Plasma catecholamine metabolites and treatment response at neuroleptic steady state

Bowers, Malcolm B.; Swigar, Mary E.; Jatlow, Peter; Hoffman, Frederick J.

doi:10.1016/0006-3223(89)90245-x

Cited by 63 publications

(47 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the baseline plasma HVA concentration and the initial increase occurring upon initiation of neuroleptic treatment both correlate with treatment response (Chang et al, 1988;Davila et al, 1988). Plasma HVA concentrations decrease with treatment in responders, whereas they are essentially unchanged in nonresponders (Bowers et al, 1984). Patients with predominantly negative schizophrenic symptoms show a lower initial increase in HVA concentrations and a flat subsequent decrease (Davila et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Subchronic Haloperidol Downregulates Dopamine Synthesis Capacity in the Brain of Schizophrenic Patients In Vivo

Gründer¹,

Vernaleken²,

Müller³

et al. 2002

Neuropsychopharmacol

103

View full text Add to dashboard Cite

The antipsychotic effect of neuroleptics cannot be attributed entirely to acute blockade of postsynaptic D 2 -like dopamine (DA) receptors, but may arise in conjunction with the delayed depolarization block of the presynaptic neurons and reduced DA synthesis capacity. Whereas the phenomenon of depolarization block is well established in animals, it is unknown if a similar phenomenon occurs in humans treated with neuroleptics. We hypothesized that haloperidol treatment should result in decreased DA synthesis capacity. We used 6-[ 18 F]fluoro-L-dopa (FDOPA) and positron emission tomography (PET) in conjunction with compartmental modeling to measure the relative activity of DOPA decarboxylase (DDC) (k D 3 , min À1 ) in the brain of nine unmedicated patients with schizophrenia, first in the untreated condition and again after treatment with haloperidol. Patients were administered psychometric rating scales at baseline and after treatment. Consistent with our hypothesis, there was a 25% decrease in the magnitude of k D 3 in both caudate and putamen following 5 weeks of haloperidol therapy. In addition, the magnitudes of k D 3 in cerebral cortex and thalamus were also decreased. Psychopathology as measured with standard rating scales improved significantly in all patients. The decrease of k D 3 in the thalamus was highly significantly correlated with the improvement of negative symptoms. Subchronic treatment with haloperidol decreased the activity of DDC in the brain of patients with schizophrenia. This observation is consistent with the hypothesis that the antipsychotic effect of chronic neuroleptic treatment is associated with a decrease in DA synthesis, reflecting a depolarization block of presynaptic DA neurons. We link an alteration in cerebral catecholamine metabolism in human brain with the therapeutic action of neuroleptic medication.

show abstract

Section: Discussionmentioning

confidence: 99%

Subchronic Haloperidol Downregulates Dopamine Synthesis Capacity in the Brain of Schizophrenic Patients In Vivo

Gründer¹,

Vernaleken²,

Müller³

et al. 2002

Neuropsychopharmacol

103

View full text Add to dashboard Cite

show abstract

“…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 response (Koreen et al 1994). In addition, several groups have studied both metabolites and found that while pretreatment plasma HVA predicts response, plasma MHPG does not (Mazure et al 1991;Bowers et al 1984Bowers et al , 1986Chang et al 1990).…”

mentioning

confidence: 99%

“…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).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

Kelley

Yao

Kammen

1999

Neuropsychopharmacology

View full text Add to dashboard Cite

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...

show abstract

“…These have included sex differences in premorbid history, social adjustment, obstetric complications, and perinatal factors, symptom expression, and plasma levels of drug (Goldstein 1995;Haas and Castle 1997;Seeman 1995;Szymanski 1996). With respect to the latter factor, female subjects have been reported to have higher neuroleptic levels than males while receiving fluphenazine decanoate (Simpson et al 1990) and clozapine (Szymanski et al 1995), and to have higher prolactin and homovanillic acid levels (Szymanski et al 1995;Bowers et al 1984;Meltzer et al 1983). Three facts, however, lessen the likelihood that pharmacokinetic factors alone underlie the PET differences observed.…”

Section: Possible Causes Of the Sex-specific Response To Neurolepticsmentioning

confidence: 99%

The Brain Metabolic Patterns of Clozapine- and Fluphenazine-Treated Female Patients with Schizophrenia Evidence of a Sex Effect

Cohen

Nordahl

Semple³

et al. 1999

Neuropsychopharmacology

View full text Add to dashboard Cite

The regional cerebral glucose metabolic rates of clozapinetreated and fluphenazine-treated women with schizophrenia and normal controls were obtained by positron emission tomography (PET) using [ 18 F]-2-fluoro-2-deoxy-D-glucose (FDG) asIn reviewing the literature, Goldstein (1995), concluded that, as compared to women, men with schizophrenia have an earlier age of onset, have a poorer premorbid history, and express symptoms differentially. Women tend to have a better prognosis, including fewer hospitalizations, shorter lengths of hospitalization, less psychopathology during remission, and superior social adjustment than men do. To account for the apparent better treatment response of women early in the disorder, a number of possibilities have been suggested (Seeman 1995), including a differential gender effect on the number and severity of prenatal complications, the age of onset of the disorder, the pretreatment duration of symptoms, as well as the possibility that neuroleptic treatment, itself, might act differentially in the sexes.For the most part, neuroimaging studies of neuroleptics have not been analyzed with respect to sex. Specifically, with respect to positron emission tomography From the Laboratory of Cerebral Metabolism (RMC, DP),

show abstract

Plasma catecholamine metabolites and treatment response at neuroleptic steady state

Cited by 63 publications

References 14 publications

Subchronic Haloperidol Downregulates Dopamine Synthesis Capacity in the Brain of Schizophrenic Patients In Vivo

Subchronic Haloperidol Downregulates Dopamine Synthesis Capacity in the Brain of Schizophrenic Patients In Vivo

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

The Brain Metabolic Patterns of Clozapine- and Fluphenazine-Treated Female Patients with Schizophrenia Evidence of a Sex Effect

Contact Info

Product

Resources

About