Drug-naive Schizophrenic Patients Research Articles

SPEM impairment in drug-naive schizophrenic patients: Evidence for a trait marker

Smooth-pursuit eye movements (SPEM) were assessed in healthy subjects and in drug-naive, chronic, and residual schizophrenic patients. SPEM gain was found to be decreased in all the schizophrenic patients who also exhibited a significant increase in the rate of saccades. The frequency of square-wave jerks was the same in schizophrenic patients and normal controls, suggesting that the primary abnormality in schizophrenic patients was a low gain rather than a defect of the saccadic system. Patients were retested 1 month later, and stability of gain was high even in formerly drug-naive subjects who had been treated for 1 month with neuroleptic drugs. Altogether these results confirm the conclusions of most previous studies, extend them to drug-naive schizophrenic patients, and favor the hypothesis that SPEM impairment is a trait marker in schizophrenia.

Biogenic amine metabolites in plasma of drug-naive schizophrenic patients: Associations with symptomatology

The main metabolites of dopamine, noradrenaline, and serotonin, homovanillic acid, methoxyhydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA), were estimated in plasma of 20 drug-naive young male schizophrenic patients and 21 healthy controls. Although there were no significant differences between the two groups, multiple regression analysis revealed strong associations of the patients' 5-HIAA and MHPG plasma levels to their scores in the Brief Psychiatric Rating Scale items. 5-HIAA levels were mainly related positively to hostility and negatively to somatic concern, and MHPG positively to disorientation and negatively to emotional withdrawal and uncooperativeness. The results suggest that levels of the neurotransmitter metabolites may be related to certain psychological dysfunctions of the patients rather than to disease entities.

PET studies of D 1 and D 2 dopamine receptors in drug naive schizophrenic patients

PET studies of D 1 and D 2 dopamine receptors in drug naive schizophrenic patients

Decreased substance P- and increased calcitonin gene-related peptide immunoreactivities in the cerebrospinal fluid of drug-naive schizophrenic patients

Decreased substance P- and increased calcitonin gene-related peptide immunoreactivities in the cerebrospinal fluid of drug-naive schizophrenic patients

Event-related potentials in drug-naive schizophrenic patients

Decreased amplitudes of late components of event-related potentials (ERPs) in schizophrenia were ascribed to either psychotic features or to neuroleptic treatment of the patients. To rule out the drug effect, ERPs to stroboscopic stimuli were recorded in drug-naive schizophrenics and control subjects during no-task and simple-task sessions. Patients had significantly lower amplitudes of the late ERP components during both sessions, thus confirming similar results with treated schizophrenics. On the other hand, drug-naive patients did not differ from controls in the task-related relative facilitation of late ERP components. These results differ from findings of minimal ERP facilitation to task in treated schizophrenics. This discrepancy is discussed in the context of the effects of neuroleptic treatment and task demands on ERPs.

Comparison of the In Vitro Receptor Binding Properties of N‐[3H]Methylspiperone and [3H]Raclopride to Rat and Human Brain Membranes

The aim of the present investigation was to study and compare the in vitro binding properties of the two radioligands N-[3H]methylspiperone ([3H]NMSP) and [3H]raclopride. These compounds, labeled with 11C, have been extensively used in positron emission tomography studies on central dopamine D2 receptors in schizophrenic patients, although with diverging results. One study (using [11C]NMSP) showed an increased dopamine receptor density in drug-naive schizophrenic patients, whereas in another study (using [11C]raclopride) the density in schizophrenic patients was no different from that in healthy controls. In the present study, using in vitro binding techniques, the density of the binding sites was found to be similar irrespective of which of the two radioligands was used (20 fmol/mg wet weight in rat striatum and 10 fmol/mg in human putamen; the 5-hydroxytryptamine 2 receptors were blocked with 40 nM ketanserin). [3H]NMSP had a 10-fold higher affinity (KD, 0.3 nM in rat striatum and 0.2 nM in human putamen) than [3H]raclopride (KD, 2.1 nM in rat striatum and 3.9 nM in human putamen), which was consistent with the longer dissociation half-life of [3H]NMSP compared with [3H]raclopride (14.8 and 1.19 min, respectively). There was an approximate overall similarity between the inhibition constants for five dopamine antagonists, chlorpromazine, haloperidol, raclopride, remoxipride, and NMSP, when using either radioligand. The Ki values were, however, two- to four-fold higher when using [3H]NMSP as the radioligand, irrespective of inhibiting compound, except for chlorpromazine (and haloperidol in human putamen). NMSP was found to inhibit the binding of [3H]raclopride competitively, whereas raclopride inhibited the binding of [3H]NMSP both competitively and noncompetitively. This difference suggests that part of the binding site is exclusively used by NMSP and can only be allosterically interfered with by raclopride. It is proposed that [3H]NMSP binds to an additional set of accessory binding sites, presumably located more distantly from the agonist binding active site than the sites to which [3H]raclopride binds.

