Prenatal antidepressant exposure associated with CYP2E1 DNA methylation change in neonates

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

Visual language discrimination

Recognizing and learning one’s native language requires knowledge of the phonetic and rhythmical characteristics of the language. Few studies address the rich source of language information available in a speaker’s face. Solely visual speech permits language discrimination in adults (Soto-Faraco et al., 2007). This thesis tested infants and adults on their ability to use only information available in a speaker’s face to discriminate rhythmically dissimilar languages. Monolingual English infants discriminated French and English using only visual speech at 4 and 6 months old, but failed this task at 8 months old. To test the role of language experience, bilingual (English/French) 6 and 8-month-old infants were tested and successfully discriminated the languages. An optimal period for sensitivity to visual language information necessary for discriminating languages may exist in early life. To confirm an optimal period, adults who had acquired English as a second language were tested. If English was learned before age 6 years, adults discriminated English and French, but if English was learned after age 6, adults performed at chance. Experience with visual speech information in early childhood influences adult performance. To better understand the developmental trajectory of visual language discrimination, visual correlates of phonetic segments and rhythmical information were examined. When clips were manipulated to remove rhythmical information, infants used segmental visual phonetic cues to discriminate languages at 4, but not 8 months old. This suggests that a decline in non-native visual phonetic discrimination (similar to the decline seen for non-native auditory phonetic information; Werker & Tees, 1984), may be impairing language discrimination at 8 months. Infants as young as newborn use rhythmical auditory information to discriminate languages presented forward, but not backward (Mehler et al., 1988). This thesis showed that both 4 and 8-month-old infants could discriminate French from English when shown reversed language clips. Unlike auditory speech, reversed visual speech must conserve cues that permit language discrimination. Infants’ abilities to distinguish languages using visual speech parallel auditory speech findings, but also diverge to highlight unique characteristics of visual speech. Together, these studies further enrich our understanding of how infants come to recognize and learn their native language(s).Medicine, Faculty ofGraduat

Age-related sensitive periods influence visual language discrimination in adults

Adults as well as infants have the capacity to discriminate languages based on visual speech alone. Here, we investigated whether adults' ability to discriminate languages based on visual speech cues is influenced by the age of language acquisition. Adult participants who had all learned English (as a first or second language) but did not speak French were shown faces of bilingual (French/English) speakers silently reciting sentences in either language. Using only visual speech information, adults who had learned English from birth or as a second language before the age of 6 could discriminate between French and English significantly better than chance. However, adults who had learned English as a second language after age 6 failed to discriminate these two languages, suggesting that early childhood exposure is crucial for using relevant visual speech information to separate languages visually. These findings raise the possibility that lowered sensitivity to non-native visual speech cues may contribute to the difficulties encountered when learning a new language in adulthood.This research was supported by Research grants from the Natural Sciences and Engineering Research Council (NSERC) and the Social Sciences and Humanities Research Council (SSHRC) to Janet F. Werker, by NSERC and SSHRC Fellowships to Whitney M. Weikum, and by grants PSI2009-12859, PSI2012-39149 and RYC-2008-03672 from Ministerio de Economía y Competitividad (Spanish Government), and the European COST action TD0904 to Jordi Navarra. Salvador Soto-Faraco was supported by ERC (StG-2010263145), MICINN (PSI2010-15426 and Consolider INGENIO CSD2007-00012) and AGAUR (SGR2009-092)

Age-related sensitive periods influence visual language discrimination in adults

Adults as well as infants have the capacity to discriminate languages based on visual speech alone. Here, we investigated whether adults' ability to discriminate languages based on visual speech cues is influenced by the age of language acquisition. Adult participants who had all learned English (as a first or second language) but did not speak French were shown faces of bilingual (French/English) speakers silently reciting sentences in either language. Using only visual speech information, adults who had learned English from birth or as a second language before the age of 6 could discriminate between French and English significantly better than chance. However, adults who had learned English as a second language after age 6 failed to discriminate these two languages, suggesting that early childhood exposure is crucial for using relevant visual speech information to separate languages visually. These findings raise the possibility that lowered sensitivity to non-native visual speech cues may contribute to the difficulties encountered when learning a new language in adulthood.This research was supported by Research grants from the Natural Sciences and Engineering Research Council (NSERC) and the Social Sciences and Humanities Research Council (SSHRC) to Janet F. Werker, by NSERC and SSHRC Fellowships to Whitney M. Weikum, and by grants PSI2009-12859, PSI2012-39149 and RYC-2008-03672 from Ministerio de Economía y Competitividad (Spanish Government), and the European COST action TD0904 to Jordi Navarra. Salvador Soto-Faraco was supported by ERC (StG-2010263145), MICINN (PSI2010-15426 and Consolider INGENIO CSD2007-00012) and AGAUR (SGR2009-092)

