Trajectories of childhood adversity and mortality in early adulthood: a population-based cohort study.

BACKGROUND: Childhood is a sensitive period with rapid brain development and physiological growth, and adverse events in childhood might interfere with these processes and have long-lasting effects on health. In this study, we aimed to describe trajectories of adverse childhood experiences and relate these to overall and cause-specific mortality in early adult life. METHODS: For this population-based cohort study, we used unselected annually updated data from Danish nationwide registers covering more than 1 million children born between 1980 and 1998. We distinguished between three different dimensions of childhood adversities: poverty and material deprivation, loss or threat of loss within the family, and aspects of family dynamics such as maternal separation. We used a group-based multi-trajectory clustering model to define the different trajectories of children aged between 0 and 16 years. We assessed the associations between these trajectories and mortality rates between 16 and 34 years of age using a Cox proportional hazards model and an Aalen hazards difference model. FINDINGS: Between Jan 1, 1980 and Dec 31, 2015, 2 223 927 children were included in the Danish Life Course cohort. We excluded 1 064 864 children born after 1998, 50 274 children who emigrated before their 16th birthday, and 11 161 children who died before their 16th birthday, resulting in a final sample of 1 097 628 children. We identified five distinct trajectories of childhood adversities. Compared with children with a low adversity trajectory, those who had early-life material deprivation (hazard ratio 1·38, 95% CI 1·27-1·51), persistent deprivation (1·77, 1·62-1·93), or loss or threat of loss (1·80, 1·61-2·00) had a moderately higher risk of premature mortality. A small proportion of children (36 081 [3%]) had multiple adversities within all dimensions and throughout the entire childhood. This group had a 4·54 times higher all-cause mortality risk (95% CI 4·07-5·06) than that of children with a low adversity trajectory, corresponding to 10·30 (95% CI 9·03-11·60) additional deaths per 10 000 person-years. Accidents, suicides, and cancer were the most common causes of death in this high adversity population. INTERPRETATION: Almost half of Danish children in our study experienced some degree of adversity, and this was associated with a moderately higher risk of mortality in adulthood. Among these, a small group of children had multiple adversities across social, health, and family-related dimensions. This group had a markedly higher mortality risk in early adulthood than that of other children, which requires public health attention. FUNDING: None.

Changes in Emotional Vitality as a Predictor of Levels and Change in Allostatic Load: Longitudinal Results From the Whitehall II Cohort Study.

OBJECTIVE: Increasing evidence has shown an association between reduced psychological well-being and long-term morbidity. However, longitudinal studies addressing potential biobehavioral mechanisms, such as physiological function, are lacking. The aim of this study is to examine the association between changes in emotional vitality on levels and changes in allostatic load (AL), a measure of multisystem physiological dysregulation, as well as its composite risk markers. METHODS: Participants comprised 5919 British civil servants from phases 3, 5, and 7 of the Whitehall II study. Psychological well-being was operationalized as emotional vitality. AL was measured using nine biomarkers of the cardiovascular, metabolic, and immune system. Linear mixed-effect models were used to determine the association between changes in emotional vitality between phases 3 and 5 and subsequent levels and change in AL from phases 5 to 7. Generalized linear models were used to address the association between changes in emotional vitality and individual risk markers. RESULTS: Increase in emotional vitality was associated with a lower mean level of AL, whereas the AL slope was not markedly affected. Among the included risk markers, only interleukin-6 was weakly associated with changes in emotional vitality, with a 7% reduced risk of high levels of interleukin-6 per one-unit increase in emotional vitality. CONCLUSION: This study found that an increase in emotional vitality was associated with subsequent lower levels, but not rate of change, of AL over time. Further research is needed to address the relationship between trajectories of psychological well-being and physiological dysregulation.

Both High and Low Levels of Negative Emotions Are Associated with Higher Blood Pressure: Evidence from Whitehall II Cohort Study.

