Treatment with dehydroepiandrosterone sulfate increases NMDA receptors in hippocampus and cortex

Shao, Wang; Dong, Kai; Onolfo, J. P.; Vincens, M

doi:10.1016/s0014-2999(01)01383-8

Cited by 45 publications

(22 citation statements)

References 4 publications

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“…Overall, it is still possible that the endocrine findings are not related to a diagnostic specificity, and the elevated cortisol/DHEA(S) ratios in schizophrenia patients may be associated with impaired stress-response (Wolf and Kirschbaum, 1999;Boudarene and Legros, 2002;Kimonides et al, 1999) and may lead to dysregulated neurotransmission (Akwa and Baulieu, 2000), resulting in chronic and progressive deterioration in cognitive, emotional, and psychosocial functions (Wen et al, 2001;Johnson et al, 2002). Indeed, clinical investigations produced evidence of the involvement of neuroactive steroids in conditions such as fatigue during pregnancy, premenstrual syndrome, postpartum depression, epilepsy, dementia, depressive, and anxiety disorders (Stoffel-Wagner, 2001;Pisua and Serra, 2004).…”

Section: Commentmentioning

confidence: 99%

“…Neurosteroids exert multiple effects in the central nervous system mediated through its nongenomic actions on several neurotransmitter systems, such as gamma-aminobutyric acid (GABA A ), N-methyl-D-aspartate (NMDA), and sigma receptors (Majewska, 1992;Debonnel et al, 1996;Wen et al, 2001), modulating neuronal excitability and plasticity, as well as presenting neuroprotective properties (Kimonides et al, 1998;Cardounel et al, 1999;Wolf and Kirschbaum, 1999;Lhullier et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Cortisol/Dehydroepiandrosterone Ratio and Responses to Antipsychotic Treatment in Schizophrenia

Ritsner

Gibel

Maayan

et al. 2005

Neuropsychopharmacol

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Dehydroepiandrosterone (DHEA) or their sulfate conjugate (DHEAS) (together abbreviated DHEA(S)) exert multiple effects in the central nervous system, and may be involved in the pathophysiological processes in schizophrenia. This prospective study aimed to investigate whether serum cortisol/DHEA(S) molar ratios are associated with response to antipsychotic treatment during the exacerbation of schizophrenia. Serum DHEA(S) and cortisol were determined at baseline, and 2 and 4 weeks later for 43 medicated schizophrenia inpatients with acute exacerbation. The patients were treated with stable doses of antipsychotic agents up to 2 weeks prior to entering the study and for the 4-week duration of the study after which they were classified as either responders or nonresponders to treatment. Findings suggest that responders had significantly higher serum cortisol levels and cortisol/DHEA(S) ratios compared with nonresponders. These differences remained significant at three time points controlling for gender, age, severity of symptoms and emotional distress, benzodiazepines, type or dosage of antipsychotic agents, and background variables. The logistic regression model shows advantages of both cortisol/DHEA(S) molar ratios vs serum cortisol and DHEA(S) concentrations for prediction of responsivity to antipsychotic treatment. No significant canonical correlations were observed between changes from baseline through end-of-study in hormonal values and severity of symptoms and emotional distress among responders and nonresponders. Thus, these data provide evidence that elevated serum cortisol and cortisol/DHEA(S) ratios may serve as markers of biological mechanisms that are involved in responsivity of schizophrenia patients to antipsychotic treatment.

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Section: Commentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cortisol/Dehydroepiandrosterone Ratio and Responses to Antipsychotic Treatment in Schizophrenia

Ritsner

Gibel

Maayan

et al. 2005

Neuropsychopharmacol

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“…The latter observation, if replicated in larger studies, would support the notion on general and direct involvement of a glutamatergic hypofunction in schizophrenia [Tsai and Coyle, 2002]. Remarkably, a recent trial [Strous et al, 2003] reported that treatment with the hormone dehydroepiandrosterone (DHEA), known to enhance NMDA neurotransmission [Wen et al, 2001] improved negative symptoms in schizophrenia patients, maybe via conversion to DHEA-sulfate in the brain. It remains to be seen if these encouraging observations will be replicated in large-scale trials, and if DHEA administration might be more beneficial for schizophrenia patients carrying risk alleles for G72 or DAAO.…”

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confidence: 68%

Pharmacogenomics of schizophrenia: Towards personalized psychiatry

Genevieve

2003

Drug Development Research

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Psychiatry is among the primary medical disciplines to focus on the potential benefits from the cloning of the human genome and the subsequent implementation of personalized medicine. This viewpoint reflects the evident difficulties of current psychiatric practice compared with other disciplines, most notably the limited understanding of disease etiologies, the lack of reliable and objective diagnostic tools, and the paucity of relevant animal models. These aspects of psychiatry face major changes as a consequence of the recent identification of several schizophrenia risk genes. The reviews presented in this issue illustrate the potential for innovative drug discovery and personalized pharmacotherapy for schizophrenia. Drug Dev. Res. 60:71-74, 2003.

