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Biomedical subjects

I Hanin

Publications and source records attributed to I Hanin.

At least 127 records · Page 7Linked to original sources

Electroencephalographic sleep, aging, and psychopathology: new data and state of the art.

Dysregulation of sleep-wake function is an important problem in both normal aging and in the two most common neuropsychiatric disorders of old age, depression and primary degenerative dementia. Since considerable overlap of symptoms in depression and dementing disorders (e.g., sleep disturbance, dysphoria, and cognitive impairment) often results in patients with a "mixed" syndrome, the development of specific, objective indicators as diagnostic markers, using electroencephalographic sleep patterns, was undertaken. Patients with dementia showed significantly less sleep continuity disturbance than patients with depression, less rapid eye movement activity, a different temporal distribution of REM density, and a longer REM latency. A discriminant function analysis using three variables (REM latency, REM density, and scaled sleep maintenance) correctly identified eight of nine depressives and six of nine dementing patients (78%) (k = 0.56, p = 0.008). These differences in REM sleep timing and density may be related to several factors: (i) defects in acetylcholine production in dementia; (ii) cholinergic mechanisms of REM sleep; and (iii) increased cholinergic induction of REM sleep in depression. The data suggest the utility of EEG sleep measures in the differential diagnosis of dementia and depression in the elderly.

Age Factors↗

Pre-treatment neurotransmitter metabolites and response to imipramine or amitriptyline treatment.

Preliminary data are presented from the NIMH Collaborative Study on the psychobiology of depression, biological studies, dealing with relationships between the pre-treatment levels of the neurotransmitter metabolites 3-methoxy-4-hydrophenethyleneglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) and the subsequent therapeutic response of depressed patients to imipramine or amitriptyline. Eighty-seven depressed patients were studied during pre-treatment and treatment periods. It has been found that (1) both low pre-treatment urinary MHPG and low CSF 5-HIAA values are associated with a response to imipramine; these relationships were not artefacts due to sex or age; (2) there were no significant relationships between pre-treatment urinary MHPG, CSF MHPG, 5-HIAA, or HVA values and the subsequent response, or failure of response, to amitriptyline; (3) there was not a bimodal distribution for CSF 5-HIAA. For both males and females, there were positive and statistically significant correlations between CSF MHPG and urinary MHPG; for the females, there were positive and significant correlations between both urinary and CSF MHPG and CSF 5-HIAA. The theoretical and practical implications of these findings are discussed.

Amitriptyline↗

EEG sleep and tricyclic blood levels: acute and chronic administration in depression.

An understanding of the effects of antidepressants on sleep can be aided by determinations of tricyclic plasma levels in relationship to sleep. Previous studies have been established that steady state plasma levels of amitriptyline relate to certain aspects of rapid eye movement (REM) sleep. The present investigations attempt to replicate the REM sleep/tricyclic plasma level relationships in a larger group of psychiatric hospitalized patients for depression and to study whether such relationships persist in a group of ambulatory patients studied longitudinally for 1 to 2 years. In an acute treatment study of 38 patients, REM sleep percent and average REM activity demonstrated a significant relationship with plasma levels, even when controlled for age and severity. The sleep-plasma level relationships seem more prominent with amitriptyline levels than with nortriptyline plasma levels. In a long term comparison of plasma levels, tricyclic plasma levels showed a significant correlation with REM latency, REM percent and average REM activity. Thus, it appears that changes in REM sleep such as REM suppression correlate significantly with tricyclic plasma levels both on a short (4 weeks) and long term basis (1 to 2 years). The implications of these findings are discussed.

Adult↗

Long-term central cholinergic hypofunction induced in mice by ethylcholine aziridinium ion (AF64A) in vivo.

Ethylcholine mustard aziridinium ion (AF64A), a neurotoxic choline analog, was evaluated for its interactions with the cholinergic system in mice. Parenterally administered AF64A was lethal (LD50 = 32.6 mumol/kg i.v.) and the lethality could be antagonized even at 8 LD50 doses by pretreatment with choline (714 mumol/kg i.p.) 2 min earlier. Mice that were protected by choline slowly developed neurological motor disturbances such as ataxia and hypokinesia, and lost weight. Intracerebroventricular administration of 65 nmol of AF64A was not acutely lethal, but produced similar delayed behavioral effects similar to those found after parenteral administration of AF64A. Seven days after a single injection of 65 nmol of AF64A i.c.v., there was a significant decrease in acetylcholine content in the cortex, striatum and hippocampus, but no change in choline levels. Acetylcholine content was still significantly reduced in the hippocampus at 3 weeks after this treatment. The reduction in activity of choline acetyltransferase and high-affinity choline transport paralleled the reduction in acetylcholine measured at 7 days post AF64A treatment, whereas muscarinic receptors in all three brain areas were unchanged. These combined data indicate that AF64A is a presynaptic chemical neurotoxin, capable of inducing a persistent deficiency in central cholinergic transmission.

