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Biomedical subjects

J W Newcomer

Publications and source records attributed to J W Newcomer.

36 records · Page 2Linked to original sources
PubMed1995

Platelet serotonin markers and depressive symptomatology.

Dysfunction of brain serotonergic symptoms may be a factor in the mood and behavioral disturbances associated with depression. Platelet serotonin measures represent indirect but easily obtainable indices of brain serotonin function. To examine the specificity of relationships between cognitive and vegetative symptom groupings and platelet serotonin measures, we assessed 35 depressed outpatients using the Hamilton Rating Scale for Depression and collected platelets after a minimum 3-week drug-free period. Platelets were also collected from 14 controls. The results showed that depressed patients had lower platelet serotonin (5-HT) uptake site density values than controls and that 5-HT uptake site density values were inversely correlated with the severity of cognitive symptoms of depression. Platelet 5-HT2 receptor density values were higher in depressed patients than controls, and there was a trend toward a direct correlation between the cognitive symptoms of depression and 5-HT2 receptor density values. Neither platelet measure showed any relationship with the severity of the vegetative symptoms of depression.

Adolescent↗
PubMed1994

Effects of raclopride treatment on plasma and CSF HVA: relationships with clinical improvement in male schizophrenics.

Thirty-two acutely psychotic, male schizophrenic patients received raclopride, at 2, 6, or 12 mg/day, or haloperidol, 15 mg/day for 4 weeks after randomized, double-blind assignment. Twenty-six patients, including 19 who had been assigned one of the three doses of raclopride, completed the study. Raclopride, particularly at 12 mg/day, increased CSF homovanillic acid (HVA) at 4 weeks, and plasma HVA at 2 days, of treatment. The clinical response to raclopride was significantly correlated with plasma raclopride concentrations and baseline plasma HVA concentrations. Although raclopride is a substituted benzamide with atypical properties in animals, these results suggest that the doses of raclopride required for clinical efficacy and elevation of clinical indices of brain dopamine turnover are similar.

Adult↗
PubMed1994

Chronic corticosterone treatment impairs spontaneous alternation behavior in rats.

The present study used behavioral and morphological measures to assess hippocampal integrity in adult male rats after 8 weeks of daily corticosterone (10 mg/kg) injections. Behavioral testing during the final week of treatment revealed that spontaneous alternation behavior, a behavioral marker of hippocampal damage, was reduced in experimental animals without influencing exploration. Physiological assessment indicated that steroid exposure produced functional changes characteristic of prolonged exposure to stress or elevated plasma corticosterone, i.e., lower body weight and thymic involution. However, hippocampal cell loss was not observed in experimental rats. The data suggest that prolonged elevation of plasma corticosterone may significantly disrupt a hippocampal-sensitive behavior without producing gross morphological changes.

Animals↗
PubMed1994

Are there neurochemical indicators of risk for schizophrenia?

The genetic predisposition for certain forms of schizophrenia may involve heritable abnormalities in the functioning of neurochemical systems that project to and modulate limbic brain structures. However, with regard to both dopaminergic and serotonergic systems, there is little evidence that either basal cerebrospinal markers or plasma markers predict increased risk for the development of schizophrenia. Either their validity as correlates of brain monoamine function is uncertain or they are highly dependent upon clinical state. Both (1) platelet and neuroendocrine markers of serotonergic function and (2) an individual's capacity to decrease plasma homovanillic acid concentrations following neuroleptic blockade appear to be less state dependent, and these are worthy of further study as markers of risk for the development of schizophrenia.

Dopamine↗
PubMed1994

Correlations between akathisia and residual psychopathology: a by-product of neuroleptic-induced dysphoria.

Patients developing neuroleptic-induced akathisia have been reported to show higher levels of psychopathology. We sought to replicate this finding and determine its symptom specificity. We confirmed a significant relationship between ratings of akathisia and total score on the Brief Psychiatric Rating Scale (BPRS) during both acute and maintenance neuroleptic treatment. Using stepwise regression models, BPRS anxious-depressive subscale scores were the strongest predictors of akathisia during both treatment conditions. Paranoid subscale scores predicted akathisia only during maintenance treatment. These results suggest that neuroleptic-induced dysphoria largely explains the relationship between akathisia and residual psychopathology during both acute and maintenance neuroleptic treatment.

Adult↗
PubMed1994

Glucocorticoid-induced impairment in declarative memory performance in adult humans.