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“…The site of a DHEA-S action that protects the ANS cannot be determined from our study. However, DHEA-S readily crosses the blood-brain barrier and peripheral infusions have been found to affect various sites in the brain (20,23,41). We would therefore speculate that DHEA-S can influence ANS responses via direct brain sensing, but future studies will be needed to determine whether this is in fact the case.…”

Section: Discussionmentioning

confidence: 96%

“…Brain N-methyl-D-aspartate (NMDA) and ␥-aminobutyric acid (GABA) receptors are known to have excitatory and inhibitory effects on neuronal norepinephrine release, and thus ANS function, respectively. Although DHEA-S has been shown to have stimulatory effects on NMDA activity (21) and receptor number (41) and inhibitory effects on GABA receptor activity (42), corticosterone has been found to increase the affinity of GABA receptors (43). Therefore, DHEA-S could be stimulatory to the ANS (stimulatory to NMDA and inhibitory to GABA receptors), whereas cortisol may be inhibitory (i.e., may increase activity of GABA receptors).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Dehydroepiandrosterone Sulfate on Counterregulatory Responses During Repeated Hypoglycemia in Conscious Normal Rats

et al. 2004

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We previously determined that both antecedent hypoglycemia and elevated cortisol levels blunt neuroendocrine and metabolic responses to subsequent hypoglycemia in conscious, unrestrained rats. The adrenal steroid dehydroepiandrosterone sulfate (DHEA-S) has been shown in several studies to oppose corticosteroid action. The purpose of this study was to determine if DHEA-S could preserve counterregulatory responses during repeated hypoglycemia. We studied 40 male Sprague-Dawley rats during a series of 2-day protocols. T he Diabetes Control and Complications Trial established that intensive glucose control in type 1 diabetic patients can slow the progression or significantly reduce the onset of diabetic microvascular complications (e.g., retinopathy, nephropathy, neuropathy) (1). Unfortunately, the study also established that intensive glucose treatment causes an approximate threefold increase in the frequency of severe hypoglycemia (2). This increased frequency of hypoglycemia is at least partially caused by deficient autonomic nervous system (ANS) counterregulatory responses to hypoglycemia (3-5). Repeated exposure to hypoglycemia reduces neuroendocrine, ANS, and metabolic (endogenous glucose production [EGP], lactate, and glycerol) counterregulatory responses to subsequent hypoglycemia by as much as 50% in nondiabetic and type 1 diabetic subjects (6 -9). These blunted counterregulatory responses are significant contributing factors to a vicious cycle of hypoglycemia for type 1 diabetic patients (9).The mechanisms responsible for the blunted counterregulatory responses seen after antecedent hypoglycemia are not fully understood. Controversy exists regarding the role played by corticosteroids in the pathophysiology of blunted ANS responses during hypoglycemia (10 -14). Reports in rodents (12) and humans (15) have demonstrated that, similar to antecedent hypoglycemia, antecedent increases of cortisol can blunt neuroendocrine and metabolic counterregulatory responses to next day hypoglycemia. In addition, patients with adrenocortical failure have preserved catecholamine, pancreatic polypeptide, glucagon, growth hormone, and muscle sympathetic nerve activity responses to hypoglycemia after antecedent hypoglycemia (16). Other animal studies have found that corticosteroids can blunt catecholamine responses to a variety of stressors, including insulin-induced hypoglycemia in sheep (17) and immobilization stress in rats (18,19). However, in contrast to the above studies, three other reports have indicated that prior corticosterone administration has little or no effect on ANS responses to subsequent hypoglycemia in the conscious rat (10,13,14).

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Treatment with dehydroepiandrosterone sulfate increases NMDA receptors in hippocampus and cortex

Cited by 45 publications

References 4 publications

Cortisol/Dehydroepiandrosterone Ratio and Responses to Antipsychotic Treatment in Schizophrenia

Cortisol/Dehydroepiandrosterone Ratio and Responses to Antipsychotic Treatment in Schizophrenia

Pharmacogenomics of schizophrenia: Towards personalized psychiatry

The Effects of Dehydroepiandrosterone Sulfate on Counterregulatory Responses During Repeated Hypoglycemia in Conscious Normal Rats

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