MAO-A and COMT genotypes as possible regulators of perinatal serotonergic symptoms after in utero exposure to SSRIs.
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.
Hilli
Johanna
J
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland. johanna.hilli@utu.fi
Heikkinen
Tuija
T
Rontu
Riikka
R
Lehtimäki
Terho
T
Kishida
Ikuko
I
Aklillu
Eleni
E
Bertilsson
Leif
L
Vahlberg
Tero
T
Laine
Kari
K
D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D003863:Depression / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000097:blood; D008995:Monoamine Oxidase / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000235:genetics; D011297:Prenatal Exposure Delayed Effects; D011388:Prolactin / Q000097:blood; D011446:Prospective Studies; D012189:Retrospective Studies; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D020230:Serotonin Syndrome / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D018709:Statistics, Nonparametric
D002394:Catechol O-Methyltransferase; D003577:Cytochrome P-450 Enzyme System; D008734:Methoxyhydroxyphenylglycol; D008995:Monoamine Oxidase; D011388:Prolactin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human; C010117:3,4-dihydroxyphenylglycol