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

HYPOTHESIS:

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).

LIMITATIONS:

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.

CONCLUSION:

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: Nicole E De Long, Eric J Barry, Christopher Pinelli, Geoffrey A Wood, Daniel B Hardy, Katherine M Morrison, Valerie H Taylor, Hertzel C Gerstein, Alison C Holloway
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 285 Issue 1 Pg. 32-40 (May 15 2015) ISSN: 1096-0333 [Electronic] United States
• PMID: 25771129 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Blood Glucose
• Ccl2 protein, rat
• Chemokine CCL2
• Interleukin-6
• Serotonin Uptake Inhibitors
• Tumor Necrosis Factor-alpha
• Fluoxetine

Topics

• Adiposity (drug effects)
• Animals
• Blood Glucose (drug effects, metabolism)
• Chemical and Drug Induced Liver Injury (blood, etiology)
• Chemokine CCL2 (metabolism)
• Diabetes Mellitus, Type 2 (blood, chemically induced, physiopathology)
• Dyslipidemias (blood, chemically induced)
• Female
• Fluoxetine (toxicity)
• Interleukin-6 (metabolism)
• Liver (drug effects, metabolism)
• Male
• Maternal Exposure
• Metabolic Syndrome (blood, chemically induced, physiopathology)
• Non-alcoholic Fatty Liver Disease (blood, chemically induced)
• Pregnancy
• Prenatal Exposure Delayed Effects
• Rats, Wistar
• Risk Assessment
• Selective Serotonin Reuptake Inhibitors (toxicity)
• Sex Factors
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)
• Weight Gain (drug effects)