Acetylcholine↗

The AF64a-treated mouse: possible model for central cholinergic hypofunction.

A loss in the number of functional, sodium ion-dependent, high-affinity choline transport sites was observed in the cortex and hippocampus of mice given an intracerebroventricular injection of 65 nanomoles of AF64A (ethylcholine mustard aziridinium ion) 3 days earlier. Such an effect was not observed in the striatum. This effect of AF64A represents a long-term neurochemical deficit at cholinergic nerve terminals in some brain regions which can lead to a persistent deficiency in central cholinergic transmission. The AF64A-treated animal may thus be a model for certain psychiatric or neurological disorders that appear to involve central cholinergic hypofunction.

Animals↗

Transmembrane distribution of lithium and sodium in erythrocytes of depressed patients.

In this investigation the intracellular: extracellular distribution of lithium across the erythrocyte membrane (RBC lithium distribution) was studied in vitro and in vivo. The in vitro studies were conducted by incubating cells from drug-free subjects in lithium-containing physiologic media. The in vivo studies consisted of measurements of plasma and erythrocyte (RBC) lithium and sodium concentrations during lithium carbonate treatment. Previous observations of a correlation between in vitro and in vivo RBC lithium distribution values were verified, and it was found that addition of 0.1 mM ouabain to the in vitro incubation media abolished this correlation. To examine the relationship between RBC lithium distribution and specific clinical features of depression, in vitro studies were conducted with RBCs from 20 depressed patients and 14 nondepressed control subjects. The patients were categorized as having bipolar (manic-depressive), unipolar, or secondary depressive disorders. After in vitro incubation with lithium for 48 h, the RBCs from bipolar patients had lithium distribution values that were similar to those observed in ouabain-treated cells. It appears that the lithium transport characteristics of RBCs of bipolar patients may differ from those of other depressed patients or nondepressed subjects.

Depression↗

RBC and plasma choline levels in control and depressed individuals: a critical evaluation.

Red blood cell (RBC) and plasma choline (Ch) were measured in 78 depressed, drug-free patients and in 23 normal, drug-free control subjects. RBC Ch levels displayed a huge variability among the patients, in contrast to those measured in normal controls. Plasma Ch levels, on the other hand, were more consistent within each group, and were correlated with age among the two populations studied. RBC Ch levels would appear to be independent of plasma Ch levels, and to be highly individualized and reproducible within each subject. A segment of the depressed population exhibited significantly higher RBC Ch levels than those seen in the normal control population. A clinical correlation of RBC and plasma Ch levels within the depressed population indicated that the patients with RBC Ch levels exceeding 35 nmole/ml might represent a diagnostically distinct subpopulation with specific clinical characteristics. Results presented here, although preliminary, suggest a role for RBC Ch as a biological marker in certain categories of depressive illness.

Adolescent↗

Biological component of the NIMH clinical research branch collaborative program on the psychobiology of depression: II. Methodology and data analysis.

A preceding paper has reviewed the history, background, and rationale for this collaborative effort exploring the biologic basis of the affective disorders. This paper details the "flow" of a subject through the experimental protocol, the instrumentation used to obtain the clinical and behavioural data, and the biologic methodologies employed in the analysis of the body fluids. Data management and analysis techniques developed for this study are also examined.

Adrenocorticotropic Hormone↗

Urinary MHPG and clinical response to amitriptyline in depressed patients.

The authors treated 18 rigorously diagnosed depressed patients with amitriptyline after baseline urine samples were collected for the measurement of 3-methoxy-4-hydroxphenylglycol (MHPG). Neither age nor severity of depression before treatment correlated with MHPG excretion. There was also no significant correlation between baseline MHPG excretion and clinical response at the end of at least 25 days' treatment with amitriptyline. The authors discuss the relevance of amitriptyline and nortriptyline plasma levels to MHPG and the noradrenergic/serotonergic theories of depression.

Adolescent↗