Biomedical subjects
Publications and source records attributed to J C Gillin.
Acute pretreatment with either a Type A monoamine oxidase inhibitor (MAOI), clorgyline, or a Type B MAOI, pargyline, markedly reduced the dose of phenylethylamine (PEA) required to produce checking and a variety of other behavioral changes in rhesus monkeys. Doses of PEA (5 or 10 mg/kg) which previously were without effect, now produced significant behavioral changes in pretreatment animals.
The sleep of six Tourette patients (drug-free and while taking haloperidol was compared with that of nine normal volunteers. The untreated patients had 30% less delta sleep, which returned to values indistinguishable from those of volunteers when they received haloperidol.
The hypotensive drug clonidine, which stimulates central alpha-adrenergic receptors, was administered to psychiatric patients in a preliminary double-blind study. Two schizophrenic patients became more agitated and aggressive during the trial. The drug showed some antidepressant effects in three of five depressed patients. Clonidine withdrawal appeared to potentiate symptoms in a manic patient. Drug treatment reduced blood pressure and rapid eye movement sleep. Interpretation of behavioral effects of clonidine is limited by uncertainty about the balance of its pre- and postsynaptic effects.
Human growth hormone and saline were administered for one night each to normal volunteers in a cross-over study. A dose of 2 units im given 15 min before bedtime had no effect on sleep EEG parameters. In contrast, 5 units resulted in a 19% decrease in slow-wave sleep (p < 0.01) and a 13% increase in REM sleep (p < 0.05). Neither doe, when given during daytime, affected tests of affect or serial learning.
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The effects of a single night of total sleep deprivation were observed in 16 primary depressed patients. Responders to treatment were rated as significantly more depressed and revealed a more "depressed" EEG sleep pattern prior to sleep deprivation than did nonresponders. Following sleep deprivation, patients who improved experienced a rebound in REM sleep during the second night of recovery sleep.
The role of cholinergic mechanisms in the regulation of CNS functions was studied in normal humans. The purpose was to develop in vivo pharmacological techniques to assess central neurotransmitter activity in normals and apply them in primary affective illness and other neuropsychiatric conditions. Central cholinergic stimulation by cholinomimetics induced rapid eye movement (REM) sleep, dreaming, cortical arousal, and accelerated the REM cycle. Effects on memory included enhancement of serial learning, short-term consolidation of low-imagery words, and retrieval of clustered information. Analgesia and reduction of the P100 component of visual EEG evoked responses were also noted after physostigmine. Using the induction of REM sleep by arecoline as a "marker" of central cholinergic functioning, it was possible to (i) demonstrate the phenomenon of pharmacological denervation supersensitivity in normal humans after pretreatment with scopolamine, and (ii) demonstrate a significantly faster REM induction by arecoline in two groups of patients with primary affective illness (remitted and depressed) compared to normals. Rapid REM induction was found, not only in remitted patients who were drug-free for 2 weeks, but in patients who had never received somatic therapy. Pretreatment with scopolamine on three consecutive mornings also induced sleep changes at night in normals similar to several sleep abnormalities reported in primary affective illness. This was confirmed by a multivariate discriminate analysis program, which had previously been shown to separate depressed patients, insomniacs, and normals. On the basis of these data, it is proposed that cholinergic abnormalities may be present in primary affective illness during both the ill and the well states.
Repeated electroconvulsive shocks (ECS) cause an increase of [met5]-enkephalin (ME) content in hypothalamus and some limbic areas such as n. accumbens, septum and amygdala. The temporal characteristics of this increase resemble the time course of the clinical effects of electroconvulsive therapy (ECT). Single shock failed to change the ME content in any part of the brain. After 6 daily shocks ME content increases by 60% in hypothalamus and maximal effect (100% increase) was obtained after 10 daily shocks. The increase of ME content persists 6 days after the termination of ECS. Subconvulsive shocks failed to alter the content of ME in all the brain gions determined. When the seizure induced by ECS was prevented by pretreatment with an anesthetic dose of phenobarbital, the ECS-induced increase in hypothalamic and septal ME content was also blocked. beta-Endorphin content of hypothalamus remained unchanged after repeated ECS despite a two-fold increase in the ME content in the same region. These observations indicate that the time constant for the increase in ME content induced by ECS resembles the time constant for the appearance of the clinical benefits by ECT and may give credence to the possibility that the ME increase may participate in the antidepressive action of ECS.
