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Biomedical subjects

J C Gillin

Publications and source records attributed to J C Gillin.

At least 145 records · Page 8Linked to original sources

Phototherapy for depressive disorders: a review.

The use of bright light (phototherapy) for psychiatric disorders has recently generated much interest among researchers and the lay population. The authors review the treatment studies of phototherapy for seasonal and non-seasonal depressive disorders, and the empirical evidence for theories of the psychophysiology of phototherapy. Although its mechanism of action remains to be explained, phototherapy appears to be a safe and effective treatment for seasonal depression and a promising treatment for non-seasonal depression. Further questions and future research directions are presented.

Depressive Disorder↗

Peripheral white blood cells and HPA axis neurohormones in major depression.

Alterations in peripheral blood leukocyte distribution in major depression, including leukocytosis, neurotrophilia and lymphopenia, have been described. To assess peripheral white blood cells and the hypothalamic-pituitary (HP) axis in drug-free patients with major depression, we measured the total white blood cell count (WBC), and percentage of lymphocytes, and the plasma levels of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH) and prolactin (PRL). Twenty male patients with major depression had relative lymphopenia and leukocytosis when compared with 20 age, sex and racematched control subjects. Elevated Beck and Hamilton depression scores correlated with a decreased percentage of lymphocytes, in a group of all subjects combined. There was a weak tendency for elevated growth hormone to correlate with relative lymphopenia in the control subjects only. Relative lymphopenia and leukocytosis may be a part of the psychobiology of major depression.

Adrenocorticotropic Hormone↗

Rebound insomnia: a critical review.

Rebound insomnia, a worsening of sleep compared with pretreatment levels, has been reported upon discontinuation of short half-life benzodiazepine hypnotics. This paper reviews the existing sleep laboratory studies for the presence or absence of rebound insomnia following treatment with triazolam, temazepam, and flurazepam in insomniac patients or poor sleepers and, when possible, in normals. The results indicate that rebound insomnia is a distinct possibility after discontinuation of triazolam in both insomniacs and normal controls. Compared with baseline, disturbed sleep was reported in insomniacs or poor sleepers for the first 1 or 2 nights of withdrawal in seven of nine polygraphically recorded sleep studies following triazolam 0.5 mg and in one of two studies following triazolam 0.25 mg. In one study conducted in normal volunteers, rebound insomnia was observed following triazolam 0.5 mg but not triazolam 0.25 mg. In another study, which used subjective reports of sleep rather than polygraphic recordings, rebound insomnia was significantly attenuated after triazolam 0.5 mg by tapering the dose over 4 nights. The risk of rebound insomnia after temazepam 15 or 30 mg was low. In keeping with its long elimination half-life, flurazepam (30 mg) continued to exert beneficial effects for the first 2-3 withdrawal nights, but the possibility of a mild rebound insomnia cannot be dismissed during the intermediate withdrawal period (nights 4-10) following prolonged, consecutive, nightly administration (more than 30 nights). The benzodiazepine hypnotics are generally preferred over other types (barbiturates or nonbenzodiazepine, nonbarbiturate), but there are advantages and disadvantages related to half-life of the benzodiazepines. The risk of rebound insomnia is greater with the short half-life as compared with the long half-life benzodiazepines.

Anti-Anxiety Agents↗

Gender differences in the circadian temperature rhythms of healthy elderly subjects: relationships to sleep quality.

Body core temperature and subjective sleep quality were measured in 22 healthy elderly men and women while they lived at home and continued their normal daily activities. The acrophase of body temperature was phase-advanced by an average of 1.25 h in the older women compared to the age-matched men. Habitual bedtimes did not differ between men and women, but usual wakeup time and average sleep duration did: women awakened earlier and slept for shorter durations. Women were also less satisfied with their sleep than were the men. For the group, the acrophase of body temperature was significantly positively correlated with habitual bedtime and wakeup time. These data support the notion that age-related changes in the circadian timing system are, in large part, gender-dependent. The findings are also consistent with the hypothesis that alterations in sleep timing and quality that typically accompany aging are closely tied to age-related changes in circadian physiology.

Aged↗

Cholinergic neurons from the dorsolateral pons project to the medial pons: a WGA-HRP and choline acetyltransferase immunohistochemical study.

In this study we determined that cholinergic neurons from the lateral dorsal tegmental (LDT) and peribrachial pontine region (PPG) innervate the medial pontine reticular formation (medial PRF), a region involved in the generation of REM sleep. Wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected into the medial PRF and the brainstem tissue was processed using a combined retrograde transport/immunocytochemical procedure. Results showed that 10-15% of choline acetyltransferase (ChAT) immunoreactive neurons in the LDT and PPG project to the medial PRF. It is hypothesized that these neurons play an important role in the generation of the REM sleep state.

Animals↗

Genetic and pharmacological models of cholinergic supersensitivity and affective disorders.

