Cumulative exposure to estrogen and psychosis: a peak bone mass, case-control study in first-episode psychosis

The organizational structural effects of estrogen may be cumulative and permanent by impacting on neurodevelopment, giving rise to “neuroprotective” effects and eventually reduction of psychosis risk. Reduction in bone mineral density (BMD, in g/cm2), as a biological marker of reduced cumulative exposure to estrogen, may be a marker of increased psychosis risk. A sample of 19 first-episode female psychosis patients with minimal previous antipsychotic exposure (mean 10 weeks) and 20 female controls underwent advanced fan-beam dual X-ray absorptiometry (DXA) to assess lumbal spine BMD of the region of L1-L4. Mean BMD was around one standard deviation lower in patients (1.13, S.D.=0.10) than in controls (1.25, S.D.=0.12; p=0.0021), and 84% of patients scored below the median value of the controls (OR=5.3, 95% CI: 1.2, 24.2). The results are compatible with the hypothesis that psychosis in women may be associated causally with a reduced protective effect of estrogen over the course of development.