553–9.CrossRefGoogle Scholar
27.Markianos, M, Botsis, A, Arvanitis, Y. Biogenic amine metabolites in plasma of drug-naive schizophrenic patients: associations with symptomatology. Biol Psychiat 1992;32:288–92.CrossRefGoogle ScholarPubMed
28.Kahn, RS, Siever, LJ, Gabriel, S, et al.Serotonin function in schizophrenia: effects of meta-chlorophenylpiperazine in schizophrenic patients and healthy subjects. Psychiat Res 1992;43:112.CrossRefGoogle ScholarPubMed
29.Iqbal, N, Asnis, GM, Wetzler, S, et al.The MCPP challenge test in schizophrenia: hormonal and behavioral responses. Biol Psychiat 1991;30:770–8.CrossRefGoogle ScholarPubMed
30.Owen, RR, Gutierrez Esteinou, R, et al.Effects of clozapine and fluphenazine treatment on response to m-chlorophenylpiperazine infusions in schizophrenia. Arch gen Psychiat 1993;50:636–44.CrossRefGoogle ScholarPubMed
31.Krystal, JH, Seibyl, JP, Price, LP, et al.MCPP effects in schizophrenic patients before and after typical and atypical neuroleptic treatment. [Abstract] Schizophr Res 1991;4:350CrossRefGoogle Scholar
32.Lee, HS, Bastani, B, Friedman, L, et al.Effect of the serotonin agonist, MK-212 on body temperature in schizophrenia. Biol Psychiat 1992;31:460–70.Google ScholarPubMed
33.Lerer, B, Ran, A, Blacker, M, et al.Neuroendocrine responses in chronic schizophrenia. Evidence for serotonergic dysfunction. Schizophr Res 1988;1:405–10.CrossRefGoogle ScholarPubMed