Adjunctive pregnenolone ameliorates the cognitive deficits in recent-onset schizophrenia



This study aimed to examine the effect of add-on treatment with the neurosteroid pregnenolone (PREG) on neurocognitive dysfunctions of patients with recent-onset schizophrenia (SZ) and schizoaffective disorder (SA).

Sixty out-and inpatients that met DSM-IV criteria for SZ/SA were randomized an 8-week, double-blind, randomized, placebo-controlled, 2-center trial. Participants received either pregnenolone (50 mg/d) or placebo added on to antipsychotic medications. Computerized Cambridge Automated Neuropsychological Test Battery measures were administered at baseline and after 4 and 8 weeks of treatment. ANOVA and paired t or z-tests were applied to examine between- and within-group differences over time.RESULTS: Compared to placebo, adjunctive PREG significantly reduced the deficits in visual attention measured with the Matching to Sample Visual Search task (p=0.002) with moderate effect sizes (d= 0.42). In addition, a significant improvement was observed from baseline to end-of-study with respect to the visual (p= 0.008) and sustained attention (Rapid Visual Information Processing, p=0.038) deficits, and executive functions (Stockings of Cambridge, p=0.049; Spatial Working Memory, p<0.001) among patients receiving PREG, but not among those receiving placebo (all p’s >0.05). This beneficial effect of PREG was independent of the type of the antipsychotic agents, gender, age, education, and illness duration.CONCLUSIONS: Pregnenolone augmentation demonstrated significant amelioration of the visual attention deficit in recent-onset SZ/SA. Long-term, large-scale studies are required to obtain greater statistical significance and more confident clinical generalization.