Genetics, Epigenetics and Early Life Development
Health Psychology in the Context of Biology, Society and Methodology
’Health will be defined as a function of gene—environmental homeostasis.
The brain is an extraordinary organ showing high levels of epigenetic features.
Delgado-Morales and Esteller (2017)
While undernutrition kills in early life, it also leads to a high risk of disease and death later in life. This double burden of malnutrition has common causes, inadequate foetal and infant and young child nutrition followed by exposure (including through marketing practices) to unhealthy energy dense nutrient poor foods and lack of physical activity. The window of opportunity lies from pre-pregnancy to around 24 months of a child’s age.’
UN Standing Committee on Nutrition (2006)
The passage from the gametes to a fully functioning adult human involves a matrix of intricate, interacting genetic and environmental processes. All living organisms store genetic information using DNA and RNA with different genes having their expression switched on or off by DNA methylation. Genetic processes lay down scripts that are edited by epigenetic processes that produce lifelong alterations in individual development, health and disease. Early life development is a formative and critical stage that requires nurturing care for optimal outcomes and maximum protection from sources of adversity.
The 1971 novel The Dice Man by Luke Rhinehart tells of a psychiatrist who decides to make life decisions based on the rolling of dice. The Dice Man is based on a reckless and scary conceit which, due to its subversive content, with issues such as rape, murder and sexual experimentation, led to the banning of the novel in several countries, no doubt increasing sales. It is alleged that the author wrote the book based on his experiences of using dice to make decisions while studying psychology. The cover bore the confident sub-heading: ’Few novels can change your life. This one will.’ However, another, more profound truth does not feature in The Dice Man story. That is the fact that the most crucial ’dice of life’ are cast long before we can say ’ABC’ — the dice of biological determination and early life development (Figure 3.1), the topics of this chapter.
Figure 3.1 The ’dice of life’ — genetics, epigenetics, and early life development
Genetics and Heritability
The science of genetics began with Hippocrates. His theory of ’pangenesis’ suggested that heredity material in the form of ’pangenes’, collected from around the body, enters the sperm and ovaries. Information from specific parts of the parents’ bodies were communicated to the offspring to create the corresponding body part. For example, information from the parents’ hearts, lungs and limbs was believed to transmit directly from these body parts to create the offspring’s heart, lungs and limbs. The theory that inheritance was based on the ’blending’ of parental traits was also popular and could not be dismissed until the research by Gregor Mendel (1822—1884), an Austrian monk. Mendel cultivated and tested the physical characteristics of 28,000 pea plants, which made excellent study items as they have easily recognizable and constant features, such as seed texture, colour and height. Mendel observed seven traits that existed in one out of two possible forms, for example the flower colour is white or purple, the seed shape is either round or wrinkled, and the seed colour and pod colour are both green or yellow. With only one of two possible results from cross-pollination, Mendel could determine which traits were passed down to the offspring with what frequency. The modern-day science of genetics was born.
A world-wide survey of human mitochondrial DNA (mtDNA)1 led to the claim that ’all mitochondrial DNAs stem from one woman’ and that she probably lived around 200,000 years ago in Africa (Cairn et al., 1987). This prolific woman has been called ’Mitochondrial Eve’ or ’African Eve’. Allowing 25 years per generation, that is just 8,000 generations to create the entire human population of more than 7.5 billion people alive today. How does the science of genetics explain the huge diversity of descendants from Mitochondrial Eve?
1. Mitochondria are structures within cells that convert the energy from food into a usable form.
First, the blending theory of the ancients was found to be inadequate. In his study of peas, Mendel proposed that there can be no blending because the gene alternate for yellow is ’dominant’ over the gene alternate for green. The dominant trait is observed whenever a single copy of its gene is inherited. When Mendel crossed the hybrid offspring, green seeds would reappear in one-quarter of plants in the next generation. Mendel concluded that the ’recessive’ green trait appears only when a copy of the recessive gene form is inherited from each parent. Although Mendel published his discoveries in 1866, Mendel’s ideas were not appreciated until the early twentieth century (Figure 3.2).
In 1905, the study of meiosis revealed that gender is based on chromosomes, thread-like structures inside the nucleus of animal and plant cells. Each chromosome is made of protein and a single molecule of DNA. Chromosome keeps DNA tightly wrapped around spool-like proteins called histones. Without this tight packaging, DNA molecules would be too long to fit inside cells. For example, if all of the DNA molecules in a single human cell were unwound from their histones and placed end-to-end, they would stretch six feet. Bearing in mind that the body contains 37.2 trillion cells, one can appreciate the need for histones.
In humans, each cell normally contains 23 pairs of chromosomes, a total of 46. Of these pairs, called autosomes, 22 look the same in both males and females. The twenty-third pair, the sex chromosomes, differ between males and females. One sex chromosome (X) is much bigger than the other (Y). A mismatched pair of one X and one Y chromosome occurs in male cells, while a matched pair of X chromosomes occurs in female cells. Females produce eggs with only X chromosomes, while males produce sperm with an X or a Y chromosome.
Thomas Morgan studied inheritance in the common fruit fly by crossing white-eyed male flies with red-eyed female flies which produced only red-eyed offspring. However, white-eyed mutants reappeared in the following generation, indicating a recessive trait, but only in males of the second generation. Morgan correctly concluded that being white-eyed must be a sex-linked recessive trait, with the gene for eye colour being physically located on the X chromosome.
Recessive inheritance has explained genetic disorders such as alkaptonuria and albinism, while other disorders are based on dominant genes such brachydactyly (short fingers), congenital cataracts and Huntington’s chorea. Duchenne muscular dystrophy, red-green colour blindness and haemophilia are also sex-linked disorders.
Mendel’s ideas were exploited and taken into a scientific cul-de-sac by the eugenics movement, which proposed that the human species could be improved by breeding from ’superior’ white stock, while reproduction of the ’genetically unfit’ was to be stopped. Eugenicists misused ideas of dominant and recessive genes to explain in simplistic terms complex human behaviours and mental illnesses, and failed to take account of environmental effects in human development. Eugenics reached its lowest point in the ’Final Solution’ of Nazism and the Holocaust of Jewish and Romani people in the Second World War.
As early as 1881 Albrecht Kossel had isolated five nucleotide bases — adenine, cytosine, guanine, thymine and uracil — which were all later shown to be basic building blocks of DNA and RNA in all living things. Deoxyribonucleic acid (DNA) carries the instructions used in the growth, development, functioning and reproduction of all known living organisms and many viruses. DNA is composed of nucleotide deoxyribose sugar, a phosphate group and one of four nitrogen bases — adenine (A), thymine (T), guanine (G) and cytosine (C). Phosphates and sugars of adjacent nucleotides link to form a long polymer. The ratios of A to T and G to C are found to be constant in all living things. Uracil is only present in RNA, replacing thymine.
