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.
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