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Cerebral Ventricular Enlargement and Dopamine Synthesis Inhibition in Chronic Schizophrenia

Henry A. Nasrallah, MD; Joel E. Kleinman, MD, PhD; Daniel R. Weinberger, MD; J. Christian Gillin, MD; Richard Jed Wyatt, MD
Arch Gen Psychiatry. 1980;37(12):1427-1427. doi:10.1001/archpsyc.1980.01780250113018
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To the Editor.—  The Archives has published a series of studies by Weinberger et al related to lateral cerebral ventricular enlargement and apparent atrophic brain changes on computerized tomographic (CT) scans in over 50% of patients with chronic schizophrenia.1-3 In their January 1980 Archives article,3 Weinberger et al report the finding of poor response to neuroleptic treatment in chronic schizophrenic patients with ventricular enlargement compared with a matched control group of chronic schizophrenic patients who have normal ventricular size. Insofar as neuroleptics are dopamine (DA) receptor blockers, the poor response to these drugs in schizophrenic patients with ventricular enlargement suggests that the DA hypothesis may not be applicable to this group of schizophrenic patients.In light of this finding, we have reexamined the results of two earlier studies that failed to show a neuroleptic-potentiating effect in chronic schizophrenia of α-methyl-p-tyrosine (metyrosine), a dopamine synthesis inhibitor.4.5

REFERENCES

Weinberger DR, Torrey EF, Neophytides AN, et al:  Lateral cerebral ventricular enlargement in chronic schizophrenia . Arch Gen Psychiatry 1979;;36:735-739.
Weinberger DR, Torrey EF, Neophytides AN, et al:  Structural abnormalities in the cerebral cortex of chronic schizophrenic patients . Arch Gen Psychiatry 1979;;36:935-939.
Weinberger DR, Bigelow LB, Kleinman JE, et al:  Cerebral ventricular enlargement in chronic schizophrenia: An association with poor response to treatment . Arch Gen Psychiatry 1980;;37:11-13.
Nasrallah HA, Donnelly EF, Bigelow LB, et al:  Inhibition of dopamine synthesis in chronic schizophrenia: Clinical ineffectiveness of metyrosine . Arch Gen Psychiatry 1977;;34:649-655.
Gillen JC, Kleinman JE, Nasrallah HA, et al:  Inhibition of dopamine synthesis in chronic schizophrenia: A follow-up study , in Usdin E, Kopin IJ, Barchas JD (eds): Catecholamines: Basic and Clinical Frontiers . New York, Pergamon Press, 1979;, pp 1839-1842.
Carlsson A, Persson T, Roos BE, et al:  Potentiation of phenothiazines by alpha-methylpara-tyrosine in treatment of chronic schizophrenia . J Neurol Transm 1972;;33:83-90.
Carlsson A, Roos BE, Walinder J, et al:  Further studies on the mechanism of antipsychotic action: Potentiation by alpha-methyl-tyrosine of thioridazine effects in chronic schizophrenia . J Neurol Transm 1973;;34:125-132.
Wålinder J, Skott A, Carlsson A, et al:  Potentiation by metyrosine of thioridazine effects in chronic schizophrenics: A long-term trial using a double-blind crossover design . Arch Gen Psychiatry 1976;;33:501-505.
Magelund G, Gerlach J, Casey DE:  Neuroleptic-potentiating effects of α-methyl-p-tyrosine compared with haloperidol and placebo in a double-blind cross-over trial . Acta Psychiatr Scand 1979;;60:185-189.

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Weinberger DR, Torrey EF, Neophytides AN, et al:  Lateral cerebral ventricular enlargement in chronic schizophrenia . Arch Gen Psychiatry 1979;;36:735-739.
Weinberger DR, Torrey EF, Neophytides AN, et al:  Structural abnormalities in the cerebral cortex of chronic schizophrenic patients . Arch Gen Psychiatry 1979;;36:935-939.
Weinberger DR, Bigelow LB, Kleinman JE, et al:  Cerebral ventricular enlargement in chronic schizophrenia: An association with poor response to treatment . Arch Gen Psychiatry 1980;;37:11-13.
Nasrallah HA, Donnelly EF, Bigelow LB, et al:  Inhibition of dopamine synthesis in chronic schizophrenia: Clinical ineffectiveness of metyrosine . Arch Gen Psychiatry 1977;;34:649-655.
Gillen JC, Kleinman JE, Nasrallah HA, et al:  Inhibition of dopamine synthesis in chronic schizophrenia: A follow-up study , in Usdin E, Kopin IJ, Barchas JD (eds): Catecholamines: Basic and Clinical Frontiers . New York, Pergamon Press, 1979;, pp 1839-1842.
Carlsson A, Persson T, Roos BE, et al:  Potentiation of phenothiazines by alpha-methylpara-tyrosine in treatment of chronic schizophrenia . J Neurol Transm 1972;;33:83-90.
Carlsson A, Roos BE, Walinder J, et al:  Further studies on the mechanism of antipsychotic action: Potentiation by alpha-methyl-tyrosine of thioridazine effects in chronic schizophrenia . J Neurol Transm 1973;;34:125-132.
Wålinder J, Skott A, Carlsson A, et al:  Potentiation by metyrosine of thioridazine effects in chronic schizophrenics: A long-term trial using a double-blind crossover design . Arch Gen Psychiatry 1976;;33:501-505.
Magelund G, Gerlach J, Casey DE:  Neuroleptic-potentiating effects of α-methyl-p-tyrosine compared with haloperidol and placebo in a double-blind cross-over trial . Acta Psychiatr Scand 1979;;60:185-189.

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