Frieda S. Halpern

Clozapine: Plasma levels and prolactin response

Serial plasma clozapine levels and serum prolactin levels were determined in two schizophrenic patients receiving clozapine, a novel antipsychotic drug. Despite marked therapeutic response and substantial clozapine blood levels, prolactin levels obtained 11–12 h after the last oral dose were unaffected or only minimally elevated. This confirms previous evidence of clozapines unusal characteristics.

Relative insulin insensitivity and cortisol secretion in depressed patients

Relative insulin insensitivity occurs in a substantial portion of patients with major endogenous depressions, and about half such cases also hypersecrete cortisol in the afternoon and evening. This study assessed the relation between these two abnormalities in 16 patients with major endogenous depression. Over several days, insulin tolerance tests (ITTs) were performed in the morning and evening, and measures of cortisol secretion taken: plasma cortisol at 0800, 1600, and 2300 hours, both before and after dexamethasone; baseline cortisol before ITTs; and mean 24-hour plasma cortisol concentrations (in 10 cases). After clinical recovery, some of these patients had repeat ITTs (n = 10) and repeat predexamethasone and postdexamethasone cortisol assessments (n = 9). Additionally two control groups of 15 normal subjects and of 12 schizophrenic patients received morning ITTs. None of the control subjects manifested insulin insensitivity. However, during illness, 8 of the 16 depressed patients manifested relative insulin insensitivity (glucose drop less than 50%, glucose nadir greater than 50 mg/dl); compared to the insulin responsive depressed group, the insensitive group had insignificantly greater afternoon and evening cortisol secretion by nearly all indices. After clinical recovery, hypoglycemic response for the entire group was significantly greater than during illness; this improvement was accounted for by the increased insulin responsivity of the previously insulin resistant subgroup. There was also substantial plasma cortisol reduction in the previously insulin resistant group after clinical recovery, but not in the insulin sensitive group.

Cortisol hypersecretion in prepubertal depressive illness: a preliminary report.

Abstract (1) Plasma cortisol was measured every 20 min for 10–24 hr in 4 prepubertal children fitting unmodified Research Diagnostic Criteria (RDC) for major depressive disorder, endogenous subtype. (2) Hormonal assessments were made before treatment and after clinical recovery. (3) Two of the 4 subjects presented evidence of cortisol hypersecretion during illness, subsiding after clinical recovery, similar to that seen in adult endogenous depressives. (4) These preliminary data support the hypothesis that child and adult major depressive disorders are basically the same illness occurring at different points in development.

Endocrine responses to thyrotropin-releasing hormone in major depressive disorders

The endocrine response to thyrotropin-releasing hormone (TRH) was studied in severely endogenously depressed patients during illness (n = 21) and after recovery (n = 18). The thyroid-stimulating hormone (TSH) response to TRH was blunted (deltaTSH less than 5 microIU/ml) in over one third of depressives during illness and remained blunted in most even after recovery. There was no correlation between multiple measures of cortisol secretion (the mean 24-hour plasma cortisol, dexamethasone suppression test, and plasma cortisol during the TRH procedure) and the TSH response during illness and after recovery. The TSH and prolactin (PRL) responses to TRH, as well as the baseline PRL, were significantly lower during illness. The role of possible abnormalities in dopamine and/or serotonin in depression contributing to these endocrine disturbances is discussed.

Growth Hormone, Prolactin, and Growth Responses in Hyperkinetic Males Treated with D-Amphetamine

Abstract Growth patterns in previously unmedicated hyperactive boys were assessed monthly for 1 year or more while they received treatment with d-amphetamine (N = 13) or phenothiazines (N = 8). The d-amphetamine group, who sustained their behavior improvement throughout the study, underwent sleep and endocrine studies before and after 6 months on drug therapy. By 1 year, the phenothiazine group had achieved a 7-point increase in weight percentile and a 4-percentile gain in height, but the d-amphetamine group had lost 16 percentile points in weight and 10 percentile points in height. Height and weight velocities had fallen significantly (p

Three tests of cortisol secretion in adult endogenous depressives.