Figure 3.2 Inheritance of traits
In Mendel’s research with round and wrinkled peas, Mendel observed that a quater of the peas were wrinkled in the second generation, suggesting that the characteristic is produced by two ’factors’ (genes)
Source: Public domain, Mariana Ruiz Villarreal, 12 September 2008
In 1953, an American, James Watson, and an Englishman, Francis Crick, described the structure of DNA as a double helix, shaped like a twisted ladder. This discovery was in part based on an image produced by Raymond Gosling and Rosalind Franklin using X-ray crystallography, ’Photo 51’. On 28 February 1953 in a pub in Cambridge, Crick allegedly announced that he and Watson had ’discovered the secret of life’. Two months later the discovery was reported in Nature (Watson and Crick, 1953). Crick and Watson demonstrated that alternating deoxyribose and phosphate molecules formed the twisted uprights of the DNA ladder, while the rungs of the ladder are formed by complementary pairs of nitrogen base, with A always paired with T and G always paired with C, an elegant and beautiful structure (Figure 3.3). Maurice Wilkins of King’s College London later shared the 1962 Nobel Prize in Physiology or Medicine with Watson and Crick. Rosalind Franklin was not included because she had died of ovarian cancer four years earlier. [Another explanation of Franklin’s apparent sidelining has been critical of Wilkins’ professional conduct (Weinstein, 2017)].
An important molecule related to DNA is ribonucleic acid (RNA), which carries out coding, decoding, regulation and expression of genes. As noted above, RNA and DNA are both nucleic acids, and, along with proteins and carbohydrates, constitute the four macromolecules that are necessary for all known forms of life. The type of RNA which transcribes information from DNA as a sequence of bases and transfers it to a ribosome is called messenger RNA. Messenger RNA translates instructions from DNA to make proteins, without which we would not have evolved from the slime that we apparently evolved from.
Figure 3.3 The DNA double helix
Source: Reproduced from National Institutes of Health/National Human Genome Research Institute (2017). Public domain
The Human Genome
A genome is any organism’s complete set of DNA, including all of its genes. An organism’s genome contains all of the information needed to build and maintain the organism. Accompanied by much fanfare and hype as a ’landmark in science’, the first draft of the human genome appeared on 12 February 2001. In humans, a copy of the genome with all of its 3,234.83 mega-basepairs is contained in each and every one of the body’s cells.
Knowing the complete sequence of the human genome is similar to having a manual on how to construct the human body. However, this manual has more than 3 billion pages and is not easy to read. Great expectations were raised by the scientists involved with the human genome project. However, understanding how the 3.4 billion complex parts work to create human life, health and disease is a challenge. It is currently estimated that there are 19,000—20,000 human protein-coding genes, although this estimate may be reduced over time. Figure 3.4 gives a graphical representation of the idealized human karotype showing the organization of the genome into chromosomes. The drawing shows both the female (XX) and male (XY) versions of the twenty-third chromosome pair.
Figure 3.4 The idealized human karotype divided into 23 chromosome pairs
Source: Public domain
With the human genome project came the formation of new organizations to capitalize on the project. The National Institutes of Health/National Human Genome Research Institute is steering many research programmes on the human genome. One objective is to identify any gene suspected of causing an inherited disease. More than 2,000 genetic tests enable patients and families to be informed about their genetic risks for disease and to help professionals diagnose disease. The cost of sequencing an individual’s genome is being reduced to below US$1,000. When this cost eventually falls, people will be able to carry copies of their karotype on their smart phones. Comparative genomic studies are identifying the causes of rare diseases. These scientific advances do not come without consequences for human liberty, privacy and rights.
Ethical, legal and social implications may affect individuals, families and the whole of society in four areas:
· Privacy and fairness in the use of genetic information, including the potential for genetic discrimination in education, employment, immigration and insurance. There is potential for a new, indelible type of stigmatization.
· The integration of new genetic technologies, such as genetic testing, into the practice of clinical medicine.
· Ethical issues surrounding the design and conduct of genetic research with people, including the process of informed consent. People will need the right to refuse the holding of their genome in databases.
· The education of health care professionals, policy makers, students and the public about genetics and the complex issues that result from genomic research.
We inherit from our parents all of the information necessary to create the proteins that make up our bodies. This inherited information, together with the influence of the environment, creates the complete human being. Much research has focused on the obvious question: How important is heredity and how important is the environment in human behaviour, health and well-being?
Heritability of Human Traits
Finding answers to the nature/nurture question has kept many scientific minds busy for over a century. Yet despite all of this research, the specific nature of the influences of genes and environment on human traits remains controversial. In part, this may rest on the fact that the question implies a dichotomy that in reality is a continuum of genetic-plus-environmental influence. The study of the influence of genetics on behaviour is called ’behaviour genetics’. One of the main techniques for unravelling nature and nurture has been the study of identical (monozygotic) and non-identical (dizygotic) twins, either reared together or reared apart. Such studies require meticulous attention to detail and the recruitment of large samples of twin participants, which tends to be time-consuming. Data from twin studies are open to interpretation and have often led to controversy.
In discussing heritability, we need to distinguish between a person’s genotype and phenotype. The genotype is the part of the genetic makeup of an individual which determines their potential characteristics, for example eye colour, height, weight, general intelligence and personality traits. The phenotype is the set of observable characteristics of an individual resulting from the interaction of the genotype with the environment. A particular person’s phenotype is the sum of genetic and environmental effects:
Phenotype (P) = Genotype (G) + Environment (E)
Likewise, the phenotypical variance in the trait — Var (P) — is the sum of effects, as follows:
Var(P) = Var(G) + Var(E) + 2 Cov(G,E)
In a planned experiment Cov(G,E) can be controlled and held at 0. In this case, heritability, H2, is defined as:
H2 = Var(G)/Var(P)
An H2 estimate is the proportion of trait variation among individuals that is a consequence of genetic factors; it is not the degree of genetic influence on that trait in any particular individual. For example, if the heritability of personality traits is .60, we can not say that 60% of an individual’s personality is inherited from her/his parents and 40% from the environment. In most usual circumstances, the proportions of genetic and environmental influence for any individual and trait are unknown. In rare cases, when there is an autosomal dominant condition such as Huntington’s disease (1 in 15,000 births) or familial hypercholesterolemia (1 in 500 births), then there is a 50% chance of inheritance in each new birth, providing there is only one affected parent.
