A. Steiger

Effects of Intravenous Corticotropin-Releasing Hormone upon Sleep-Related Growth Hormone Surge and Sleep EEG in Man

Corticotropin-releasing hormone (CRH) plays a key role in coordinating neuroendocrine, metabolic and behavioral responses in stress and affective disorders. To further investigate the effects of enhanced pituitary-adrenocortical activity upon sleep-related phenomena we administered four intravenous injections of 50 micrograms human (h)-CRH or saline to 11 normal males at 10 p.m., 11 p.m., 12 p.m. and 1 a.m. and measured plasma levels of cortisol and growth hormone (GH) as well as sleep EEG recordings throughout the night. Treatment with h-CRH resulted in a significant increase of mean (+/- SEM) cortisol secretion between 11 p.m. and 3 a.m. (h-CRH: 100.6 +/- 9.5 ng/ml; saline: 39.0 +/- 1.5 ng/ml; p less than 0.01). This initial cortisol increase after repeated h-CRH stimulations was followed by a period of attenuated plasma cortisol between 3 and 7 a.m. (h-CRH: 70.3 +/- 7.0 ng/ml; saline: 115.5 +/- 8.0 ng/ml; p less than 0.01). Cortisol surges after h-CRH were associated with a significant blunting of sleep-related GH release expressed as areas under concentration curves (h-CRH: 1.245 +/- 0.32 ng/ml/min.10(3); saline: 2.462 +/- 0.92 ng/ml/min.10(3), p less than 0.01). In addition to these hormonal effects, h-CRH induced a decrease of REM and slow wave sleep (stages III and IV) while the amount of more shallow sleep (stages I and II) increased. These effects upon sleep structure were more pronounced during the second part of the night.(ABSTRACT TRUNCATED AT 250 WORDS)

Sleep EEG and nocturnal secretion of cortisol and growth hormone in male patients with endogenous depression before treatment and after recovery

The authors conducted a sleep-endocrine evaluation among 10 unmedicated male patients with major endogenous depression during their depressive episode and following full clinical remission and drug withdrawal. While abnormally high values for cortisol secretory activity normalized after return to euthymia, growth hormone release and characteristic disturbances of EEG sleep remained unchanged. Whether or not neuroendocrine and sleep EEG abnormalities, which are present in remission, are trait markers remains undecided until premorbid sleep-endocrine data are available.

ACTH and multisteroid responses to corticotropin-releasing factor in depressive illness: Relationship to multisteroid responses after ACTH stimulation and dexamethasone suppression ☆

One hundred micrograms of ovine-corticotropin releasing factor (o-CRF) was administered intravenously to eight unmedicated patients with severe endogenous depression. Responses of immunoreactive (ir)-ACTH and the adrenal glucocorticosteroids corticosterone (B), 11-deoxycortisol (S), cortisol (F) and cortisone (E) were measured and compared with those following synthetic corticotropin stimulation and dexamethasone suppression. A comparative evaluation of the three pituitary--adrenal function tests suggests that hypersecretion of ir-ACTH and adrenal corticosteroids (B, S, F, and E) in depression reflects a central dysfunction rather than an altered responsiveness of the pituitary or adrenal glands. The data illustrate that the o-CRF paradigm is a valuable instrument to further support the hypothesis that a limbic--hypothalamic overdrive is the basic mechanism underlying exaggerated adrenocortical output in the endogenous subgroup of depressed patients.

Mean 14.00–17.00 h plasma cortisol concentration and its relationship to the 1 mg‐dexamethasone suppression response in depressives and controls

ABSTRACT– Three‐hour cortisol‐profiles and cortisol responses to a 1 mg dose of dexamethasone were recorded in 31 depressed patients and nine controls. The data indicate that the likelihood of detecting non‐suppressible cortisol concentrations after dexamethasone is significantly increased in depressed patients with a hypersecretion of cortisol. However, a considerable subsample of normosecretors shows abnormal DST results. Conversely, hypersecretion is often associated with dexamethasone suppression. In this study a 1 mg‐DST did not reflect the adrenocortical activity with ultimate accuracy. Therefore any attempts which correlate psychopathological or biological data with pituitary‐adrenal activity and use a DST‐result as measure are criticizable. Data derived from volunteers illustrate that medical factors such as weight‐loss, steroid‐containing contraceptives and sleep deprivation can make a pituitary‐adrenal activity test ambiguous.