Increased muscarinic sensitivity has been associated with altered hormonal states (hypothyroidism and hyperadrenocorticism), chronic administration of muscarinic antagonists or antidepressants with muscarinic actions, selective breeding for anticholinesterase sensitivity, and certain inbred strains of rats and mice. Thus, both genetic and environmental factors may influence muscarinic receptor sensitivity. The reasonably detailed studies on the selectively-bred rats have revealed that the Flinders Sensitive Line (FSL) rats weigh less, are less active, are more sensitive to muscarinic agonists and to stressors, and have higher concentrations of hippocampal and striatal muscarinic receptors than 'normal', or the selectively-bred, Flinders Resistant Line (FRL) rats. Thus, there are a number of parallels between FSL rats and depressed humans. The FSL rats may be the first animal model of depression to mimic the actual trait of depression, and not just the state.

Acetylcholine↗

Exposure to light in healthy elderly subjects and Alzheimer's patients.

Exposure to light was recorded from 10 healthy elderly adults and 13 age-matched subjects with senile dementia of the Alzheimer's type (SDAT). Data were recorded in the home, for an average of 5 days, while subjects continued their normal daily activities. Subjects were exposed to remarkably small intervals of illumination exceeding 2000 lux. Subjects with SDAT were exposed to bright light significantly less than healthy controls (0.5 vs. 1.0 hr). Whether or not they had SDAT, males were exposed to illumination exceeding 2000 lux significantly more than were females. Healthy elderly received about two-thirds the duration of bright light received by healthy younger subjects. These findings suggest an association between decreased exposure to bright light and the declines in sleep quality which typically accompany normal and pathological aging.

Aged↗

Immune cells and the hypothalamic-pituitary axis in major depression.

To explore changes in immune cell status with changes in the hypothalamic-pituitary (HP) axis in 20 patients with major depression as compared with 20 age-, sex-, and race-matched control subjects, we examined peripheral blood mononuclear cells (PBMC) for total T-cells (T3), total B-cells (B1), two T-cell subsets (T4 and T8), and natural killer cells (NKH1), and we measured the plasma level of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), and prolactin (PRL). The ratio of T4/T8 was increased in the patients. Within the group of control subjects only, increasing age correlated significantly with decreasing plasma PRL. Within the group of patients only, GH positively correlated significantly with T8 and NKH1, as did PRL with NKH1. No between-groups difference was found for T3, B1, T4, T8, NKH1, cortisol, ACTH, GH, or PRL.

Adult↗

Neutrophilia and lymphopenia in major mood disorders.

Alterations in peripheral blood leukocyte distribution in major depression, including lymphopenia, neutrophilia, eosinopenia, and monocytopenia, have been described. The present study was designed to replicate these results, but with methodological improvements, including age-, sex-, and race-matched control subjects; DSM-III and Research Diagnostic Criteria diagnoses based on the Schedule for Affective Disorders and Schizophrenia interview; objective and subjective severity of depression measured quantitatively; and consideration of psychosocial stressors (DSM-III, Axis IV). We found relative lymphopenia and absolute neutrophilia and leukocytosis in depression, but did not find decreased numbers of eosinophils or monocytes. The relative lymphopenia and absolute neutrophilia were present in the subgroup of only unipolar depressed patients, but not in the bipolar, currently depressed subgroup. However, these blood cell changes were not found in a subgroup of patients who had been medication free greater than or equal to 1 month but only in the subgroup of patients using medication at the time of phlebotomy. Groups formed on the basis of psychosocial stress levels were not found to have significant significant intergroup differences in white blood cell (WBC) counts. The clinical significance of these findings needs study. While leukocytosis and neutrophilia can be found in major depression, these changes are perhaps secondary to medication use.

Adult↗

Cellular immunity and the hypothalamic-pituitary axis in major affective disorder: a preliminary study.

To assess cellular immune status and the hypothalamic-pituitary axis in patients with major depression, we examined peripheral blood mononuclear cells and measured the plasma levels of four neurohormones. Eleven patients with major depression had increased % of T4 lymphocytes and decreased concanavalin (Con A) stimulated T lymphocyte proliferation when compared with 11 age-, sex-, and race-matched control subjects. Percent of total lymphocytes labeled as all T lymphocytes, all B lymphocytes, and natural killer cells did not differ in the two groups, nor did mitogen-induced interleukin-2 production. These findings support theories of interaction between depression and immune cell function.

Adrenocorticotropic Hormone↗

Human growth hormone releasing factor infusion effects on plasma growth hormone in affective disorder patients and normal controls.

In a preliminary, prospective pilot study, five patients with major depressive disorder and eleven age and sex matched normal controls received intravenous human growth hormone releasing factor (hGRF) (1 microgram/kg in 5 cc of normal saline infused over five minutes) and placebo. Thirty minutes after insertion of the catheter, blood was sampled every 15 minutes for thirty minutes prior to and for 2 hours subsequent to intravenous infusion of hGRF or placebo. hGRF but not placebo caused significant elevations of plasma growth hormone levels in all subjects. Of interest, the depressed patients had a significantly attenuated rise in plasma growth hormone concentrations when compared with the normal controls. These results must be considered preliminary awaiting replication with a larger subject population.

