Muscarinic receptor density in skin fibroblasts and autopsied brain tissue in affective disorder.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J C Gillin.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Infusion of the cholinomimetic drug physostigmine led to profound increases in serum epinephrine levels and slight increases in serum norepinephrine levels among 38 patients with affective disorder and 22 control subjects. Preliminary results suggest that physostigmine may induce relatively blunted increases in serum epinephrine levels in patients with affective disorders.
All-night sleep EEGs were compared in the following age-equivalent groups: seven men with Korsakoff's psychosis (KP), six men and two women with presumptive Alzheimer's disease, and six healthy men and three healthy women. KP patients had significantly increased intermittent time awake than both controls and Alzheimer patients, and shorter REM latency minus time awake than controls. Alzheimer patients had significantly reduced delta sleep than controls. Differences in the pattern of sleep EEG abnormalities may be due to different pathogenic mechanisms, but their utility in differential diagnosis requires further study.
A 39-year-old man with schizoaffective disorder experienced somnambulism only when taking a combination of lithium carbonate, chlorpromazine, triazolam, and benztropine. This was confirmed in the sleep laboratory. The sleepwalking occurred during Stage 2 sleep; the sleep record showed a marked paucity of REM sleep. The patient's brother had had one episode of somnambulism, also following exposure to a substance affecting the CNS. A role for CNS-active medications in triggering some pathologic sleep phenomena in predisposed individuals is hypothesized. Medications with central anticholinergic activity may be particularly important.
Sleep electroencephalographic activity, circadian rhythms in motor activity and rectal temperature, and clinical state were monitored longitudinally in four affectively ill patients (two depressed, one manic, and one rapidly cycling between depression and mania) who lived in isolation from external time cues (zeitgebers) for 3 to 4 weeks. In these conditions it was possible to observe the intrinsic or free-running behavior of circadian pacemakers and thereby to test several hypotheses about the role of sleep and circadian rhythms in the pathogenesis of depression. No hypothesis was consistently supported by the results. We found that the intrinsic rhythm of a circadian pacemaker appeared to free-run with an abnormally fast frequency in one patient. No patient remained stably depressed during temporal isolation. Our experience suggests that this type of study can be carried out safely with appropriate precautions. Temporal isolation is a means to test decisively predictions of several chronobiological hypotheses about affective illness and should be applied to additional patients.
Therapeutic responses to the tricyclic antidepressant clomipramine have been demonstrated in five double blind studies of patients with obsessive compulsive disorder. Biological alterations in patients with obsessive compulsive disorder resemble those of depressed patients for the dexamethasone suppression test, for some measures of sleep physiology, and in similar neuroendocrine responses to clonidine. Clomipramine's antiobsessional effect does not require high baseline depression ratings or biological abnormalities similar to those seen in depressives. Preliminary results suggest that in contrast to depressives, patients with obsessive compulsive disorder may respond to clomipramine but not to the tricyclic antidepressant desipramine.
In order to test whether exposure to bright artificial light at night is a necessary condition for the antidepressant response to sleep deprivation therapy, five patients were totally sleep-deprived on two separate nights, once in very bright light and once in nearly total darkness. During the day after the sleep-deprivation night patients were found to have responded equally well to sleep deprivation in both conditions. During the sleep-deprivation night, however, antidepressant responses may have been greater in the bright light condition. Thus, light at night is not necessary for the antidepressant response to sleep deprivation, but we cannot rule out the possibility that the effects of light exposure and sleep deprivation are additive or that exposure to light at some time after sleep deprivation begins (including during the following day) is necessary for the response.
Seasonal affective disorder (SAD) is a syndrome characterized by recurrent depressions that occur annually at the same time each year. We describe 29 patients with SAD; most of them had a bipolar affective disorder, especially bipolar II, and their depressions were generally characterized by hypersomnia, overeating, and carbohydrate craving and seemed to respond to changes in climate and latitude. Sleep recordings in nine depressed patients confirmed the presence of hypersomnia and showed increased sleep latency and reduced slow-wave (delta) sleep. Preliminary studies in 11 patients suggest that extending the photoperiod with bright artificial light has an antidepressant effect.
