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Biomedical subjects

S Potkin

Publications and source records attributed to S Potkin.

At least 19 recordsLinked to original sources
PubMed2000

Effects of temporal variability on p50 and the gating ratio in schizophrenia: a frequency domain adaptive filter single-trial analysis.

BACKGROUND: Deficits in attention and cognition are common in schizophrenia. Using an auditory dual-click paradigm, a number of studies have found that, compared with normal controls, patients with schizophrenia show impaired inhibition, or gating, of repeated stimulation as measured by the average P50 evoked response to the second click. Since responses to many trials are collected to study the average response, fluctuations in the timing of the P50 response from trial to trial may influence the differences observed. We present a computerized, objective procedure that evaluates temporal variability in brain responses of patients with schizophrenia. METHODS: Ten normal controls and 10 patients diagnosed with schizophrenia were studied using the dual-click procedure. For each single trial, the temporal shift in P50 that yielded the best alignment with the average P50 response was used to derive a measure of P50 temporal variability from trial to trial and to form P50 averages corrected for temporal variability. RESULTS: Patients with schizophrenia had significantly more temporal variability than normal controls. Correction for temporal variability in the P50 responses increased the size of P50 for both patients with schizophrenia and normal controls. Patients with schizophrenia had smaller P50 responses to the first click than controls and less inhibition to the second click before, but not after, correction for temporal variability. CONCLUSIONS: These findings suggest that temporal variability contributes significantly to the P50 response as measured using the gating procedure. The measure of temporal variability may provide a new index of inhibitory and attentional function in schizophrenia.

Acoustic Stimulation↗
PubMed1997

Differential labeling of dopamine and sigma sites by [3H]nemonapride and [3H]raclopride in postmortem human brains.

The difference between the binding of [3H]nemonapride and [3H]raclopride has been used to quantify dopamine D4 receptors in postmortem schizophrenic brain studies. Recent work, however, has suggested that at least part of the differential between [3H]nemonapride and [3H]raclopride binding may represent sigma rather than D4 receptor sites. We applied the nemonapride-raclopride subtraction method to postmortem, non-schizophrenic human striatum to examine the variation in dopaminergic receptor binding labeled by these ligands. Variation in sigma receptor binding labeled by [3H]nemonapride was studied in frontal cortex, striatum and cerebellum. Specific binding was defined by sulpiride (dopamine receptor ligand), PPAP (sigma receptor ligand) and haloperidol (mixed dopaminergic/sigma agent), respectively. Haloperidol defined a combination of sites, which were approximately the sum of the dopaminergic and sigma components defined by sulpiride and PPAP, respectively. Significant inter-individual variation in the amount of specific binding for dopaminergic and sigma receptor sites was observed. However, no significant nor consistent observation of striatal dopamine D4 receptors or D4-like binding sites was observed in the striatum even though two independent sets of tissues, with different dissections were used. The inconsistencies in some previous postmortem studies appear to be at least partially explained by the inclusion of both sigma and dopaminergic components in [3H]nemonapride binding and the inherent high inter-individual variability of the different components.

Adult↗
PubMed1996

New directions in the prevention and treatment of schizophrenia: a biological perspective.

Our current treatments for schizophrenia are, at best, palliative. With the exception of counseling those families with a known high risk for having schizophrenic offspring, no preventive measures are currently available. The not too distant future, however, promises to bring improvements in somatic treatments as well as the possible introduction of preventive measures. We are fully aware that current biological treatments work best when they are combined with psychosocial intervention, and expect that future biological treatments and preventions will also involve appropriate nonbiological considerations. Psychosocial treatments are covered elsewhere in this issue. Here we look at how modern genetics, pre- and perinatal factors, early and sustained intervention, and new medications are likely to decrease both the number of individuals with schizophrenia and the severity of the illness.

Antipsychotic Agents↗
PubMed1993

Olfactory memory in unmedicated schizophrenics.

