scholarly journals Pharmacological Treatment for Neonatal Abstinence Syndrome is Associated with Altered DNA Methylation and Neurobehavior

2021 ◽  
Author(s):  
Marie Camerota ◽  
Jonathan M Davis ◽  
Lynne M. Dansereau ◽  
Erica L Oliveira ◽  
James F Padbury ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Pharmacological Treatment ◽  
Receptor Gene ◽  
Post Treatment ◽  
Neonatal Abstinence Syndrome ◽  
Abstinence Syndrome ◽  
Oprm1 Gene ◽  
Cpg Sites ◽  
Length Of Treatment ◽  
Before And After

Objective: To determine whether pharmacological treatment for neonatal abstinence syndrome (NAS) is associated with changes in DNA methylation (DNAm) of the mu-opioid receptor gene (OPRM1) and improvements in neonatal neurobehavior.Study Design: Buccal swabs were collected from 37 neonates before and after morphine treatment for NAS. Genomic DNA was extracted and DNAm was examined at four CpG sites within the OPRM1 gene. The NICU Network Neurobehavioral Scales (NNNS) was also performed before and after NAS treatment. Changes in DNAm (DNAmpost-tx – DNAmpre-tx) and NNNS summary scores (NNNSpost-tx – NNNSpre-tx) were then calculated. Path analysis was used to examine associations among pharmacologic treatment (length of treatment and total dose of morphine), changes in DNAm, and changes in NNNS summary scores. Results: DNAm significantly decreased from pre- to post-treatment at 1 of 4 CpG sites within the OPRM1 gene. Neonates also demonstrated decreased excitability, hypertonia, lethargy, signs of stress and abstinence, and increased quality of movement and regulation from pre- to post-treatment. Increased length of treatment and higher morphine doses were associated with greater decreases in DNAm; greater decreases in DNAm were associated with greater decreases in excitability and hypertonia on the NNNS.Conclusions: Pharmacological treatment of NAS is associated with decreased DNAm of the OPRM1 gene and improved neonatal neurobehavior. Epigenetic changes may play a role in these changes in neonatal neurobehavior.

scholarly journals Variations in Infant CYP2B6 Genotype Associated with the Need for Pharmacological Treatment for Neonatal Abstinence Syndrome in Infants of Methadone-Maintained Opioid-Dependent Mothers

2017 ◽  
Vol 34 (09) ◽  
pp. 918-921 ◽  
Author(s):  
Poppy McLaughlin ◽  
Cheryl Gillis ◽  
Michael Osselton ◽  
Helen Mactier
Keyword(s):  
Pharmacological Treatment ◽  
Maternal Blood ◽  
Maternal Plasma ◽  
Genomic Variation ◽  
Neonatal Abstinence Syndrome ◽  
Abstinence Syndrome ◽  
Buccal Swabs ◽  
Cyp2b6 Gene ◽  
Observational Cohort

Background Neonatal abstinence syndrome (NAS) in infants of methadone-maintained opioid-dependent (MMOD) mothers cannot be predicted in individual cases. We investigated whether variation in infant genotype is associated with severity of NAS. Methods This is a pilot observational cohort study of 21 MMOD mothers and their newborns. Infant buccal swabs were obtained soon after delivery, together with a maternal blood sample for the determination of maternal plasma methadone concentration. Genomic variation in five opioid-related genes (ABCB1, COMT, CYP2B6, CYP2D6, and OPRM1) was ascertained from infant buccal swabs and related to need for pharmacological treatment of NAS. Results Out of 21 infants, 11 (52%) required treatment for NAS. Mothers of treated infants tended to have been prescribed higher doses of methadone, but plasma methadone concentrations did not differ between mothers of treated or untreated babies. Treated and untreated babies did not differ in terms of method of feeding. Treated infants were more likely to carry the normal (homozygous) allele at 516 and 785 regions of CYP2B6 gene (p = 0.015 and 0.023, respectively). There were no differences in any other genes between infants who did or did not require treatment for NAS. Conclusion Genomic variation in CYP2B6 may explain, at least in part, severity of NAS.

scholarly journals Predicting length of treatment for neonatal abstinence syndrome in methadone-exposed neonates

2008 ◽  
Vol 199 (4) ◽  
pp. 396.e1-396.e7 ◽  
Author(s):  
Neil S. Seligman ◽  
Nicole Salva ◽  
Edward J. Hayes ◽  
Kevin C. Dysart ◽  
Edward C. Pequignot ◽  
...  
Keyword(s):  
Neonatal Abstinence Syndrome ◽  
Abstinence Syndrome ◽  
Length Of Treatment

scholarly journals Neonatal abstinence syndrome: Neurobehavior at 6 weeks of age in infants with or without pharmacological treatment for withdrawal

2017 ◽  
Vol 59 (5) ◽  
pp. 574-582 ◽  
Author(s):  
Nicole A. Heller ◽  
Beth A. Logan ◽  
Deborah G. Morrison ◽  
Jonathan A. Paul ◽  
Mark S. Brown ◽  
...  
Keyword(s):  
Pharmacological Treatment ◽  
Neonatal Abstinence Syndrome ◽  
Abstinence Syndrome

scholarly journals Epigenetic Variation in the Mu-Opioid Receptor Gene in Infants with Neonatal Abstinence Syndrome