ABSTRACT Seventy‐nine drug‐free adult patients fitting RDC criteria for major depressive disorder endogenous subtype (EMDD), and 64 normal adult volunteers, were studied al pretreatment with at least one of three tests of cortisol secretion. The tests were: 1) Mean half‐hourly cortisol concentrations from 1 p.m. to 4 p.m. (1‐4 PM CORT); 2) plasma cortisol response to 0.15 mg/kg of dextroamphetamine hydrochloride (DACT) in the afternoon; 3) dexamethasone suppression test (DST) using 1 or 2 mg. Thirty‐six depressives and 27 volunteers underwent all three tests. Analysis of the data was performed for each test singly, for all pairs of tests and for all three tests in same subjects. Results show that the single most sensitive cortisol test for depressions is the DACT (72 %), with a specificity of 88 %. These tests may measure different underlying path (c)physiologies associated with depression.

Normal prolactin responses in tardive dyskinesia.

Tardive dyskinesia has been hypothesized to be caused by a neuroleptic-induced dopamine hypersensitivity in the nigrostriatal system. This study evaluated with dopamine antagonists the possibility that such dopamine hypersensitivity extends to the tuberoinfundibular dopamine (TIDA) system, which regulates, by inhibition, pituitary prolactin secretion. Plasma prolactin concentrations in six patients with tardive dyskinesia were asessed in four conditions: During chronic haloperidol therapy; serially after abrupt haloperidol withdrawal; while unmediated; and in response to an acute dose of 0.5 mg IM haloperidol. In all four conditions, prolactin responses did not differ from those observed in normal subjects and schizophrenic patients without tardive dyskinesia. It is concluded that there is no evidence for post-synaptic dopamine hypersensitivity in the TIDA-pituitary pathway in patients with tardive dyskinesia, consistent with other reports assessing hormonal responses to dopamine agonists in such cases. It is further suggested that neuroleptic-induced dopamine hypersensitivity does not occur in the TIDA-pituitary system in humans, since it was not manifest in these tardive dyskinesia patients who would be thought particularly prone to develop it.

Plasma testosterone and sleep: relationship to sleep stage variables.

&NA; A study was performed to determine whether the pattern of secretion of testosterone (T) during the night bears a systematic relationship to the cyclically recurring periods of rapid eye movement (REM) and non‐REM (NREM) sleep. In four healthy male volunteers, 10‐20 min sampling of plasma for T was carried out through a long indwelling catheter in conjunction with all‐night polysmonography. Analysis of plasma T, comparing the samples drawn during the REM and NREM stages, did not reveal a significant difference in the mean concentration of T between the two sleep stages or among specified time segments of the NREM‐REM cycles. A more exacting approach to exploring for a correlation of the secretory pattern with the sleep‐stage cycle was then undertaken. This method used the NREM‐REM cycle as the independent variable in the analysis. We were able to demonstrate that the positions of the peaks and troughs of T concentration in each REM‐NREM cycle are discriminable when examined in relation to the time of REM sleep onset in each cycle. The tendency for peaks in T concentration to be associated with repetitive inaugurations of REM sleep is coordinate with a pattern of serial “upswing” in T concentrations that occurs in the period from 30 to 10 min before the transition from NREM to REM sleep. Accordingly, it proved possible to demonstrate certain signs of interaction between the activity of the pituitary‐gonadal system and the mechanisms that regulate central nervous system state in sleep. The more traditional parameter of comparison (mean concentration of hormone in REM and NREM sleep) did not detect the association.

Effect of dopamine and neuroleptics on plasma growth hormone and prolactin in normal men.

Abstract (1) This study investigates further the locus of action of dopamine (DA) and DA antagonists in affecting growth hormone (GH) and prolactin (PRL) secretion in normal subjects. (2) Each of three normal men was tested twice with a continuous DA infusion (0.3 mg/min) over 90 min. (3) Mean plasma GH concentration was significantly ( p

Diurnal growth hormone responses to dextroamphetamine in normal young men and postmenopausal women

Abstract (1) D-amphetamine stimulates growth hormone (GH) secretion, probably through its catecholaminergic effects. (2) In normal post-menopausal women we found the GH response to dextroamphetamine to be small and significantly less than that seen in young normal men. (3) In post-menopausal women but not in young men, the GH response to amphetamine was significantly higher in the evening than in the morning. (4) The reduced GH responses to dextroamphetamine in postmenopausal women may be due to sex difference, hypoestrogenism, or to reduced brain catecholamines associated with age. (5) The diurnal variation of the GH response to d-amphetamine in post-menopausal women may reflect a diurnal variation in hypothalamic nor-adrenergic activity higher in the evening, which was not masked by a reciprocal variation in estradiol levels.