Sleep in depressed patients resembles sleep in normal subjects whose circadian rhythms of temperature and rapid-eye-movement sleep are phase-advanced (shifted earlier) relative to their sleep schedules. If this analogy is relevant to the pathophysiology of depressive illness, advancing the time of sleep and awakening should temporarily compensate for the abnormal timing of depressed patients' circadian rhythms. Four of seven manic-depressive patients studied longitudinally spontaneously advanced their times of awakening (activity onset) as they emerged from the depressive phase of their illness. In a phase-shift experiment, a depressed manic-depressive woman was twice brought out of depression for 2 weeks by advancing her sleep period so that she went to sleep and arose 6 hours earlier than usual. The antidepressant effect of the procedure was temporary and similar in duration to circadian desynchronization induced by jet lag in healthy subjects. This result supports the hypothesis that abnormalities of sleep patterns in some types of depression are due to abnormal internal phase relationships of circadian rhythms.
Increases in plasma prolactin concentrations produced by alpha-methyl-p-tyrosine, a catecholamine synthesis inhibitor, varied inversely with baseline platelet monoamine oxidase activity in 12 patients with chronic schizophrenia. In normal volunteers with low monoamine oxidase activity and in unmedicated patients with chronic schizophrenia, plasma prolactin concentrations varied directly with platelet monoamine oxidase activity. No such relationship was found in normal subjects with high platelet monoamine oxidase activity. These data suggest that platelet monoamine oxidase activity reflects monoaminergic activity in the tubero-infundibular system, which in turn affects plasma prolactin concentrations. This relationship may be important in patients with low platelet monoamine oxidase activity, such as some chronic schizophrenics.
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Data from all-night EEG sleep studies were used to distinguish normal subjects, primary depressed patients, and primary insomniac patients. In part 1, we compared 41 normal subjects, 56 depressed patients, and 18 insomniacs. In a univariate comparison with normal subjects, depressed patients showed less total sleep, longer sleep latency, more early morning awake time, more intermittent awake time, less delta sleep, less sleep efficiency, and shorter rapid eye movement (REM) latencies; compared with insomniacs, depressed patients showed greater early morning awake time, shorter REM latency, greater REM index, and greater REM density. Using multivariate discriminant analysis, 82% of the sample were correctly classified by diagnosis: 100% of the normal subjects, 72% of the depressed patients, and 77% of the insomniacs. Eight variables contributed to the multivariate separation of depressed individuals from insomniacs and normals: total sleep time, total recording period, sleep efficiency, sleep latency, early morning awake time, awake time, REM time and REM%. When the discriminant functions were applied to a second group of 18 primary depressed patients, 82% were correctly classified as depressed. These results suggest that primary depressed patients and primary insomniac patients may show relatively characteristic patterns of sleep abnormality.
Frontal cerebral cortex brain samples from schizophrenics and controls have been assayed for binding associated with muscarinic cholinergic, serotonin (5HT), gamma-aminobutyric acid (GABA), and beta-adrenergic receptors as well as for the activity of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). Binding levels of tritium-LSD, presumably associated with postsynaptic 5HT receptors, were reduced 40% to 50% in samples from schizophrenics in three independent studies, whereas no other consistent alteration was observed in levels of binding associated with other receptors or in the activity of GAD. This change in receptor binding levels does not seem to be attributable to postmortem changes, to influence of drugs received by the patients, or to demographic features of the patient populations.