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J E Kleinman

Publications and source records attributed to J E Kleinman.

At least 127 records · Page 7Linked to original sources
PubMed1988

The neuropathology of schizophrenia.

Insofar as schizophrenia is a neuropsychiatric syndrome involving the brain, neuropathology is a promising, if not essential investigative approach. Although traditional neuropathology has yet to yield a pathognomonic lesion in schizophrenia, there have been no shortages of findings. Unfortunately, many of these findings have not only failed to be pathognomonic, but they have not been consistently replicated. Fortunately, newer neuropathological techniques, such as post-mortem neurochemistry, have resulted in findings among the most reproducible in schizophrenia research. Although one of these, increased dopamine receptors in the basal ganglia of schizophrenic patients, has been replicated many times, it suffers from doubts as to its clinical relevance. Are these increases in dopamine receptors primary to the illness or a side effect of the treatment? This article discusses the relevance of this finding, reviews other highlights of post-mortem neurochemistry and traditional neuropathology, and discusses new horizons such as autoradiography, immunocytochemistry, and neuronal morphometrics.

Brain↗
PubMed1988

Dementia praecox revisited. Age disorientation, mental status, and ventricular enlargement.

Thirty-nine patients with DSM-III diagnoses of schizophrenia were examined for age disorientation, an inability to produce one's correct chronological age upon request. Six patients were age-disoriented and demented (as defined by Mini-Mental State evaluation), while two patients had delusions concerning their age, but were not demented. Age-disoriented, demented patients had very large cerebral ventricles and very low Mini-Mental State scores. This group differed on the cognitive and neuroanatomic variables from other demented, but not age-disoriented, patients, as well as from non-demented patients who were age-oriented. The age-disoriented patients appeared to be at an extreme end of the dementia spectrum in schizophrenia.

Adult↗
PubMed1987

Dopamine receptor subtype imbalance in schizophrenia.

We have investigated the radioligand binding properties of D1 and D2 dopamine receptors in postmortem brains from schizophrenic patients. Consistent with previous reports, the schizophrenic population demonstrated a significant 56% increase in D2 dopamine receptor density. Importantly, the D1 dopamine receptor density was significantly reduced by 43%. These alterations in dopamine receptor densities resulted in a highly significant difference in the ratio of D2/D1 dopamine receptors between schizophrenic patients and controls. A correlation between D1 dopamine receptor density and age was apparent in the schizophrenic patients: D1 dopamine receptor density decreased markedly with age and the linear regressions of D1 dopamine receptor density versus age in both the controls and schizophrenic patients had similar slopes. These results may have clinical implications for the treatment of schizophrenia and tardive dyskinesia.

Adult↗
PubMed1987

Spontaneous asymmetric circling behavior in hemi-parkinsonism; a human equivalent of the lesioned-circling rodent behavior.

When induced experimentally in rodents, hemispheric asymmetry in basal ganglia dopamine results in spontaneous asymmetric circling toward the hemisphere with the lower level of dopamine. A similar asymmetry has long been thought to exist in the brains of hemi-Parkinsonian patients. Using an electronic turn counter, we demonstrated that, like unilaterally lesioned rats, and without being aware of it, five ambulating outpatients with hemi-Parkinson's disease exhibit spontaneous rotation toward the hemisphere containing less striatal dopaminergic activity.

Aged↗
PubMed1987

Central catecholamines, cognitive impairment, and affective state in elderly schizophrenics and controls.

Central catecholamine concentrations were determined in autopsy samples from older schizophrenic and control subjects for both the hypothalamus and the nucleus accumbens. The results of these analyses and demographic variables were regressed on antemortem measures of cognitive function and mood state. In the hypothalamus, there are significant direct relationships of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) with depressed mood, as measured by an adaptation of the Hamilton Rating Scale for depression. In the nucleus accumbens, dopamine (DA) and MHPG had significant inverse relationships with antemortem cognitive function, as measured by an adaptation of the Mini Mental State Exam. Results in this sample indicate that after controlling for age, the catecholamine concentrations accounted for approximately 50% of the variance in the antemortem measures of mood or cognition, depending on the loci measured.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

A postmortem study of the effect of chronic opiate abuse on psychotomimetic binding sites of human frontal cortex.