To explore the relationship between obsessive-compulsive disorder (OCD) and affective disorder, patients with OCD were studied using a series of biological markers which have been previously reported to be abnormal in patients with affective illness. These "markers" included the dexamethasone suppression test, sleep electroencephalography, the plasma growth hormone response to clonidine, and platelet 3H-imipramine binding. Results from each of these studies suggested similarities between patients with obsessional disorder and those with affective illness. Many of these biological abnormalities were evident in obsessional patients who did not manifest depressive symptoms. As a tricyclic antidepressant, clomipramine, has been found to reduce obsessional symptoms, the relationship between these "affective-like" laboratory findings and the clinical response to clomipramine was studied in a subgroup of OCD patients. Preliminary results suggest that none of the markers studied predict clomipramine response.
Ten insomniacs and matched control subjects, in whom major physiologic disorders such as sleep apnea and nocturnal myoclonus were ruled out, underwent studies of sleep, temperature, motor activity, cognitive performance, and perception of depth of sleep. Subjective descriptions of sleep differed significantly between insomniacs and normals on a variety of variables. In contrast, polysomnographic evaluation showed increased intermittent waking time and decreased sleep efficiency, and only a tendency toward decreased total sleep and increased sleep latency. Minnesota Multiphasic Personality Inventory (MMPI) evaluation revealed that insomniacs had higher scores on the F, D, and SI scales, and lower values on the K scale. On cognitive testing, insomniacs did well on tests of episodic (recent) memory, but displayed major deficits in accessing semantic memory (retrieval of material already known). Compared to normals, insomniacs described rapid eye movement (REM) sleep as relatively "light" sleep.
Electroencephalographic sleep recordings were compared in patients with panic disorder and normal controls. Correlation coefficients of standard sleep parameters versus ratings of anxiety, depression, and panic attack frequency were calculated in the panic-anxious patients. Overall findings are discussed in the context of previous sleep studies in patients with depressive, anxiety, and obsessive-compulsive disorders.
Supersensitive muscarinic cholinergic receptors may underlie mood, neuroendocrine, and sleep disturbances in depression. To test this hypothesis, we examined muscarinic binding sites in the brains of suicides and controls in a matched-pair design, using the radioligand 3H-quinuclidinyl benzilate (QNB) and focusing on regions (frontal cortex, hypothalamus, and pons) mediating those functions. Receptor densities and binding affinities did not differ between suicide and control brains in any brain region studied, although there was a trend for both density and affinity to be lower in hypothalami from suicides. We discuss the implications of these findings for the cholinergic-adrenergic balance hypothesis of depression and the methodological limitations of our preliminary study.
Basal growth hormone levels were measured every 20 minutes over 24 hours in eight long-term survivors of acute lymphoblastic leukemia and in 13 age- and pubertal stage-matched normal children. Among the patients, the median total basal growth hormone output (AUC) was 43 units, compared with 341 units in the normal control group (P less than 0.001). In the patients, mean pulse amplitude (6.9 ng/ml) and frequency (4.6) over 24 hours also were reduced, compared with the control values (32 ng/ml and 8.5, P less than 0.001 and P less than 0.05, respectively). In addition, normal children secreted more GH at night (median AUC 280) than during the day (113, P less than 0.001). However, this diurnal pattern was absent in three of the patients studied. These data suggest that perturbations of spontaneous pulsatile GH secretion are common after standard therapy for ALL and may be a sensitive means of detecting therapy-related neuroendocrine damage. Blunting of spontaneous pulsatile GH secretion may contribute to the abnormalities in growth seen in children with ALL.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The symptom of insomnia concerns not only psychiatrists, but other physicians as well. Most cases of insomnia resolve with the passage of time or when the underlying medical or psychiatric condition is treated. For situational insomnias or psychophysiologic insomnias, consider nonpharmacologic interventions before prescribing a sedative-hypnotic. When a sedative-hypnotic is indicated, the BZs are the drugs of choice because of their better margin of safety and lower potential for abuse. In most cases, limit the use of a sedative-hypnotic to several days to a few weeks.