Differences in blood pregnenolone and dehydroepiandrosterone levels between schizophrenia patients and healthy subjects

Tel Aviv University, Tell Afif, Tel Aviv, Israel
European Neuropsychopharmacology (Impact Factor: 4.37). 05/2007; 17(5):358-65. DOI: 10.1016/j.euroneuro.2006.10.001
Source: PubMed


Contradictory and confusing reports on serum dehydroepiandrosterone (DHEA) levels in schizophrenia led us to compare the serum concentration of its precursor, pregnenolone (PREG), between medicated schizophrenia patients and healthy subjects. The neurosteroid levels were monitored for two months and the relationship of these neurosteroids with schizophrenic symptomatology, emotional distress, and anxiety was examined.
We determined blood levels of PREG, and DHEA in 15 schizophrenia patients and 12 healthy controls at four time points: at the start of the study, after 2, 4 and 8 weeks. Analysis of covariance and canonical correlations across four time points were applied.
Controlling for age, serum concentrations of PREG were lower, while the DHEA level and the molar ratio values of DHEA/PREG were higher in schizophrenia patients compared to healthy controls. Both levels of PREG and DHEA and their molar ratio did not change significantly during the study's period either among schizophrenia patients or healthy controls. The blood levels of PREG appear to be associated with trait-anxiety scores in the schizophrenia patients, while associations of clinical symptoms with two neurosteroids did not reach a significant level when the confounding effect of emotional distress, and anxiety scores was controlled.
Low serum pregnenolone concentrations in schizophrenia appear to be associated with trait-anxiety scores independent of symptoms. Further research into the role of pregnenolone in schizophrenia is warranted.

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Available from: Michael S. Ritsner
    • "Although findings on blood levels of DHEA and its sulfate (DHEAS) in schizophrenia are inconsistent, high levels of DHEA appear to be related to lower symptom severity (Harris et al., 2001; Marx et al., 2004). In addition, serum concentrations of pregnenolone are found to be lower in schizophrenia patients compared to healthy controls (Ritsner et al., 2007). "
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    ABSTRACT: Sex differences in incidence, onset and course of schizophrenia suggest sex hormones play a protective role in the pathophysiology. Such a role is also proposed for oxytocin, another important regulator of reproduction function. Evidence on the efficacy of sex hormones and oxytocin in the treatment of schizophrenia is summarized. Double-blind, placebo-controlled, randomized studies were included, examining augmentation with estrogens, selective estrogen receptor modulators (SERMs), testosterone, dehydroepiandrosterone (DHEA), pregnenolone, and oxytocin. Outcome measures were total symptom severity, positive and negative symptom subscores, and cognition. In meta-analyses, combined weighted effect sizes (Hedges' g) per hormone were calculated. Twenty-four studies were included, examining 1149 patients. Significant effects were found for estrogen action (k=10), regarding total symptoms (Hedges' g=0.63, p=0.001), positive (Hedges' g=0.42, p<0.001), and negative symptoms (Hedges' g=0.35, p=0.001). Subgroup analyses yielded significant results for estrogens in premenopausal women (k=6) for total, positive, and negative symptoms, and for the SERM raloxifene in postmenopausal women (k=3) for total and negative, but not positive symptoms. Testosterone augmentation in males (k=1) was beneficial only for negative symptoms (Hedges' g=0.82, p=0.027). No overall effects were found for DHEA (k=4), pregnenolone (k=4), and oxytocin (k=6). Results for cognition (k=12) were too diverse for meta-analyses, and inspection of these data showed no consistent benefit. Estrogens and SERMs could be effective augmentation strategies in the treatment of women with schizophrenia, although potential side effects, partially associated with longer duration use, should be taken into account. Future trials are needed to study long-term effects and effects on cognition. Copyright © 2015 Elsevier B.V. All rights reserved.
    No preview · Article · Apr 2015 · Schizophrenia Research
    • "Likewise , DHEA to PREG molar ratio, serum concentrations of PREG, and DHEA did not reach a significant level between schizophrenia patients who received first-, second-generation , and both types of antipsychotic agents (Ritsner et al., 2006b). Patients who received first-, second-generation antipsychotic agents had comparable serum DHEA(S) and their metabolite levels (Ritsner et al., 2007a). However, it should be noted that antipsychotic treatment and elevated prolactin might stimulate the adrenal cortex to secrete DHEA. "

    No preview · Article · Oct 2014
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    • "In a recent study, serum pregnenolone levels were significantly reduced in first-episode antipsychotic-naïve participants with schizophrenia in both males and females (Bicikova et al. 2013). A prior study also reported lower serum pregnenolone levels in participants with schizophrenia (Ritsner et al. 2007). In contrast, pregnenolone levels in postmortem brain tissue samples (posterior cingulate and parietal cortex) were higher in schizophrenia (Marx et al. 2006c), potentially reflecting medication-induced pregnenolone elevations . "
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    ABSTRACT: Preclinical and clinical data suggest that pregnenolone may be a promising therapeutic in schizophrenia. Pregnenolone is neuroprotective and enhances learning and memory, myelination, and microtubule polymerization. Treatment with pregnenolone elevates allopregnanolone (a neurosteroid that enhances GABAA receptor responses) and pregnenolone sulfate (a positive NMDA receptor modulator). Pregnenolone could thus potentially mitigate GABA dysregulation and/or NMDA receptor hypofunction in schizophrenia via metabolism to other neurosteroids.
    Full-text · Article · Jul 2014 · Psychopharmacology
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