Health Psychology. Michael Murray
the general links that occur between parental problems and offspring outcomes (Bowers and Yehuda, 2016). 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.
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. Britto et al. (2017) collated the findings