Membranes were prepared from area 8 of human frontal cortex harvested from five controls and five opiate addicts. Psychotomimetic binding sites were assayed using tritiated 1-(1-[2-thiethyl]cyclohexyl)piperidine ([3H]TCP) to label phencyclidine binding sites and 1,3-Di(2-[5-3H]tolyl)guanidine ([3H]DTG) to label the "haloperidol-sensitive sigma binding site." The results demonstrated no significant differences between the control and experimental groups, suggesting that in the region of the human brain sampled in this study, chronic abuse of opiates is not accompanied by alterations in psychotomimetic binding sites.

Adult↗
PubMed1987

Neurotransmitter amino acids in post-mortem brains of chronic schizophrenic patients.

Neurotransmitter amino acids were measured in post-mortem caudate nucleus, nucleus accumbens, frontal cortex, amygdala, and hypothalamus of chronic schizophrenic and normal control subjects. The concentrations of upsilon-aminobutyric acid (GABA), taurine, glycine-threonine, glutamate, aspartate, glutamine, tryptophan, and alanine were similar in both groups, with the exception of decreased GABA and tryptophan in the amygdala of the schizophrenic group. Strong positive correlations were obtained between the concentration of tryptophan, a putative agonal status marker of post-mortem brain tissue, and the concentration of GABA in all brain areas. When the GABA concentrations were adjusted for tryptophan concentrations in amygdala, the difference between the schizophrenic and control samples was no longer significant, suggesting that the original difference may have been due to different agonal or post-mortem changes in the tissues. There were, however, no significant correlations between GABA and post-mortem interval. The present results do not support the aminoacidergic hypotheses of chronic schizophrenia, although a GABA deficiency cannot be entirely excluded.

Adult↗
PubMed1987

[3H]GBR-12935 binding to the dopamine transporter is decreased in the caudate nucleus in Parkinson's disease.

The specific binding of [3H]GBR-12935 to membranes prepared from human caudate nucleus is saturable (Bmax 1.36 +/- 0.18 pmol/mg protein), sodium dependent and of high affinity (KD 2.34 +/- 0.18 nM). Freezing of tissue from rat brain, or refrigeration followed by freezing, results in a small but significant (less than or equal to 20%) decrease in specific [3H]GBR-12935 binding when compared to the binding observed in fresh (nonfrozen) tissue, and this decrease may account, in part, for the differences in specific binding between rat and human brain membranes. Despite small differences in binding site density between fresh and frozen tissue there is a good correlation (r = 0.98; p less than 0.01) between the potencies of a series of drugs in displacing specific [3H]GBR-12935 binding to human caudate membranes and rat striatum as well as in inhibiting dopamine uptake in rat striatal synaptosomes (r = 0.96; p less than 0.01). The specific binding of [3H]GBR-12935 to membranes prepared from the caudate nuclei of patients with Parkinson's disease is decreased compared to membranes prepared from age- and sex-matched controls. These data suggest that [3H]GBR-12935 binds in a sodium-dependent fashion to the dopamine transport complex in human brain and that specific binding is decreased by a pathological degeneration of dopaminergic neurons to the caudate nucleus.

Caudate Nucleus↗
PubMed1987

Relationship between tryptophan and serotonin concentrations in postmortem human brain.

The present study was planned to test a recent observation of positive correlation between tryptophan and 5-hydroxyindole concentrations in postmortem human hypothalamic samples. Four other brain areas were studied, but no significant correlations were observed between tryptophan and serotonin or 5-hydroxyindoleacetic acid concentrations, except in the nucleus accumbens samples of a suicide victim group. A possible in vivo correlation may have been obscured by postmortem changes. The use of tryptophan concentrations as an index for normalising postmortem brain serotonin data is not supported by the present results.

Brain↗
PubMed1986

Serotonin and 5-hydroxyindoleacetic acid in brains of suicide victims. Comparison in chronic schizophrenic patients with suicide as cause of death.

