Psychological Distress Across the Life Course and Cardiometabolic Risk

Psychological Distress Across the Life Course and Cardiometabolic Risk
Findings From the 1958 British Birth Cohort Study
Ashley Winning, ScD, MPH, et al.
J Am Coll Cardiol. 2015;66(14):1577-1586.
http://content.onlinejacc.org/article.aspx?articleID=2445329

Background  Research suggests cardiovascular and metabolic diseases are influenced by psychological distress in adulthood; however, this research is often limited to adult populations and/or a snapshot measure of distress. Given emerging recognition that cardiometabolic diseases have childhood origins, an important question is whether psychological distress earlier in life influences disease development.

Objectives  This study sought to assess whether life course patterns of psychological distress assessed from childhood through adulthood predict biomarkers of cardiometabolic risk in adulthood and whether effects of sustained distress differ from more limited exposure.

Methods  The sample (n = 6,714) consists of members of the 1958 British Birth Cohort Study who completed repeated measures of psychological distress and a biomedical survey at age 45 years. Psychological distress profiles over the life course (no distress, childhood only, adulthood only, or persistent distress) were identified from 6 assessments between ages 7 and 42 years. Cardiometabolic risk was assessed by combining information on 9 biomarkers of immune, cardiovascular, and metabolic system function. Covariate adjusted linear regression models were used to assess associations between distress profiles and cardiometabolic risk.

Results  Compared with those with no distress, cardiometabolic risk was higher among people with psychological distress in childhood only (β = 0.11, SE = 0.03, p = 0.0002), in adulthood only (β = 0.09, SE = 0.03, p = 0.007), and persistent across the life course (β = 0.26, SE = 0.04, p < 0.0001).

Conclusions  Psychological distress at any point in the life course is associated with higher cardiometabolic risk. This is the first study to suggest that even if distress appears to remit by adulthood, heightened risk of cardiometabolic disease remains. Findings suggest early emotional development may be a target for primordial prevention and for promoting lifelong cardiovascular health.

journalistic version
http://www.npr.org/sections/health-shots/2015/09/29/444451363/childhood-stress-may-prime-pump-for-chronic-disease-later

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The Real Wealth is Health

Hooked, Hacked, Hijacked: Reclaim Your Brain from Addictive Living
Dr. Pam Peeke at TEDxWallStreet
http://tedxwallstreet.com
Nov 26, 2013

Dr. Pamela Peeke is an internationally renowned physician, scientist and exper t in the fields of nutrition, metabolism, stress and fitness. Triathlete and marathoner, Dr. Peeke is nationally known as the “doc who walks the talk” inspiring through example. Dr. Peeke is the lifestyle exper t for WebMD’s 90 million members, and a regular blogger on cutting edge science in health and wellness. Presently, Dr. Peeke is Senior Science Advisor to Elements Behavioral Health, the nation’s most preeminent network of eating disorders and addiction centers. Her current research focuses on how addictive behaviors have subtly and often profoundly penetrated daily lifestyle habits.

related:

https://franzcalvo.wordpress.com/2017/04/30/no-one-will-truly-invest-in

Transgenerational epigenetic inheritance (2013)

Transgenerational epigenetic inheritance: how important is it?
Nature Reviews Genetics 14, 228-235 (March 2013)
Ueli Grossniklaus, William G. Kelly, Anne C. Ferguson-Smith, Marcus Pembrey & Susan Lindquist
http://www.nature.com/nrg/journal/v14/n3/full/nrg3435.html

Many of these parental (and sometimes grandparental) effects will not have an epigenetic basis.
This is particularly important when considering environmentally induced effects, for which an epigenetic basis can be inferred only if they last over multiple generations.

In a pregnant mammal, for instance, not only are the mother and fetus exposed to the same environmental influences but so are the fetus’s primordial germ cells, which will eventually produce the grandchildren.
For instance, expression of the methylation-sensitive, metastable agouti viable yellow (Avy) allele, which determines mouse coat colour and shows meiotic epigenetic inheritance, is modulated by the animal’s diet. The specific dietary conditions in which a pregnant female is raised can change the inheritance pattern over two generations, but this change gets lost in the third generation.
Thus, while this specific diet leads to parental and grandparental effects, the induced epigenetic changes are not transgenerationally inherited.

… It is worth noting that most of the factors that guide these epigenetic processes in C. elegans have orthologues in most eukaryotes, so it is certainly plausible that these routes to epigenetic inheritance exist in many organisms.

