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oai:recercat.cat:2445/1110682025-12-05T09:23:03Zcom_2072_1057col_2072_478799col_2072_478824col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Gurnot, Cécile author Martín-Subero, José Ignacio author Mah, Sarah M. author Weikum, Whitney author Goodman, Sarah J. author Brain, Ursula author Werker, Janet F. author Kobor, Michael S. author Esteller, Manel author Oberlander, Tim F. author Hensch, Takao K. author 2017-05-16T09:27:59Z 2017-05-16T09:27:59Z 2015-06 2017-05-16T09:27:59Z Some but not all neonates are affected by prenatal exposure to serotonin reuptake inhibitor antidepressants (SRI) and maternal mood disturbances. Distinguishing the impact of these 2 exposures is challenging and raises critical questions about whether pharmacological, genetic, or epigenetic factors can explain the spectrum of reported outcomes. Using unbiased DNA methylation array measurements followed by a detailed candidate gene approach, we examined whether prenatal SRI exposure was associated with neonatal DNA methylation changes and whether such changes were associated with differences in birth outcomes. Prenatal SRI exposure was first associated with increased DNA methylation status primarily at CYP2E1(βNon-exposed = 0.06, βSRI-exposed = 0.30, FDR = 0); however, this finding could not be distinguished from the potential impact of prenatal maternal depressed mood. Then, using pyrosequencing of CYP2E1 regulatory regions in an expanded cohort, higher DNA methylation status both the mean across 16 CpG sites (P < 0.01) and at each specific CpG site (P < 0.05) was associated with exposure to lower 3rd trimester maternal depressed mood symptoms only in the SRI-exposed neonates, indicating a maternal mood x SRI exposure interaction. In addition, higher DNA methylation levels at CpG2 (P = 0.04), CpG9 (P = 0.04) and CpG10 (P = 0.02), in the interrogated CYP2E1 region, were associated with increased birth weight independently of prenatal maternal mood, SRI drug exposure, or gestational age at birth. Prenatal SRI antidepressant exposure and maternal depressed mood were associated with altered neonatal CYP2E1 DNA methylation status, which, in turn, appeared to be associated with birth weight. Antidepressius Depressió psíquica Embaràs Infants nadons ADN Metilació Neurotransmissors Serotonina Antidepressants Mental depression Pregnancy Newborn infants DNA Methylation Neurotransmitters Serotonin Prenatal antidepressant exposure associated with CYP2E1 DNA methylation change in neonates