Dehydroepiandrosterone Augmentation in the Management of Negative, Depressive, and Anxiety Symptoms in Schizophrenia

Strous, Rael D.; Maayan, Rachel; Lapidus, Raya; Stryjer, Rafael; Lustig, Michal; Kotler, Moshe; Weizman, Abraham

doi:10.1001/archpsyc.60.2.133

Cited by 189 publications

(113 citation statements)

References 54 publications

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“…For instance, synthetic androgens might also induce and precipitate psychotic-like abnormalities (Trenton and Currier, 2005). Conversely, testosterone and dehydroepiandrosterone may have antipsychotic potential (Strous, 2005;Strous et al, 2003;Van den Buuse and Eikelis, 2001) and their levels are typically low in schizophrenia patients (Goyal et al, 2004;Huber et al, 2005;Taherianfard and Shariaty, 2004).…”

Section: Introductionmentioning

confidence: 99%

Antipsychotic-Like Properties of 5-α-Reductase Inhibitors

Bortolato

Frau

Orrù

et al. 2008

Neuropsychopharmacol

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Recent evidence indicates that neuroactive steroids may participate in the pathogenesis of schizophrenia spectrum disorders, yet the mechanisms of this involvement are elusive. As 5-a-reductase (5AR) is the rate-limiting enzyme of one of the two major metabolic pathways in brain steroidogenesis, we investigated the effects of its blockade in several rat models of psychotic-like behavior. The 5AR inhibitor finasteride (FIN, 60 or 100 mg/kg, intraperitoneal, i.p.) dose-and time-dependently antagonized prepulse inhibition (PPI) deficits induced by apomorphine (APO, 0.25 mg/kg, subcutaneous, s.c.) and d-amphetamine (AMPH, 5 mg/kg, s.c.), in a manner analogous to haloperidol (HAL, 0.1 mg/kg, i.p.) and clozapine (CLO, 5 mg/kg, i.p.). Similar results were observed with the other 5AR inhibitors dutasteride (DUT, 40 or 80 mg/kg, i.p.) and SKF 105111 (30 mg/kg, i.p.). FIN (60 or 100 mg/kg, i.p.) also reduced hyperlocomotion induced by AMPH (1 or 3 mg/kg, s.c.) and attenuated stereotyped behaviors induced by APO (0.25 mg/kg, s.c.). Nevertheless, FIN (100 mg/kg, i.p.) did not reverse the PPI disruption induced by the N-methyl-d-aspartate receptor antagonist dizocilpine (0.1 mg/kg, s.c.). FIN (60-300 mg/kg, i.p.) induced no catalepsy in either the bar test or the paw test. Our results suggest that 5AR inhibitors elicit antipsychotic-like effects in animals and may be proposed as a putative novel target in the management of psychotic disorders.

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Section: Introductionmentioning

confidence: 99%

Antipsychotic-Like Properties of 5-α-Reductase Inhibitors

Bortolato

Frau

Orrù

et al. 2008

Neuropsychopharmacol

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“…The adrenal steroid dehydroepiandrosterone (DHEA) has antiglucocorticoid properties that may prove useful regulating high cortisol levels and glucocorticoid action in the brains of psychiatric patients 108 . Studies using DHEA in addition to antipsychotic medication in already-medicated schizophrenic patients found a significant improvement in the negative, depressive and anxiety symptoms of the disease 109 .…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Os efeitos do estresse na função do eixo hipotalâmico-pituitário-adrenal em indivíduos com esquizofrenia

Guest

Martins-de-Souza²,

Rahmoune

et al. 2012

Arch. Clin. Psychiatry (São Paulo)

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Over the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA) axis. Variations in the manifestation of these effects could be related to the differences in clinical symptoms between affected individuals as well as to differences in treatment response. Such effects can also arise from the complex interaction between genes and environmental factors. Here, we review the effects of maternal stress on abnormalities in HPA axis regulation and the development of psychiatric disorders including schizophrenia. Studies in this area may prove critical for increasing our understanding of the multi-dimensional nature of schizophrenia. Further research in this area could ultimately lead to the development of improved diagnostics and novel therapeutic approaches for treating this debilitating psychiatric condition.Guest FL, et al. / Rev Psiq Clín. 2013;40(1):20-7 Keywords: Psychiatric disorders, schizophrenia, HPA axis dysfunction, diagnosis, biomarkers. ResumoNas últimas décadas, têm surgido evidências sugerindo que a patogênese de desordens psiquiátricas, tais como a esquizofrenia, pode envolver perturbações no eixo hipotalâmico-pituitário-adrenal (HPA). Variações na manifestação desses efeitos poderiam estar relacionadas a diferenças em sintomas clínicos entre os indivíduos afetados, assim como a diferenças na resposta ao tratamento. Tais efeitos podem também ser originados de complexas interações entre genes e fatores ambientais. Aqui, revisamos os efeitos do estresse maternal em anormalidades na regulação do eixo HPA e desenvolvimento de desordens psiquiátricas, incluindo a esquizofrenia. Estudos nessa área podem gerar o aumento do nosso entendimento da natureza multidimensional da esquizofrenia. Posterior pesquisa nesse campo poderia, em última instância, levar ao desenvolvimento de melhores diagnósticos e novas abordagens terapêuticas para essa debilitante condição psiquiátrica.Guest FL, et al. / Rev Psiq Clín. 2013;40(1):20-7 Palavras-chave: Desordens psiquiátricas, esquizofrenia, disfunção do eixo HPA, diagnóstico, biomarcadores.

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“…156,157 Indeed, a doubleblind study of DHEA as an adjunct to antipsychotic treatment in chronic schizophrenic patients with prominent negative symptoms suggests some efficacy at improving negative symptoms, especially in women, 158 though further studies are needed.…”

Section: Neurotensin Receptorsmentioning

confidence: 99%

The pipeline and future of drug development in schizophrenia

2007

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While the current antipsychotic medications have profoundly impacted the treatment of schizophrenia over the past 50 years, the newer atypical antipsychotics have not fulfilled initial expectations, and enormous challenges remain in long-term treatment of this debilitating disease. In particular, improved treatment of the negative symptoms and cognitive dysfunction in schizophrenia which greatly impact overall morbidity is needed. In this review we will briefly discuss the current pipeline of drugs for schizophrenia, outlining many of the strategies and targets currently under investigation for the development of new schizophrenia drugs. Many of these compounds have great potential as augmenting agents in the treatment of negative symptoms and cognition. In addition, we will highlight the importance of developing new paradigms for drug discovery in schizophrenia and call for an increased role of academic scientists in discovering and validating novel drug targets. Indeed, recent breakthroughs in genetic studies of schizophrenia are allowing for the development of hypothesis-driven approaches for discovering possible disease-modifying drugs for schizophrenia. Thus, this is an exciting and pivotal time for the development of truly novel approaches to drug development and treatment of complex disorders like schizophrenia.

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Dehydroepiandrosterone Augmentation in the Management of Negative, Depressive, and Anxiety Symptoms in Schizophrenia

Cited by 189 publications

References 54 publications

Antipsychotic-Like Properties of 5-α-Reductase Inhibitors

Antipsychotic-Like Properties of 5-α-Reductase Inhibitors

Os efeitos do estresse na função do eixo hipotalâmico-pituitário-adrenal em indivíduos com esquizofrenia

The pipeline and future of drug development in schizophrenia

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