Biomedical subjects

John G Csernansky

Publications and source records attributed to John G Csernansky.

45 records · Page 3Linked to original sources

PubMed2002

Abnormalities of thalamic volume and shape detected in fetally irradiated rhesus monkeys with high dimensional brain mapping.

BACKGROUND: Prior research has indicated neuroanatomical abnormalities of the thalamus in schizophrenia. To study the possible pathogenesis, an animal model of neurodevelopmental thalamic damage has been developed by applying low-dose radiation to rhesus monkeys in early gestation. Irradiated monkeys sacrificed as infants demonstrate neuronal losses in specific thalamic nuclei and decreases in cortical neuropil. METHODS: Magnetic resonance scans were collected in adult Rhesus monkeys exposed to irradiation during thalamic neurogenesis (E33-42), after thalamic neurogenesis (E70-81), and in nonirradiated control animals. High dimensional brain mapping was used to compare thalamic volumes and shape characteristics in the three groups of animals. RESULTS: Animals exposed to irradiation at E33-42 showed a significant bilateral loss of thalamic volumes (> 20%) compared with controls and with animals irradiated at E70-81 when total brain volume was used as a covariate in the analysis. Thalamic volume loss was associated with a nonuniform deformation of thalamic shape. CONCLUSIONS: A first-trimester, neurodevelopmental insult in the nonhuman primate during thalamic neurogenesis produces a complex pattern of thalamic volume loss and shape deformation in adulthood. Low-dose irradiation of the fetal primate may be useful for modeling key features of the pathology described in schizophrenic patients.

Animals↗

PubMed2002

A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia.

BACKGROUND: Prevention of relapse is a major goal of maintenance treatment in patients with psychotic disorders. We performed a long-term comparison of a newer, atypical antipsychotic drug, risperidone, and an older, conventional neuroleptic drug, haloperidol, in terms of the rate of relapse in patients with schizophrenia and schizoaffective disorder. METHODS: In a double-blind, prospective study at 40 sites, we randomly assigned adult outpatients in stable condition with chronic schizophrenia or schizoaffective disorder to receive treatment with flexible doses of either risperidone or haloperidol for a minimum of one year. RESULTS: Of the 397 patients who underwent randomization, data from 2 were excluded because they did not receive study medication; data from all 30 patients from one site were excluded by the sponsor, the Janssen Research Foundation, because of concern about the integrity of the data. The median duration of treatment was 364 days in the risperidone group and 238 days in the haloperidol group (P=0.02). Of the 177 patients assigned to risperidone and the 188 assigned to haloperidol who remained in the analysis, 44.1 percent and 52.7 percent, respectively, discontinued treatment for reasons other than relapse. The Kaplan-Meier estimate of the risk of relapse at the end of the study was 34 percent for the risperidone group and 60 percent for the haloperidol group (P<0.001); the risk ratio for relapse with haloperidol, from the Cox model, was 1.93 (95 percent confidence interval, 1.33 to 2.80; P<0.001). Early discontinuation of treatment for any reason was more frequent among haloperidol-treated patients (risk ratio, 1.52; 95 percent confidence interval, 1.18 to 1.96). Patients in the risperidone group had greater reductions in the mean severity of both psychotic symptoms and extrapyramidal side effects than those in the haloperidol group. CONCLUSIONS: Adult outpatients with clinically stable schizophrenia or schizoaffective disorder have a lower risk of relapse if they are treated with risperidone than if they are treated with haloperidol.

Adult↗

PubMed2002

Kainic acid lesions disrupt fear-mediated memory processing.

Previous research has shown that hippocampal lesions impair the expression of fear conditioning. This fear conditioning deficit may be due to memory impairment or a reduction in fear in lesioned animals. To address these possibilities, the authors examined unconditioned and conditioned fear in male Sprague-Dawley rats that had received intracerebroventricular (ICV) infusions of kainic acid (KA) 30 days prior to testing. Animals that had received bilateral ICV infusions of KA (1.0 microl of 0.8 mg/ml solution per side) exhibited cell loss that was primarily confined to the CA3 region of the dorsal hippocampus. Kainic acid lesions impaired contextual and cued fear conditioning but did not affect unconditioned fear in a light:dark test of anxiety. Moreover, animals with KA lesions did not habituate to the light:dark apparatus when tested over a 3-day period. These data suggest that decreases in fear conditioning produced by hippocampal lesions reflect a memory deficit and not a lack of fear.

Animals↗

PubMed2002

The effects of excitotoxic hippocampal lesions in rats on risperidone- and olanzapine-induced locomotor suppression.

Previous studies have shown that excitotoxic hippocampal lesions in rats attenuate the ability of different doses of haloperidol, but not of clozapine, to suppress locomotor activity. The purpose of the present study was to determine if kainic acid-induced hippocampal damage reduces the degree of locomotor suppression produced by two relatively newer antipsychotic drugs, risperidone and olanzapine. Young adult male rats received bilateral intracerebroventricular infusions of the excitotoxin, kainic acid (KA), or vehicle and were tested for locomotor responses to drug treatment 30 days later. Infusions of KA produced neuronal loss in the CA3 region of the dorsal hippocampus in every rat. As reported previously, KA lesions reduced the ability of haloperidol (0.35 mg/kg) to completely suppress the locomotor activity elicited by amphetamine (1.5 mg/kg) relative to the effect of haloperidol in non-lesioned controls. Lesioned animals treated with a moderate dose of risperidone (1.4 mg/kg) also exhibited significantly more locomotor activity after amphetamine treatment in comparison to control animals. A trend toward greater activity was also observed in the lesioned group relative to the control group after olanzapine (3.0 mg/kg) injection (p =.09, 2-tailed). The locomotor effects of lower and higher doses of risperidone and olanzapine were not altered by kainic acid lesions. These data suggest that the locomotor-suppressive effects of moderate doses of risperidone and, perhaps, olanzapine involve hippocampal neurons, but that higher doses of each drug can suppress activity in a hippocampal-independent manner.