There has been a large amount of research using the monozygotic versus dizygotic twin design. Polderman et al. (2015) reported a mammoth meta-analysis of twin correlations with variance estimates for 17,804 traits from 2,748 publications based on 14,558,903 partly dependent twin pairs, i.e., virtually all published twin studies of complex traits. Estimates of heritability were found to cluster strongly within different functional domains. Across all traits the reported, heritability was 49%, indicating an almost exactly equal contribution of genes and environment. For 69% of traits, the observed twin correlations were consistent with a simple, parsimonious model in which twin resemblance is solely due to additive genetic variation (Figure 3.5). The authors concluded that the dataset was ’inconsistent with substantial influences from shared environment or non-additive genetic variation’ (Polderman et al., 2015). In other words, nurture and nature were independent and equal contributors to individual differences in traits.
Figure 3.5 Twin correlations and heritabilities for all human traits studied
(a) Distribution of rMZ and rDZ estimates across the traits investigated in 2,748 twin studies published between 1958 and 2012. rMZ estimates are based on 9,568 traits and 2,563,628 partly dependent twin pairs; rDZ estimates are based on 5,220 traits and 2,606,252 partly dependent twin pairs. (b) Relationship between rMZ and rDZ, using all 5,185 traits for which both were reported
Source: Reproduced by permission from Polderman et al. (2015)
On the basis of the Polderman et al. (2015) study, it can be concluded that nature and nurture are of equal importance in determining human abilities and character. However, the relative proportions of influence differ from 50:50 for specific functions and characteristics. The largest heritability estimates were for traits in the ophthalmological domain (H2 = 0.71, s.e.m. = 0.04), followed by the ear, nose and throat (H2 = 0.64, s.e.m. = 0.06), dermatological (H2 = 0.60, s.e.m. = 0.04) and skeletal (H2 = 0.60, s.e.m. = 0.02) domains. The lowest heritability estimates were found for traits in the environmental, reproductive and social value domains (Polderman et al., 2015). Nature is more important for structural and anatomical differences, while nurture has greater influence on psychological and social differences.
One example of a psychological variable is emotional overeating (EOE), the tendency to eat more in response to negative emotions. Herle et al. (2017) examined the relative genetic and environmental influences on EOE in toddlerhood and early childhood in 2,402 British twins born in 2007. Genetic influences on EOE were found to be minimal, while shared environmental influences explained most of the variance. Herle et al. (2017) stated that EOE is ’moderately stable from 16 months to 5 years and continuing environmental factors shared by twin pairs at both ages explained the longitudinal association’.
A new approach to the study of nature and nurture has been the genome-wide association studies (GWAS). GWAS examine a genome-wide set of genetic variants in a large sample of individuals to see whether any variant is associated with a trait. GWAS typically focus on associations between single nucleotide polymorphisms (SNPs, pronounced ’snips’) and traits or major human diseases. A SNP is a DNA sequence variation occurring when a single nucleotide adenine (A), thymine (T), cytosine (C) or guanine (G) in the genome (or other shared sequence) differs between individuals or between paired chromosomes in an individual. SNPs occur throughout a person’s DNA once in every 300 nucleotides on average, which means there are roughly 10 million SNPs in one human genome. Most commonly, SNP variations are found in the DNA lying between genes.
One approach in GWAS is the case-control design, which compares two large groups of individuals, one healthy control group and one case group affected by a disease. Initially, all individuals are genotyped for commonly known SNPs. The exact number of SNPs varies but is typically 1 million or more. For each SNP, the investigators examine whether the allele frequency is significantly altered between the case and the control group. The statistic for reporting effect sizes is the odds ratio, the ratio of disease for individuals having a specific allele and the odds of disease for individuals who do not have that allele. A p-value is calculated using a chi-squared test. An odds ratio that departs significantly from 1.0 indicates that a SNP is associated with disease.
In spite of the precision of the method, GWAS findings have been disappointing. There is a lack of consistency in findings across studies and the amount of variance explained in traits or diseases is very low. For example, known SNPs explain less than 2% of the variation in body mass index (BMI) despite the evidence of greater than 50% heritability from twin and family studies, a phenomenon termed ’missing heritability’. Llewellyn et al. (2013) used a novel method (Genome-wide Complex Trait Analysis, GCTA) to estimate the total additive genetic influence due to common SNPs on whole-genome arrays. This study provided the first GCTA estimate of genetic influence on adiposity in children. Participants were from the Twins Early Development Study (TEDS), a British twin birth cohort. Selecting one child per family (n = 2,269), GCTA results from 1.7 million DNA markers were used to quantify the additive genetic influence of common SNPs. For direct comparison, a standard twin analysis in the same families estimated the additive genetic influence as 82%. GCTA explained 30% of the variance in BMI-SDS. These results indicate that 37% of the twin-estimated heritability (30/82%) were explained by additive effects of multiple common SNPs, which is indicative of a strong genetic influence on adiposity in childhood. To fully explain this ’missing heritability’, larger sample sizes are required to improve statistical power. Also, most variants that are associated with obesity from current GWAS are correlational, not causative (Xia and Grant, 2013).
In discussing obesity, Marti and Ordovas (2011: 190) reflected on the lack of progress on the tenth anniversary of the publications that reported the initial human genome sequence: ’It was stated that the complete genome sequence would “revolutionize the diagnosis, prevention, and treatment of most, if not all, human diseases.” Whereas this is probably true, the question remains about “when” and “how”’. Seven years later the situation remains the same, and it is apparent that the human genome project has yet to reach its full potential. New approaches are required to identify the causative genes for the late onset and progressive nature of most common diseases, complex traits, and the mechanism by which the environment can modulate genetic predisposition to commonly occurring diseases.
Genetic counselling provides patients or relatives at risk of an inherited disorder with advice and support concerning the consequences and nature of the disorder, the probability of developing or transmitting it, and the options open to them in management and family planning. The main elements of genetic counselling have been described by Harper (2000) as follows:
· Diagnostic and clinical aspects
· Documentation of family and pedigree information
· Recognition of inheritance patterns and risk estimation
· Communication and empathy
· Information of available options and further measures
· Support in decision-making and for decisions already taken.
According to the National Society of Genetic Counselors (NSGC, 2017), meeting with a genetic counsellor is beneficial in cases where a person or close relative has experienced one or more of the following:
· Early age onset of disease (excluding less than 50 years of age for breast and colon cancer)
· More than one cancer diagnosis
· Three or more relatives on the same side of the family with the same type of cancer
· Triple negative breast cancer
· Ovarian cancer
· Male breast cancer
· Aggressive form of prostate cancer (Gleason grade 7 or higher)
· A genetic mutation confirmed in a family member.
