title: Antenatal exposure to the selective serotonin reuptake inhibitor fluoxetine leads to postnatal metabolic and endocrine changes associated with type 2 diabetes in Wistar rats.
abstract: OBJECTIVE
  10-15% of women take antidepressant medications during pregnancy. A recent clinical study reported that the use of selective serotonin reuptake inhibitor antidepressants during pregnancy is linked with an increased risk of postnatal obesity. While obesity is often associated with fatty liver, dyslipidemia and inflammation, to date, the effects of perinatal exposure to SSRIs on these outcomes are unknown.
  
  
  METHODS
  Female nulliparous Wistar rats were given vehicle (N=15) or fluoxetine hydrochloride (FLX 10mg/kg/d; N=15) orally for 2 weeks prior to mating until weaning. We assessed glucometabolic changes and hepatic pathophysiology in the offspring.
  
  
  RESULTS
  Fluoxetine exposed offspring demonstrated altered glucose homeostasis without any alterations to beta cell mass. FLX-exposed offspring had a significant increase in the number of offspring with mild to moderate NASH and dyslipidemia. There was also increased inflammation of the liver in FLX-exposed offspring; males had significant elevations in TNFα, IL6 and monocyte chemoattractant protein 1 (MCP1), while female offspring had higher expression of TNFα, and increased macrophage infiltration (MCP1).
  
  
  CONCLUSIONS
  This is an animal study. Further research examining the metabolic outcomes of children exposed to antidepressants in utero are required, given the increase in childhood obesity and psychiatric medication use during pregnancy.
  
  
  CONCLUSIONS
  These data demonstrate that fetal and neonatal exposure to FLX results in evidence of increased adiposity, fatty liver and abnormal glycemic control. Since these are all hallmarks of the metabolic syndrome, this raises concerns regarding the long term metabolic sequelae of fetal exposure to SSRIs in human populations.
authors.affiliation: Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: Nicole E
authors.initials: NE
authors.lastname: De Long
authors.affiliation: Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Barry
authors.affiliation: Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Pinelli
authors.affiliation: Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, Canada.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Wood
authors.affiliation: Department of Obstetrics and Gynecology, Physiology and Pharmacology, University of Western, London, ON N6A 3K6, Canada.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Hardy
authors.affiliation: Department of Pediatrics, McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Morrison
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, ON M5S 1A1, Canada.
authors.forename: Valerie H
authors.initials: VH
authors.lastname: Taylor
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada.
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
authors.affiliation: Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON L8S 4K1, Canada. Electronic address: hollow@mcmaster.ca.
authors.forename: Alison C
authors.initials: AC
authors.lastname: Holloway
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology; D018932:Chemokine CCL2 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D050171:Dyslipidemias / Q000097:blood / Q000139:chemically induced; D005260:Female; D005473:Fluoxetine / Q000633:toxicity*; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D024821:Metabolic Syndrome / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000139:chemically induced; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017208:Rats, Wistar; D018570:Risk Assessment; D017367:Selective Serotonin Reuptake Inhibitors / Q000633:toxicity*; D012737:Sex Factors; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D018932:Chemokine CCL2; D005473:Fluoxetine; D015850:Interleukin-6; D017367:Selective Serotonin Reuptake Inhibitors; D014409:Tumor Necrosis Factor-alpha; C491766:Ccl2 protein, rat
keywords: Adiposity; Beta cell; Depression; Dyslipidemia; Inflammation; Nonalcoholic steatohepatitis