BACKGROUND: Previous studies of negative emotions and blood pressure (BP) produced mixed findings. Based on the functionalist and evolutionary perspective on emotions, we hypothesized that the association between negative emotions and BP is U-shaped, i.e., that both very high levels of negative emotions and the absence thereof are related to high BP. METHODS: Data from 7479 British civil servants who participated in Phases 1-11 (years 1985-2013) of the Whitehall II cohort study was used. Negative emotions were operationalized as negative affect and depressive and anxiety symptoms. Negative affect was measured at Phases 1 and 2. Anxiety and depressive symptoms were assessed at each phase. BP was measured at every other phase. For each negative emotion measure, an average across all phases was computed and used as a predictor of PB levels throughout the follow-up period using growth curve models. RESULTS: Very high values of anxiety and depressive symptoms, but not negative affect, were associated with higher levels of systolic BP. However, low to moderate levels of all negative emotions were associated with lower blood pressure than the absence of negative emotions. CONCLUSIONS: The article offers a theoretical explanation for a previously observed inverse association between negative emotions and blood pressure and underscores that moderate levels of negative emotions that naturally occur in everyday life are not associated with risks of heightened blood pressure.

Life Events, Emotions, and Immune Function: Evidence from Whitehall II Cohort Study.

Stressful life events have been shown to increase vulnerability to infections. However, the effects may be dependent on specific emotional responses associated with these events. In general, negative emotions are thought to exacerbate and positive emotions to protect from the adverse effects of stressors on health. In this study, we adopted an evolutionary and functionalist perspective on emotions and hypothesized that both positive and negative emotions in response to stressful events are protective, whereas absence of emotional reactions exacerbates vulnerability to infections. We assessed immune function using lymphocytes to white blood cells ratio as a proxy for current viral infection in 3,008 British civil workers (30% women). No main effect of stressful life events or emotions on lymphocyte ratio was observed in either sex. However, in men, there was an interaction of life events with both positive and negative emotions as well as a combined measure of general affect. Supporting our hypothesis, stressful life events were associated with impaired immune function in men who reported very low levels of both positive and negative emotions but not in others. We discuss potential benefits of negative and positive emotions in the context of stress and immunity.

Moderate emotional reactions to stressful life events are associated with lowest risk of increased alcohol consumption: evidence from the Whitehall II study.

BACKGROUND: Research investigating the associations between stress-related negative emotions and alcohol consumption often assumes a linear dose-response relationship. Based on the current theories of emotions, we questioned this assumption and hypothesized that both very low and very high levels of negative emotional response (NER) to stressful life events are related to increased alcohol consumption. METHODS: We used data from Phases 1 (1985-88) and 2 (1989-90) of the British Whitehall II study. At both phases, participants reported on their alcohol consumption, recent stressful events and the NER to the events. Two thousand and sixteen participants without recent stressful events at baseline were selected. Logistic regression was used to model the association between emotional response at baseline and increased frequency of alcohol consumption between the two phases. RESULTS: The likelihood of increased alcohol consumption increased with the number of recent stressful events. Among participants with at least one event, 17% increased alcohol consumption, compared with 14% of those who reported no events. Participants with average NER were at lowest risk (14%) of increasing alcohol consumption after major life events. Those with highest NER were significantly more likely to increase alcohol consumption (20%) than those with average NER, but the difference between those with highest NER and those with lowest NER (17%) was not statistically significant. CONCLUSIONS: Increases in alcohol consumption following stressful events are least likely if people experience moderate levels of NER to events. Negative emotions in moderate doses should not be regarded as a risk factor for unhealthy behaviours, but rather a potentially protective factor.

Weekly hours of informal caregiving and paid work, and the risk of cardiovascular disease.

Background: Little is known on the association between weekly hours of informal caregiving and risk of cardiovascular disease (CVD). The objective was to investigate the individual and joint effects of weekly hours of informal caregiving and paid work on the risk of CVD. Methods: Pooled analysis with 1396 informal caregivers in gainful employment, from the Swedish Longitudinal Occupational Survey of Health and the Whitehall II study. Informal caregiving was defined as care for an aged or disabled relative. The outcome was CVD during 10 years follow-up. Analyzes were adjusted for age, sex, children, marital status and occupational grade. Results: There were 59 cases of CVD. Providing care >20 h weekly were associated with a higher risk of CVD compared to those providing care 1-8 h weekly (hazard ratio = 2.63, 95%CI: 1.20; 5.76), irrespectively of weekly work hours. In sensitivity analyzes, we found this risk to be markedly higher among long-term caregivers (6.17, 95%CI: 1.73; 22.1) compared to short-term caregivers (0.89, 95%CI: 0.10; 8.08). Caregivers working ≥55 h weekly were at higher risk of CVD (2.23, 95%CI: 1.14; 4.35) compared to those working 35-40 h weekly. Those providing care >8 h and working ≤40 h weekly had a higher risk of CVD compared to those providing care 1-8 h and working ≤40 h (3.23, 95%CI: 1.25; 8.37). Conclusion: A high number of weekly hours of informal caregiving as opposed to few weekly hours is associated with a higher risk of CVD, irrespectively of weekly work hours. The excess risk seemed to be driven by those providing care over long periods of time.