The association between prenatal greenspace exposure and Autism spectrum disorder, and the potentially mediating role of air pollution reduction: A population-based birth cohort study

Background: Autism spectrum disorder (ASD) incidence has increased in past decades. ASD etiology remains inconclusive, but research suggests genetic, epigenetic, and environmental contributing factors and likely prenatal origins. Few studies have examined modifiable environmental risk factors for ASD, and far fewer have examined protective exposures. Greenspace has been associated with positive child development, but very limited greenspace research has examined ASD risk or prenatal exposures. Only one ecological study in 2017 has evaluated the association between greenspace and ASD, observing protective benefits. Greenspace may have direct effects on ASD risk and indirect effects by reducing air pollution exposure, a growing suspected ASD risk factor. Objectives: To measure the association between prenatal greenspace exposure and ASD risk and examine if reduced air pollution levels in areas of higher greenspace mediate this association. Methods: We linked a population-based birth cohort of all deliveries in Metro Vancouver, Canada, from 2004 to 2009, with follow-up to 2014. Diagnoses were based on Autism Diagnostic Observation Schedule and Autism Diagnostic Interview-Revised instruments. Greenspace was quantified as the average of the annual mean Normalized Difference Vegetation Index (NDVI) within a 250 m buffer of a residential postal code. Air pollutant exposures-particulate matter with a diameter less than 2.5 µm (PM2.5), nitric oxide (NO), and nitrogen dioxide (NO2)-were derived from previously developed and temporally adjusted land use regression models. We estimated air pollutant exposures as the mean concentration per month during pregnancy. We calculated odds ratios (ORs) using logistic regression per NDVI interquartile range (IQR) increase, adjusting for child sex, birth month and year, maternal age and birthplace, and neighborhood-level urbanicity and income. To estimate the health impact of greenspace on ASD at the population level, we used the logistic regression model and marginal standardization to derive risk differences (RDs). Lastly, to quantify the mediating effect of greenspace on ASD risk through air pollution reduction, we used marginal structural models and a potential outcomes framework to calculate marginal risk differences (RDs) to decompose the total effect of greenspace on ASD into natural direct and indirect effects. Results: Of 129,222 births, 1,921 (1.5 %) children were diagnosed with ASD. The adjusted OR for ASD per NDVI IQR (0.12) increase was 0.96 (95 % CI: 0.90, 1.02) in 250 m buffer zones and 0.94 (95 % CI: 0.89, 1.00) in 100 m buffer zones. On the additive scale, the adjusted RDs were null. Natural direct, natural indirect, and total effect RDs were null for PM2.5, NO, and NO2 mediation models. Conclusion: Prenatal greenspace exposure was associated with reduced odds of ASD, but in the additive scale, this effect was null at the population level. No mediating effect was observed through reduced air pollution, suggesting that air pollution may act as a confounder rather than as a mediator.This work was supported by the Canadian Institutes of Health Research (grant number 156152) and by the European Union's Horizon 2020 research and innovation programme under a Marie Skłodowska-Curie grant agreement No. 891538. We acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S) and support from the Generalitat de Catalunya through the CERCA Program. NDVI metrics, indexed to DMTI Spatial Inc. postal codes, were provided by the Canadian Urban Environmental Health Research Consortium

Prenatal antidepressant exposure associated with CYP2E1 DNA methylation change in neonates

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 two 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 methylation status, which, in turn, appeared to be associated with birth weight.Arts, Faculty ofMedicine, Faculty ofOther UBCNon UBCMedical Genetics, Department ofPediatrics, Department ofPsychology, Department ofReviewedFacultyGraduat

Prenatal antidepressant exposure associated with CYP2E1 DNA methylation change in neonates

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