Neuroleptic-Induced Decrease in Plasma Homovanillic Acid and Antipsychotic Activity in Schizophrenic Patients

Abstract

Plasma-free homovanillic acid, a major metabolite of dopamine, was measured in chronically ill schizophrenic patients both before and during treatment with the antipsychotic phenothiazine, fluphenazine. Neuroleptic treatment was associated with a significant time-dependent decrease in plasma homovanillic acid from pretreatment values, which were significantly elevated when compared with those of age- and sex-matched healthy control subjects. Further, both the absolute concentrations as well as the neuroleptic-induced reductions in plasma homovanillic acid determined over 5 weeks of neuroleptic treatment were statistically significantly correlated with ratings of psychosis and improvement in psychosis, respectively. These findings suggest that the delayed effects of neuroleptic agents on presynaptic dopamine activity may more closely parallel their therapeutic actions than do their immediate effects in blocking postsynaptic dopamine receptors and that a decrease in dopamine "turnover" may be responsible for their antipsychotic effects.

Nonstereotyped Responding in Positive Schizotypy after a Single Dose of Levodopa

“…In fact, preselected and unselected schizotypal individuals, thought to be 'psychosis-prone' (Chapman et al, 1994;Kwapil et al, 1997), perform similar to patients with schizophrenia for cognitive (Gooding et al, 1999;Park, 1999), attentional (Sarkin et al, 1998;Mohr et al, 2003a), behavioral (Barnett and Corballis, 2002;Mohr et al, 2003b) and physiological (Klein et al, 1999;Pizzagalli et al, 2000) measures. Finally, alterations of dopaminergic responsivity may accompany the schizophrenia spectrum disorders in a continuous manner; the DA metabolite homovanillin acid (HVA) correlated with severity of positive symptoms in schizophrenia (Pickar et al, 1984;Davidson and Davis, 1988) and the extent of schizotypal personality disorder (Siever et al, 1991(Siever et al, , 1993. …”

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). …”

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

“…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.…”

“…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.…”

“…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 treatment that also parallels the decrease in psychosis (Davila et al 1988(Davila et al , 1995Duncan et al 1993), while others did not observe this effect (Pickar et al 1986).…”