Prolactin responses to haloperidol in normal young women.

The prolactin (PRL) responses to intramuscular haloperidol (HPD) (0.5, 1.0, and 1.5 mg) were evaluated in six normal premenopausal women during the follicular and luteal phases of their menstrual cycles. These were compared to the PRL responses to these doses of HPD in normal young men. PRL responses to HPD did not differ between the follicular and luteal phases. The mean log-transformed PRL response to the lowest HPD dose (0.5 mg) in women was less than that in the men, but the women had greater PRL responses than the men to the higher haloperidol doses (1.0 mg and 1.5 mg).

Plasma growth hormone response to oral l-dopa in infantile autism.

In order to assess further the occurrence of hypothalamic dysfunction in infantile autism and its possible relationship to dopaminergic abnormalities, the l-dopa provocative test was performed in 22 patients fulfilling DSM-III criteria for this disorder. The results indicate a high incidence (at least 30%) of blunted plasma growth hormone (GH) responses following oral administration of l-dopa in this sample. These data suggest an alteration of hypothalamic dopamine receptor sensitivity in the patients with blunted responses. Thus, a subgroup of autistic patients within a descriptively homogeneous diagnostic category shows evidence of hypothalamic dysregulation and dopaminergic abnormalities.

The cortisol response to desipramine in endogenous depressives and normal controls: preliminary findings.

Plasma cortisol levels were monitored for 2 hours after an intramuscular injection of 75 mg desipramine in 13 endogenous depressives and 20 normal controls. Endogenous depressives had a significantly reduced cortisol response in comparison to normal controls, not explained by sex, age, or baseline cortisol differences between groups. A lack of a cortisol rise of 1.5 micrograms/dl above baseline by 45 minutes discriminated best, with 7 of 13 depressives (55%) being identified in contrast to only 1 of 20 normals (5%). The results suggest that this may be a useful biological test with acceptable sensitivity (55%) and excellent specificity (95%). Furthermore, these data suggest that norepinephrine may be stimulatory to cortisol in man.

Three tests of cortisol secretion in adult endogenous depressives.

Seventy-nine drug-free adult patients fitting RDC criteria for major depressive disorder endogenous subtype (EMDD), and 64 normal adult volunteers, were studied at 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 depressive 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 pathophysiologies associated with depression.

Growth hormone secretion in prepubertal children with major depression. II. Sleep-related plasma concentrations during a depressive episode.

Plasma growth hormone (GH) concentrations were determined every 20 minutes during sleep in 71 prepubertal children: 22 had endogenous major depressive disorder, 20 had nonendogenous major depressive disorder, 21 had nondepressed neurotic disorders, and eight were normal. Both depressive groups secreted significantly more GH during sleep than did controls. Measures included maximal GH plasma peak and area under the curve (AUC) during the total sleep period, during the first three hours after sleep onset, and during the first five hours after sleep onset. An AUC cutoff of 2,000 ng X min/mL identified positively half the prepubertal children with major depression; with a specificity of 78% (v neurotics) and 100% (v normal children). Increased GH secretion during sleep may be a marker of illness, a past episode, or trait for prepubertal major depression regardless of endogenicity.

Growth hormone secretion in prepubertal children with major depression. IV. Sleep-related plasma concentrations in a drug-free, fully recovered clinical state.

Prepubertal children with major depressive disorder have shown increased growth hormone (GH) secretion during sleep while in a depressive episode. When restudied in a fully recovered state (for at least three months) and drug free (for at least one month), their increased GH secretory pattern during sleep had not changed. Illness-recovery correlations using area under the curve for GH secretion during sleep were highly significant, whereas paired comparisons showed no significant differences. In addition, children who had recovered from major depressive episodes secreted significantly more GH during sleep than did nondepressed neurotic and normal children. No significant differences in delta-sleep were found in the depressed group between ill and recovered states nor among those who had recovered from major depressive episodes or controls. It is concluded that increased GH secretion during sleep is independent of depressive episodes, remains unaltered after full recovery, and may be a true marker of trait for major depressive disorder in prepuberty.

Growth hormone secretion in prepubertal children with major depression. I. Final report on response to insulin-induced hypoglycemia during a depressive episode.

Insulin tolerance tests (ITTs) were carried out on 46 drug-free prepubertal children with severe emotional disorders. Thirteen met unmodified Research Diagnostic Criteria for major depressive disorder, definite endogenous subtype, 17 met the criteria for nonendogenous major depressive disorder, and 16 fit DSM-III criteria for nondepressed neurotic disorders. The group with endogenous depression had significant hyposecretion of growth hormone (GH) in this test when compared with the other groups. Since GH hyposecretion in response to ITT has been found in most studies to be associated with endogenous major depression in adults, the data support the validity of the diagnosis of prepubertal endogenous major depressive disorder and the hypothesis of similarity or identity of prepubertal and adult major depressive disorders.

Growth hormone secretion in prepubertal children with major depression. III. Response to insulin-induced hypoglycemia after recovery from a depressive episode and in a drug-free state.

Insulin tolerance tests (ITTs) were performed after at least four months of sustained recovery from an episode of a major depressive disorder in 18 drug-free prepubertal children. Eleven had a definite endogenous subtype; seven did not. Sixteen children with nondepressed neurotic disorders made up a control group. The children with past endogenous depression continued to have significant hyposecretion of growth hormone (GH) in this test when compared with the other groups. Illness-recovery correlations were highly significant for the major depressive group as a whole. Paired comparisons of both depressive groups were not significantly different from illness to recovery. We conclude that prepubertal children with endogenous major depression continue to have hyposecretion of GH in response to ITTs in a recovered state and that this neuroendocrine marker is state independent. A GH hyporesponse to ITT may be a true marker of a past episode or of trait for endogenous major depressive disorder in prepuberty.