Parental break-ups and stress: roles of age & family structure in 44 509 pre-adolescent children.

Background: Parental break-up is wide spread, and the effects of parental break-up on children's well-being are known. The evidence regarding child age at break-up and subsequent family arrangements is inconclusive. Aim: to estimate the effects of parental break-up on stress in pre-adolescent children with a specific focus on age at break-up and post-breakup family arrangements. Methods: We used data from the Danish National Birth Cohort. Participants included 44 509 children followed from birth to age 11. Stress was self-reported by children at age 11, when the children also reported on parental break-up and post break-up family arrangements. Results: Twenty-one percent of the children had experienced a parental break-up at age 11, and those who had experienced parental break-up showed a higher risk of stress (OR:1.72, 95%CI:1.55;1.91) regardless of the child's age at break-up. Children living in a new family with stepparents (OR = 1.63, 95%CI:1.38;1.92), or shared between the parents (OR = 1.48, 95%CI:1.26;1.75) reported higher stress than children of intact families. Single parent families reported markedly higher stress levels than children in intact families (OR = 2.18, 95%CI:1.90;2.50) and all other family types. Children who were satisfied with their living arrangements post-break-up reported the same stress level as children living in intact families (OR = 1.01, 95%CI:0.86;1.18). Conclusion: Children who experience parental break-up have higher stress levels, also many years after the break-up, and those living in a single parent household post break-up seem to be most vulnerable. Living arrangements post-breakup should be further investigated as a potential protective factor.

Work stress, caregiving, and allostatic load: prospective results from the Whitehall II cohort study.

OBJECTIVES: Studies investigating health effects of work and family stress usually consider these factors in isolation. The present study investigated prospective interactive effects of job strain and informal caregiving on allostatic load (AL), a multisystem indicator of physiological dysregulation. METHODS: Participants were 7007 British civil servants from the Whitehall II cohort study. Phase 3 (1991-1994) served as the baseline, and Phases 5 (1997-1999) and 7 (2002-2004) served as follow-ups. Job strain (high job demands combined with low control) and caregiving (providing care to aged or disabled relatives) were assessed at baseline. AL index (possible range, 0-9) was assessed at baseline and both follow-ups based on nine cardiovascular, metabolic, and immune biomarkers. Linear mixed-effect models were used to examine the association of job strain and caregiving with AL. RESULTS: High caregiving burden (above the sample median weekly hours of providing care) predicted higher AL levels, with the effect strongest in those also reporting job strain (b = 0.36, 95% confidence interval = 0.01-0.71); however, the interaction between job strain and caregiving was not significant (p = .56). Regardless of job strain, participants with low caregiving burden (below sample median) had lower subsequent AL levels than did non-caregivers (b = -0.22, 95% confidence interval = -0.06--0.37). CONCLUSIONS: The study provides some evidence for adverse effects of stress at work combined with family demands on physiological functioning. However, providing care to others may also have health protective effects if it does not involve excessive time commitment.

Children's Emotionality Moderates the Association Between Maternal Responsiveness and Allostatic Load: Investigation Into Differential Susceptibility.

While emotionality is often thought of as a risk factor, differential susceptibility theory argues that emotionality reflects susceptibility to both positive and negative environmental influences. The present study explored whether emotional children might be more susceptible to the effects of both high and low maternal responsiveness on allostatic load, a physiological indicator of chronic stress. Participants were 226 mother and child dyads. Mothers reported on children's emotionality at child age 9. Maternal responsiveness was measured at age 13 using self-reports and behavioral observation. Allostatic load was measured at age 13 and 17 using neuroendocrine, cardiovascular, and metabolic biomarkers. Emotionality was associated with higher allostatic load if self-reported responsiveness was low, but with lower allostatic load, when self-reported responsiveness was high.

