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Biomedical subjects

J G Csernansky

Publications and source records attributed to J G Csernansky.

At least 55 records · Page 3Linked to original sources
PubMed1996

CSF excitatory amino acids and severity of illness in Alzheimer's disease.

Researchers have proposed that increased release of excitatory amino acids (EAAs) is involved in the pathogenesis of dementia of the Alzheimer type (DAT), and CSF EAA concentrations have been measured to obtain evidence in support of this hypothesis. However, previous comparisons of CSF EAA concentrations in patients with DAT and in controls have yielded inconsistent results, perhaps because patient samples have been heterogeneous as to dementia severity. To determine whether there are changes in CSF concentrations of EAAs related to severity of illness in patients with DAT, we measured CSF concentrations of glutamate, aspartate, and taurine in 32 subjects with DAT, in whom we also assessed the severity of illness using clinical and neuropsychological measures, and 11 age-matched controls. The results suggested that increased CSF aspartate and glutamate concentrations, as well as decreased taurine concentrations, may occur in some persons with more advanced symptoms of DAT.

Aged↗
PubMed1995

Platelet paroxetine binding in major depressive disorder with and without comorbid obsessive-compulsive disorder.

Platelet 3H-paroxetine binding measures were compared in three age-matched groups each containing 11 individuals: a group with DSM-III-R major depressive disorder (MDD) and comorbid obsessive-compulsive disorder (OCD), a group with DSM-III-R MDD alone, and a psychiatrically screened normal comparison group. No differences were found between groups in Bmax values. The patients with MDD only were found to have significantly higher Kd values than either the group with comorbid OCD or the normal subjects. No significant correlations were found between binding measures and either depressive or OCD symptoms. Our data suggest that inconsistencies remain in the literature on 3H-imipramine binding in OCD and that a variety of confounding factors may explain them. Duration of illness, for example, may be one such factor as decreases in uptake site number tend to dissipate with longer duration of illness.

Adult↗
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↗
PubMed1995

Kainic acid decreases hippocampal neuronal number and increases dopamine receptor binding in the nucleus accumbens: an animal model of schizophrenia.

Intracerebroventricular (i.c.v.) administration of kainic acid (KA) produces graded neuronal loss in the hippocampus and other regions of the medial temporal lobe. Many of these brain regions send excitatory projections to the nucleus accumbens, a dopaminergic brain area implicated in psychotomimetic and antipsychotic drug action. In the present study, neurochemical function in the nucleus accumbens and anterior caudate-putamen was examined one week after i.c.v. administration of 1.5, 4.5, or 6.6 nmol of KA. As expected, i.c.v. KA produced dose-dependent neuronal loss in the dorsal and ventral hippocampus. Extrahippocampal neuronal loss was also observed in the thalamus and piriform cortex in some of the KA-treated rats. While ambient levels of dopamine turnover and excitatory amino acids in the nucleus accumbens were unaltered by KA, administration of the highest KA dose elevated [3H]spiperone binding exclusively in the accumbens. Finally, behavioral hyperactivity was observed in KA-treated rats over a five-week period following i.c.v. administration. The pattern of neuronal loss, receptor upregulation, and behavioral hyperactivity found after i.c.v. KA administration may provide a useful animal model of the limbic neuropathology and neurochemical dysfunction associated with schizophrenia.

Animals↗
PubMed1995

Platelet binding characteristics distinguish placebo responders from nonresponders in depression.

To determine whether there are characteristics distinguishing placebo responders from nonresponders, we studied 37 outpatients meeting DSM-III-R criteria for depression who were enrolled in controlled drug trials and 14 control subjects. Clinical data and blood samples were collected on admission and after a 7- to 10-day placebo washout. All patients experiencing a 40% drop in the Hamilton Rating Scale for Depression (HRSD) at the time of the second evaluation were considered placebo responders. There were no statistically significant differences between the two groups in clinical variables. Platelet markers distinguished the groups: Most notably, placebo nonresponders had the lowest 5-HT uptake site density values, placebo responders had intermediate values, and normal controls had the highest values. Placebo responders and placebo nonresponders had higher 5-HT uptake affinity values. No significant differences were observed among the groups in platelet 5-HT2 receptor site density or affinity values. These results suggest that platelet serotonin characteristics, but not common clinical characteristics, may distinguish depressed patients who do and do not respond to placebo.

Adult↗
PubMed1994

ERPs in schizophrenia: effects of antipsychotic medication.

