Mäki et al. reported in the Journal last month that prenatal maternal depression is a second risk factor that appears to affect the risk for schizophrenia, also in an interaction with genetic risk (3). As Clarke et al. reported for maternal pyelonephritis, maternal depression by itself did not significantly increase the risk for schizophrenia in the offspring. However, maternal depression increased the effect of familial genetic risk by nearly fourfold. Depression increases a number of maternal hormones, including both cortisol and the cytokines, any or all of which might have effects on fetal brain development similar to those proposed to occur during maternal infection. In the past several years, a number of articles on the prevalence of prenatal depression and the risks and benefits of its treatment have appeared in the Journal (4). While we do not know if successful treatment will reduce the effects of maternal depression on fetal brain development and the risk for later mental illness, these epidemiological studies suggest that psychiatrists and other physicians need to be vigilant with regard to the prevention and treatment of depression in expectant mothers. For example, a woman contemplating pregnancy whose spouse has a family history of major mental illness and who herself has a history of recurrent depression might be counseled about adequate treatment for her depression by the time of conception. As always, our psychiatric advice should recognize that self-medication with abused substances occurs as well. Yet another recent epidemiological study found that maternal substance abuse, particularly smoking, also significantly increases the risk of schizophrenia in the offspring (5).