The results suggest that it would be unlikely for second-generation antipsychotics to raise the risk of major malformations more than 10-fold beyond that observed in the general population or among control groups using other psychotropic medications. If the estimate stabilizes around the null with ongoing data collection, findings may be reassuring for both clinicians and women trying to make risk-benefit treatment decisions about using atypical antipsychotics during pregnancy. These findings are timely given the renewed focus of regulatory agencies on reproductive safety.

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Maternal infection during pregnancy has been linked to increased risk of offspring depression. Additionally, maternal stress during pregnancy has been consistently linked with adverse offspring outcomes associated with depression. Relatedly, stress has been associated with increased risk of infection; however no study has investigated stress-infection interactions during pregnancy and risk for offspring depression. Participants were drawn from the Child Health and Development Study (CHDS), a prospective, longitudinal study that enrolled pregnant women from 1959-1966. Maternal health and birth outcome information were collected, as well as open-ended interviews about worrisome events during pregnancy. The present study included participants from a subsample of women whose offspring (n = 1,711) completed self-reports of depressive symptoms during adolescence. Results indicated that maternal infection during only the second trimester was associated with higher scores on adolescent offspring depressive symptoms, while controlling for maternal education at birth, adolescent age, and maternal depressive symptoms at adolescence. Maternal experiences of daily stress during pregnancy moderated this association, such that mothers diagnosed with second trimester infection and who experienced daily stress had offspring with significantly higher depression scores than mothers of adolescents diagnosed with an infection alone. Findings have potential implications for prevention and intervention strategies.

We studied the steady-state rate staircase in isolated rat ventricular cells stimulated at frequencies ranging up to 6 Hz at 37 degrees C. When contractility was measured as displacement of the cell edge, amplitude of motion decreased while stimulation rates were increased from rest to 1 Hz (negative staircase). With further increases in the rate of stimulation to 6 Hz, amplitude of motion increased for each increment in stimulation rate (positive staircase). Ryanodine at a concentration of 100 nM was a negative inotrope and abolished the rested state contraction and the negative staircase seen between rest and 1 Hz (P less than 0.05) but had no significant effect on twitch amplitude or the staircase at stimulation rates between 1 and 6 Hz. L-type Ca2+ channel inhibition with verapamil (0.2 microM) had little effect on twitch or the negative staircase from rest to 1 Hz, but twitch amplitude was diminished and the staircase was converted from positive to negative at stimulation rates between 1 and 6 Hz (P less than 0.05). We conclude that in rat ventricular cells studied at 37 degrees C, the rate staircase is biphasic: negative from rest to 1 Hz and positive from 1 to 6 Hz. This phenomenon is dominated by Ca2+ release from the sarcoplasmic reticulum at rates less than 1 Hz and by Ca2+ entry through L channels at rates greater than 1 Hz.

Purpose of Review-Disruptions in fetal development (via genetic and environmental pathways) have been consistently associated with risk for schizophrenia in a variety of studies. Although multiple obstetric complications (OCs) have been linked to schizophrenia, this review will discuss emerging evidence supporting the role of prenatal maternal stress (PNMS) in the etiology of schizophrenia spectrum disorders (SSD). In addition, findings linking PNMS to intermediate phenotypes of the disorder, such as OCs and premorbid cognitive, behavioral, and motor deficits, will be reviewed. Maternal immune and endocrine dysregulation will also be explored as potential mechanisms by which PNMS confers risk for SSD. Recent Findings-PNMS has been linked to offspring SSD; however, findings are mixed due to inconsistent and retrospective assessments of PNMS and lack of specificity about SSD outcomes. PNMS is also associated with various intermediate phenotypes of SSD (e.g., prenatal infection/ inflammation, decreased fetal growth, hypoxia-related OCs). Recent studies continue to elucidate the impact of PNMS while considering the moderating roles of fetal sex and stress timing, but it is still unclear which aspects of PNMS (e.g., type, timing) confer risk for SSD specifically. Summary-PNMS increases risk for SSD, but only in a small portion of fetuses exposed to PNMS. Fetal sex, genetics, and other environmental factors, as well as additional pre-and postnatal insults, likely contribute to the PNMS-SSD association. Longitudinal birth cohort studies are needed to prospectively illuminate the mechanisms that account for the variability in outcomes following PNMS.