"Epidemiological and clinical life cycle studies have indicated that the more favorable illness course and the better response to antipsychotic drugs (APDs) in women with schizophrenia correlate with high levels of estrogen, whereas increased vulnerability to exacerbation and relapse and reduced sensitivity to treatment are associated with low estrogen levels. Accordingly, the estrogen hypothesis of schizophrenia proposes that estrogen has a neuroprotective effect in women vulnerable to schizophrenia," researchers in Tel Aviv, Israel report (see also Schizophrenia).

"Latent inhibition (LI), the capacity to ignore stimuli that received nonreinforced preexposure prior to conditioning, is disrupted in acute schizophrenia patients and in rats and humans treated with the psychosis inducing drug amphetamine. Disruption of LI is reversible by typical and atypical APDs. The present study tested whether low levels of estrogen induced by ovariectomy (OVX) would lead to disruption of LI in female rats and whether such disruption would be normalized by estrogen replacement treatment and/or APDs. OVX led to LI disruption, which was reversed by 17 beta-estradiol (150 mu g/kg) and the atypical APD clozapine (5 mg/kg), but not by the typical APD haloperidol (0.1, 0.2, 0.3 mg/kg). Haloperidol regained efficacy when administered with 17 beta-estradiol (50 mu g/kg). These results provide the first demonstration in rats that low levels of hormones can induce a pro-psychotic state that is resistant to at least typical antipsychotic treatment," wrote M. Arad and colleagues, Tel-Aviv University.

The researchers concluded: "This constellation may mimic states seen in schizophrenic women during periods associated with low levels of hormones such as the menopause."

Arad and colleagues published their study in Psychopharmacology (Disruption of latent inhibition induced by ovariectomy can be reversed by estradiol and clozapine as well as by co-administration of haloperidol with estradiol but not by haloperidol alone. Psychopharmacology, 2009;206(4 Sp. Iss.):731-740).

For additional information, contact I. Weiner, Tel Aviv University, Dept. of Psychology, IL-69978 Tel Aviv, Israel.

Publisher contact information for the journal Psychopharmacology is: Springer, 233 Spring St., New York, NY 10013, USA.