2014 ◽  
Vol 165 (3) ◽  
pp. 472-478 ◽  
Author(s):  
Elisha M. Wachman ◽  
Marie J. Hayes ◽  
Barry M. Lester ◽  
Norma Terrin ◽  
Mark S. Brown ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Receptor Gene ◽  
Mu Opioid Receptor ◽  
Neonatal Abstinence Syndrome ◽  
Epigenetic Variation ◽  
Abstinence Syndrome ◽  
Mu Opioid

scholarly journals Risperidone-induced changes in DNA methylation from peripheral blood in first-episode schizophrenia parallel neuroimaging and cognitive phenotype

2020 ◽  
Author(s):  
Maolin Hu ◽  
Yan Xia ◽  
Xiaofen Zong ◽  
John A. Sweeney ◽  
Jeffrey R Bishop ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Drug Treatment ◽  
Treatment Effect ◽  
Post Treatment ◽  
Response To Treatment ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Systematic Analysis ◽  
Cpg Sites ◽  
Wide Range

ABSTRACTToday, second generation anti-psychotics such as clozapine and risperidone are the favored treatment for schizophrenia. Yet, the absence of relevant biomarkers that can decode their neurobiological effect shackles our ability to accurately predict and track response to treatment. While researchers have investigated DNA methylation as a biomarker for schizophrenia risk, none have performed a systematic analysis of the effect of antipsychotics upon DNA methylation. We hypothesize that disease-related methylation changes occur before treatment, and that acute antipsychotic treatment may affect DNA methylation. We designed a longitudinal DNA methylation study to estimate risperidone’s effect on DNA methylation and how changes in DNA methylation might influence risperidone’s therapeutic effect on behavioral and neuroimaging phenotypes. Thirty-eight patients with first-episode drug-naïve schizophrenia (FES) and 38 demographically-matched individuals (healthy controls) participated. We identified brain related pathways enriched in 8,204 FES-associated methylation sites. Risperidone administration altered methylation in 6,143 CpG DNA sites. Post-treatment FES associated with methylation in 6760 CpG sites. Majority of the DNA methylation changes were treatment effect in the overall CpG sites, the FES associated CpG sites, and risperidone associated CpG sites, except for the post-treatment FES associated CpG sites. There were 590 DNA methylation cites normalized by risperidone treatment. The methylation changes of these 590 CpG sites were related to alterations in symptom severity, spontaneous neurophysiological activity, and cognitive function. To our knowledge, this is the first longitudinal methylation study of drug treatment effect and side effect in psychiatric disorders to include parallel studies of neuroimaging and cognitive phenotypes. We identified FES-associated CpG sites not confounded by drug treatment as potential SCZ biomarkers. The normalization effect of risperidone monotherapy suggests that DNA methylation changes may serve as a predictive biomarker for treatment effect. The constructed methylation-phenotype network revealed a relationship between methylation and a wide range of biological and psychological variables.

A Tissue Comparison of DNA Methylation of the Glucocorticoid Receptor Gene (Nr3c1) in European Starlings

2019 ◽  
Vol 59 (2) ◽  
pp. 264-272 ◽  
Author(s):  
Stefanie J Siller ◽  
Dustin R Rubenstein
Keyword(s):  
Dna Methylation ◽  
Glucocorticoid Receptor ◽  
Glucocorticoid Receptors ◽  
Epigenetic Modification ◽  
Receptor Gene ◽  
Putative Promoter ◽  
European Starlings ◽  
Cpg Sites ◽  
Glucocorticoid Receptor Gene ◽  
The Brain

Abstract Negative feedback of the vertebrate stress response via the hypothalamic–pituitary–adrenal (HPA) axis is regulated by glucocorticoid receptors in the brain. Epigenetic modification of the glucocorticoid receptor gene (Nr3c1), including DNA methylation of the promoter region, can influence expression of these receptors, impacting behavior, physiology, and fitness. However, we still know little about the long-term effects of these modifications on fitness. To better understand these fitness effects, we must first develop a non-lethal method to assess DNA methylation in the brain that allows for multiple measurements throughout an organism’s lifetime. In this study, we aimed to determine if blood is a viable biomarker for Nr3c1 DNA methylation in two brain regions (hippocampus and hypothalamus) in adult European starlings (Sturnus vulgaris). We found that DNA methylation of CpG sites in the complete Nr3c1 putative promoter varied among tissue types and was lowest in blood. Although we identified a similar cluster of correlated Nr3c1 putative promoter CpG sites within each tissue, this cluster did not show any correlation in DNA methylation among tissues. Additional studies should consider the role of the developmental environment in producing epigenetic modifications in different tissues.

scholarly journals 253: Predicting length of treatment for neonatal abstinence syndrome in methadone exposed neonates

2007 ◽  
Vol 197 (6) ◽  
pp. S82
Author(s):  
Neil Seligman ◽  
Edward Hayes ◽  
Marie O’Neill ◽  
Benjamin Leiby ◽  
Jennifer Kern ◽  
...  
Keyword(s):  
Neonatal Abstinence Syndrome ◽  
Abstinence Syndrome ◽  
Length Of Treatment
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