Previous studies have indicated that schizophrenic patients have olfactory deficits. The question as to whether olfactory deficits are due to chronic effects of medication has not been addressed. This is the first paper to report that never-medicated schizophrenic patients also have olfactory deficits. Twenty four normal subjects and twenty unmedicated schizophrenic patients were examined with two tests of olfactory function: the University of Pennsylvania Smell Identification Test (UPSIT) and a match-to-sample olfactory memory test. Results indicated that schizophrenics did poorly on both the UPSIT and the olfactory match-to-sample memory test relative to sex and age-matched controls. ANCOVA showed that the deficit in performance on the olfactory match-to-sample test was still present even when the variance due to the UPSIT was taken out of the analysis. Deficits in olfactory identification and olfactory memory are consistent with the concept that schizophrenics have dysfunctional limbic systems.

Blood Glucose↗
PubMed1991

Activating tasks for the study of visual-spatial attention in ADHD children: a cognitive anatomic approach.

The clinical label attention deficit hyperactivity disorder (ADHD) suggests that this syndrome is a disorder of attention. However, the presumed attentional deficits have not been linked either to specific cognitive operations or to specific neural systems. To provide this link, theories of the cognitive anatomy of attention were used to generate hypotheses about specific visual-spatial attentional deficits in children with ADHD. A cued reaction-time test was used to assess covert and overt shifts of attention theoretically linked to two neuroanatomically defined attentional systems in the posterior and anterior parts of the human brain. The early, posterior-based covert shift of attention was found to be normal in ADHD children, but a later, anterior-based overt shift of attention was abnormal as reflected by a significant lateral difference in reaction time. This was interpreted as a failure to sustain focused attention.

Analysis of Variance↗
PubMed1990

Glucose metabolic rate in normals and schizophrenics during the Continuous Performance Test assessed by positron emission tomography.

Local cerebral uptake of glucose labelled with fluorine-18 was measured by positron emission tomography in 13 patients with schizophrenia and 37 right-handed volunteers. Patients received no medication for a minimum of 31 days and a mean of 30 weeks. The subjects were administered the labelled deoxyglucose just after the beginning of a 32-minute sequence of blurred numbers as visual stimuli for the Continuous Performance Test. In normal controls, task performance was associated with increases in glucose metabolic rate in the right frontal and right temporoparietal regions; occipital rates were unchanged. Patients with schizophrenia showed both absolutely and relatively reduced metabolic rates in the frontal cortex and in the temporoparietal regions compared with normal controls.

Adult↗
PubMed1988

Neuroleptic-induced hypothermia associated with amelioration of psychosis in schizophrenia.

Body temperature is a regulatory function of the hypothalamus. Recently, DeMet et al. (Society for Neuroscience Abstracts Vol 12, 1986) reported that apomorphine stimulation of dopamine autoreceptors caused a significant decrease in metabolic rate in the posterior heat-conserving area of the hypothalamus. The logical hypothesis to follow is that apomorphine administration should induce a decrement in body temperature; this in fact was demonstrated by Cutler et al. (Commun Psychopharmacol 3:375-382, 1979) in humans. It is well known that neuroleptics also disrupt thermoregulation (Clark: Neurosci Biobehav Rev 3:179-231, 1979) and affect dopamine autoreceptors. Therefore, eight chronic treatment-resistant schizophrenics underwent a 6-week single-blind trial of haloperidol and then a subsequent 6-week double-blind trial of clozapine. Both haloperidol and clozapine significantly lowered oral body temperatures relative to baseline washout temperatures. More interestingly, clozapine relative to haloperidol was found to induce a greater decrement in body temperature and was associated with greater clinical improvement. Possible confounding variables are discussed, as is the possible neurochemical basis for the amelioration of psychosis associated with hypothermia.

Adult↗
PubMed1985

Lower CSF level of dynorphin(1-8) immunoreactivity in schizophrenic patients.

Using a highly specific and sensitive radioimmunoassay for dynorphin(1-8) (D 1-8), and a singly blind test design, we measured D(1-8) immunoreactivity (ir D 1-8) in CSF of 35 first break cases of acute schizophrenic patients. All patients were free of psychotropic medication for at least one week before the study. Another 31 neurological patients suffered from cervical arthrosis, tumor, myelopathy etc. were studied as controls. The ir D(1-8) in CSF of schizophrenic patients were significantly lower than that of controls (91.8 +/- 5.6, means +/- S.E.M., and 131.9 +/- 6.8 fmol/ml CSF respectively, p less than 0.001).