Plasma cortisol secretion and REM period latency in adult endogenous depression.

The authors studied the relationship of plasma cortisol secretion and REM period latency in 25 patients with endogenous depression. The 8 patients (32%) with cortisol hypersecretion had a significantly shortened REM period latency in comparison with the 17 with normal cortisol secretion. Furthermore, an extremely short REM latency (20 minutes or less) occurred almost exclusively in those with cortisol hypersecretion. The authors discuss possible neurotransmitter disturbances responsible for these abnormalities and the clinical implications of these findings.

A preliminary study of sex-related differences in prolactin responses to dopamine blockade and insulin hypoglycemia and in penfluridol plasma levels in schizophrenic patients.

Twelve healthy chronic schizophrenic patients were treated with the long-acting oral dopamine (DA) receptor blocker penfluridol (100 mg orally) for 6 weeks. Plasma prolactin (PRL) levels were measured during insulin-tolerance tests (ITT) performed at the end of the drug-free period (7-10 days) and during weeks 1 and 6 of penfluridol treatment. Simultaneous PRL and penfluridol plasma levels were determined just prior to, and at 8, 72 and 120 h after penfluridol administration during weeks 1, 5, and 6. During penfluridol treatment women (N = 4) had a greater increase in their maximal PRL increments after ITT as compared to the men (N = 8). Analyses of (peak) plasma penfluridol and PRL concentrations 8 h after penfluridol administration revealed a trend towards lower plasma penfluridol levels during weeks 5 and 6 and significantly higher PRL levels in women compared to men during weeks 1 (P less than 0.01), 5 (P less than 0.02), and 6 (P less than 0.02). The consistent sex-related differences in the PRL responses to DA blockade, and to insulin-induced hypoglycemia and in the penfluridol plasma levels in our study support the view that sex-related changes need to be considered not only in the hormonal responses to various pharmacological agents, but also in the assessment of the plasma levels of these drugs.

Plasma testosterone and sleep: relationship to sleep stage variables.

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.

Growth hormone response to dextroamphetamine in depressed patients and normal subjects.

The human growth hormone (HGH) response to dextroamphetamine sulfate (doses, 0.1 and 0.15 mg/kg) was determined in both the morning and evening in patients with endogenous and atypical depression and in normal young men and normal postmenopausal women. Although the HGH response was found to be reduced in endogenously depressed postmenopausal women, it was equally reduced in normal postmenopausal women and in patients with atypical depression. Depressed and normal men had larger HGH responses, but there were no differences between depressed and normal men. These results do not confirm an earlier report that the reduced HGH response to dextroamphetamine is specific to endogenous depression. The results do suggest the importance to control for other variables in studies of HGH responses in psychiatric patients.

Diurnal hormonal responses to thyrotropin-releasing hormone in normal men.

Bolus injections of synthetic thyrotropin-releasing hormone (TRH) were administered to five young normal men in the morning (0900 hr) and the evening (1800 hr) on different days. Frequent blood samples for prolactin (PRL) and TSH analyses were collected before and after TRH infusion. Although there were no differences between the morning and the evening basal PRL levels, a significantly greater PRL response to TRH in the evening was observed (delta PRL, a.m. vs p.m., p less than 0.025). Since TRH stimulates PRL through a direct effect on the pituitary, our data suggest that there is a diurnal variation in the pituitary lactotroph responsiveness to TRH. On the other hand, a.m. and p.m. basal and TRH-stimulated TSH responses were virtually identical.

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.

Paradoxical cortisol responses to dextroamphetamine in endogenous depression.

Dextroamphetamine hydrochloride was administered intravenously (IV) in the morning and evening to 22 unmedicated patients with severe endogenous depressions and 18 normal control subjects. While the normal subjects generally had a sharp increase in plasma cortisol level by 30 minutes after drug administration, two thirds of the depressed patients showed instead a paradoxical suppression of cortisol levels by 60 minutes. Discrimination between normal subjects and depressives was greatest in the evening. These results are consistent with other reports of abnormal cortisol responses in depressed patients to smaller IV doses of dextroamphetamine and larger doses of methamphetamine hydrochloride. A defect in activation or noradrenergic alpha receptors may account, in part, for the abnormal cortisol responses. The dextroamphetamine cortisol test in other patient populations requires study before its diagnostic use in endogenous depression can be established.

Cortisol secretion and dexamethasone response in depression.

The authors administered 2 mg of dexamethasone at 11:00 p.m. to 37 unmedicated hospitalized endogenously depressed patients and assessed their plasma cortisol response at 4:00 and 11:00 p.m. the next day. In addition, on nondexamethasone days 26 of these patients had mean 24-hour plasma cortisol concentration determinations from samples taken at 30-min intervals and 32 had plasma determinations from a single sample taken at 4:00 and 11:00 p.m. Mean 24-hour plasma cortisol concentration was elevated in 50%; only 7 of the 26 were dexamethasone resistant, and 6 of these 7 were hypersecretors. The authors suggest that dexamethasone resistance reflects the abnormality of cortisol hypersecretion in depression and that the 2-mg dexamethasone suppression test is a highly specific but not very sensitive indicator of hypersecretion.