During a first appointment, the counsellor will draw a family tree using information about grandparents, aunt/uncles, and cousins on both sides of the family. It is not uncommon for this to take more than one session while the client searches family history for relevant information. For cancer genetics, the kind of cancer, the age of the relative at diagnosis, current ages or ages at death for each relative will all be taken into consideration. The NSGC (2017) recommends that it is also useful for the counsellor to inquire about colon polyps, the age at diagnosis, the number of polyps and the type (pre-cancer vs. benign). Information about past surgeries, such as removal of the uterus or ovaries, is also useful for a risk assessment.
All of this information helps the genetic counsellor to estimate the lifetime chance of developing cancer and to discuss testing options and how the test results will impact on treatment. The genetic counsellor will coordinate with the GP/family physician to personalize the medical care of the client.
When an inherited condition is diagnosed in an individual there are potential consequences for other family members. However, privacy legislation and ethical considerations restrict health professionals’ ability to communicate the diagnosis with other family members, and it is normally the person who first receives the diagnosis who is responsible for sharing the news with their relations. There are many possible barriers to sharing this information, including stigma, fear, guilt and shame (James et al., 2006).
Owing to the complexity of genetic counselling as an intervention, there have been few randomized controlled trials (RCTs) to evaluate it. One recent trial of telephone genetic counselling conducted in Australia obtained a non-significant treatment effect. Hodgson et al. (2016) conducted an RCT in six public hospitals to assess whether a telephone counselling intervention improved family communication about a new genetic diagnosis. Only 26% (142/554) of the intervention group relatives made contact with genetic services, compared with 21% (112/536) of the control group relatives (P = 0.40).
A systematic review by Mendes et al. (2016) examined the dissemination of information within families, finding it to be actively encouraged and supported by genetic counselling professionals, following guidelines and recommendations from professional bodies. People requiring support or showing difficulties can receive psycho-educational guidance and written information aids as ’cues for action’. A more direct approach is for genetics services to send letters to at-risk relatives informing them of their risks and the availability of counselling services. According to Mendes et al. (2016), this direct approach is acceptable to relatives and effective in promoting clarification of relatives’ genetic status.
We now turn to consider the second of the three ’dice of life’, epigenetics.
Epigenetics and Intergenerational Transmission
Epigenetics is the study of heritable changes in a chromosome other than changes in the underlying DNA sequence. The epigenetic inheritance system has been described as ’soft inheritance’ in comparison to genetics, which is ’hard inheritance’ (Mayr and Provine, 1980). The inheritance of traits in genetics occurs as a result of rare genetic mutations that involve DNA mutation, but selection is slow in making adaptations to the constantly changing environment. The soft inheritance system of epigenetics, on the other hand, is able to adapt to fluctuations in the environment, such as changes in nutrition, stress and toxins (Wei et al., 2015).
Epigenetics at the cellular level produces cell differentiation by determining the functional types of cell, such as hepatocytes in the liver, neurones in the brain, or skin cells, as well as influencing whether or not they become cancerous. Within the CNS, epigenetics are involved in various neurodegenerative disorders and physiological responses, such as Alzheimer’s disease, depression, schizophrenia, glioma, addiction, Rett syndrome, alcohol dependence, autism, epilepsy, multiple sclerosis and stress. As neurones are incapable of dividing and cannot be replaced after degeneration, epigenetic alterations that cause neuronal dysfunction have to be targeted and modified to prevent chronic kinds of neurodegeneration, which can prove fatal (Adwan and Zawia, 2013).
Epigenetic changes include DNA methylation and histone modification, both of which regulate gene expression without altering the linear sequence of DNA. DNA methylation adds methyl groups to the DNA molecule, which can change the activity of a DNA segment without changing the sequence. DNA methylation typically acts to repress or switch off gene transcription. DNA methylation is implicated in a wide range of processes, including chromosome instability, X-chromosome inactivation, cell differentiation, cancer progression and gene regulation. The flexibility in gene expression is seen early in childhood and can be demonstrated in identical twins, who, even when raised in the ’same’ environment, can have a different expression of genes. Essentially, DNA methylation is a switch that switches genes in the genotype on or off to produce the phenotype, the human being we actually become, rather than the one determined by a random mix from the gene bank of ’Mum and Dad’ (Figure 3.6).
Epigenetics can be viewed as a set of bridging processes between the genotype and the creation of the all-important phenotype — a phenomenon that changes the final outcome of a locus or chromosome without changing the underlying DNA sequence (Goldberg et al., 2007). We turn to consider the role of epigenetics in developmental plasticity and the ’Foetal Origins Hypothesis’, which is concerned with the role of nutrition and malnutrition in healthy foetal development.
Developmental plasticity and the Foetal Origins Hypothesis
Malnutrition during foetal life and infancy have been linked to the development of coronary heart disease, stroke, Type 2 diabetes, hypertension, osteoporosis and certain cancers, including breast cancer. All of these conditions can originate through the developmental plasticity process of foetal life. Geographical studies led David Barker (2007) to propose the ’Foetal Origins Hypothesis’, that undernutrition in utero and during infancy permanently changes the body’s structure, physiology and metabolism, causing coronary heart disease and stroke in adult life:
Like other living creatures in their early life human beings are ’plastic’ and able to adapt to their environment. The development of the sweat glands provides a simple example of this. All humans have similar numbers of sweat glands at birth but none of them function. In the first three years after birth a proportion of the glands become functional, depending on the temperature to which the child is exposed. The hotter the conditions, the greater the number of sweat glands that are programmed to function. After three years the process is complete and the number of sweat glands is fixed. Thereafter, the child who has experienced hot conditions will be better equipped to adapt to similar conditions in later life, because people with more functioning sweat glands cool down faster. This brief description encapsulates the essence of developmental plasticity: a critical period when a system is plastic and sensitive to the environment, followed by loss of plasticity and a fixed functional capacity. For most organs and systems, the critical period occurs in utero. (Barker, 2013: 5)
Figure 3.6 A schematic diagram of DNA pulled from a chromosome, showing the double helix wrapped around histones, and some epigenetic modifications to both the DNA and the histones
Source: Reproduced by permission from Hadas et al. (2017)
Developmental plasticity has been described as the phenomenon by which one genotype can give rise to a range of different physiological or morphological states in response to different environmental conditions during development (West-Eberhard, 1989). One area in which to explore the developmental origins of chronic disease is cardiovascular disease. Barker’s team had earlier identified groups of men and women in middle or late life whose birth size had been recorded. Their birthweight could be related to the later occurrence of coronary heart disease (CHD). In Hertfordshire, UK, from 1911 onwards, women with babies were attended by a midwife, who recorded the birthweight. After the birth, a health visitor went to the baby’s home at intervals throughout infancy, and the weight at 1 year was recorded. In 10,636 men born between 1911 and 1930, hazard ratios for CHD fell with increasing birthweight. There were stronger trends with weight at 1 year. A later study found a similar trend of decreased hazard ratios for CHD with increasing birthweight among women born during this time but no trend with weight at 1 year. The association between low birthweight and CHD has since been replicated in Europe, North America and India. Because the associations are independent of the duration of gestation, they can be assumed to be the result of slow foetal growth (Barker, 2007). The findings from ecological studies have been confirmed in studies with individuals. Barker (2007: 416) concluded that the ’orthodox view that cardiovascular disease results from adult lifestyles and genetic inheritance has not provided a secure basis for prevention of these disorders. The developmental model of the origins of chronic disease now offers a new way forward’. If true, Barker’s hypothesis means that the majority of work in public health and in much of health psychology, which is designed to help adults change ’lifestyles’, is redundant. [Hmmm. No need for this textbook then! However, Barker’s hypothesis is only true to a certain extent. Adults’ behaviours, such as smoking, drinking and unhealthy eating, are all examples of known risk factors for cancers and cardiovascular disease.]
