Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia.

摘要: The neurosteroid pregnenolone and its sulfated derivative enhance learning memory in rodents. Pregnenolone sulfate also positively modulates NMDA receptors could thus ameliorate hypothesized receptor hypofunction schizophrenia. Furthermore, clozapine increases rodent hippocampus, possibly contributing to superior efficacy. We therefore investigated adjunctive for cognitive negative symptoms patients with schizophrenia or schizoaffective disorder receiving stable doses of second-generation antipsychotics a pilot randomized, placebo-controlled, double-blind trial. Following 2-week single-blind placebo lead-in, were randomized (fixed escalating 500 mg/day) placebo, 8 weeks. Primary end points changes BACS MCCB composite total SANS scores. Of 21 18 completed at least 4 weeks treatment (n=9/group). was well tolerated. Patients demonstrated significantly greater improvements scores (mean change=10.38) compared change=2.33), p=0.048. Mean not different placebo. However, serum predicted the group (rs=0.81, p=0.022). Increases allopregnanolone, GABAergic metabolite, (rs=0.74, p=0.046). In addition, baseline (rs=−0.76, p=0.037), (rs=−0.83, p=0.015), allopregnanolone levels p=0.015) inversely correlated scores, further supporting possible role neurosteroids cognition. p<0.0001). may be promising therapeutic agent merits investigation