title: Sertraline exposure leads to small left heart syndrome in adult mice.
abstract: BACKGROUND
  Sertraline, a selective serotonin reuptake inhibitor (SSRI), is the most commonly prescribed therapy for maternal depression. Epidemiologic studies have linked SSRI exposure with decreased fetal growth, altered autonomic regulation, and cardiac malformations. We hypothesized that SSRI exposure decreases left-ventricular (LV) volumes and increases adult sympathetic nervous system activation, resulting in increased adult heart rates.
  
  
  METHODS
  C57BL/6 mice received saline or sertraline (5 or 15 mg/kg/day i.p.) on postnatal days 1-14. Adult phenotypes were assessed at 5 mo.
  
  
  RESULTS
  Sertraline-exposed mice had smaller LV internal diameters in diastole (control 4.0 ± 0.1 mm, SSRI 3.7 ± 0.1 mm, P < 0.05), decreased stroke volumes (control 46 ± 2.6 µl, SSRI 37 ± 2.3 µl, P < 0.05), higher heart rates (control 530 ± 13 beats per minute (bpm), SSRI 567 ± 6 bpm, P <0.05), and increased urinary excretion of noradrenaline (control 174 ± 29.4 ng/ml, SSRI 276 ± 35.1 ng/ml, P < 0.05). These changes were associated with increased cerebral serotonin transporter (5-HTT) expression.
  
  
  CONCLUSIONS
  Neonatal sertraline exposure causes long-term changes in cardiac morphology and physiology. We speculate that early-life SSRI exposure impairs cardiomyocyte growth and central serotonin signaling, leading to a small left heart syndrome in adult mice.
authors.affiliation: Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA. sarah-haskell@uiowa.edu
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Haskell
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Hermann
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Reinking
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Volk
authors.forename: Veronica A
authors.initials: VA
authors.lastname: Peotta
authors.forename: Vivian
authors.initials: V
authors.lastname: Zhu
authors.forename: Robert D
authors.initials: RD
authors.lastname: Roghair
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism; D004452:Echocardiography; D006339:Heart Rate / Q000187:drug effects; D018636:Hypoplastic Left Heart Syndrome / Q000139:chemically induced* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000652:urine; D009929:Organ Size / Q000187:drug effects; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D020280:Sertraline / Q000009:adverse effects* / Q000494:pharmacology; D013686:Telemetry
chemical_list: D009638:Norepinephrine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; C493231:Slc6a4 protein, mouse