210 research outputs found
Maternal self-reported prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation.
Prenatal maternal psychological distress increases risk for adverse infant outcomes.
However, the biological mechanisms underlying this association remain unclear.
Prenatal stress can impact fetal epigenetic regulation that could underlie changes in
infant stress responses. It has been suggested that maternal glucocorticoids may
mediate this epigenetic effect. We examined this hypothesis by determining the
impact of maternal cortisol and depressive symptoms during pregnancy on infant
NR3C1 and BDNF DNA methylation. Fifty-seven pregnant women were recruited
during the second or third trimester.
Participants self-reported depressive symptoms
and salivary cortisol samples were collected diurnally and in response to a stressor.
Buccal swabs for DNA extraction and DNA methylation analysis were collected from
each infant at two months of age, and mothers were assessed for postnatal depressive
symptoms. Prenatal depressive symptoms significantly predicted increased NR3C1 1F
DNA methylation in male infants ( 2.147 = Řł , P = 0.044). Prenatal depressive
symptoms also significantly predicted decreased BDNF IV DNA methylation in both
male and female infants ( -3.244 = Řł , P = 0.013). No measure of maternal cortisol
during pregnancy predicted infant NR3C1 1F or BDNF promoter IV DNA
methylation. Our findings highlight the susceptibility of males to changes in NR3C1
DNA methylation and present novel evidence for altered BDNF IV DNA methylation
in response to maternal depression during pregnancy. The lack of association between
maternal cortisol and infant DNA methylation suggests that effects of maternal
depression may not be mediated directly by glucocorticoids. Future studies should
consider other potential mediating mechanisms in the link between maternal mood
and infant outcome
Bisphenol A shapes children’s brain and behavior: towards an integrated neurotoxicity assessment including human data
The authors gratefully acknowledge editorial assistance provided by Richard
Davies. VM is under contract within the Human Biomonitoring for Europe
Project (European Union Commission H2020-EJP-HBM4EU). The authors acknowledge the funding received from the Biomedical Research Networking
Center-CIBER de EpidemiologĂa y Salud PĂşblica (CIBERESP), and the Instituto
de Salud Carlos III (ISCIII) (FIS-PI16/01820 and FIS-PI16/01812). The funders
had no role in the study design, data.Concerns about the effects of bisphenol A (BPA) on human brain and behavior are not novel; however, Grohs and
colleagues have contributed groundbreaking data on this topic in a recent issue of Environmental Health. For the first time,
associations were reported between prenatal BPA exposure and differences in children’s brain microstructure, which
appeared to mediate the association between this exposure and children’s behavioral symptoms. Findings in numerous
previous mother-child cohorts have pointed in a similar worrying direction, linking higher BPA exposure during pregnancy
to more behavioral problems throughout childhood as assessed by neuropsychological questionnaires. Notwithstanding, this
body of work has not been adequately considered in risk assessment. From a toxicological perspective, results are now
available from the CLARITY-BPA consortium, designed to reconcile academic and regulatory toxicology findings. In fact, the
brain has consistently emerged as one of the most sensitive organs disrupted by BPA, even at doses below those
considered safe by regulatory agencies such as the European Food Safety Authority (EFSA). In this Commentary, we
contextualize the results of Grohs et al. within the setting of previous epidemiologic and CLARITY-BPA data and express our
disquiet about the “all-or-nothing” criterion adopted to select human data in a recent EFSA report on the appraisal
methodology for their upcoming BPA risk assessment. We discuss the most relevant human studies, identify emerging
patterns, and highlight the need for adequate assessment and interpretation of the increasing epidemiologic literature in this
field in order to support decision-making. With the aim of avoiding a myopic or biased selection of a few studies in
traditional risk assessment procedures, we propose a future reevaluation of BPA focused on neurotoxicity and based on a
systematic and comprehensive integration of available mechanistic, animal, and human data. Taken together, the
experimental and epidemiologic evidence converge in the same direction: BPA is a probable developmental neurotoxicant
at low doses. Accordingly, the precautionary principle should be followed, progressively implementing stringent preventive
policies worldwide, including the banning of BPA in food contact materials and thermal receipts, with a focus on the
utilization of safer substitutes.European Union (EU): H2020-EJP-HBM4EUBiomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP)Instituto de Salud Carlos III
FIS-PI16/01820
FIS-PI16/0181
Epigenetic management of major psychosis
Epigenetic mechanisms are thought to play a major role in the pathogenesis of the major psychoses (schizophrenia and bipolar disorder), and they may be the link between the environment and the genome in the pathogenesis of these disorders. This paper discusses the role of epigenetics in the management of major psychosis: (1) the role of epigenetic drugs in treating these disorders. At present, there are three categories of epigenetic drugs that are being actively investigated for their ability to treat psychosis: drugs inhibiting histone deacetylation; drugs decreasing DNA methylation; and drugs targeting microRNAs; and (2) the role of epigenetic mechanisms in electroconvulsive therapy in these disorders
DNA Methylation in the Human Cerebral Cortex Is Dynamically Regulated throughout the Life Span and Involves Differentiated Neurons
The role of DNA cytosine methylation, an epigenetic regulator of chromatin structure and function, during normal and pathological brain development and aging remains unclear. Here, we examined by MethyLight PCR the DNA methylation status at 50 loci, encompassing primarily 5′ CpG islands of genes related to CNS growth and development, in temporal neocortex of 125 subjects ranging in age from 17 weeks of gestation to 104 years old. Two psychiatric disease cohorts—defined by chronic neurodegeneration (Alzheimer's) or lack thereof (schizophrenia)—were included. A robust and progressive rise in DNA methylation levels across the lifespan was observed for 8/50 loci (GABRA2, GAD1, HOXA1, NEUROD1, NEUROD2, PGR, STK11, SYK) typically in conjunction with declining levels of the corresponding mRNAs. Another 16 loci were defined by a sharp rise in DNA methylation levels within the first few months or years after birth. Disease-associated changes were limited to 2/50 loci in the Alzheimer's cohort, which appeared to reflect an acceleration of the age-related change in normal brain. Additionally, methylation studies on sorted nuclei provided evidence for bidirectional methylation events in cortical neurons during the transition from childhood to advanced age, as reflected by significant increases at 3, and a decrease at 1 of 10 loci. Furthermore, the DNMT3a de novo DNA methyl-transferase was expressed across all ages, including a subset of neurons residing in layers III and V of the mature cortex. Therefore, DNA methylation is dynamically regulated in the human cerebral cortex throughout the lifespan, involves differentiated neurons, and affects a substantial portion of genes predominantly by an age-related increase
Microbiome to Brain:Unravelling the Multidirectional Axes of Communication
The gut microbiome plays a crucial role in host physiology. Disruption of its community structure and function can have wide-ranging effects making it critical to understand exactly how the interactive dialogue between the host and its microbiota is regulated to maintain homeostasis. An array of multidirectional signalling molecules is clearly involved in the host-microbiome communication. This interactive signalling not only impacts the gastrointestinal tract, where the majority of microbiota resides, but also extends to affect other host systems including the brain and liver as well as the microbiome itself. Understanding the mechanistic principles of this inter-kingdom signalling is fundamental to unravelling how our supraorganism function to maintain wellbeing, subsequently opening up new avenues for microbiome manipulation to favour desirable mental health outcome
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