The platelet polyphosphoinositide system in Schizophrenia: The effects of neuroleptic treatment

Signal transduction, mediated by the thrombin-stimulated polyphosphoinositide (PPI) turnover was studied in platelets from 44 schizophrenic patients and 33 healthy volunteers. The stimulated generation of inositol phosphates in the schizophrenic group was significantly greater than that in the control group. There was a lack of correlation between this augmented response and a variety of clinical parameters. The response in 9 drug-naive schizophrenic patients was not significantly different from that in controls. The response was significantly augmented in patients receiving neuroleptic treatment and in patients who had been off neuroleptics for at least 4 months. These results indicate that neuroleptic treatment may produce a long-term modification of signal transduction via the PPI system. Further studies are required to elucidate the exact nature of this modification and to explore the possibility that this effect of the neuroleptics may provide a novel approach to understanding the neurochemistry of schizophrenia and to monitoring the neuroleptic treatment.

The application of positron emission tomography in psychiatry

Positron emission tomography (PET) is a new quantitative imaging technique making it possible to study brain function in both cortical and subcortical structures of the living human brain. In psychiatry, PET has mainly been used in the study of regional brain function or glucose metabolism in schizophrenic patients. These studies have demonstrated changes in regional metabolic rates indicating cerebral dysfunction in schizophrenia. PET allows the visualization and the regional analysis of neuroreceptor distribution and binding characteristics in the living human brain. The use of saturation analysis had made it possible to determine Bmax and Kd-values for D2-dopamine receptors in human subjects. Characteristics of D2-dopamine receptors in putamen were determined in drug naive schizophrenic patients and healthy volunteers. No differences between the groups were found. The application of PET for functional studies of the brain and the determination of neuroreceptor characteristics opens up new perspectives ...

PET scanning--a new tool in clinical psychopharmacology.

Quantitative methods were developed for the determination of dopamine and benzodiazepine receptor characteristics in the living human brain by positron emission tomography (PET). As ligands, the 11C-labelled analogues of the selective antagonists of dopamine receptor subtypes, SCH 23390 and raclopride, and the benzodiazepine antagonist, Ro 15-1788, were used. Tracer amounts of the ligands were injected intravenously into healthy volunteers and schizophrenic patients. The distribution of ligand indicated high densities of D1 as well as D2 dopamine receptors in the basal ganglia. Binding of [11C]-SCH 23390 was also significant in the neocortex where it was shown to represent binding to D1 as well as to 5-HT2 serotonin receptors. High densities of specific benzodiazepine receptor binding were obtained in most neocortical brain areas and in the cerebellum. Using saturation procedures, Bmax and Kd values could be obtained for D2 and benzodiazepine receptors. A comparison of D2 receptor densities in drug-naive schizophrenic patients and healthy volunteers demonstrated similar receptor characteristics in the major basal ganglia in these groups of subjects. Different chemical classes of conventional and unconventional antipsychotic drugs produced a 65%-85% occupancy of D2 receptors when given in clinical doses to schizophrenic patients. High does of diazepam produced a marked occupancy of benzodiazepine receptors during the first hours after oral administration to healthy volunteers. These in vivo methods should be valuable tools for the further analysis of the effects of drug on neuroreceptors in the living brain of neuropsychiatric patients.