Adult↗

Age, cellular immunity and the HP axis in major depression.

1. To assess the effect of age on cellular immune status and the HP axis in patients with major depression, we examined peripheral blood mononuclear cells (PBMC) and measured the plasma level of four neurohormones. 2. In 36 subjects, decreasing T lymphocyte response to con A covaried with age. Percent of lymphocytes labeled as T8 lymphocytes tended to decrease and T4/T8 ratio tended to increase with increasing age. 3. Hamilton and Beck scores were significantly different between the two sex and race matched groups of 18 depressed patients and 18 control subjects, and plasma prolactin was significantly higher in depressed subjects. 4. Increasing age correlated with decreasing T lymphocyte response to con A in the combined group of all subjects, and in the control group, but not in the patient group. 5. Hamilton and Beck scores correlated inversely with T lymphocytes response in the combined group of all subjects. 6. Differences in mitogen responsiveness between patient and control groups were not found, having been obscured by the effect of age. 7. These findings indicate the need to age match subjects when studying the interaction between depression and immune cell function.

Adult↗

Increased REM sleep in rats selectively bred for cholinergic hyperactivity.

We have examined the sleep profile of the Flinders Sensitive Line (FSL) of rats, which were selectively bred for supersensitive responsivity to an acetylcholinesterase inhibitor (DFP). These animals have an increased density of muscarinic receptors in striatum and hippocampus and display a number of behavioral and neuroendocrine characteristics that may represent a rodent analogue of clinical depression. A continuous 48-hour sleep EEG recording was obtained. Compared to control rats (the Flinders Resistant Line), the FSL rats had selectively more rapid-eye-movement (REM) sleep as a percentage of total sleep time. In addition, the REM sleep latency was significantly shorter and the REM-REM cycle length was significantly faster in the FSL than in the FRL strain. The two strains did not differ in total sleep time, drowsy sleep, or slow-wave sleep. The increased REM sleep in the FSL rats is consistent with the amassed evidence that cholinergic mechanisms selectively promote REM sleep, and suggests that the FSL rats may be useful in understanding the mechanism responsible for short REM latency in depression and narcolepsy.

Animals↗

The use of triazolam in phase-advanced sleep.

The need for optimal nocturnal performance continues to increase in our society. Nighttime function is dependent upon the ability to sleep effectively during the day. The current study examined daytime sleep after placebo, 0.125 mg (364 nmol), 0.25 mg (729 nmol), or 0.50 mg (1458 nmol) of triazolam, and nocturnal performance in the work shift that followed. Forty-one normal young adult subjects participated in a repeated-measures design in which each subject received each medication dose level in a separate week. The results indicated that day sleep increased as a linear function of drug dose from 234 to 374 minutes. Nocturnal alertness, as measured by subjective report and objective nap latency test, increased significantly following the use of triazolam, 0.25 and 0.50 mg, for the day sleep period. Nocturnal performance, as measured by auditory vigilance and additions, also increased significantly following the use of triazolam. Marginal evidence for medication hangover was found at the 0.50-mg dose, and it was therefore recommended that the use of the 0.50-mg dose be monitored carefully if performance demand were to follow medication use by less than 12 hours. The results for the study were interpreted as indicating that under certain conditions, triazolam could effectively increase daytime sleep and improve alertness and performance in the following nocturnal work period.

Adult↗

Distribution of choline acetyltransferase immunoreactive somata in the feline brainstem: implications for REM sleep generation.

In the present study we examined the distribution of cholinergic and catecholaminergic neurons, in the feline brainstem, as defined by choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) immunohistochemistry. In the dorsal tegmentum, ChAT immunoreactive neurons were distributed in the parabrachial area [the pedunculopontine group (PPG)] and along the medial adjacent central gray [the lateral dorsal tegmental group (LDT)]. The cholinergic neurons in the LDT area were larger than those in the PPG. When adjacent tissue sections were labeled with TH we noted extensive overlap between catecholamine and cholinergic neurons in the PPG, suggesting that REM sleep may occur as a result of an interaction between these transmitters in this area rather than the medial pontine reticular formation where no cholinergic or catecholamine neurons were found. Cholinergic neurons were also found in the cranial nerve nuclei and the nucleus ambiguus. The presence of cholinergic neurons in the PPG and LDT suggest that these neurons may play an important role in the generation of some of the tonic and phasic components of REM sleep, such as cortical desynchronization, pontogeniculo occipital waves, and muscle atonia.

Acetylcholine↗

The diagnostic dilemma of myxedema and madness, axis I and axis II: a longitudinal case report.

A patient with presumed chronic paranoid schizophrenia had chronic thyroiditis and Grade I hypothyroidism. Psychosis cleared following treatment with thyroid replacement. The probable presence of two axis II disorders may have contributed to the missed medical diagnosis and the patient's eventual suicide. The personality disorders were a major problem in the patient's medical and psychiatric care. The differential diagnosis among hypothyroidism and primary axis I psychotic and depressive psychopathology has always been problematic. When axis II pathology is also present, the diagnostic dilemma is increased.

Adult↗