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Cardiovascular Morbidity and Mortality in Finnish Men and Women Separated Temporarily From Their Parents in Childhood—A Life Course Study
Abstract
Early-life stress may influence health later in life. We examined morbidity and mortality from cardiovascular disease over 60 years in individuals separated temporarily from their parents in childhood due to World War II.
We studied 12,915 members of the Helsinki Birth Cohort Study born from 1934 to 1944, of whom 1726 (13.4%) had been evacuated aboard without their parents to temporary foster families for an average of 1.8 (standard deviation = 1.1) years at an average age of 4.6 (standard deviation = 2.4) years. Data on parental separations were extracted from the Finnish National Archives. Information on use of medication for coronary heart disease and hypertension was derived from the National Register of Medication Reimbursement, and information on coronary events, stroke, and cardiovascular deaths was derived from Finnish Hospital Discharge Register and Causes of Death Register between Years 1971 and 2003.
Participants who were separated in childhood used medications for coronary heart disease more frequently than those who were not separated (7.2% versus 4.5%, respectively; hazard ratio [HR] = 1.29, 95% confidence interval [CI] = 1.04-1.59; p = .02). No associations between separation and all-cause mortality (HR = 1.04, 95% CI = 0.90-1.20) or cardiovascular mortality (HR = 0.94, 95% CI = 0.72-1.21) or hospitalizations for cardiovascular disease or stroke were observed.
Early-life stress may possibly be a factor predisposing to coronary heart disease decades later, but no evidence was found for increased risk of hospitalizations or mortality.
... 6 In recent years, there has been a rise in the prevalence of looked-after children in several countries, such as the USA and the UK; 7-9 although estimates vary by country and ethnicity, the prevalence might be as high as 13%. 10 The decision to transfer to state care is predicated upon providing a better opportunity for the child to flourish. However, there is growing evidence that these children continue to be disadvantaged in several ways. ...
... Although some studies have found that placement into care is associated with an increased risk of total and suicide mortality, these are not universal findings. 10,[27][28][29][30] To the best of our knowledge, there is no comprehensive and systematic synthesis of the evidence base for the potential effect of pre-adult care on later death, illness, and injury. As such, at least two fundamental issues require clarification. ...
... 27,28 The maximum age at follow-up was 78 years. 28 Two studies used participants who were part of a wartime intercountry foster-care programme, 10,53 whereas the remainder were based on within-country movement. Seven studies were generated solely from linkage of participants to population registers, [27][28][29][47][48][49]53 with a further six also involving field work (four published 10,50-52 and two unpublished). ...
Background: Removal from family of origin to state care can be a highly challenging childhood experience and is itself linked to an array of unfavourable outcomes in adult life. We aim to synthetise evidence on the risk of adult mortality in people with a history of state care in early life, and assess the association according to different contexts.
Methods: In this systematic review and meta-analysis, we focused on four health outcomes hypothesised to be associated with exposure to early state care: total mortality, cardiovascular disease, cancer, and suicide. We searched the electronic databases PubMed and Embase from inception to Jan 21, 2022, for studies fulfilling the following criteria: it was a prospective study in which the assessment of care was made up to 18 years of age; it included an unexposed comparator group; the focus of the study was temporary out-of-home care and not adoption; mortality surveillance was extended into adulthood; standard estimates of association (eg, relative risk, odds ratios, or hazard ratios) and variance (eg, CIs and SE) were provided; the study appeared in a peer-reviewed journal; and the study was published in English. An adapted Cochrane Risk of Bias Tool was used to assess study quality. We extracted estimates of association and variance from qualifying studies and augmented these findings with analyses of unpublished data from individual participants in two UK birth cohorts—ie, the 1958 and 1970 studies (total n=21 936). We computed hazard ratios with accompanying 95% CIs for care and each health outcome separately for each study, and then pooled the results using a random-effects meta-analysis. This review is registered at PROSPERO, CRD42021254665.
