Background: The lowering of high serum cholesterol levels may be associated with increased non-cardiac mortality due to behavioral changes, although such endpoints are likely rare. Objective: This current study sought to determine if hormonal changes accompany pharmacologically induced decreases in serum cholesterol levels. Method: Cholesterol, dopamine, homovanillic acid (HVA), serotonin, 5-HIAA, testosterone, cortisol and pregnenolone were measured at baseline and after 4 weeks of treatment. Results: Subjects' cholesterol levels significantly declined within 4 weeks. Concomitant significant increase in dopamine and HVA were noted. Conclusion: Although this study is limited in size, it raises the possibility that cholesterol-lowering drug treatment is associated with hormonal perturbations.

The treatment of hypercholesterolemia may be associated with greater noncardiac mortality. This current pilot study sought to determine which behaviors, if any, are associated with decreases in cholesterol level. Twelve subjects received one of two cholesterol-reducing drugs or placebo. Cholesterol and behavioral ratings were measured at baseline, 4, and 52 weeks with standardized scales. Cholesterol levels markedly declined with concomitant significant increases in impulsivity ratings at 4 weeks. At 52 weeks, the increase in impulsivity ratings was no longer apparent, but depression ratings showed a significant improvement. This pilot study, although limited in size, raises the possibility that cholesterol-lowering drugs are associated with mild, time-limited increases in impulsivity and with mild, time-delayed improvements in depression ratings.

Background:Hypercortisolemia is frequently observed in major depression but its pathophysiologic significance is unknown. In patients in whom hypercortisolism contributes to depressive symptomatology, antiglucocorticoid agents should have antidepressant effects.Methods: Twenty medication-free depressed patients (eight of whom were hypercortisolemic and twelve of wham were not) received either the cortisol biosynthesis inhibitor, ketoconazole (400-800 mg/d p.o.) or placebo for 4 weeks in a-double-blind manner, and behavioral ratings were performed weekly.Results: Ketoconazole, compared to placebo, was associated with improvements in depression ratings in the hypercortisolemic, but not in the non-hypercortisolemic patients. The hormonal changes seen (decreased dehydroepiandrosterone and testosterone levels and increased pregnenolone and pregnenolone-sulfate levels) are consistent with enzymatic blockade of C17,20-lyase, 11-hydroxylase, and 17-hydroxylase. Ketoconazole was generally well tolerated with no occurrence of significant side effects or laboratory abnormalities.Conclusions: This small-scale double-blind study suggests that antiglucocorticoids have antidepressant activity in hypercortisolemic depressed patients. The data are consistent with a causal role of adrenocortical dysfunction in some depressed patients and suggest the need for larger-scale : trials. (C) 1999 Society of Biological Psychiatry.

Background: Estrogen replacement therapy (ERT) may delay dementia-related cognitive decline in post-menopausal women, but few studies have longitudinally examined this relationship and none has controlled for baseline functioning or concurrent medication.Methods: We report the results of a 1-year retrospective longitudinal study examining cognitive functioning in female estrogen and nonestrogen users (n = 3128) who presented to the state of California memory disorder clinics in a naturalistic multisite study of senile dementia, Alzheimer's type (SDAT), and other cognitive impairments.Results: Ar baseline, estrogen users had significantly lower rates of SDAT diagnoses (possible and probable) than nonestrogen users, and significantly higher rates of the lesser diagnoses of "cognitive impairment" and "no dementia." ERT was significantly associated,vith higher cognitive functioning at baseline and at 1 year follow-up (n = 358), Nonestrogen users deteriorated significantly from baseline to follow-up; estrogen users did not. Results were similar in groups marched on baseline Blessed-Roth Dementia Rating Scale (BRDRS) ratings (n = 32) and in a variety of subpopulations.Conclusions: These findings are consistent with estrogen acting as a protective factor against cognitive deterioration in post-menopausal women,with SDAT and other cognitive impairments, and may suggest an increased effect in earlier stages of cognitive impairment. (C) 1999 Society of Biological Psychiatry.

Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are plentiful adrenal steroid hormones that decrease with aging and may have significant neuropsychiatric effects. In this study, six middle-aged and elderly patients with major depression and low basal plasma DHEA f1p4or DHEA-S levels were openly administered DHEA (30-90 mg/d x 4 weeks) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals. Depression ratings, as well as aspects of memory performance significantly improved. One treatment-resistant patient received extended treatment with DHEA for 6 months: her depression ratings improved 48-72% and her semantic memory performance improved 63%. These measures returned to baseline after treatment ended. In both studies, improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels. These preliminary data suggest DHEA may have antidepressant and promemory effects and should encourage double-blind trials in depressed patients.