The intrauterine period of development certainly is important in development because it includes stimuli such as nutrients, stress, drugs, trauma and smoking. A healthy intrauterine environment enables the mother to impart a rich ’maternal forecast’ for her developing foetus, predicting a healthy post-birth environment where resources will be plentiful and negative exposures are expected to be minimal. However, a relatively adverse intrauterine environment may result in a poor maternal forecast for her developing foetus, a so-called ’thrifty phenotype’ (Hales and Barker, 1992) that becomes a small, low-weight baby, preparing the child to survive in a poor post-birth environment. Maternal forecasts which inaccurately predict the post-birth environment are hypothesized to lead to ill health over the child’s later life, for example an increased risk for metabolic diseases and decreased cognitive functioning in offspring that had received a poor maternal forecast but were born into a rich environment (Knopik et al., 2012).
There can be few times in the lifespan that are more significant than the period of prenatal development. At this time there appear to be ’critical windows’ where disturbances may alter foetal growth and development, leading to health and behavioural consequences across the life course. Early life programming can have long-term effects on metabolism (Tarry-Adkins and Ozanne, 2011) via mechanisms that include: (1) permanent structural changes resulting from suboptimal concentrations of an important factor during a critical period of development (e.g., the permanent reduction in B cell mass in the endocrine pancreas); (2) persistent alterations in epigenetic modifications that lead to changes in gene expression (e.g., several transcription factors are susceptible to reprogrammed gene expression); and (3) permanent effects on the regulation of cellular ageing (e.g., increases in oxidative stress that lead to macromolecular damage, including that to DNA and specifically to telomeres2). Prevention and intervention to combat the burden of common diseases such as Type 2 diabetes and cardiovascular disease may be developed as a consequence of improved understanding of early life programming.
2. A telomere is a region of repetitive nucleotide sequences at each end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighbouring chromosomes.
Intergenerational Transmission, Social Epigenetics and Maternal Stress
’Intergenerational transmission’ occurs when enduring epigenetic changes in parental biological systems in response to maternal exposure are transmitted to the offspring and to the offspring of the offspring. Nutritional status, exposure to toxins and drugs, and the experiences of interacting with varied environments can all modify an individual’s epigenome. Epigenetic programming changes how and when certain genes are turned on or off and triggers temporary or enduring health problems. Research suggests that epigenetic changes occurring in the foetus can be passed on to later generations, affecting children, grandchildren and their descendants. For example, turning on genes that increase cell growth, while at the same time switching off genes that suppress cell growth, can cause cancer. Repetitive, stressful experiences can cause epigenetic changes that alter the biological systems that manage one’s response to adversity later in life. We illustrate these ideas with recent examples of epigenetic research on maternal stress.
Stress exposures of parents may occur before conception, at the time of conception, at the time of pregnancy, or in the early postnatal period, where the environment of mothers influences the epigenetic patterning of their offspring, which can have a life-long influence on their behaviour, emotions and well-being, both mental and physical. Children of mothers who are exposed to poverty, hunger, poor diet, smoking, stress, war or violence prenatally are prone to epigenetic influences on their offspring’s later well-being.
Research from Moshe Szyf and colleagues has provided significant findings on the epigenetic influences of prenatal maternal stress. This work has been labelled ’social epigenetics’ (Szyf, 2013). One study looked at the offspring of mothers exposed to severe ice storms in southern Quebec, Canada, in 1998. For several days in January 1998 freezing rain storms covered everything in layers of ice. The heavy weight of the ice coating toppled high tension power lines and utility poles, collapsing the power grid in the Montérégie region of Quebec. Power outages ranged from a few hours to as long as six weeks for 3 million Québécois. Without electricity, central heating, pumps for well water, farm and factory equipment stopped working. Security forces went door to door to rescue isolated individuals in danger from cold and hypothermia, asphyxiation from unconventional heating devices, and fire due to blocked chimneys. More than 30 deaths were attributed to the ice storm.
The investigators of a research project called ’Project Ice Storm’ have reported that maternal hardship and subjective distress predicted a variety of developmental outcomes. One focus for the project was the potential influence of prenatal maternal stress (PNMS) on the offspring (Box 3.1).
Intergenerational transmission to offspring from parental exposures and characteristics can be more specific than the general links that occur between parental problems and offspring outcomes (Bowers and Yehuda, 2015). Parents can model behaviours, and children can learn to react to their environments in a manner similar to their parents. Phenotypic changes can also occur as a consequence of child rearing and offspring can also experience parental trauma vicariously or by imagining traumas that they know their parents experienced from parents’ stories. The observation of biological changes in offspring associated with parental trauma may indicate similar genetic risks in both generations, rather than intergenerational transmission of biological sensitivity. The idea that an observed biological change in offspring may be transmitted from the parent first arose following studies of pregnant women exposed to starvation during the Dutch famines (Barker, 1990, 1998). Adult offspring of Holocaust survivors were found to be at greater risk for the development of post-traumatic stress disorder (PTSD), depression and anxiety disorders (Yehuda et al., 2008). Women who develop PTSD as a result of trauma during pregnancy, for example having to evacuate the World Trade Center on 9/11, also give birth to affected offspring with evidence of a trimester effect (Yehuda et al., 2005). The evidence suggests that the third trimester is a more sensitive period for in utero effects in intergenerational transmission of risk than the second trimester.
