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In This Issue of JAMA Psychiatry
October 2019


JAMA Psychiatry. 2019;76(10):997. doi:10.1001/jamapsychiatry.2018.3005


Estradiol is reported to have antipsychotic properties, but this has not been independently replicated. Weiser and colleagues conducted a single-site 8-week randomized placebo-controlled trial of 200 μg of estradiol in a patch in 100 women of childbearing age and found that the estradiol patch led to significantly greater improvement in the primary outcome than placebo, with the strongest effect in older women. These results replicate the finding that estradiol is antipsychotic in women of childbearing age and they have implications for new therapeutic approaches.

Editor’s Note

Continuing Medical Education

Most genome-wide association studies in schizophrenia have been conducted in European populations to date. Periyasamy and colleagues present a study of 1321 Indian participants with schizophrenia, 885 family controls, and 886 unrelated controls and report a novel genome-wide significant association between schizophrenia and a chromosome 8q24.3 locus that directly modifies niacin metabolism and is associated with abnormal brain development. These results suggest that niacin status may have implications for schizophrenia susceptibility. In an Editorial, Nimgaonkar discusses the implications of genome-wide association studies in non-European populations.


No individual-level study to date has estimated additive genetic, maternal, and environmental effects in autism spectrum disorder. Bai and colleagues examined population-based cohorts from 5 countries followed up from birth until age 16 years and found median autism spectrum disorder heritability of 80.8% and a maternal effect of around 1%. These results indicate that autism spectrum disorder variation in the population is mostly owing to inherited genetic influences with little support for contribution from maternal effects. In an Editorial, Jutla and colleagues discuss implications for autism research.


Recent meta-analyses of randomized clinical trials have challenged clozapine’s superiority over other antipsychotics, but patients in clinical trials are not always generalizable to clinical practice. Masuda and colleagues conducted a meta-analysis of individual cohort studies including 109 341 patients and found that, despite greater illness severity, patients receiving clozapine were significantly less likely to be hospitalized and to discontinue medication, although clozapine was associated with increases in body weight and type 2 diabetes. Thus, cohort studies support greater efficacy for clozapine. In an Editorial, Stroup discusses implications for clinical practice.


Cannabinoid 1 receptor has been implicated in the pathophysiology of psychosis, but its brain levels in early stages of psychosis are unknown. In a cross-sectional positron emission tomography study of 2 independent samples, Borgan and colleagues studied brain availability of cannabinoid 1 receptor in 27 male patients with first-episode psychosis and 31 male control individuals and found that it was significantly lower in multiple brain regions in patients compared with controls. These findings suggest cannabinoid 1 receptor may be a target for treatment of psychotic disorders.