Epigenetics: We are more than just the sequence of our genes

Finding the missing heritability of complex diseases. Nature 461, 747-753(8 October 2009)

Ten years of genetics and genomics: what have we achieved and where are we heading?
Nat Rev Genet. 2010 Oct;11(10):723-33.
Heard E, et al.
http://www.ncbi.nlm.nih.gov/pubmed/20820184

Epigenetics provides hope that we are more than just the sequence of our genes–and our destiny and that of our children can be shaped, to some extent, by our lifestyle and environment.

… structural variants, such as highly repetitive DNA sequences, that may be inaccessible to the current high-throughput genotyping platforms.

One intriguing possibility is that a small portion of familial clustering is due to transgenerational effects— gene–environmental interaction events in parents, grandparents or beyond that alter the phenotypes and behaviors of the current generation.

debates rage on about ‘missing heritability’.

common alterations to gene expression and function do not map to obviously functional DNA changes, illustrating how little we know about genome function.

A recurrent theme emerging from such systematic, unbiased, high-throughput analyses is how much more complicated the molecular organization of the cell appears to be relative to what was originally revealed using focused, hypothesis-driven, reductionist molecular biology approaches.
Transcriptomes, both protein-coding and non-coding, are more complex than initially thought, by at least an order of magnitude, with more than 80% of the genome seemingly transcribed in humans.

estimates of the numbers of protein–protein and DNA–protein interactions that can happen in a single cell are in the range of 10exp5 to 10exp6.

The ‘gene number paradox’, according to which organisms of different complexity have similar numbers of protein-coding genes (for example, humans and worms both have approximately 20,000 genes)

Part of the confusion goes back to how we interchangeably use the concept of the gene as both a molecular encoding unit and a unit of heredity. but this classical problem has been enormously amplified in the past decade.
At the molecular level, it is increasingly harder to define the exact boundaries of both protein- and non-coding genes.
At the level of heredity, GWA studies now identify genes whose relative contribution to a particular phenotype of interest can be no more than a few per cent.

the kinds of genetic changes possible at any particular time in history and in each lineage depend on what kinds of transposable elements are present and active.

related:
Estimating Trait Heritability
2008
http://www.nature.com/scitable/topicpage/estimating-trait-heritability-46889

Transgenerational effects

Transgenerational effects
http://en.wikipedia.org/wiki/Vinclozolin

Vinclozolin has been demonstrated to have trangenerational effects, meaning that not only is the initial animal affected, but effects are also seen in subsequent generations.
One study demonstrated that vinclozolin impaired male fertility not only in the first generation that was exposed in utero, but in males born for three generations and beyond.[1] …
After three generations, male offspring continued to show low sperm count, prostate disease and high rates of testicular cell apoptosis.[1][2]

It has been reported that these transgenerational reports correlate with epigenetic changes, specifically, an alteration in DNA methylation in the male germ line.[3]

[1] Gilbert, Scott; Epel, David (2009). Ecological Developmental Biology [Integrating Epigenetics, Medicine, and Evolution]. MA: Sinauer Associates. p. 231. ISBN 978-0-87893-299-3.

[2] “Epigenetic Transgenerational Actions of Vinclozolin on the Development of Disease and Cancer”. Critical Reviews in Oncogenesis.

[3] “Epigenetic Transgenerational Actions of Vinclozolin on Promoter Regions of the Sperm Epigenome”.

Chemical ‘clock’ tracks ageing more precisely than ever before

DNA methylation suggests cancerous tissue ages faster than healthy tissue.

Chemical ‘clock’ tracks ageing more precisely than ever before
DNA methylation could shed light on why some tissues are prone to cancer.
Amanda Mascarelli
Nature. 21 October 2013
http://www.nature.com/news/chemical-clock-tracks-ageing-more-precisely-than-ever-before-1.13981

In a paper published today in Genome Biology, Horvath reveals how methylation levels change in human tissues from before birth to the age of 101, and shows that it is a near-perfect predictor of age for non-cancerous tissues.
The study “represents the most convincing demonstration so far” of age-associated changes in DNA methylation that are consistent across most tissue types, says Andrew Teschendorff, a computational biologist at University College London.

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DNA methylation age of human tissues and cell types
Genome Biology 2013, 14(10):R115
Steve Horvath
http://genomebiology.com/2013/14/10/R115

Conclusions: I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer and aging research.

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ScienceClub: Oct. 29, 2013