Box 3.1 Prenatal Maternal Stress Predicts a Wide Variety of Behavioural and Physical Outcomes in the Offspring
Although epigenetic processes may be responsible for prenatal maternal stress (PNMS) effects, human research is hampered by the lack of experimental methods that parallel controlled animal studies. Disasters, however, provide natural experiments that can present models of prenatal stress. This study took advantage of a natural disaster to carry out fundamental research on prenatal maternal stress.
Five months after the 1998 Quebec ice storm Cao-Lei and colleagues recruited women who had been pregnant during the disaster and assessed their degrees of objective hardship and subjective distress. Thirteen years later, they investigated DNA methylation profiling in T cells obtained from 36 of the children, and compared selected results with those from saliva samples obtained from the same children at age 8.
Prenatal maternal objective hardship was correlated with DNA methylation levels in 1,675 CpGs (or ’CGs’ — CGs are regions of DNA where a cytosinenucleotide is followed by a guanine nucleotide) affiliated with 957 genes predominantly related to immune function; maternal subjective distress was uncorrelated. DNA methylation changes in SCG53 and LTA,4 both of which highly correlated with maternal objective stress, were comparable in T cells, peripheral blood mononuclear cells and saliva cells.
3 The SCG5 gene encodes the neuroendocrine protein 7B2 in humans; 7B2 is widely distributed in neuroendocrine tissues.
4 The LTA gene encodes lymphotoxin-alpha (LT-α) or tumour necrosis factor-beta; LT-α has a significant role in the maintenance of the immune system.
These data provide the first evidence in humans supporting the idea that PNMS results in a lasting, broad and functionally organized DNA methylation in several tissues in offspring. By using a natural disaster model, the investigators could infer that the epigenetic effects found in Project Ice Storm were due to objective levels of hardship experienced by the pregnant woman rather than to her level of sustained distress.
Source: Cao-Lei et al. (2014)
Figure 3.7 indicates three levels at which biological stress effects in parents can potentially have a direct impact on offspring (Bowers and Yehuda, 2016). Other relevant mechanisms are genetics, social learning, parenting and shared environmental contexts. ’Intergenerational transmission’ of stress effects that are inherited is reflected in biological changes in the offspring, consisting of neuroendocrine, epigenetic and neuroanatomical changes.
Figure 3.7 Parental stress can be transmitted via gametes, the gestational uterine environment, and early postnatal care
Source: Reproduced by permission from Bowers and Yehuda (2016)
Theoretical models are needed to explain how early life adversities are epigenetically programmed towards life-long alteration in hormonal responses to stressors. Acute stress normally produces a biobehavioural response which, following its removal, is corrected by homeostasis, which restores the system to baseline functioning. Reactivity to acute stress is a trait that is both genetically and epigenetically determined. The effects of acute stressors can persist over time due to long-term changes in thresholds to stress triggers.
Figure 3.8 illustrates a theory of epigenetic processes suggested by Klengel and Binder (2015: 1344), as follows:
Stress and, in particular, early life adversities activate the stress hormone system and may epigenetically program the system toward a lifelong alteration of the hormonal response to even minor stressors. The neuropeptides corticotrophin-releasing hormone (CRH) and vasopressin (AVP), released from the hypothalamus in response to stress, activate the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland, finally leading to an increased systemic cortisol secretion from the adrenal gland. Cortisol binds to steroid receptors, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), that act as transcriptional activators or repressors in the nucleus through binding to glucocorticoid response elements. This influences the expression of numerous genes involved in the stress response, immune function, and metabolism. Binding of the GR and transcriptional activation of, for example, FKBP5 provide an ultrashort feedback to the GR, terminating the stress response and secretion of cortisol.
Figure 3.8 Stress and, in particular, early life adversities activate the stress hormone system and may epigenetically programme the system towards a life-long alteration of the hormonal response to even minor stressors
Source: Reproduced by permission from Klengel and Binder (2015)
Figure 3.8 is based on evidence suggesting that the effects of parental stress can be directly transmitted to offspring via gametes (oocytes and sperm), the uterine environment during pregnancy, or during early postnatal care of newborns. In Holocaust and Dutch Famine survivors’ offspring, the parental trauma occurred years before conception, suggesting that effects in offspring might be due in part to some biological change in gametes. Stress effects that are inherited via an ’intergenerational transmission’ mode are reflected in offspring biological changes, including neuroendocrine, epigenetic and neuroanatomical changes.
Although there have already been a number of significant findings, our knowledge of the role of the epigenome in shaping human behaviour across generations is at the beginning stages and very little is yet certain. Epigenetics has the potential to provide a foundation for the hypothesis that interventions to promote nurturing care, and to improve the cognitive and socio-emotional well-being of children, have positive transgenerational consequences. We await new developments with great interest.
Brave New World
Having a baby is one of, if not the most important decision(s) a woman can ever take. If she thinks rationally about the decision, she will probably consider factors such as her age, her ability to provide for the baby, her life circumstances, her career and her relationships. If she is in a long-term relationship with a partner, she will wish to consider the views of her partner because the decision will have an impact on both of their lives. It is never a decision that is undertaken lightly. In the following hypothetical example, we consider a decision about a pregnancy with a known male partner.
Imagine a near future when it is believed that it should be possible to consider when it is both genetically and epigenetically safe to have a baby. Many of the genetic risk factors are already known and can be discussed with a genetic counsellor (e.g., a woman’s chances of giving birth to a child with Down syndrome increase with age). In the near future epigenetic factors that are heritable are also likely to be established as risk factors for certain ’dread diseases’ (e.g., cancer, diabetes, heart disease and obesity). In this case, it is predicted that epigenetic markers in gametes, together with other factors, should enable the prediction of susceptibility to certain non-genetic diseases in offspring. This type of diagnosis would potentially be helpful in preventing some chronic non-genetic metabolic disorders, such as obesity and Type 2 diabetes in the offspring (Wei et al., 2015). One possible decision tree that uses a traffic signal approach is shown in Figure 3.9.
The decision is based on the following tests. For the woman, the first polar body5 (PB1) and second polar body (PB2) are dispensable for embryonic development and can be used for epigenetic diagnosis. If the epigenetic pattern is identical to the standard model, embryo transfer with this oocyte should result in a healthy baby. Otherwise, the pattern may indicate susceptibility to certain non-genetic diseases. For the man, the epigenomic patterns tend to represent the father’s physiological and metabolic conditions at each specific time. If the epigenetic pattern of the sperm is consistent with the standard model, it is a perfect time for a father to have a baby. If not, it may be advantageous for the couple to wait until the father improves his health (e.g., quits smoking, drinks less alcohol) and to have a baby when their epigenetic diagnosis passes both tests. This may all sound like science fiction, but epigenetic embryonic forecasting could become regular practice within one or two decades.