Orthographic consistency affects spoken word recognition at different grain-sizes.

A number of previous studies found that the consistency of sound-to-spelling mappings (feedback consistency) affects spoken word recognition. In auditory lexical decision experiments, words that can only be spelled one way are recognized faster than words with multiple potential spellings. Previous studies demonstrated this by manipulating feedback consistency of rhymes. The present lexical decision study, done in English, manipulated the spelling of individual vowels within consistent rhymes. Participants recognized words with consistent rhymes where the vowel has the most typical spelling (e.g., lobe) faster than words with consistent rhymes where the vowel has a less typical spelling (e.g., loaf). The present study extends previous literature by showing that auditory word recognition is affected by orthographic regularities at different grain sizes, just like written word recognition and spelling. The theoretical and methodological implications for future research in spoken word recognition are discussed.

Cohort profile: the DANish LIFE course (DANLIFE) cohort, a prospective register-based cohort of all children born in Denmark since 1980.

PURPOSE: The DANish LIFE course (DANLIFE) cohort is a prospective register-based study set up to investigate the complex life course mechanisms linking childhood adversities to health and well-being in childhood, adolescence and young adulthood including cumulative and synergistic actions and potentially sensitive periods in relation to health outcomes. PARTICIPANTS: All children born in Denmark in 1980 or thereafter have successively been included in the cohort totalling more than 2.2 million children. To date, the study population has been followed annually in the nationwide Danish registers for an average of 16.8 years with full data coverage in the entire follow-up period. The information is currently updated until 2015. FINDINGS TO DATE: DANLIFE provides information on a wide range of family-related childhood adversities (eg, parental separation, death of a parent or sibling, economic disadvantage) with important psychosocial implications for health and well-being in childhood, adolescence and young adulthood. Measurement of covariates indicating demographic (eg, age, sex), social (eg, parental education) and health-related factors (eg, birth weight) has also been included from the nationwide registers. In this cohort profile, we provide an overview of the childhood adversities and covariates included in DANLIFE. We also demonstrate that there is a clear social gradient in the exposure to childhood adversities confirming clustering of adverse experiences within individuals. FUTURE PLANS: DANLIFE provides a valuable platform for research into early life adversity and opens unique possibilities for testing new research ideas on how childhood adversities affect health across the life course.

Mental and physical health effects of meaningful work and rewarding family responsibilities.

Positive feelings about work and family responsibilities benefit psychological well-being, but their physical health effects remain unexplored. The study assessed whether meaningful work and reward from taking care of family benefitted physical health to the same degree as mental health. Participants were 181 Danes aged 49-51. Participants reported on working conditions, providing care to family, depressive symptoms, and perceived stress. Physical health was operationalized as a physiological dysregulation (e.g., hypertension, high levels of blood sugar and cholesterol, high body mass index). A multidimensional index of physiological dysregulation was created using parameters of cardiovascular, metabolic, and immune function. As expected, meaningful work and sense of reward from taking care of family members were associated with better mental health. However, in women, the very same factors were positively associated with higher physiological dysregulation. We conclude that work and family factors promoting psychological well-being may have physical health trade-offs, particularly in women.

Externalizing Behaviors Buffer the Effects of Early Life Adversity on Physiologic Dysregulation.

The present study examined the counterintuitive hypothesis that externalizing behaviors such as aggression, although in many respects detrimental, may be functional and protect against the detrimental health consequences of early life adversity. In particular, in line with evolutionary models of development, we argue that externalizing problems moderate the association between chronic stress exposure and allostatic load, a biological marker of chronic physiological dysregulation. Prospective interactive effects of externalizing behaviors and cumulative risk (a confluence of multiple risk factors) on children's allostatic load were assessed in 260 children (46% female, baseline age = 9). Exposure to early life adversity was assessed at baseline using a cumulative risk index. Externalizing behaviors were reported by parents at baseline. Allostatic load was measured at baseline and at ages 13 and 17, using endocrine, cardiovascular and metabolic parameters. Results of linear-mixed effects models indicated that the association between cumulative risk and allostatic load was attenuated for adolescents who scored high on externalizing behaviors. Further examination of sex differences indicated that the findings were more pronounced among males than females.

Objective and subjective stress, personality, and allostatic load.

