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

•Plasma pregnenolone pathways were assessed between controls (HC) and first–episode schizophrenia (SZ) before antipsychotic treatment (AT).•Levels of pregnenolone (PREG) were significantly higher and allopregnanolone (ALLO) were lower in first–episode patients with SZ than in HC.•In response to AT for one month (1 - m), ALLO levels in SZ patients were markedly elevated whereas PREG and progesterone (PROG) levels decreased.•SZ patients with lower levels of PROG at baseline may predict better therapeutic outcome after 1 - m antipsychotic treatment.•PREG–PROG–ALLO pathway was abnormal early in psychosis, and future study may inform alternative and innovative therapeutic targets for SZ.