The effect of bright light on plasma prolactin.
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Biomedical subjects
Publications and source records attributed to S C Risch.
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Natural killer cell (NK) activity, which is important in the defense against tumors and viral infections, is reduced in women undergoing conjugal bereavement. The relationship between NK activity and plasma cortisol was investigated in three groups of subjects: women who were anticipating the death of their husbands, women whose husbands had recently died, and controls. Bereaved women showed reduced NK activity and increased plasma cortisol levels as compared to controls. Anticipatory bereaved women also showed significant reductions in NK activity, but had levels of plasma cortisol comparable to those of controls. The reduction of NK activity during anticipatory and actual bereavement cannot be explained solely on the basis of increased cortisol secretion.
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.
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.
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.
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.
Plasma levels of ACTH were evaluated in 18 sons of alcoholics and 18 sons of nonalcoholics before and after they consumed placebo, 0.75 ml/kg of ethanol, and 1.1 ml/kg of ethanol. The analyses revealed significant changes in ACTH levels over time, an effect of ethanol on ACTH overall, and significantly lower ACTH levels in the sons of alcoholics than in the control subjects following the high-dose ethanol challenge. The data corroborate the earlier finding that sons of alcoholics have less intense responses to ethanol and are consistent with the conclusion that changes in cortisol level associated with drinking include a pituitary response as well as effects on the adrenal glands.
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.
The neuroendocrine effects of 5 and 10 mg of oral diazepam were assessed in 10 normal subjects under baseline (prestress) and laboratory-controlled stressful conditions. Although the 10-mg diazepam dose had no effect on cortisol at baseline, it significantly reduced the increase in cortisol produced by 15 minutes of exposure to a painful electrical stimulus. There were no significant effects on growth hormone, beta-endorphin or ACTH, either at baseline or after painful stimulation.
When 500 micrograms of TRH is given intravenously, an increase in TSH, blood pressure, plasma catecholamines and positive emotions follows. Four groups of patients with major, minor or bipolar depression or schizoaffective disorder increased their TSH levels by similar amounts after TRH. The neurohormone also significantly increased diastolic blood pressure by 5.5 +/- 1.6 mm Hg, and decreased heart rate by 7.6 +/- 1.3 beats/min. There was a weak trend for bipolar depressives to have less cardiovascular response to TRH than the other groups. Plasma norepinephrine (NE) was higher after TRH than after placebo. The NE response differed between patient groups (P = .0023) because of a smaller response by major depressives. TRH decreased anger, tension and depression, and increased friendliness. Positive emotional responses were significantly greater in the bipolar depressives than in other groups. Forty-one other studies have found a subnormal TSH response does not distinguish between subtypes of the affective disorders, but cardiovascular, catecholamine and mood responses may do so.
Plasma concentrations of ACTH and prolactin were measured in psychiatric inpatients at 8 a.m. and 4 p.m. before and after the standard 1 mg overnight Dexamethasone Suppression Test (DST). Plasma concentrations of cortisol were measured at 8 a.m. and 4 p.m., and 11 p.m. before and after 1 mg dexamethasone. Dexamethasone suppressed plasma concentrations of ACTH, prolactin and cortisol in the subject group as a whole. "Cut Points" obtained using Fisher's Exact Test identified plasma ACTH values at 8 a.m. baseline, 4 p.m. baseline and 8 a.m. post-dexamethasone and plasma prolactin values at all four times that significantly differentiated patients with bipolar depressive disorder and major depressive disorder from other psychiatric patients. There were no cut points found at any of the six times for plasma levels of cortisol that significantly differentiated between these two diagnostic groups. Of interest in this subject population, basal (pre-dexamethasone) plasma concentrations were of more diagnostic information than post-dexamethasone values. These pilot findings suggest that monitoring plasma prolactin and ACTH concentrations before and after dexamethasone might increase the sensitivity and specificity of this laboratory test for depression.
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Central administration of corticotropin releasing factor (CRF) in rats produces pituitary-adrenal activation and a variety of "anxiogenic-like" effects. The present study was designed to explore the contribution of the peripheral pituitary-adrenocortical axis in mediating these CRF responses. Intraventricularly administered CRF produced suppression of responding in the conflict test and a marked locomotor activation. Neither behavioral effect was altered by the prior administration of dexamethasone in a dose that blocked pituitary-adrenal activation to CRF. These results support the hypothesis that behavioral effects of CRF are mediated by its action at central sites and not via an action on the pituitary-adrenocortical system.
Cultured adult skin fibroblasts were studied for binding and functional evidence of muscarinic receptors in order to assess their utility as a model of cholinergic function in affective illness. Saturable, specific, high affinity binding could be demonstrated in intact cells from some cell lines with [3H]-NMS, but not [3H]-QNB, presumably because of intracellular trapping of unbound [3H]-QNB. [3H]-NMS specific binding indicated a single site with a KD of approximately 210 pM. [3H]-NMS was displaced by cholinergic agonists and antagonists with relative affinities similar to muscarinic receptors in brain. Many cell lines, however, showed no specific binding. No functional response to carbachol could be demonstrated with respect to inhibition of isoproterenol-stimulated cyclic AMP formation, stimulation of cyclic GMP formation or stimulation of phosphoinositide hydrolysis in any cell line regardless of either high or no specific [3H]-NMS binding.
Serum corticosterone levels were determined following administration of the cholinergic agonist arecoline (4 mg/kg) to rats selectively bred for differences in cholinergic function. The Flinders Sensitive Line (FSL) of rats exhibited both greater suppression of behavioural activity and enhanced elevation fo serum corticosterone than the Flinders Resistant Line of rats. These enhanced responses to arecoline in the FSL rats parallel those reported in depressed humans, suggesting that these rats may provide a new animal model of affective disorders.
The mechanism by which physostigmine exerts its behavioral, neuroendocrine and cardiovascular effects was explored in two separate experiments. In the first, the centrally-acting cholinesterase inhibitor physostigmine was compared with the non-centrally-acting agent neostigmine. In contrast to physostigmine, neostigmine caused no effects. In the second experiment, pretreatment with scopolamine, in contrast to methscopolamine, attenuated physostigmine's effects. The results suggest that physostigmine exerts its effects via a central muscarinic mechanism.