An epigenetic clock for gestational age at birth based on blood methylation data

BACKGROUND: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. RESULTS: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry. CONCLUSIONS: DNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

‘Everyone thought I was a very very bad person… no one want to know you like the nurses and doctors’:using focus groups to elicit the views of adults with learning disability who use challenging behaviour services

and Tables S1–S3. (PDF 3090 kb

An epigenetic clock for gestational age at birth based on blood methylation data

Background: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. Results: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry. Conclusions: DNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances.Peer reviewe

Correction to: The Role of Oxytocin in Early Life Adversity and Later Psychopathology: a Review of Preclinical and Clinical Studies

The original publication of this article is missing a disclosure statement for Dr. Amalia Londono Tobon

Parental depression: animal models of an adverse life event

This article reviews findings in preclinical research on the adverse impact of parental depression on the development of offspring, with emphasis on the relevance of this research for the psychiatric care of depressed parents. The authors reviewed literature from the last 40 years reporting laboratory animal studies pertaining to the persistent effects of parental stress and parenting deficits on neurobehavioral and neurobiological development in offspring. Animal studies indicate that disrupted parenting produces a persistent, deleterious biobehavioral impact on offspring. Stressors, including maternal separation, variable foraging, and a variety of prenatal maternal challenges, produce offspring behaviors reminiscent of the cardinal features of anxiety and affective disorders. The stress paradigms also uniformly produce persistent hyperresponsivity in hypothalamic-pituitary-adrenal axis activity secondary to hypersecretion of corticotropin-releasing hormone. These findings bear striking similarities to findings for stress-related illnesses in humans, including major depression. Data from research on animal parenting reinforce the idea that parental mental illness may pose the first adverse life event for a child. A thorough risk-benefit assessment for the psychiatric care of parents of young children must consider the impact on the infant of exposure both to treatment and to parental illness. Preclinical data regarding the risk to offspring posed by untreated parental mental illness should be incorporated into clinical decision making in the treatment of parents with mental illness

Maternal depression: a child's first adverse life event

Can the effects of maternal depression upon offspring development be extrapolated to the prebirth environment, making it the earliest of adverse life events? Increasing clinical and laboratory data indicate that maternal stress and depression during critical developmental windows carry a diverse array of harmful sequelae for the offspring. The effects witnessed in animal research include neurobiological and behavioral alterations that persist into adulthood. Paralleling the preclinical literature are human studies indicating similar acute effects. The clinical implications for the psychiatric treatment of depressed women who have children will be discussed

The onset of postpartum depression: Implications for clinical screening in obstetrical and primary care

Inconsistent diagnostic criteria fail to delineate guidelines for postpartum depression surveillance. This study evaluates the validity of commonly accepted postpartum onset criteria. Consecutive referrals to the Emory Women's Mental Health Program for evaluation of postpartum depression fulfilling criteria for major depression and taking no psychotropic medication were included. Diagnostic interview, demographics, depression scales, and the time of illness onset were obtained. Descriptive analysis was conducted for 3 participant groups: pregnancy onset, early postpartum onset within 6 weeks of delivery, and late postpartum onset. Among participants, 11.5% reported prenatal onset, 22.0% late postpartum onset, and 66.5% early postpartum symptom onset. Those reporting pregnancy onset were more likely to be unmarried, and those with a late postpartum onset were less likely to report a past history of postpartum depression. The perinatal vulnerability to depression begins before delivery and extends beyond 6 weeks postpartum. Depression surveillance is therefore warranted during prenatal visits, at the postnatal check up, and at pediatric visits during the initial 6 months of the first postnatal year