Findings: We identified 210 potentially eligible published articles, of which 14 met our inclusion criteria (two studies were unpublished). Of 3 223 580 individuals drawn from 13 studies, those who were exposed to care in childhood had twice the risk of total mortality in adulthood relative to those without a history of care in childhood (summary risk ratio 2·21 [95% CI 1·62–3·02]), with study-specific estimates varying between 1·04 and 5·77 (I2 =98%). Despite some attenuation, this association remained following adjustment for other measures of early-life adversity; extended into middle and older age; was stronger in higher-quality studies; and was of equal magnitude according to sex, geographical region, and birth year. There was some suggestion of sensitive periods of exposure to care, whereby individuals who entered state care for the first time in adolescence (2·47 [0·98–6·52]) had greater rates of mortality than those doing so early in the life course (1·75 [1·25–2·45]). In four studies including 534 890 people, children in care had more than three times the risk of completed suicide in adulthood relative to their unexposed peers (3·35 [2·41–4·68]), with study-specific estimates ranging between 2·42 and 5·85 (I2=72%). The magnitude of this association was weaker after adjustment for multiple covariates; in men than in women; and in lower-quality studies.
Interpretation: Our results for adult mortality suggest child protection systems, social policy, and health services following care graduation are insufficient to mitigate the adverse experiences that might have preceded placement into care and those that might accompany it.
... War evacuees had higher systolic BP than non-evacuees, and the longer the separation from their biological parents the more prevalence for hypertension (Alastalo et al., 2009). In a separate study to determine the prevalence of CVD-related treatment, war evacuation was associated with being treated for coronary heart disease before and after adjusting for low SES (Alastalo et al., 2012). Of the deceased participants, the mortality and morbidity rates were also higher in war evacuees than non-evacuees (Alastalo et al., 2012). ...
... In a separate study to determine the prevalence of CVD-related treatment, war evacuation was associated with being treated for coronary heart disease before and after adjusting for low SES (Alastalo et al., 2012). Of the deceased participants, the mortality and morbidity rates were also higher in war evacuees than non-evacuees (Alastalo et al., 2012). These findings showed that as the number of ACEs increased so does the prevalence of smoking and the use of illicit drugs. ...
Adverse childhood experiences (ACEs), defined as traumatic events in childhood that range from various of forms of abuse to household challenges and dysfunction, have devastating consequences on adult health. Epidemiological studies in humans and animal models of early life stress (ELS) have revealed a strong association and insight into the mechanistic link between ACEs and increased CVD risks. This review focuses on the mechanistic links of ACEs in humans and ELS in mice and rats to vasoactive factors and immune mediators associated with CVD and hypertension risk, as well as sex differences in these phenomena. Major topics of discussion in this review are as follows: (1) epidemiological associations between ACEs and CVD risk focusing on hypertension, (2) evidence for association of ACE exposures to immune‐mediated and/or vasoactive pathways, (3) rodent models of ELS‐induced hypertension risk, (4) pro‐inflammatory mediators and vasoactive factors as mechanisms of ELS‐induced hypertension risk, and (5) overall conclusions and future research directions.
... In rodents, fathers' exposure to social defeat, footshock, and fear conditioning in the immediate period preceding conception affect offspring behavioral and physiological development (Saavedra-Rodríguez and Feig, 2013;Franklin, Russig, Weiss, Gräff, Linder, Michalon, Vizi, & Mansuy, 2010;Dias & Ressler, 2014;Mychasiuk, Harker, Ilnytskyy, & Gibb, 2013;Rodgers, Morgan, Bronson, Revello, & Bale, 2013;Hoyer, Richter, Brandwein, Riva, & Gass 2013). Less is known about paternal early life stress, although some evidence suggests that paternal exposure to early stress shapes health in subsequent generations in humans: cardiovascular risk is greater in offspring of males that experienced temporary separations from parents as children (Alastalo et al., 2012), and paternal grandparent exposure to famine impacts mortality ratios in a sex-specific manner in humans (Kaati et al., 2005). ...
