MAO-A and COMT genotypes as possible regulators of perinatal serotonergic symptoms after in utero exposure to SSRIs

Eur Neuropsychopharmacol. 2009 May;19(5):363-70. doi: 10.1016/j.euroneuro.2009.01.006. Epub 2009 Feb 14.

Abstract

Intrauterine exposure to SSRIs in late pregnancy can cause various serotonergic symptoms in the newborns. We associated the severity of these symptoms to neurotransmitter concentrations and genetic polymorphisms in the cytochrome P450, MAO-A and COMT enzymes. Altogether 20 children with prenatal exposure to citalopram or fluoxetine were genotyped. Infants with two high-activity alleles of the MAO-A gene had significantly higher serotonergic symptom scores than infants with at least one low-activity allele (mean 8.8 vs. 2.4, p=0.024). These infants had also higher cord blood DHPG concentrations (p=0.0054). Carriers of the high-activity COMT alleles had higher cord blood prolactin concentrations (p=0.044). According to our results, the higher serotonergic symptom score and cord blood DHPG concentration in rapid MAO-A metabolizers suggest that norepinephrine may modify the severity of perinatal serotonergic symptoms. The COMT 1947G>A polymorphism may affect the occurrence of respiratory distress symptoms in infants with prenatal SSRI-exposure via a mechanism involving prolactin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catechol O-Methyltransferase / genetics*
  • Child
  • Child, Preschool
  • Cytochrome P-450 Enzyme System / genetics
  • Depression / drug therapy
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Methoxyhydroxyphenylglycol / analogs & derivatives
  • Methoxyhydroxyphenylglycol / blood
  • Monoamine Oxidase / genetics*
  • Polymorphism, Genetic / genetics
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / genetics
  • Prenatal Exposure Delayed Effects*
  • Prolactin / blood
  • Prospective Studies
  • Retrospective Studies
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Serotonin Syndrome / blood
  • Serotonin Syndrome / chemically induced*
  • Serotonin Syndrome / diagnosis
  • Statistics, Nonparametric

Substances

  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Methoxyhydroxyphenylglycol
  • Prolactin
  • Cytochrome P-450 Enzyme System
  • Monoamine Oxidase
  • Catechol O-Methyltransferase
  • 3,4-dihydroxyphenylglycol