Thirty unmedicated schizophrenics were compared to 29 age-matched controls on auditory and visual event-related brain potential (ERP) paradigms. Twenty-one of these patients were tested again after 1 week on placebo and after 4 weeks on antipsychotic medication. Before treatment, N1, N2, and P3 components of the auditory ERP were smaller in the schizophrenics than in the controls. Although visual N2 was smaller in schizophrenics, visual P3 was not. In spite of significant clinical improvement with antipsychotic treatment, amplitudes of auditory and visual N1, N2, and P3 were not significantly changed. Higher blood levels of antipsychotic medication were related to reductions in auditory P3 latency, however. In addition, higher levels of cerebrospinal fluid (CSF) MHPG (methoxyhydroxyphenylglycol) were associated with larger auditory N1s and larger auditory and visual P3s, suggesting an influence of arousal on these components in schizophrenics. In spite of this influence, reduction of the auditory P3 in schizophrenia is an enduring trait of the disease, which is not affected by antipsychotic medication or clinical improvement.

Adult↗
PubMed1994

Volumetric MRI assessment of temporal lobe structures in schizophrenia.

This magnetic resonance imaging (MRI) study was designed to investigate whether patients with schizophrenia have focal or lateralized deficits in the volumes of temporal lobe structures. Estimated volumes of the temporal lobes, hippocampi, superior temporal gyri, lateral ventricles, third ventricle, temporal horns of the lateral ventricles, and a frontal-parietal reference area (FPRA) were quantified for each hemisphere. The schizophrenic group had less gray matter (GM) in the temporal lobes and the FPRA relative to controls. Ventricular volumes were significantly larger in the schizophrenic group, as was cerebrospinal fluid (CSF) volume for temporal lobe sulci. No significant differences in hippocampal volumes emerged between groups. The magnitude of GM deficit was not greater in the temporal lobes relative to the FPRA. These results confirm the presence of bilateral GM volume deficits of the temporal lobes in schizophrenia but do not support the hypothesis that structural changes preferentially affect the temporal lobes or the left cerebral hemisphere.

Adult↗
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

The effect of chronic alprazolam on sleep and bioamine metabolites in depression.

Alprazolam administered for 43 days in doses of 6 to 10 mg/day had an antidepressant effect in four of nine depressed patients. Decreases in slow wave sleep, increases in rapid eye movement (REM) latency, and decreases in REM minutes and percent and REM sleep eye movements were found in the group as a whole. The drug had a general hypnotic effect with a trend toward increased total sleep time. Nonsignificant changes in the concentrations of 3-methyl-4-hydroxyphenylglycol and homovanillic acid in the cerebrospinal fluid (CSF) were qualitatively similar to those found after treatment with tricyclic antidepressant drugs; however, only the larger decreases in CSF 5-hydroxyindoleacetic acid achieved statistical significance. Baseline sleep and CSF metabolites and changes in these measures on drug did not predict the therapeutic effects of alprazolam.

Adult↗
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

Mianserin-induced up-regulation of serotonin receptors on normal human platelets in vivo.

The antidepressant, mianserin, is a serotonin receptor (5-HT2) antagonist and produces down-regulation of 5-HT2 and 5-HT1c receptors in the cerebral cortex of rats. In preparation for testing the validity of platelets as a model system for changes in 5-HT2 receptors during antidepressant drug treatment, mianserin (40 mg daily), was given to five human volunteers for five days, and platelets were collected on days 0, 1, 6, and 8. 5-HT2 receptor affinity and density were measured by specific binding of 125I-LSD, with and without an excess of spiperone. 5-HT uptake site affinity and density were determined by 3H-paroxetine binding, with and without an excess of fluoxetine. Platelet serotonin content was measured using high pressure liquid chromatography and electrochemical detention. Platelet 5-HT2 receptor density was increased and the ligand affinity was decreased during mianserin administration. In contrast, platelet 5-HT content was not altered significantly by mianserin administration, nor was platelet uptake site density and ligand affinity.

Analysis of Variance↗
PubMed1993

Abnormalities of serotonin metabolism and nonpsychotic psychiatric disorders.

Abnormalities of brain serotonin (5-hydroxytryptamine; 5-HT) metabolism have been proposed as the neurobiological basis of a vulnerability to depression and of a long-standing tendency toward impulsivity and aggression. Results from studies that have employed a variety of 5-HT measures, including the assessment of cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations, 5-HT uptake site densities, and 5-HT2 receptor densities in brain tissue and on platelets, and prolactin increases following fenfluramine administration, provide support for these two hypotheses. The goal of future research should be to better define the pathophysiological role of 5-HT dysfunction for both mood instability and impulsivity, in the service of developing improved treatments for these psychopathological conditions.

Brain↗