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A reexamination of copper and ceruloplasmin-like enzymes in schizophrenia
74A
Neurobiology of SchizophreniaII
BIOL PSYCHIATRY 1989;25:169A-384A
as well as with the delta (peak minus basal) GH response (r = .43; p = .03). The GH responses to TRH were unrelated to age, but were significantly higher among females. GH response to TRH is predominantly under cholinergic control. Negative symptoms in schizophrenia have recently been proposed to be related to cholinergic excess. Increased GH response to TRH may thus identify a subgroup within schizophrenia with cholinergic excess and negative symptoms. (Supported by NIMH Small Grant lR03MH43680-01 and MHCRC Seed Grant R139.)
353 A REEXAMINATION OF COPPER AND CERULOPLASMIN-LIKE ENZYMES IN SCHIZOPHRENIA Joan Kotun, Alan Douglas, Richard W. Topham, James H. Meador-Woodruff Ann Arbor, MI, and Richmond,
VA
Copper has been occasionally implicated in the pathogenesis of schizophrenia. This consideration has face validity, as copper is a cofactor for the activities of tyrosine hydroxylase and dopamine beta-hydroxylase, enzymes central to dopamine synthesis. One strategy to study copper has been to measure levels of cerulo$+amin (Cp), the copper-transport protein in the blood. Results of this type of study have been remarkably heterogeneous, often confounded by a number of factors. Over the past decade, it has become apparent that the primary physiological role for Cp is that of an iron ox&se. Surprisingly, patients with Wilson’s disease, characterized by low levels of Cp as well as copper deposition in various tissues, show no abnormality in iron metabolism. This interesting observation led to the discovery of a second, non-Cp iron oxidase, which has been named ferroxidase II (which is correspondingly increased in Wilson’s disease). Some of the variation that has been reported in plasma Cp levels in schizophrenia may be partially accounted for by changes in either absolute or relative amounts of ferroxidase II in these patients. Since levels of ferroxidase II have not been determined in schizophrenia, we undertook this prospective study of ten schizophrenic and eight normal control subjects. We have measured plasma levels of Cp (assayed by both phenylenediamine and iron oxidation), ferroxidase II, copper, iron, and total iron binding capacity. These results will hopefully clarify any role of copper in schizophrenia, by examining this important source of variation.
354 ACUTE ADMINISTRATION OF ALPRAZOLAM HAS NO EFFECT ON PLASMA HOMOVANILLIC ACID CONCENTRATION IN NORMAL SUBJECTS R. Kaminsky, Z. Zemishlany, T. Ryan, M. Davidson, K. Davis New York, NY Alprazolam has been suggested as an adjuvant to neuroleptic drugs in the treatment of schizophrenic patients. Although not without problems, most evidence still suggest that the neuroleptic therapeutic benefit is mediated by their effect on central dopaminergic neurotransmission. This study is an attempt to investigate whether alprazolam has also an effect on dopaminergic neurotransmission. Pharmacological perturbations of the central dopaminergic system have been shown to produce parallel changes in pHVA concentrations in animals and human subjects. Hence pHVA concentrations
Neurobiology of SchizophreniaII
BIOL PSYCHIATRY 1989;25:169A-384A
as well as with the delta (peak minus basal) GH response (r = .43; p = .03). The GH responses to TRH were unrelated to age, but were significantly higher among females. GH response to TRH is predominantly under cholinergic control. Negative symptoms in schizophrenia have recently been proposed to be related to cholinergic excess. Increased GH response to TRH may thus identify a subgroup within schizophrenia with cholinergic excess and negative symptoms. (Supported by NIMH Small Grant lR03MH43680-01 and MHCRC Seed Grant R139.)
353 A REEXAMINATION OF COPPER AND CERULOPLASMIN-LIKE ENZYMES IN SCHIZOPHRENIA Joan Kotun, Alan Douglas, Richard W. Topham, James H. Meador-Woodruff Ann Arbor, MI, and Richmond,
VA
Copper has been occasionally implicated in the pathogenesis of schizophrenia. This consideration has face validity, as copper is a cofactor for the activities of tyrosine hydroxylase and dopamine beta-hydroxylase, enzymes central to dopamine synthesis. One strategy to study copper has been to measure levels of cerulo$+amin (Cp), the copper-transport protein in the blood. Results of this type of study have been remarkably heterogeneous, often confounded by a number of factors. Over the past decade, it has become apparent that the primary physiological role for Cp is that of an iron ox&se. Surprisingly, patients with Wilson’s disease, characterized by low levels of Cp as well as copper deposition in various tissues, show no abnormality in iron metabolism. This interesting observation led to the discovery of a second, non-Cp iron oxidase, which has been named ferroxidase II (which is correspondingly increased in Wilson’s disease). Some of the variation that has been reported in plasma Cp levels in schizophrenia may be partially accounted for by changes in either absolute or relative amounts of ferroxidase II in these patients. Since levels of ferroxidase II have not been determined in schizophrenia, we undertook this prospective study of ten schizophrenic and eight normal control subjects. We have measured plasma levels of Cp (assayed by both phenylenediamine and iron oxidation), ferroxidase II, copper, iron, and total iron binding capacity. These results will hopefully clarify any role of copper in schizophrenia, by examining this important source of variation.
354 ACUTE ADMINISTRATION OF ALPRAZOLAM HAS NO EFFECT ON PLASMA HOMOVANILLIC ACID CONCENTRATION IN NORMAL SUBJECTS R. Kaminsky, Z. Zemishlany, T. Ryan, M. Davidson, K. Davis New York, NY Alprazolam has been suggested as an adjuvant to neuroleptic drugs in the treatment of schizophrenic patients. Although not without problems, most evidence still suggest that the neuroleptic therapeutic benefit is mediated by their effect on central dopaminergic neurotransmission. This study is an attempt to investigate whether alprazolam has also an effect on dopaminergic neurotransmission. Pharmacological perturbations of the central dopaminergic system have been shown to produce parallel changes in pHVA concentrations in animals and human subjects. Hence pHVA concentrations