5 The first and second polar bodies are non-functioning egg cells, which disintegrate because the spermatozoon cannot fertilize them but chemically triggers their disintegration.
Early Life Development
Two profound changes over recent decades have produced a dramatically altered landscape for early childhood in many countries (Phillips and Shonkoff, 2000). First, research reviewed in this chapter has advanced our understanding of early development. Second, there have been changes in the social and economic circumstances in which families with young children are living: (1) work patterns of parents with young children; (2) high levels of economic hardship among families; (3) increasing cultural diversity and the persistence of significant racial and ethnic disparities in health and developmental outcomes; (4) growing numbers of young children spending considerable time in childcare settings; and (5) greater awareness of the negative effects of stress on young children. The findings of many thousands of studies on the characteristics of nurturing care have been collated in a recent systematic review (see Box 3.2).
Figure 3.9 Choosing a perfect time to have a baby. Schematic charts for epigenetic diagnosis with gametes to predict and prevent specific non-genetic disease
Source: Reproduced by permission from Wei et al. (2015)
Early environmental experiences can have lasting impact on a child’s later success in school and life more generally. It has been claimed that differences in the size of children’s vocabulary first appear at 18 months of age, based on whether they were born into a family with high education and income or low education and income (Hart and Risley, 1995). By age 3, children with college-educated parents or primary caregivers have vocabularies two to three times larger than those whose parents had not completed high school. Unless they are engaged in a language-rich environment in early life by school age, children are already behind their peers.
Adverse living circumstances impair a child’s development in the first 24—36 months of life, and the greater the degree of adversity, the greater the odds of developmental delay. Risk factors include poverty, caregiver mental illness, child maltreatment, single parenthood and low maternal education, which can collectively have a cumulative impact. Maltreated children who are exposed to up to six additional risks face a 90—100% likelihood of having one or more delays in their cognitive, language or emotional development (Barth et al., 2008).
Box 3.2 Nurturing Care: Promoting Early Childhood Development
· Advances in basic and intervention science indicate that early childhood is a period of special sensitivity to experiences that promote development, and that critical time windows exist when the benefits of early childhood development interventions are amplified.
· The most fundamental promotive experiences in the early years of life come from nurturing care and protection received from parents, family and community, which have lifelong benefits including improved health and wellbeing, and increased ability to learn and earn.
· Nurturing care and protection are supported by a range of interventions delivered pre-pregnancy and throughout birth, the newborn period, infancy and early childhood. Many of these interventions have shown benefits for child development, nutrition and growth, and reductions in morbidity, mortality, disability and injury.
· Interventions that integrate nurturing care and protection can target multiple risks to developmental potential at appropriate times, and can be integrated within existing preventive and promotive packages.
· Preventive and promotive packages can build on existing platforms, such as community-based strategies and social safety nets, for delivering parental and child services at scale to vulnerable and difficult-to-reach populations, enhancing their effectiveness and sustainability.
Source: Britto et al. (2016: 91). Reproduced by permission
Early experiences can actually get ’under the skin’ and have life-long effects on cognitive and emotional well-being, and on long-term physical health as well. Significant childhood adversity is a predictor of adult health problems, including diabetes, hypertension, stroke, obesity and some forms of cancer. Adults who recall having seven or eight serious adverse experiences in childhood are three times more likely to have cardiovascular disease as an adult (Dong et al., 2004).
We summarize here a huge number of findings on the influence of nurturing care on early life development, extracted from the review by Britto et al. (2016).
6 Extracts from a major cross-national review by Britto et al. (2016) in the following sections are included by permission. The majority of quantitative data such as means and confidence intervals have been deleted, as have references to specific categories of country, as they are not relevant.
Opportunities for stimulation, responsive parent—child interactions, child-directed and focused enrichment, early learning and positive parenting are crucial for children’s development. Parenting programmes increased scores on measures of psychosocial development and motor development in addition to child cognitive development. However, the effect of parenting programmes on child growth was not significant. A notable gap in published reviews has been the role of fathers. Parenting programmes that combine nutrition and stimulation have been effective in improving child cognitive and language development outcomes. Taken together, the results suggest that parenting support programmes that promote nurturing care and protection can substantially augment the positive effects of basic health and nutrition, education and protection interventions on early child development outcomes (Britto et al., 2016).
Attachment and Bonding
Different brain systems enhance nurturing by supporting infant—mother attachment, as well as emotional well-being, learning and memory, attention, and executive functions. Secure attachment forms with a caregiver who provides security, safety, affection and comfort. Aspects of nurturing care during birth and labour include early initiation of breastfeeding and interventions such as ’Kangaroo Mother Care’, which is a method of holding a baby that involves skin-to-skin contact. The baby, who is naked except for a nappy and a piece of cloth covering his or her back (either a receiving blanket or the parent’s clothing), is placed in an upright position against a parent’s bare chest. Kangaroo Mother Care has been associated with an increase in bonding indicators, such as infant—mother attachment at 3 months, infant growth, and rates of early exclusive breastfeeding (at 1—3 months) (Britto et al., 2016).
Although it has always been a controversial topic, breastfeeding has clear short-term benefits for child health, reducing mortality and morbidity from infectious diseases, encouraging healthy food preferences, and promoting the establishment of a healthy gut microbiome. A recent review of 17 observational studies of breastfeeding presents evidence that optimal breastfeeding supports improved performance in intelligence tests in childhood and adolescence, demonstrating an intelligence quotient (IQ) increase of 3.44 points (95% confidence interval (CI) 2.30—4.58). Findings from a 2015 analysis of the Pelotas birth cohort in Brazil also showed a dose—response association between breastfeeding duration and increased child intelligence, educational attainment and income at the age of 30 years. A prospective, population-based birth cohort study of neonates was launched in 1982 in Pelotas, Brazil (Victora et al., 2015). Information about breastfeeding was recorded in early childhood. At 30 years of age, the investigators studied the IQ (Wechsler Adult Intelligence Scale, third version), educational attainment and income of the participants. In 2012 and 2013, information about IQ and breastfeeding duration was available for 3,493 participants from the original sample of 5,914 neonates. The results showed that the durations of total breastfeeding and predominant breastfeeding (breastfeeding as the main form of nutrition with some other foods) were positively associated with IQ, educational attainment and income.
