Pregnenolone-progesterone-allopregnanolone pathway as a potential therapeutic target in first-episode patients with schizophrenia

SzAdmin · February 17, 2018, 2:52pm

Converging evidence indicates a pattern of reduced Pregnenolone and its related endogenous steroids in schizophrenia (SZ). Low levels of serum Pregnenolone have been found in SZ patients compared to healthy controls (HC) (Ritsner et al., 2007). Levels of plasma CORT in male SZ patients with moderate negative symptoms were significantly higher than HC (Shirayama et al., 2002).

Also, significant correlations between levels of plasma CORT and severity of negative symptom were observed in male SZ patients (Shirayama et al., 2002), suggesting that this endogenous steroid may serve as a biological marker for the severity of negative symptoms in SZ patients. In another study, following metabolic stress induced by injection of 2-deoxyglucose, SZ patients exhibited a significantly greater increase in plasma PROG compared to HC (Breier and Buchanan, 1992).

Moreover, findings from a proof-of-concept trial with adjunctive Pregnenolone treatment suggested that increases in serum Pregnenolone and allopregnanolone levels may predict cognitive outcome after 8 weeks (Marx et al., 2009). In a recent follow-up clinical trial, this same group of investigators further concluded that PREG improved functional capacity in SZ pa- tients, but did not improve cognitive symptoms after 8 weeks of treatment, suggesting that neurosteroids offer partial promise as a new therapeutic agent for SZ.

Full Research Paper Here (PDF download):

http://sci-hub.tw/http://linkinghub.elsevier.com/retrieve/pii/S0306453017314488#

Summary:

ncbi.nlm.nih.gov

Pregnenolone-progesterone-allopregnanolone pathway as a potential therapeutic target in first-episode antipsychotic-naïve patients with schizophrenia.

H Cai, X Zhou, GG Dougherty, RD Reddy, GL Haas, DM Montrose, M Keshavan and JK Yao, Psychoneuroendocrinology, Feb 2018 07

Neurosteroids are both endogenous and exogenous steroids that rapidly alter neuronal excitability through interactions with ligand-gated ion channels and other cell surface receptors. They are originated from cholesterol and have important implications for schizophrenia (SZ) pathophysiology and treatment strategies. Specifically, pregnenolone (PREG), progesterone (PROG) and allopregnanolone (ALLO) exhibit similar psychotropic properties. Using enzyme immunoassay, we compared the neurosteroids in PREG downstream pathways in plasma between healthy controls (HC, n = 43) and first-episode antipsychotic-naïve patients with SZ (FEAN-SZ, n = 53) before antipsychotic drug (APD) treatment. Comparisons were also made particularly along PREG-PROG-ALLO pathway in the same FEAN-SZ patients across multiple time points following initiation of treatment for 12 months (m). Firstly, at baseline, levels of PREG were significantly higher and those of ALLO were lower in FEAN-SZ than in HC, whereas PROG, cortisol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) were not different. Consequently, the molar ratios of ALLO/PREG and ALLO/PROG in FEAN-SZ were significantly reduced. Secondly, in response to APD at 1 month, ALLO levels in FEAN-SZ were markedly elevated, whereas PREG and PROG levels decreased. Thirdly, among FEAN-SZ, lower levels of PROG (reflecting higher conversion to ALLO) at baseline may predict better therapeutic outcome after 1 month of APD treatment. These findings point to the perturbations of the PREG-PROG-ALLO pathway early in psychosis, and further study of this pathway may inform alternative and innovative therapeutic targets for SZ.

pretzel · February 17, 2018, 2:55pm

I’m finally going to ask you, why are your posts always about medication? I don’t read them much because I don’t understand them.

SzAdmin · February 17, 2018, 2:57pm

This is a nutritional supplement - that you can purchase from any vitamin store. I generally post news on anything that might be helpful for people with schizophrenia - and that typically is medications, vitamins and supplements, and psychotherapies…

pretzel · February 17, 2018, 3:01pm

ok. Maybe it’s because I am happy with my meds. Also, supplements are pricy. No comments on day to day life?? My personal opinion is that a good environment is essential for our healing, too.

Green · February 17, 2018, 6:16pm

I just ordered some off Amazon.uk for £7.

Will this help in any way shape or form.

I’ve had schizophrenia for 15 years.

Green · February 17, 2018, 6:57pm

I’m looking forward to trying this, even if it doesn’t help.

I’m not that bad anyway.