Adolescent↗
PubMed1984

Phenylacetic acid excretion in schizophrenia and depression: the origins of PAA in man.

Urinary phenylacetic acid (PAA) excretion was found to be decreased in a group of chronic schizophrenic patients, particularly in a nonparanoid subtype. No significant change in PAA excretion was observed in a group of 21 unipolar depressed patients. Urinary PAA was studied following the administration of phenylethylamine, monoamine oxidase inhibitors, a dopa decarboxylase inhibitor, a low phenylalanine diet, and phenylalanine loads in several groups of psychiatric patients and normal volunteers. While Phenylethylamine ingestion increased urine PAA, inhibition of both phenylethylamine metabolism and synthesis failed to alter urine PAA. These studies suggest that urine PAA is primarily derived from phenylalanine transamination or pathways not involving monoamine oxidase or both. The observed decrease in PAA excretion in some schizophrenic patients may reflect an alteration in this pathway. The high phenylethylamine excretion previously reported in some chronic schizophrenic patients is not directly related to the observed low PAA excretion. Therefore measurement of urine PAA is not expected to be useful in assessing any phenylethylamine abnormalities in psychiatric disorders. The possible contribution of reduced phenylalanine transamination and its subsequent increased availability for the possible synthesis of phenylethylamine in schizophrenia is discussed.

Carbidopa↗
PubMed1981

Quantitative determination of immunoglobulins in CSF and plasma of chronic schizophrenic patients.

Immunoglobulins, IgG, IgA and IgM were quantified in cerebrospinal fluid (CSF) and plasma from chronic schizophrenic patients and controls using an immunofluorescent antibody technique. A generalized reduction in immunoglobulin levels was observed in the schizophrenic patients compared with controls. While this study supports other reports of abnormal immune functioning in schizophrenia, it failed to replicate previous findings of elevations in CSF IgG and elevations in serum IgA. The aetiology and significance of these findings are hypothesized but remain elusive.

Adult↗
PubMed1979

A correlation between platelet monoamine oxidase activity and plasma prolactin concentrations in man.

Increases in plasma prolactin concentrations produced by alpha-methyl-p-tyrosine, a catecholamine synthesis inhibitor, varied inversely with baseline platelet monoamine oxidase activity in 12 patients with chronic schizophrenia. In normal volunteers with low monoamine oxidase activity and in unmedicated patients with chronic schizophrenia, plasma prolactin concentrations varied directly with platelet monoamine oxidase activity. No such relationship was found in normal subjects with high platelet monoamine oxidase activity. These data suggest that platelet monoamine oxidase activity reflects monoaminergic activity in the tubero-infundibular system, which in turn affects plasma prolactin concentrations. This relationship may be important in patients with low platelet monoamine oxidase activity, such as some chronic schizophrenics.

Blood Platelets↗
PubMed1977

Inhibition of dopamine synthesis in chronic schizophrenia. Clinical ineffectiveness of metyrosine.

According to the dopamine (DA) hypothesis of schizophrenia, there is a functional excess of dopaminergic activity within unspecified areas of the brain in schizophrenic patients. As a clinical test of this hypothesis, we administered metyrosine for three weeks to symptomatic chronic male schizophrenic patients who were maintained on suboptimal doses of neuroleptic agents. Metyrosine inhibits tyrosine hydroxylase, the rate-limiting enzymatic step in the synthesis of DA. No clinical improvement was observed, using the National Institute of Mental Health Inpatient Behavioral Rating Scale or the Brief Psychiatric Rating Scale. Central inhibition of DA synthesis by metyrosine was suggested, however, by (1) the development of extrapyramidal side effects and (2) a significant increase in plasma prolactin concentrations. Plasma chlorpromazine concentrations remained unchanged during metyrosine treatment. There was, nevertheless, a significant improvement on the scores of the Wechsler Adult Intelligence Scale Comprehension subtest, which measures judgment and common sense. This finding suggests that DA may be involved in the regulation of subtle psychological processes. The results are discussed in light of the DA hypothesis of schizophrenia and previous reports suggesting that metyrosine potentiates the antipsychotic effect of neuroleptics in schizophrenia.

Adult↗