Serotonin (5-HT) and 5-hydroxyindoleacetic acid concentrations were determined in various brain areas of nonschizophrenic suicide victims, chronic schizophrenic patients with or without suicide as the cause of death, and normal control subjects without psychiatric or neurologic disorders. Serotonin concentrations in the basal ganglia were significantly elevated in suicide victims and chronic schizophrenic patients, as were 5-hydroxyindoleacetic acid concentrations in the occipital cortex. These differences were not specific to either patient group and may have been caused by neuroleptic or antidepressant treatment. A decreased 5-HT concentration was found in the hypothalamus of nonschizophrenic suicide victims. Among the chronic schizophrenic patients, there was no significant difference in the hypothalamic 5-HT content between the suicide victims and others, indicating that low 5-HT levels in the hypothalamus are not characteristic of schizophrenic patients who died of suicide.

Adolescent↗
PubMed1986

Postmortem neurochemistry in schizophrenia.

The renaissance in postmortem studies in schizophrenia is in full bloom. Although there is no shortage of findings, there have been significant problems with replications and interpretations. Regardless, the postmortem approach remains a valid and promising one. Thus far, it has allowed for the testing of a number of hypotheses involving catecholamines, indoleamines, and neuropeptides in schizophrenia. It is hoped that new approaches, such as autoradiography and automated cell counting, will add new dimensions to postmortem studies of schizophrenia. If these studies can be coupled with premortem exams of patients, perhaps new inroads can be made in the understanding and treatment of the schizophrenic syndrome.

Acetylcholine↗
PubMed1986

Alpha-adrenergic receptors and cyclic AMP production in a group of schizophrenic patients.

Alpha 2-adrenergic receptor function was measured in platelets from chronic schizophrenic patients and normal controls. The number of alpha 2-receptors was greater in patients' platelets, and the prostaglandin E1 (PGE1)-stimulated cyclic AMP (cAMP) production lower, when compared with the normal controls. The changes measured may occur only in the platelet, but if central nervous system neurons share with platelets these changes, one might speculate that an increase in the number of alpha 2-receptors and a decrease in cAMP production may relate to the psychopathology of schizophrenia.

Adult↗
PubMed1985

Neuropeptides in human brain--postmortem studies.

Four neuropeptides (substance P, methionine-enkephalin, neurotensin and cholecystokinin) were measured by radioimmunoassays in a number of brain regions of deceased patients with mental illnesses and controls. The most striking finding in these studies was that methionine-enkephalin concentrations in caudate nuclei of chronic paranoid schizophrenic patients were reduced relative to several control groups. Neuroleptics had no obvious effects on any of the four measured neuropeptides. These findings are not inconsistent with the hypothesis that methionine-enkephalin may be involved in some of the pathology of the schizophrenic syndrome.

Adult↗
PubMed1985

Postmortem central catecholamines and antemortem cognitive impairment in elderly schizophrenics and controls.

Central catecholamine concentrations were determined in autopsy brain samples from 19 elderly schizophrenic patients and controls. Data from the hypothalamus and nucleus accumbens demonstrate altered catecholamine metabolism associated with cognitive impairment in these subjects. Both loci show decrements of norepinephrine concentrations, while the nucleus accumbens samples also show increased dopamine, dihydroxyphenylacetic acid, and 3-methoxy-4-hydroxyphenylglycol concentrations associated with dementia in these subjects. The data argue for examination of catecholamine metabolism with respect to dementia in a broad range of elderly subjects.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Reduced haloperidol in the post-mortem brains of haloperidol-treated patients.

We measured the concentrations of haloperidol and its reduced alcohol metabolite in human post-mortem tissues with high-performance/liquid chromatography using electrochemical detection. Both haloperidol and reduced haloperidol were detected and quantified in the occipital cortex of nine schizophrenic patients with a history of haloperidol treatment, but not in six samples from nontreated subjects. Reduced haloperidol concentrations were below the detection limit of the assay in several tissues of rats and mice even after 10 days of haloperidol treatment. The results suggest that reduced haloperidol is present in the brains of haloperidol-treated patients at slightly higher concentrations than haloperidol itself. Further studies are warranted to establish the possible biological importance of this haloperidol metabolite.

Adult↗