According to a systematic review by Horta and colleagues (2015), breastfeeding decreased the odds of Type 2 diabetes and, based on high-quality studies, decreased by 13% the odds of overweight/obesity. Breastfeeding was associated with a 24% reduction in overweight and/or obesity, but the reduction was only 12% in the high-quality studies, and residual confounding cannot be ruled out.
However, a comprehensive review of 84 relevant studies on breastfeeding practices and intelligence concluded that any observed associations between the two were best explained by residual confounding (Walfisch et al., 2014). Also, a prospective study by von Stumm and Plomin (2015) found that IQ growth from toddlerhood through adolescence was unrelated to breastfeeding. The jury is still out on breastfeeding and IQ.
The research showing long-term health benefits among breastfed individuals is given partial support by the literature on breastfeeding and DNA methylation. Hartwig et al. (2017) suggest that breastfeeding may be negatively associated with promoter methylation of certain genes, and may influence global methylation patterns and modulate epigenetic effects of some genetic variants. However, these results remain inconclusive due to the small number of studies and study limitations.
Micronutrients and Child Feeding
Malnutrition remains a serious challenge, undermining the survival, growth and development of young children, especially in developing countries, Stunting and severe acute malnutrition (wasting) are often associated with concomitant micronutrient deficiencies — among these, vitamin A, iron, zinc and iodine deficiencies are the most prevalent in childhood. Given the wide prevalence of multiple micronutrient deficiencies in malnourished children, there is a need to implement interventions that combine micronutrient interventions with appropriate infant and young child feeding.
Multiple micronutrient supplementation in children at risk of deficiencies improves academic performance among children aged 5—16 years. A review of iron supplementation in children found an improvement in psychomotor development at 12 months and a decrease in IQ in school grades 1—6 (children of an average age of 10 years). A second review on iron supplementation found an improvement in mental development and IQ. One other review focused on the effect of supplementary food given to socio-economically disadvantaged children aged from 3 months to 5 years and found that food supplements improved psychomotor development but found mixed effects on measures of cognitive development in different trials (Britto et al., 2016).
Prevention of Child Maltreatment
Family violence is increasingly recognized as a key public health problem. Maltreatment during childhood is associated with reduced volume of both the midsaggital area and hippocampus, brain regions involved in learning and memory. Children who receive inadequate care, especially in the first 24 months of life, are more sensitive to the effects of stress and display more behavioural problems than do children who receive nurturing care. There is increasing evidence that one of the most powerful predictors of caregiving behaviour is how caregivers, especially mothers, were cared for themselves. Children who grow up neglected or abused by their parents, or under conditions of extreme distress within their families, are at risk of developing a host of unhealthy behaviours that affect their own lives. When these children grow up, they tend to be less equipped to take on a parenting role and are more likely to perpetuate a cycle of adverse caregiving across generations. The maltreatment prevention interventions with the best evidence, which shows positive results following the intervention, are selective programmes (e.g., Nurse Family Partnership) that are characterized by intensive visits by professional home visitors and that began prenatally. The extent to which these findings are generalized beyond the specific high-income countries where they have been evaluated is unknown (Britto et al., 2016).
Formal and non-formal or community-based preschools improve scores on direct measures of children’s cognitive development and psychosocial development. The effects of early learning programmes on child growth were not significant and one study measuring motor development showed non-significant effects. Regardless of type, programme quality is a key predictor of effectiveness. Important factors of preschool quality include greater number of, variety of and challenging play materials, interactive or dialogic reading, classroom organization and instructional support. Nurturing environments, in the form of care and positive interactions and individualized attention, appear to be important in early learning programmes. A positive emotional climate at childcare centres in Chile and Ecuador, including individualized attention, positive affect or positive moods, and reinforcement of children’s behaviours, has shown positive associations with children’s early childhood cognitive and socio-emotional skills (Britto et al., 2016).
1. The developmental model of the origins of chronic disease suggested by Barker and others offers an important alternative approach to disease prevention based on the provision of nurturing care and the protection of the foetus and neonate. Economic studies of the benefits of early life prevention versus the traditional approach, which targets adult lifestyle change, are needed to inform policy and prevention.
2. Improved understanding of the epigenetic mechanisms of early life development, especially those associated with the initial critical phases, will make it possible to design effective interventions.
3. The ethical and legal implications of epigenetic embryonic forecasting need to be studied so that guidelines can be devised prior to implementation.
4. There is a need for more research to validate the GWAS approach and to examine the reasons for the high amounts of missing heritability.
1. Humans have 23 pairs of chromosomes, and thus a total of 46 chromosomes. One copy of each chromosome is inherited from the female parent and the other from the male parent. Chromosomes are made of protein and a single molecule of deoxyribonucleic acid (DNA), which contains the instructions making each human being unique.
2. It is necessary to distinguish between a person’s genotype and phenotype. The genotype is the part of the individual’s genetic makeup that determines their potential characteristics. The phenotype is the observable characteristics of an individual resulting from the interaction of the genotype with the environment.
3. Nature and nurture are of equal importance in determining human abilities and character. However, the relative proportions of influence can differ from a 50:50 split for specific functions and characteristics. Nature is more important for structural and anatomical differences, while nurture has greater influence on psychological and social differences.
4. Epigenetics is the study of heritable changes caused by mechanisms other than changes in the underlying DNA sequence. The epigenetic inheritance system has been described as ’soft inheritance’ because it is amenable to adaptation to fluctuations in environments, such as changes in nutrition, stress and toxins.
5. The ’Foetal Origins Hypothesis’ of David Barker proposed that undernutrition in utero and during infancy permanently changes the body’s structure, physiology and metabolism, causing coronary heart disease and stroke in adult life.
6. Orthodox thinking about chronic disease suggests that it results from adult lifestyles and genetic inheritance. The developmental model of the origins of chronic disease suggested by Barker and others offers an important alternative approach to disease prevention based on the provision of nurturing care and the protection of the foetus and neonate.
7. Breastfeeding has clear short-term benefits for child health, reducing mortality and morbidity from infectious diseases, encouraging healthy food preferences and promoting the establishment of a healthy gut microbiome.
8. Stress exposures of parents may occur before conception, at the time of conception, at the time of pregnancy, or in the early postnatal period. Children of mothers who are exposed to poverty, hunger, poor diet, smoking, stress, war or violence prenatally are prone to epigenetic influences on their offspring’s later well-being.
9. Maltreatment during childhood is associated with reduced volume of both the midsaggital area and the hippocampus, the two brain regions involved in learning and memory. Epigenetic changes in the CNS may be responsible for observed delays in cognitive development.
10. Children who receive inadequate care, especially in the first 24 months of life, are more sensitive to the effects of stress and display more behavioural problems than children who receive nurturing care.