INTRODUCTION: Despite the understanding of allostatic load (AL) as a consequence of ongoing adaptation to stress, studies of the stress-AL association generally focus on a narrow conceptualization of stress and have thus far overlooked potential confounding by personality. The present study examined the cross-sectional association of objective and subjective stress with AL, controlling for Big Five personality traits. METHODS: Participants comprised 5,512 members of the Copenhagen Aging and Midlife Biobank aged 49-63 years (69% men). AL was measured as a summary index of 14 biomarkers of the inflammatory, cardiovascular, and metabolic system. Objective stress was assessed as self-reported major life events in adult life. Subjective stress was assessed as perceived stress within the past four weeks. RESULTS: Both stress measures were positively associated with AL, with a slightly stronger association for objective stress. Adjusting for personality traits did not significantly change these associations. CONCLUSIONS: The results suggest measures of objective and subjective stress to have independent predictive validity in the context of personality. Further, it is discussed how different operationalizations of stress and AL may account for some of the differences in observed stress-AL associations.

Informal caregiving and diurnal patterns of salivary cortisol: Results from the Whitehall II cohort study.

The objective was to investigate the relationship between various aspects of informal caregiving and diurnal patterns of salivary cortisol, with special attention to the moderating effect of sex and work status. The study population was composed of 3727 men and women from the British Whitehall II study. Salivary cortisol was measured six times during a weekday. Aspects of caregiving included the relationship of caregiver to recipient, weekly hours of caregiving, and length of caregiving. Diurnal cortisol profiles were assessed using the cortisol awakening response (CAR) and diurnal cortisol slopes. Results showed that men, but not women, providing informal care had a blunted CAR compared with non-caregivers (PInteraction = 0.03). Furthermore, we found a dose-response relationship showing that more weekly hours of informal care was associated with a more blunted CAR for men (Ptrend = 0.03). Also, the blunted CAR for men was especially pronounced in short-term caregivers and those in paid work. In women, the steepest cortisol slope was seen among those in paid work who provided informal care (PInteraction = 0.01). To conclude, we found different cortisol profiles in male and female informal caregivers. Male caregivers had a blunted CAR, which has previously been associated with chronic stress and burnout. Future research should investigate whether results are generalizable beyond UK citizens with a working history in the civil service.

In risky environments, emotional children have more behavioral problems but lower allostatic load.

OBJECTIVE: Developmental models of temperament by environment interactions predict that children's negative emotionality exacerbates the detrimental effects of risky environments, increasing the risk for pathology. However, negative emotions may have an adaptive function. Accordingly, the present study explores an alternative hypothesis that in the context of high adversity, negative emotionality may be a manifestation of an adaptive coping style and thus be protective against the harmful effects of a stressful environment. METHOD: Prospective combined effects of negative emotionality and cumulative risk (confluence of multiple risk factors related to poverty) on children's internalizing and externalizing symptoms and allostatic load, an index of cumulative physiological dysregulation, were assessed in 239 children (46% female, baseline age = 9). Negative emotionality and cumulative risk were assessed at baseline. Internalizing and externalizing behaviors were measured at 4- and 8-year follow-ups. Allostatic load was measured at baseline and both follow-ups using neuroendocrine, cardiovascular, and metabolic parameters. Linear mixed-effect models were used to analyze the prospective associations between negative emotionality, cumulative risk, and the outcomes-allostatic load and internalizing and externalizing behaviors. RESULTS: The combination of high cumulative risk exposure and high negative emotionality was associated with highest levels of internalizing and externalizing behaviors. However, consistent with the alternative hypothesis, negative emotionality reduced the effects of high cumulative risk on allostatic load. CONCLUSIONS: In the context of risky environments, negative emotionality may offer some physical health benefits. (PsycINFO Database Record

Job strain and informal caregiving as predictors of long-term sickness absence: A longitudinal multi-cohort study.

