Prenatal Antidepressant Exposure and Child Motor Development: A Meta-analysis.

CONTEXT: There is increasing use of antidepressants in pregnancy and hence children exposed in utero. Contradictory studies exist in the literature in which researchers report on the potential impact of antenatal antidepressant exposure on subsequent child motor development. OBJECTIVE: Our objective in this systematic review and meta-analysis was to determine whether antenatal antidepressant exposure increases the risk of impaired motor development in children. DATA SOURCES: We searched PsychINFO, Embase, Medline, PubMed, and Scopus up to July 24, 2017. STUDY SELECTION: English-language cohort and case control studies in which researchers report primary data from a motor assessment of infants or children after any antidepressant exposure in pregnancy were included. DATA EXTRACTION: Of the 329 studies identified, there were 160 articles screened, 24 were included in the systematic review, and 18 met inclusion criteria for the meta-analysis. RESULTS: The total pooled results were based on random effects models and revealed a significant association between exposure to antidepressants during pregnancy and overall occurrence of poorer motor outcomes in children (effect size = 0.22; 95% confidence interval = 0.07 to 0.37) with a moderate degree of heterogeneity (I2 = 56.6%). LIMITATIONS: There was variation in the measurement both of exposure and motor development across the identified study, and few followed up to later childhood or beyond. CONCLUSIONS: A small increased risk of poorer motor development may exist for children who are exposed to antidepressant medications during pregnancy. However, the marked methodological variation among studies and the limited control for possible confounds warrants cautious interpretation of these findings.

Interference with acute nausea and anticipatory nausea in rats by fatty acid amide hydrolase (FAAH) inhibition through a PPARα and CB1 receptor mechanism, respectively: a double dissociation.

RATIONALE: Fatty acid amide hydrolase (FAAH) inhibition elevates anandamide (AEA), which acts on cannabinoid (CB1 and CB2) receptors, as well as N-palmitoylethanolamide (PEA) and N-oleoylethanolamine (OEA), which act on peroxisome proliferator-activated receptor alpha (PPARα). Here, we determine the mechanism of action of FAAH inhibition on acute and anticipatory nausea (AN). OBJECTIVE: We compared the effectiveness and mechanism of action of two FAAH inhibitors, URB597 and PF-3845, to reduce acute nausea and AN in rodent models of conditioned gaping. MATERIALS AND METHODS: For assessment of acute nausea, rats were pretreated with vehicle (VEH), URB597 (0.3 and 10 mg/kg, experiment 1a) or PF-3845 (10 mg/kg, experiment 1b) 120 min prior to a saccharin-lithium chloride (LiCl) pairing. To assess the CB1 receptor or PPARα mediation of the effect of PF-3845 on acute nausea, rats were also pretreated with rimonabant or MK886, respectively. For assessment of AN, following four pairings of a novel context with LiCl, rats received a pretreatment of VEH, URB597 (0.3 mg/kg, experiment 2a), or PF-3845 (10, 20 mg/kg, experiment 2b) 120 min prior to placement in the AN context. To assess the CB1 receptor or PPARα mediation of the effect, rats were also pretreated with rimonabant or MK886, respectively. RESULTS: PF-3845 (10 mg/kg, but not URB597 0.3 or 10 mg/kg) suppressed acute nausea via PPARα, but not CB1 receptors. URB597 (0.3 and 10 mg/kg) or PF-3845 (10 and 20 mg/kg) reduced AN via CB1 receptors, but not PPARα. CONCLUSIONS: FAAH inhibition reduces acute nausea and AN through PPARα and CB1 receptor mediated effects, respectively.