Animals↗

PubMed2002

Working and long-term memory deficits in schizophrenia: is there a common prefrontal mechanism?

This study tested the hypothesis that dorsolateral prefrontal cortex deficits contribute to both working memory and long-term memory disturbances in schizophrenia. It also examined whether such deficits were more severe for verbal than nonverbal stimuli. Functional magnetic resonance imaging was used to assess cortical activation during performance of verbal and nonverbal versions of a working memory task and both encoding and recognition tasks in 38 individuals with schizophrenia and 48 healthy controls. Performance of both working memory and long-term memory tasks revealed disturbed dorsolateral prefrontal cortex activation in schizophrenia, although medial temporal deficits were also present. Some evidence was found for more severe cognitive and functional deficits with verbal than nonverbal stimuli, although these results were mixed.

Adult↗

PubMed2002

Hippocampal deformities in schizophrenia characterized by high dimensional brain mapping.

OBJECTIVE: Abnormalities of hippocampal structure have been reported in schizophrenia subjects. However, such abnormalities have been difficult to discriminate from normal neuroanatomical variation. High dimensional brain mapping, which utilizes probabilistic deformations of a neuroanatomical template, was used to characterize disease-related patterns of changes in hippocampal volume, shape, and asymmetry. METHOD: T(1)-weighted magnetic resonance scans were collected in 52 schizophrenia and 65 comparison subjects who were similar in age, gender, and parental socioeconomic status. The schizophrenia subjects were clinically stable at the time of assessment. RESULTS: Significant abnormalities of hippocampal shape and asymmetry (but not volume after total cerebral volume was included as a covariate) were found in the schizophrenia subjects. The pattern of shape abnormality suggested a neuroanatomical deformity of the head of the hippocampus, which contains neurons that project to the frontal cortex. The pattern of hippocampal asymmetry observed in the schizophrenia subjects suggested an exaggeration of the asymmetry pattern observed in the comparison subjects. No correlations were found between the magnitude of hippocampal shape and asymmetry abnormality and the severity of residual symptoms or duration of illness. CONCLUSIONS: Schizophrenia is associated with structural deformities of the hippocampus, which suggest a disturbance of the connections between the hippocampus and the frontal cortex. However, the magnitude of these deformities are not related to severity or duration of illness.

Adult↗

PubMed2002

Relapse and rehospitalisation rates in patients with schizophrenia: effects of second generation antipsychotics.

Recent studies suggest that the risk of relapse in patients with schizophrenia is approximately 3.5% per month. Predictors of more frequent relapses include poor compliance with antipsychotic drug treatment, severe residual psychopathology, poor insight into the illness and the need for treatment, comorbid substance abuse, and poor relationships between patients, families and care providers. Although conventional antipsychotic drugs, such as haloperidol and fluphenazine, are effective in preventing relapse, second generation antipsychotic drugs, such as clozapine, risperidone and olanzapine, appear to be superior in preventing relapse and improving the patient's quality of life. The development of adverse events can undermine treatment response and relapse prevention. Minimising adverse effects thus helps to improve treatment compliance and prevent relapse. Second generation antipsychotic drugs tend to have fewer adverse effects than conventional agents, especially pseudoparkinsonism and akathisia. The societal costs of treating patients with schizophrenia can be lessened by employing strategies that decrease relapse and the need for rehospitalisation, the most costly treatment alternative.

Antipsychotic Agents↗

PubMedDate not supplied

Relationships among cerebrospinal fluid biomarkers in dementia of the Alzheimer type.

Cerebrospinal fluid (CSF) contains proteins known to be involved in the pathogenesis of Alzheimer disease (AD), including amyloid-related proteins, tau protein and apolipoprotein E. While the CSF concentrations of these proteins have been compared in subjects with and without dementia of the Alzheimer type (DAT), they have not been simultaneously assessed in carefully staged DAT subjects and control subjects to examine correlations among them. In this study, CSF concentrations of soluble amyloid precursor protein (sAPP), two forms of beta-amyloid protein (Abeta and Abeta ), tau, and apolipoprotein E were assessed in subjects with (n = 33) and without (n = 11) DAT. Direct correlations were found between CSF concentrations of sAPP and tau and Abeta, and between apolipoprotein E and Abeta within the DAT subjects and within the combined group of DAT and control subjects. A weak inverse correlation was also found between CSF concentrations of tau and Abeta within the combined group of DAT and control subjects. Moreover, increased severity of dementia was correlated with increased CSF tau concentrations and decreased sAPP and Abeta concentrations. Increased CSF concentrations of tau significantly discriminated DAT and control subjects, as did the ratios of tau to Abeta and tau to Abeta(1-42).

Aged↗

PubMedDate not supplied

Correlations between antemortem hippocampal volume and postmortem neuropathology in AD subjects.

Antemortem measures of hippocampal volume have been used to distinguish subjects with and without probable Alzheimer disease (AD). However, relatively little information is available about how well such antemortem measures correlate with postmortem measures of disease in AD subjects. In this study, antemortem magnetic resonance scans were collected from 10 subjects with probable AD and 3 nondemented controls who later came to autopsy. Significant correlations were observed between antemortem hippocampal volumes and both dementia severity and the density of hippocampal neurofibrillary tangles at autopsy. Total cerebral volumes, in contrast, were significantly correlated with the density of hippocampal senile plaques. The data suggest that hippocampal volume assessed in living subjects with probable AD is both a good marker of dementia severity and of an underlying element of the AD disease process.

Aged↗