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SynopsisUrinary free Cortisol (UFC) excretion was determined in 60 depressed inpatients and in 35 psychiatric inpatients with other disorders. The depressed patients had high daily UFC values, while the other patients excreted normal amounts. Over 40% of the depressed patients had UFC excretions in the range seen in Cushing's disease, while only 6% of the other patients excreted such high amounts of Cortisol. Age and sex differences did not account for the results. Among the depressed patients those with depressive neuroses excreted less than unipolar or bipolar depressives. Following treatment, more normal UFC excretion was found in depressed patients. The estimation of UFC and its clinical utility are discussed in detail. UFC determination is a simple and informative indicator of adrenal cortical activation and its application to psychoendocrine studies is recommended.

SynopsisPreliminary data from the National Institute of Mental Health – Clinical Research Branch Collaborative Program on the Psychobiology of Depression dealing with the human growth hormone (hGH) response to the Insulin Tolerance Test (ITT) during the pre-treatment (drug-free) period of the study are presented in this paper. Data are reported for 54 unipolar depressed, 21 bipolar depressed, and 40 normal control subjects, who represent approximately 50% of the final subject sample to be studied. In this population the unipolar depressed subjects showed a significantly greater resistance to insulin-induced hypoglycaemia than bipolar and control subjects. After applying the inclusion/exclusion criteria necessary to interpret hGH responses accurately, the data from only 54 subjects were acceptable. Mean peak hGH concentrations were not significantly different among the three groups. There was, however, a significant difference in the distributions of the hGH peak response, with the bipolar depressed population demonstrating greater variability in response than unipolar and control populations. These findings are discussed as they relate to previous reports and theoretical considerations.

SynopsisCerebrospinal fluid (CSF) cortisol levels were examined in a total group of 65 patients. Those who were not depressed (ND), and those suffering from depressive neuroses (DN) had marginally elevated values. Patients with unipolar depression (UD) and bipolar depression (BD) had levels twice as high as the ND and DN patients. Psychotic UD and BD patients had the highest values, three to four times as high as the ND and DN subjects. A significant reduction of CSF cortisol levels was observed following treatment and recovery. Manic patients had moderately elevated CSF cortisol values. The CSF results were in good agreement with plasma total cortisol levels and with urinary free cortisol excretion. Age and sex effects were not responsible for the observed differences; similar results were found in patient subgroups studied in Australia and in the United States. Preliminary equilibrium dialysis data are presented for plasma and CSF cortisol binding. CSF cortisol was 20% bound and 80% free. Plasma free cortisol levels were in good agreement with CSF free cortisol values. Depressed patients have increased tissue and central nervous system (CNS) exposure to free, physiologically active glucocorticoids. The appearance of severe depressive symptoms which manifest a diurnal rhythm may be determined in part by excessive CNS exposure to glucocorticoids.