Striatal D2 dopaminergic receptor status ascertained in vivo by positron emission tomography and 76Br-bromospiperone in untreated schizophrenics

Biochemical Findings of Negative Symptoms in Schizophrenia and Their Putative Relevance to Pharmacological Treatment

“…This finding has not been duplicated by other groups [84] and is not entirely consistent with the observation that dopamine metabolite concentrations in postmortem brains appear not to be different from controls [85]. Data on PET analysis of central dopamine D2 receptors in schizophrenic patients show that the dopamine D2 recep tor densities in the caudate nucleus may be higher in neuroleptic-naive schizophrenic patients compared to healthy subjects which points to receptor up-regulation and supports the notion of functionally lowered dopa mine availability [86], However, in other studies similar or only slightly increased dopamine D2 receptor densities were reported [87-89], Studies by Martinot et al [90,91] suggest that state-dependent fluctuations of the striatal D2 receptor density were predominated by elevation during the onset or exacerbation of psychotic symptoms, they were not elevated during the chronic course of schizo phrenia and did not fall with increasing age as seen in nor mal controls [91], The putatively decreased dopamine turnover in schizophrenic patients with negative symp toms could be stimulated with the dopamine agonist amphetamine; this was accompanied by an improvement in symptoms such as social withdrawal, blunting of affect and motor retardation [92][93][94][95], Stimulation of dopamine receptors by the dopamine agonist apomorphine is associated with an increase in growth hormone. This growth hormone response corre lated positively with thought disorder and was exagger ated in acute schizophrenia in that the largest growth hor mone response was seen in patients that were most psy chotic [96], On the other hand, the decrease in the apomorphine-stimulated release of growth hormone depend ed on the duration of the disease: it was lower in more chronic patients [97], in patients with poor premorbid functioning [96,98,99], and its outcome correlated with increased negative symptoms [100], Taken together, these data suggest diverging alterations in the dopaminergic systems in schizophrenic subgroups, i.e., a decrease in dopamine turnover during negative and an increase dur ing positive symptomatology.…”

Dose dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: a study using positron emission tomography and11C-raclopride

“…We suggest that this general approach, with a single "baseline" subject taking placebo, appears to be useful in preliminary dose finding studies. The extrapolation of the present results in normal subjects to guide clinical (phase II) studies in schizophrenics can be justified by recent studies (Farde et al 1990;Martinot et al 1990;Martinot et al 1991) which have failed to confirm the earlier finding (Wong et al 1986) of elevated D2 receptors in drug naive schizophrenics.…”

Serotonergic modulation of dopamine measured with [11C]raclopride and PET in normal human subjects

“…An initial application of these techniques to the study of neuropsychiatric disease was to address the dopamine hypothesis of schizophrenia, i.e., that schizophrenia is characterized by a hyperdopaminergic state (1)(2)(3). These studies yielded controversial results with respect to whether medication-naive schizophrenic patients showed an elevated number of dopamine D 2 receptors in the striatum, interpreted initially as being consistent with the hypothesized dopaminergic hyperactivity.…”