Glucocorticoids (GCs) have a variety of effects on the brain including site-preferential, inhibitory effects on hippocampal neurons. In the case of dexamethasone (DEX), extended rather than single-dose treatment in vivo may be required for binding to brain rather than peripheral (e.g., pituitary) GC receptors and for maximizing other biologic effects in hippocampus (e.g., GC receptor downregulation, inhibition of glucose transport). Based on the contributory role of hippocampal neurons in declarative memory performance, we investigated the cognitive consequences of DEX treatment in normal adult human subjects, hypothesizing a decrease in declarative memory performance after extended but not overnight treatment. Double-blind, placebo-controlled treatment with DEX was given at 2300 hr for four consecutive days (0.5, 1, 1, 1 mg, respectively). Plasma sampling (0800 and 1600 hr) and cognitive testing (1600 hr) were performed on study days 0 (baseline), 1, and 4, and 7 d posttreatment. Repeated-measures ANOVA found a significant interaction between study day and treatment condition for correct recall during a paragraph recall task [F(3,51) = 3.52, p = 0.02]. DEX (n = 10) in comparison to placebo (n = 9) treatment decreased correct paragraph recall on study day 4 [F(1,17) = 5.01, p = 0.04] and study day 11 [F(1,17) = 5.82, p = 0.03], with the lowest level of performance occurring on day 4 followed by a return toward baseline performance level by day 11. In the placebo-treated subjects, correct paragraph recall improved over the course of treatment, consistent with practice.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Subcortical excitatory amino acid levels after acute and subchronic administration of typical and atypical neuroleptics.

The effects of three atypical neuroleptic compounds, clozapine, sulpiride, and (-)-3-(3-hydroxyphenyl)-N-n-propyl-piperidine ((-)-3-PPP) were compared to the effects of haloperidol and saline on excitatory amino acid levels in the rodent nucleus accumbens and corpus striatum after acute (1 day) and subchronic (28 days) treatment. Equivalent doses of each drug were determined by assessing their in vivo displacement of [3H]spiperone binding in the nucleus accumbens and corpus striatum. After acute treatment, all three atypical neuroleptics, but not haloperidol, produced a significant decrease in nucleus accumbens glutamate concentrations. Acute haloperidol treatment significantly elevated glutamate concentrations in the corpus striatum when compared to all three atypical drugs. After subchronic treatment, (-)-3-PPP significantly increased glutamate concentrations in the nucleus accumbens when compared to the effects of haloperidol and clozapine. There were no major between-group differences in glutamate levels after subchronic treatment in the corpus striatum. The effects of acute and subchronic neuroleptic administration on aspartate levels in the nucleus accumbens and corpus striatum were highly variable. These findings indicate that atypical and typical neuroleptics may alter subcortical excitatory amino acid levels in a site-specific manner.

Animals↗
PubMed1993

Subcortical dopamine and serotonin turnover during acute and subchronic administration of typical and atypical neuroleptics.

The effects of acute (1 day) and subchronic (28 days) treatment with three atypical antipsychotic drugs [clozapine, (+/-)-sulpiride and (-)-3-PPP] on dopamine and serotonin turnover in both the nucleus accumbens (NA) and corpus striatum (CS) of rodents was compared to haloperidol and saline treatment. The equivalent doses of all drugs were determined based upon their ability to compete in vivo for 3H-spiperone binding in the NA and CS. All three atypical drugs, compared to haloperidol, produced preferential elevations of dopamine turnover in the NA. Further, the development of tolerance of this effect was more apparent for the three atypical drugs than for haloperidol. Surprisingly, all three atypical drugs, but not haloperidol, produced changes in serotonin turnover, despite the fact that (+/-)-sulpiride and (-)-3-PPP have no known direct effects on brain serotonin systems. All three atypical drugs produced acute increases in serotonin turnover in both the NA and CS, followed by later diseases.

Animals↗
PubMed1993

Effects of hyperglycemia on memory and hormone levels in dementia of the Alzheimer type: a longitudinal study.

The effect of hyperglycemia on hormone levels, metabolite levels, and memory performance was examined in 22 subjects with very mild and mild probable dementia of the Alzheimer type (DAT) and in 12 normal elderly adults. Subjects were tested in 3 plasma glucose conditions (fasting baseline, 175 mg/dl, and 225 mg/dl) at initial and 18-month follow-up sessions. Initially, adults with very mild DAT showed memory facilitation and elevations in plasma insulin in the 225-mg/dl glucose condition relative to baseline. At follow-up, very mild DAT patients whose dementia had progressed showed significant decreases in insulin and hyperglycemic memory facilitation. Changes in basal insulin and cortisol levels over time were correlated with memory changes for DAT subjects. These results suggest that glucoregulatory abnormalities may contribute to the pathophysiology of DAT.

Aged↗
PubMed1992

Plasma prolactin and homovanillic acid as markers for psychopathology and abnormal movements during maintenance haloperidol treatment in male patients with schizophrenia.

Measurement of plasma prolactin (PRL) concentration and plasma homovanillic acid (HVA) concentration was performed in 24 patients with schizophrenia during maintenance haloperidol treatment. A significant inverse correlation was found between plasma PRL and ratings of both dyskinesia and thought disorder. Plasma PRL was also correlated with negative symptoms. No relationship was found between plasma HVA and any symptom grouping. Twelve patients received an apomorphine challenge; a trend toward a significant inverse relationship was found between baseline dyskinesia and apomorphine-induced decreases in plasma PRL. Plasma PRL and plasma HVA may reflect different elements of dopamine function in the central nervous system during maintenance treatment; plasma PRL may be the useful marker under these conditions.