Annals of the New York Academy of SciencesVolume 774, Issue 1 p. 337-339 Antidepressant and Cognition-Enhancing Effects of DHEA in Major Depression O. M. WOLKOWITZ, O. M. WOLKOWITZ Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorV. I. REUS, V. I. REUS Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorE. ROBERTS, E. ROBERTS Department of Neurobiochemistry City of Hope Duarte, California 91010Search for more papers by this authorF. MANFREDI, F. MANFREDI Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorT. CHAN, T. CHAN Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorS. ORMISTON, S. ORMISTON Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorR. JOHNSON, R. JOHNSON Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorJ. CANICK, J. CANICK Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorL. BRIZENDINE, L. BRIZENDINE Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorH. WEINGARTNER, H. WEINGARTNER National Institute of Alcohol Abuse & Alcoholism Bethesda, Maryland 20892Search for more papers by this author O. M. WOLKOWITZ, O. M. WOLKOWITZ Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorV. I. REUS, V. I. REUS Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorE. ROBERTS, E. ROBERTS Department of Neurobiochemistry City of Hope Duarte, California 91010Search for more papers by this authorF. MANFREDI, F. MANFREDI Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorT. CHAN, T. CHAN Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorS. ORMISTON, S. ORMISTON Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorR. JOHNSON, R. JOHNSON Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorJ. CANICK, J. CANICK Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorL. BRIZENDINE, L. BRIZENDINE Department of Psychiatry UCSF San Francisco, California 94143–0984Search for more papers by this authorH. WEINGARTNER, H. WEINGARTNER National Institute of Alcohol Abuse & Alcoholism Bethesda, Maryland 20892Search for more papers by this author First published: December 1995 https://doi.org/10.1111/j.1749-6632.1995.tb17403.x-i1Citations: 68AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume774, Issue1Dehydroepiandrosterone (DHEA) and AgingDecember 1995Pages 337-339 RelatedInformation

Dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), major circulating steroids in humans which serve as precursors for both androgenic and estrogenic steroids, are pleiotropic facilitators of coordinating processes in immune, neural, and metabolic systems, and have been shown to enhance memory in young mice and improve defective recall in old mice. Both substances are diminished with aging and as a result of prolonged s~ss. As a first step in study of possible linkage between impaired memory function and steroid metabolism in patients with major depression, measurements were made of blood levels of cortisol, DHEA, DHEA-S, and of performance in the Weingartuer Memory Task in 57 depressives and 23 age and sex.matched normal controls. No significant differences between depressives and controls were found in levels of DHEA, DHEAS, or cortisol/DHEA and eortisol/DHEA-S ratios. Both groups showed a significant positive correlation of the above ratios with age, reflecting the relative constancy of cortisol and prog.'essive decrements of DHEA and DHEA-S. In the controls, cortisol/DEIEA-S ratios were negatively correlated with components of automatic (p .0009) and semantic (p .04) memory processes. Because of greater variability in cognitive and biochemical measures, correlations did not attain statistical significance in the patients. The results cited above and preliminary data in cognitively impaired individuals support the supposition that circulating androgenic steroids may interact intimately with cognitive processes, and suggest that therapeutic trials are warranted.

identified. The average dose was 300 mg/d. This study supports the f'mdings in the adult population of the anti-aggressive effect of clozapine. In this sample, there was a high comorbidity of psychosis with other disorders such as Tourette's Disorder, Obsessive-Compulsive Disorder and Posttraumatic Stress Disorder. The sample as a whole, had numerous pharmacological failures. Blood cell counts remained stable. In four patients, when clozapine was discontinued, symptomatology reemerged including the aggression, in only one patient, clozapine was discontinued because of side effects that were not hematological in nature. The most common side effects were salivation and weight gain. This study supports previous findings of the anti-aggressive effects of clozapine. Clozapine's affinity for the 5-HT 2 receptors might explain this effect.

Ketoconazole, an antiglucocorticoid drug, was administered to 10 hypercortisolemic depressed patients for up to 6 weeks. Three patients dropped out because of side effects or intercurrent illness. The remaining seven had significant ketoconazole-associated decreases in serum cortisol levels and in depression ratings. Antiglucocorticoid agents may be useful probes for investigating the sequelae of hypercortisolemia in patients with major depression.

Major depressive illness is frequently associated with cortisol hypersecretion. The pathophysiologic significance of this is unknown, although it is possible that hypercortisolemia exacerbates or perpetuates depressive symptoms. In both depression and Cushing's syndrome, certain depressive symptoms are correlated with cortisol levels and, in the latter condition, therapeutic lowering of cortisol levels is associated with remission of psychiatric symptomatology. We review the behavioral effects of anticortisolemic drug administration in Cushing's syndrome and major depression. Preliminary data from small-scale studies suggest that ratings of depressive symptoms in hypercortisolemic major depression may be lowered by such interventions. Such results, if confirmed in larger scale, double-blind studies, might help clarify the role of endocrinologic disturbance in psychiatric symptomatology and might lead to the development of a novel class of antidepressant agent for hypercortisolemic depressed patients.