Studies of Catecholamine Metabolism in Schizophrenia/Psychosis-I

Abstract

Acutely psychotic schizophrenic patients not taking tmtipsychotic medications and control subjects were studied before and during treatment with debrisoquin (DBQ), an inhibitor of monoamine oxidase, which does not penetrate into brain. Homovanillic acid (HV A) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in plasma, urine, and cerebrospinal fluid ((SF). Significant differences between patients and control subjects were more easily discerned during treatment with DBQ. In patients, HVA was increased in plasma but not in urine or CSF, although MHPG was increased in all three fluids. There were many significant correlations between plasma MHPG and HV A levels and clinical ratings of psychoticism. Plasma MHPG correlated positively with both the severity of positive and negative symptoms and plasma HV A correlated only with positive symptom severity. These data suggest that both dopamine and norepinephrine (NE) metabolism are disturbed in acutely psychotic schizophrenic patients; disturbed NE metabolism may relate to negative symptoms as well. [Neuropsychopharmacology 8:97-109, 1993J by the receptor blockade (Carlsson and Lindqvist 1963).In the aggregate, these initial and subsequent basic neu ropsychopharmacologic studies have led to the ''DA hy pothesis of schizophrenia or psychosis," which suggests that schizophrenia/psychosis is associated with either an increase in central nervous system (CNS) DA release or an increase in DA receptor sensitivity (for recent reviews see Davis et al. 1991;Seeman et al. 1987). Sub

Plasma Catecholamine Metabolites as Markers for Psychosis and Antipsychotic Response in Schizophrenia

“…Samples were stored at Ϫ 80 Њ C until the time of the assay. Patients were not treated with debrisoquin, which has been shown to decrease the peripheral contribution to plasma HVA (Maas et al 1988(Maas et al , 1993Swann et al 1980;Davidson et al 1987a;Kopin et al 1988;Duncan et al 1993). However, the low-monoamine diet, minimization of physical activity, and fasting prior to the blood draw used in this study has been shown to reduce statistical effects on plasma HVA levels (Davidson et al 1987b).…”

“…Interactions between the two systems have been well studied in the CSF and plasma of schizophrenic patients through their respective metabolites: the dopamine metabolite homovanillic acid (HVA) and the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG). Plasma HVA has been shown to reflect central or brain dopamine activity through studies in animals and humans (Bacopoulos et al 1979;Kendler et al 1982;Maas et al 1993;Lambert et al 1993;Amin et al 1992), indicating that 11-35% of plasma HVA comes from the brain.Several studies of schizophrenia have noted that the behavioral response to antipsychotic drugs (i.e., a decrease in psychosis levels) parallels a decrease in plasma HVA levels in schizophrenic patients over time (Pickar et al 1984(Pickar et al , 1986Davidson and Davis 1988;Davila et al 1988;Mazure et al 1991;Sharma et al 1989). Some studies have reported an initial increase in plasma HVA in the first week of antipsychotic drug From the VA Pittsburgh Healthcare System (MEK, JKY, DPvK), Pittsburgh, Pennsylvania; and Western Psychiatric Institute and Clinic (JKY, DPvK), University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania.…”

“…Interactions between the two systems have been well studied in the CSF and plasma of schizophrenic patients through their respective metabolites: the dopamine metabolite homovanillic acid (HVA) and the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG). Plasma HVA has been shown to reflect central or brain dopamine activity through studies in animals and humans (Bacopoulos et al 1979;Kendler et al 1982;Maas et al 1993;Lambert et al 1993;Amin et al 1992), indicating that 11-35% of plasma HVA comes from the brain.…”

Differential Effects of Mental Stress on Plasma Homovanillic Acid in Schizophrenia and Normal Controls

“…Despite some argument (Kopin et al 1988;Lambert et al 1993;Maas et al 1988), several lines of investigations have focused on plasma levels of homovanillic acid (pHVA), a major metabolite of DA, for the study of DA-related mental disorders such as schizophrenia based on the assumption that dysfunction in central dopaminergic activity is, to some extent, reflected in this peripheral measure (see Friedhoff and Amin 1997 for review). While conflicting results have been reported regarding differences in pHVA levels between patients with schizophrenia and control subjects (Doran et al 1985;Koreen et al 1994;Maas et al 1993;Pickar et al 1984;Steinberg et al 1993;Sumiyoshi et al 1997a;Whelton et al 1993), there has been accumulated evidence for the association between pHVA levels in schizophrenia and the outcome of neuroleptic treatment (Akiyama et al 1995;Chang et al 1993;Davis et al 1985;Garver et al 1997;Green et al 1993;Nagaoka et al 1997;Sumiyoshi et al 1997b). …”

The Myth of Panic Spontaneity: Consideration of Behavioral and Neurochemical Sensitization

“…Notably, positive symptoms of schizophrenia are associated with social and agoraphobic fear [161]. It should be underscored that negative symptoms of schizophrenia such as poverty of speech, flattened affect and psychomotor retardation are not associated with hypersensitivity of mesocorticolimbic DA activity (see [195] for review) or panic. It should be considered that mesocorticolimbic hypersensitivity might follow from the chronic neuroleptic regimens employed to attenuate delusions and hallucinations [196].…”