Dehydroepiandrosterone and Pregnenolone Alterations in Schizophrenia

Ritsner, Michael S.; Gibel, Anatoly; Ratner, Yaël; Weizman, Abraham

doi:10.1007/978-1-4020-6854-6_14

Cited by 7 publications

(8 citation statements)

References 220 publications

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“…PREG and its metabolites such as pregnenolone sulfate (PREGS) (both PREG and PREGS [PREG(S)]), DHEA and DHEA sulfate (DHEAS) (both DHEA and DHEAS [DHEA(S)]) are neurosteroids. Figure 1 presents biosynthesis of PREG(S), DHEA(S), and other steroids [6]. Briefly, trophic hormones activate a chain of reactions that lead to the hydrolysis of cholesterol esters into free cholesterol, and the transport of cholesterol into mitochondria where it is converted to PREG by cytochrome P450 side‐chain cleavage (P450 scc; now referred to as CYP11A1).…”

Section: Steroidogenesismentioning

confidence: 99%

“…DHEA(S) concentrations in the human brain were found to be much higher than in peripheral circulation and also exceeded their very low cerebrospinal fluid (CSF) levels, ranging from about 1% to 5% of the corresponding plasma concentrations. DHEA(S) levels decrease markedly with age in humans, and levels in elderly populations are reduced to 20 to 30% of peak levels in young adulthood (reviewed in [6]).…”

Section: Steroidogenesismentioning

confidence: 99%

“…Biological actions of PREG(S) and DHEA(S) include neuroprotection against apoptosis, N ‐methyl‐ d ‐aspartate (NMDA) or oxidative damage, promotion of neurite growth, opposition of glucocorticoids, neurite growth, and antagonistic effects on oxidants and glucocorticoids, a modulatory effect on neuronal excitability and synaptic plasticity; they have many functions associated with response to stress, mood regulation, and cognitive performance [6,13,14].…”

Section: Neuroprotective Effectsmentioning

confidence: 99%

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Pregnenolone, Dehydroepiandrosterone, and Schizophrenia: Alterations and Clinical Trials

Ritsner

2010

CNS Neuroscience & Therapeutics

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Neurosteroids, such as pregnenolone (PREG), dehydroepiandrosterone (DHEA), and their sulfates (PREGS and DHEAS) are reported to have a modulatory effect on neuronal excitability and synaptic plasticity. They also have many other functions associated with neuroprotection, response to stress, mood regulation, and cognitive performance. Furthermore, these neurosteroids have been linked to, and their levels are altered in, neuropsychiatric disorders. This review highlights what is currently known about the metabolism and mode of action of PREG and DHEA, as well as about alterations of these neurosteroids in schizophrenia. This review also provides substantial information about clinical trials with DHEA and PREG augmentation with of antipsychotic agents in schizophrenia.

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Section: Steroidogenesismentioning

confidence: 99%

Section: Steroidogenesismentioning

confidence: 99%

Section: Neuroprotective Effectsmentioning

confidence: 99%

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Pregnenolone, Dehydroepiandrosterone, and Schizophrenia: Alterations and Clinical Trials

Ritsner

2010

CNS Neuroscience & Therapeutics

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“…In addition to the possible therapeutic effects of sex hormones in schizophrenia, precursors of these sex hormones, such as dehydroepiandrosterone (DHEA; a precursor for both testosterone and estrogen) and pregnenolone, may have neuroprotective properties as well and could therefore play a modifying role in the pathophysiology of schizophrenia (Ritsner et al, 2008;Ritsner, 2010). These precursors have many functions of their own, including mood regulation, cognitive performance, and response to stress (Mellon, 2007;Maninger et al, 2009).…”

Section: Introductionmentioning

confidence: 98%

Sex hormones and oxytocin augmentation strategies in schizophrenia: A quantitative review

Heringa

Begemann

Goverde

et al. 2015

Schizophrenia Research

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“…5 There is evidence that PREG and its metabolites may be involved in the pathophysiology of schizophrenia, mood disorders, dementia and substance abuse. [6][7][8] Clinical studies demonstrated low circulating levels of PREG in the elderly, including those with dementia, 6 in individuals with major depression, 7 anxiety disorder, 9 and in chronic medicated schizophrenia patients. 10 Two clinical trials with add-on PREG in chronic SZ/SA were published.…”

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confidence: 99%

Pregnenolone treatment reduces severity of negative symptoms in recent‐onset schizophrenia: An 8‐week, double‐blind, randomized add‐on two‐center trial

Ritsner

Bawakny

Kreinin

2014

Psychiatry Clin Neurosci

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Aims: Management of recent-onset schizophrenia (SZ) and schizoaffective disorder (SA) is challenging owing to frequent insufficient response to antipsychotic agents. This study aimed to test the efficacy and safety of the neurosteroid pregnenolone in patients with recent-onset SZ/SA. Methods:Sixty out-and inpatients who met DSM-IV criteria for SZ/SA, with suboptimal response to antipsychotics were recruited for an 8-week, doubleblind, randomized, placebo-controlled, two-center add-on trial, that was conducted between 2008 and 2011. Participants were randomized to receive either pregnenolone (50 mg/day) or placebo added on to antipsychotic medications. The primary outcome measures were the Positive and Negative Symptoms Scale and the Assessment of Negative Symptoms scores. Secondary outcomes included assessments of functioning, and side-effects.Results: Analysis was by linear mixed model. Fiftytwo participants (86.7%) completed the trial. Compared to placebo, adjunctive pregnenolone significantly reduced Positive and Negative Symptoms Scale negative symptom scores with moderate effect sizes (d = 0.79). Significant improvement was observed in weeks 6 and 8 of pregnenolone therapy among patients who were not treated with concomitant mood stabilizers (arms × visit × mood stabilizers; P = 0.010). Likewise, pregnenolone significantly reduced Assessment of Negative Symptoms scores compared to placebo (d = 0.57), especially on blunted affect, avolition and anhedonia domain scores. Other symptoms, functioning, and side-effects were not significantly affected by adjunctive pregnenolone. Antipsychotic agents, benzodiazepines and sex did not associate with pregnenolone augmentation. Pregnenolone was well tolerated.Conclusions: Thus, add-on pregnenolone reduces the severity of negative symptoms in recent-onset schizophrenia and schizoaffective disorder, especially among patients who are not treated with concomitant mood stabilizers. Further studies are warranted.

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Dehydroepiandrosterone and Pregnenolone Alterations in Schizophrenia

Cited by 7 publications

References 220 publications

Pregnenolone, Dehydroepiandrosterone, and Schizophrenia: Alterations and Clinical Trials

Pregnenolone, Dehydroepiandrosterone, and Schizophrenia: Alterations and Clinical Trials

Sex hormones and oxytocin augmentation strategies in schizophrenia: A quantitative review

Pregnenolone treatment reduces severity of negative symptoms in recent‐onset schizophrenia: An 8‐week, double‐blind, randomized add‐on two‐center trial

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