Objectives The aim of this study was to investigate the individual, joint and interactive effects of job strain and informal caregiving on long-term sickness absence with special attention to gender differences. Methods The study comprised a prospective cohort study of 6798 working adults from France, 14 727 from Finland, and 5275 from the UK. A total of 26 800 participants, age 52 (interquartile range 47-56) years participated in the study. Job strain was assessed using the demand-control model. Informal caregiving was defined as care for a sick, disabled, or elderly person. Long-term sickness absence spells defined as absence >14 consecutive days were registered during two years follow-up. We used recurrent-events Cox regression in random-effects meta-analyses. Results A total of 12% men and 21% women had ≥1 long-term sickness absence spell. Among women, both high job strain [hazard ratio (HR) 1.08, 95% confidence interval (95% CI) 1.00-1.17] and informal caregiving (HR 1.13, 95% CI 1.04-1.23) were associated with a modestly higher risk of sickness absence. Women doubly exposed to high job strain and informal caregiving also showed a moderately higher risk of sickness absence (HR 1.20, 95% CI 1.03-1.41), but the excess risk was not more than expected from joint exposure to caregiving and job strain. Neither job strain nor informal caregiving predicted sickness absence for men. Conclusions High job strain and informal caregiving predicted long-term sickness absence among women. However there was no noticeable interaction in the presence of both exposures.

Role of psychosocial work factors in the relation between becoming a caregiver and changes in health behaviour: results from the Whitehall II cohort study.

BACKGROUND: The present study tested the effects of becoming a caregiver combined with adverse working conditions on changes in health behaviours. METHODS: Participants were 5419 British civil servants from the Whitehall II cohort study who were not caregivers at baseline (phase 3, 1991-1994). Psychosocial work factors were assessed at baseline. Phase 4 questionnaire (1995-1996) was used to identify participants who became caregivers to an aged or disabled relative. Smoking, alcohol consumption and exercise were assessed at baseline and follow-up (phase 5, 1997-1999). RESULTS: Those who became caregivers were more likely to increase frequency of alcohol consumption, but only if they also reported low decision latitude at work (OR= 1.65, 95% CI 1.15 to 2.37 compared with non-caregivers with average decision latitude), or belonged to low occupational social class (OR=2.38, 95% CI 1.17 to 4.78 compared with non-caregivers of high occupational social class). Caregivers were more likely to quit smoking if job demands were low (OR=2.92; 95% CI 1.07 to 7.92 compared with non-caregivers with low job demands), or if social support at work was high (OR=2.99, 95% CI 1.01 to 8.86 compared with caregivers with average social support). There was no effect of caregiving on reducing exercise below recommended number of hours per week, or on drinking above recommended number of units per week, regardless of working conditions. CONCLUSIONS: The findings underscore the importance of a well-balanced work environment as a resource for people exposed to increased family demands.

Neighborhood perceptions and allostatic load: Evidence from Denmark.

An influential argument explaining why living in certain neighborhoods can become harmful to one's health maintains that individuals can perceive certain characteristics of the neighborhood as threatening and the prolonged exposure to a threatening environment could induce chronic stress. Following this line of argumentation, in the present study we test whether subjective perceptions of neighborhood characteristics relate to an objective measure of stress-related physiological functioning, namely allostatic load (AL). We use a large dataset of 5280 respondents living in different regions of Denmark and we account for two alternative mechanisms, i.e., the objective characteristics of the living environment and the socio-economic status of individuals. Our results support the chronic stress mechanisms linking neighborhood quality to health. Heightened perceptions of disorder and pollution were found related to AL and this relationship was particularly robust for women.

Early life adversity potentiates the effects of later life stress on cumulative physiological dysregulation.

BACKGROUND AND OBJECTIVES: Previous research indicates that early life adversity may heighten stress reactivity and impair mechanisms for adaptive coping, suggesting that experience of stress in early life may also potentiate adults' physiological vulnerability to stress in later life. The study tested this hypothesis by investigating whether the experience of stressful events and circumstances (SEC) in childhood or adolescence amplified the effect of adulthood SEC on physiological dysregulation (allostatic load, AL) in later midlife. DESIGN: Observational data were used in the present study. Physiological functioning was measured in later midlife (participants' age ranged from 49 to 63 years). Both childhood/adolescence and adulthood SEC were reported retrospectively on the same occasion. METHODS: Participants were 5309 Danish men and women from Copenhagen Aging and Midlife Biobank (CAMB). SEC included socioeconomic and family factors. The AL index was based on nine cardiovascular, metabolic, and immune biomarkers. RESULTS: Experience of SEC in both early life and adulthood independently predicted higher AL. In men, experience of SEC in early life also potentiated the effect of SEC in adulthood on AL. CONCLUSIONS: The results provide further insight into the mechanisms behind the "biological embedding" of childhood stress.