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

Abstract

The objective of this study was to determine the association between the patterns of change in the dopaminergic metabolite plasma homovanillic acid (HVA), the noradrenergic metabolite The action of antipsychotic drugs on the dopamine system have led to many examinations of dopaminergic metabolites as possible markers for psychosis and antipsychotic response. However, it has also become clear that the noradrenergic system has extensive interactions with the dopamine system, and may also play a role in schizophrenia (Antelman and Caggiula 1977;Hornykiewicz 1982;van Kammen and Kelley 1991), and may play a key role in psychotic relapse (Ko et al., 1988;van Kammen et al. 1989van Kammen et al. , 1994van Kammen et al. , 1996a. 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.Address correspondence to: Mary Kelley, MS, GIM (13OU), VA Pittsburgh H.S., University Drive C, Pittsburgh, PA 15240.Received March 27, 1998; revised July 24, 1998; accepted July 28, 1998. 604 M.E. Kelley et al. N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 20 , NO . 6 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). Other studies of antipsychotic efficacy have focused on response status as the outcome measure and have shown that plasma HVA decreases were significant only in responders (Davidson et al. 1991a;Bowers et al. 1984;Chang et al. 1988;Van Putten et al. 1989). Some studies have shown that both plasma HVA and plasma MHPG decrease during neuroleptic treatment in those who respond favorably (Mazure et al. 1991;Bowers et al. 1984;Chang et al. 1990;Green et al. 1993).Higher pretreatment plasma HVA has been shown to predict better response (Mazure et al. 1991;Bowers et al. 1984Bowers et al. , 1986Chang et al. 1990;Duncan et al. 1993;Scheffer et al. 1994;van Kammen et al. 1996b), and faster time to r...

Relationship between Plasma Homovanillic Acid and Outcome in Patients with Psychosis Spectrum Disorders

“…Symptomatic improvement and reaching remission status was most pronounced in FEP patients, as repeatedly reported by other investigators [10,32]. These observations may be related with the individual's state of neuroplasticity, as reflected by the ability to alter pHVA levels, especially since lack of plasticity is hypothesized to be related with loss of antipsychotic efficacy [33,34], poor prognosis and chronic course of disease [12,35]. …”

Switching antipsychotics to aripiprazole or blonanserin and plasma monoamine metabolites levels in patients with schizophrenia

“…This is a non‐randomized open study, and pHVA of blonanserin group was higher than that of aripiprazole group at baseline, although the difference was not significant. Because pHVA is possible indicator of response to antipsychotics (Kelley et al ., ), there is possibility that blonanserin group had more responders to antipsychotics than aripiprazole group.…”

Near-infrared spectroscopy and plasma homovanillic acid levels in bipolar disorder: a case report

“…Because the HVA level change occurred in tandem with the manic symptoms during the clinical course, it is estimated that the manic episode in this case was associated with dopaminergic function. Plasma HVA levels have been considered as a possible indicator in the treatment of schizophrenia16,17 and bipolar disorder 18,19. Furthermore, because SSRIs act on dopaminergic and serotonergic neural systems,20 the increase in the plasma HVA level in this patient may have been induced by paroxetine.…”