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Thyrotropin-releasing hormone (TRH) stimulation tests were performed on 81 alcoholic men after at least 3 weeks of abstinence. Subjects were given 500 micrograms of TRH intravenously, and thyroid-stimulating hormone (TSH) and prolactin (PRL) were measured at baseline, and then 15 and 30 min later. Comparisons were made among alcoholics with (n = 27) and without (n = 54) a lifetime history of depression as determined by the Diagnostic Interview Schedule. Nine nondepressed, nonalcoholic subjects served as controls. Alcoholics with or without a depression history did not differ from each other or from control in TSH or PRL response area under the curve. Blunted TSH responses were present in 10 (12%) of the alcoholics and none of the controls when blunting was defined as a delta max TSH less than 5 microU/ml. When blunting was defined as a delta max TSH less than 7 microU/ml, 18 (22%) of the alcoholics and 1 (1%) of the controls were blunted. Conversely, 2 (2.5%) of the alcoholics had a delta max TSH greater than 32 microU/ml. All subjects were clinically euthyroid. Contrary to expectation, depressed subjects were slightly less likely to show blunted responses than nondepressed subjects. No relationship was found between neuroendocrine measurements and several measurements of alcoholism or depression. Some alcoholic subjects show a blunted TSH response to TRH injection, which may be a function primarily of the alcoholism itself. The precise mechanism remains unknown.

Although there has been much recent investigation of the role of thyroid function in affective illness, few studies have addressed the effects of the tricyclic antidepressants on the pituitary-thyroid axis. In the present study, thyroid functions (TFTs) and thyrotropin-releasing hormone (TRH) stimulation of thyroid-stimulating hormone (TSH) were measured before and after treatment with desipramine (DMI) in 13 men with a diagnosis of major depressive disorder. All subjects had normal TFTs and baseline TSH measured in a drug-free state at the initiation of the study. Both mean free thyroxine index and baseline TSH decreased after DMI treatment. The amount of decrease in baseline TSH correlated with increase in delta TSH. Four subjects had blunted delta TSH (delta TSH less than or equal to 5 microIU/ml); three of these subjects "normalized" with treatment (delta TSH less than or equal to 5 microIU/ml; greater than or equal to 20 microIU/ml). Two subjects had a high delta TSH, and both "normalized" during treatment. The decrease in both free T4 index and TSH suggests a down-regulation of the thyroid axis at the hypothalamic level. "Normalization" of subtle dysregulation of the thyroid axis is suggested as a mechanism of antidepressant therapy in the treatment of some depressions.

Major depression with psychotic features may be associated with higher cortisol secretion and a greater probability of dexamethasone nonsuppression of serum cortisol than is found in major depression without psychotic features. In this study, urinary free cortisol (UFC), a sensitive parameter of 24-hr cortisol production, was examined both before and after dexamethasone administration in 32 patients with major depression, 18 with psychotic features (MDPF), and 14 without psychotic features (MDD). A significantly larger number of MDPF patients had UFC excretion greater than 90 micrograms/24 hr before dexamethasone administration and greater than 20 micrograms/24 hr after dexamethasone administration. Although some clinical variables other than psychotic features differed between the two groups, these could not account for the UFC differences. However, the older patients (greater than 55 years) in the MDPF group accounted for the high UFC excretion, suggesting an interaction between age and diagnosis.

There has been speculation that a kindling model may have applicability to alcohol withdrawal syndromes and seizures, suggesting that repeated alcohol withdrawals may lead to increased severity of subsequent withdrawals. We evaluated historical and clinical variables of a group of male alcoholics with (n = 25) and without (n = 25) alcohol withdrawal seizures. We found that the number of detoxifications appeared to be an important variable in the predisposition to withdrawal seizures. The withdrawal seizure group had 12 of 25 (48%) patients with 5 or more previous detoxifications, compared to only 3 of 25 (12%) of the control group. A relationship between alcohol use history and withdrawal seizures was not supported by the data. These findings support the concept that previous alcohol withdrawals may "kindle" more serious subsequent withdrawal symptomatology, ultimately culminating in withdrawal seizures.

Prostaglandins are thought to act as neuromodulators of both central catecholamine and endocrine systems. Abnormalities of these systems have been described in affective disorders, in general, and in agoraphobia with panic attacks, in particular. This study measured basal prostaglandin-E (PGE) cerebrospinal fluid (CSF) levels in 20 patients with agoraphobia with panic attacks and 10 nonpsychiatric controls. In a subgroup of patients and controls, CSF levels of adrenocorticotrophic hormone (ACTH) and corticotropin-releasing factor (CRF) were also measured. There was no significant difference in CSF PGE levels between patients and controls. However, patients with higher depression scores had lower CSF PGE levels. CSF PGE levels tended to correlate with CSF ACTH, but not CSF CRF in the patient group, in general, and in the female patients, in particular. These findings do not support an abnormality in basal CNS PGE production in agoraphobia with panic attacks, but suggest further study of the PGE modulatory effect on the hypothalamic-pituitary-adrenal axis in this disorder.