Adult↗
PubMed1992

Plasma prolactin and homovanillic acid as markers for psychopathology and abnormal movements after neuroleptic dose decrease.

Plasma prolactin concentration (pPRL), plasma homovanillic acid concentration (pHVA), and symptomatology were measured in 24 male subjects with schizophrenia during maintenance haloperidol treatment. Fourteen subjects subsequently underwent 50 percent dose decreases under placebo-controlled, double-blind conditions. At baseline, a significant inverse correlation was found between pPRL and both tardive dyskinesia (TD) and "thinking disorder"; pPRL was directly correlated with negative symptoms. No such relationship was found with pHVA. In the patients who underwent a dose decrease, no relationship was found between baseline pPRL or pHVA and any clinical variable after the decrease. These data do not support the use of baseline pPRL or pHVA as markers of central dopamine function subsequent to a neuroleptic dose decrease.

Adult↗
PubMed1991

Left-handedness in male schizophrenic patients is associated with increased impairment on the Luria-Nebraska Neuropsychological Battery.

Several studies suggest increased mixed and left-handedness in schizophrenia. This is of interest as early cerebral injury can result in increased left-handedness and some investigations have suggested a role for early developmental insult (e.g., birth complications) in schizophrenia. We administered the Luria-Nebraska Neuropsychological Battery (LNNB) to 24 left-handed male schizophrenic patients and a separate group of 24 right-handed schizophrenic patients who were age and education matched to the left-handed patients. The test protocol also was administered to 15 left-handed non-psychiatric control subjects and 15 right-handed controls. Direct comparisons (t-test) of the left- to right-handed schizophrenics revealed that the left-handed patients showed significantly greater impairment on several LNNB measures sensitive to cognitive deficits in schizophrenia. There were no differences between left- and right-handed control subjects. A further 2 X 2 ANOVA pooling all subjects noted several significant interactions between handedness and diagnostic group. The findings suggest a unique interaction between left-handedness and neuropsychological impairment in schizophrenia and could support a relationship between left-handedness, early cerebral insult, and cognitive deficits.

Analysis of Variance↗
PubMed1991

Symptomatology and cognitive impairment associate independently with post-dexamethasone cortisol concentrations in unmedicated schizophrenic patients.

Serum cortisol concentrations were measured after dexamethasone administration (1 mg) in 21 neuroleptic-free schizophrenic inpatients. Patients were assessed using the Brief Psychiatric Rating Scale and a battery of cognitive tests. A significant correlation was found between negative symptoms and both 8:00 AM and 4:00 PM post-dexamethasone cortisol concentration (PDC). Cognitive impairment on several measures was also correlated with 8 AM PDC, but in an independent manner. Although positive and negative symptoms were unrelated, exploratory analysis revealed a significant inverse correlation between a positive symptom grouping and both 8:00 AM and 4:00 PM PDC.

Adult↗
PubMed1991

Clinical factors that may confound the assessment of drug efficacy.

The development of new chemical classes of psychotherapeutic drugs offers the potential for new patterns of drug efficacy as well as decreases in side effects. However, the determination of drug efficacy can be confounded by sample selection and outcome determination factors. The ability of selected clinical factors of both types to affect the outcome of antipsychotic drug trials is reviewed. Suggestions for future clinical drug trials are made.

Clinical Trials as Topic↗
PubMed1990

Distinguishing depression and negative symptoms in unmedicated patients with schizophrenia.

Depression can occur in schizophrenia but can be difficult to distinguish from negative symptoms of the illness. To evaluate whether concurrent use of the Hamilton Rating Scale for Depression (HRSD) and the Brief Psychiatric Rating Scale (BPRS) could successfully separate depression and negative symptoms, we examined ratings on 69 unmedicated schizophrenic inpatients. A classical BPRS depression subscale score correlated highly (rho = 0.80) with the HRSD total score. The classical BPRS "negative symptom" subscale score was unrelated to both the BPRS and HRSD depression summary measures. Among individual HRSD items, negative symptoms correlated only with work/activities and retardation. The findings suggest that negative and depressive symptoms may be assessed independently.

Adult↗
PubMedDate not supplied

NMDA receptor hypofunction model of schizophrenia.

Several decades of research attempting to explain schizophrenia in terms of the dopamine hyperactivity hypothesis have produced disappointing results. A new hypothesis focusing on hypofunction of the NMDA glutamate transmitter system is emerging as a potentially more promising concept. In this article, we present a version of the NMDA receptor hypofunction hypothesis that has evolved from our recent studies pertaining to the neurotoxic and psychotomimetic effects of PCP and related NMDA antagonist drugs. In this article, we examine this hypothesis in terms of its strengths and weaknesses, its therapeutic implications and ways in which it can be further tested.

Animals↗