Effects of brofaremine (CGP 11 305A), a short-acting, reversible, and selective inhibitor of MAO-A on sleep, nocturnal penile tumescence and nocturnal hormonal secretion in three healthy volunteers

The effects of brofaremine (CGP 11 305A), a short-acting, reversible and selective inhibitor of MAO-A, on sleep, nocturnal penile tumescence (NPT) and hormonal secretion during the night were studied during a long-term trial. Three healthy males underwent sleep-EEG and NPT recordings during consecutive nights (1) under placebo, (2) under stepwise increasing dosages of brofaremine and (3) under placebo after withdrawal. Hormone profiles were sampled during selected nights to analyze the plasma concentration of cortisol, HGH, prolactin, testosterone, LH and FSH. REM sleep was suppressed markedly under 150 mg brofaremine, while stages 1 and 2 increased. In comparison to the effect of irreversible MAOIs the REM suppression was shorter and did not persist after withdrawal. A decrease of the plasma concentration of the drug coincided with a return of sleep variables to baseline values. A REM rebound occurred after withdrawal of brofaremine. REM sleep and NPT showed a dissociation; NPT variables did not follow the decrease of REM sleep. The effects of REM parameters are correlated with the dosage and the plasma concentration of the substance. Intraindividually, a decrease in secretion of HGH was observed throughout the trial. No marked changes were found in the other endocrinological variables.

Multisteroid analysis after DST in depressed patients — A controlled study

111 consecutively admitted in-patients with a depressive syndrome received a dexamethasone suppression test (DST) after all known factors which might confound the test results had been carefully excluded. Plasma concentrations of cortisol, corticosterone and dexamethasone were compared with several diagnostic evaluations (RDC, DSM-III, ICD-9) in a controlled study. The positive predictive value of nonsuppressed corticosteroid levels was only moderate for each diagnostic category. Diagnostic specificities were 84.6% for major depression, endogenous subtype (RDC), 71.2% for melancholia (DSM-III) and 86.8% for endogenous depression (IDC-9) when using a post-DST cortisol value above 50 ng/ml (5 micrograms/dl) as the referent value to define DST nonsuppression. Combined determination of cortisol and corticosterone as an index of dexamethasone-induced suppression raised the sensitivity rate considerably at the cost of the predictive value for major diagnostic categories. Dexamethasone plasma levels were reciprocally correlated with cortisol levels and neglect of samples with low plasma dexamethasone contents improved the diagnostic performance for endogenous depression according to RDC and ICD-9, but not for DSM-III melancholia. Although it would be speculative to suppose that the observed low dexamethasone levels are involved in DST nonsuppression, the present findings emphasize that multisteroid analysis which includes dexamethasone is important in future studies designed to explore the clinical utility of the DST.

Effects of trimipramine on sleep EEG, penile tumescence and nocturnal hormonal secretion. A long-term study in 3 normal controls.

Sleep EEG, nocturnal penile tumescence (NPT) and nocturnal endocrine activity were studied in 3 male control subjects during placebo, under trimipramine (TR) and after withdrawal. TR did not change the sleep structure. NPT activity tended to increase under TR. Nocturnal plasma cortisol levels decreased markedly while the early morning rise of cortisol appeared delayed under 200 mg TR. After withdrawal the changes of the cortisol secretion rebounded. Nocturnal secretion of GH, testosterone, LH and FSH remained unaffected, but plasma prolactin levels increased under TR and returned to normalcy after cessation. Our data illustrate that the neurobiological effects of TR are different from those of other antidepressants. We suggest that some of the psychotropic effects of TR are mediated by suppression of cortisol.

An interdisciplinary study towards a multiaxial classification of male sexual dysfunction

The classification of male sexual dysfunction (SD) was investigated in a multidisciplinary study involving a sample of 25 outpatients whose phenomenology, course and biologic comorbidity is described. All 25 patients were suffering from arousal disorders; 9 men complained of lack of desire and 9 of orgasm disorders. For the vast majority (19/25), the arousal disorder preceded the other sexual dysfunctions. Eleven patients suffered from a psychopathological disorder according to DSM‐III or DSM‐III‐R (Axis I and II), with general anxiety, major depression and obsessive‐compulsive personality being the most common disorders. Only 6 patients were free of any organic disorder or pathological laboratory finding known to be related to sexual dysfunction. These results served as the basis for analyzing the fit of our data in the most prominent classification systems DSM‐III, DSM‐III‐R. Mainz multiaxial classification model and the traditional dichotomy model. According to our data, the comorbidity of biologic and mental conditions was very high, as most patients (60%) suffered from more than one etiologic factor known to be related to SD. Based on these results, a modification of the DSM‐III‐R system is suggested.

Neuroendocrine Dysfunctions in Affective Disorders: Effects of Clinical Changes

It is evident from current knowledge of complex interactions between hormones and neurotransmitter-receptor systems, sleep structure, gene expression, behavior, immune function, aging, psychopathology, and neuropsychological function that hormones play a key role in all aspects of affective disorders. Longitudinal studies by serial application of neuroendocrine tests allow us to investigate changes of the behavioral complex concurrently with laboratory measures.