... The most consistent effect of paternal line NR was to predict greater trait nervousness. This finding is consistent with studies demonstrating paternal line effects of stress on anxiety-and health-related traits, including our own (Alastalo et al., 2012;Kaati et al., 2005;Kinnally and Capitanio, 2015;Saavedra-Rodríguez and Feig, 2013;Franklin, et al., 2010;Dias & Ressler, 2014;Mychasiuk, et al., 2013;Rodgers et al., 2013;Hoyer, et al., 2013). Our other measures were not so consistently affected: plasma cortisol was affected by grandpaternal NR, consistent with studies demonstrating a similar effect in NR-exposed macaques (Capitanio et al., 2005), but not paternal or great-grandpaternal NR. ...
The effects of early stress may not be limited to the exposed generation, but are sometimes passed on to subsequent generations. Such non‐genetic transgenerational inheritance is a potentially important developmental and evolutionary force. We compared the transgenerational effects of maternal and paternal line early stress on anxiety‐ and health‐related traits in three non‐exposed generations (F1, F2 and F3) of semi‐naturalistically raised rhesus macaques. As infants, F0 macaques were exposed to nursery rearing (NR) or semi‐naturalistic social conditions (CONTROL). Three hundred forty non‐exposed F1–F3 descendants were CONTROL reared and physiological and behavioral measures were collected during standardized assessment at 3–4 months of age. Paternal line NR was significantly associated with greater nervousness in F1–F3 and lower immune cell counts in F1–F2. Maternal‐line NR effects were not observed. This study suggests that acquired stress‐related traits may be “inherited” across generations in primates, through complex social or germ‐line mechanisms.
... Early life stress (ELS) is an additional, relatively newly described risk factor for developing CVD (65). Epidemiological evidence shows that adverse childhood events, such as abuse, low socioeconomic status, childhood maltreatment, and parental separation, lead to increased blood pressure in adult life (2,4,66,67). Not only is blood pressure significantly elevated in adults who experienced adverse childhood events, but they also present with elevated proinflammatory markers and mediators (9,14,19). ...
... In humans, ELS is defined as prolonged adverse childhood experiences (ACE) typically occurring during the first decade of life (38). ACEs in humans are described as childhood maltreatment, physical and sexual abuse, parental divorce, war, and low socioeconomic status (2,15,67), and increasing numbers of ACEs are associated with greater emotional, immune, and cardiovascular disorders during adult life (8,9,15,67,69). Some investigators suggest that many adult diseases should be viewed as developmental disorders beginning early in life and could be reduced by the alleviation of or resilience to adversity in childhood (16,63). ...
... For instance, males born at the height of the Finnish famine lost ∼1 y of life expectancy at age 40 y (29). To our knowledge, only two studies have related early psychological stress and adult mortality (32,33). No increased mortality between age 27 and 69 y was found in the 1,726 members of the Helsinki Birth Cohort (born 1934-1944 and followed from 1971-2003) who were separated as children from their parents during the Second World War (32). ...
... To our knowledge, only two studies have related early psychological stress and adult mortality (32,33). No increased mortality between age 27 and 69 y was found in the 1,726 members of the Helsinki Birth Cohort (born 1934-1944 and followed from 1971-2003) who were separated as children from their parents during the Second World War (32). In the 1958 British birth cohort, increased all-cause mortality before age 50 y was found for the 4,543 individuals who experienced events such as parental divorce or bereavement in early life (33). ...
Significance
The First World War was a historical experiment for early-life stress. Fathers of hundreds of thousands of children of all ages were killed during the conflict. The Developmental Origins of Health and Disease hypothesis predicts long-term effects of early-life stress. We collected historical data on French orphans born 1914–1916 and their fathers’ military records and compared the orphans’ mortality in adulthood (age 31–99 y) with that of matched nonorphans. We found a strong decrease in lifespan, reflecting increased mortality before age 65 y, in persons whose fathers died before, not after, their birth. These results support the notion that maternal psychological stress in pregnancy decreases adult longevity in offspring.
... Nineteen (44%) created adversity indices from existing data (13,(16)(17)(18)(19)(20)(21)(24)(25)(26)28,29,(31)(32)(33)(34)(35)(36)(37), and 18 studies (42%) assessed adversity with standardized questionnaires (12,14,15,22,23,27,(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). Six (14%) examined indicators of adversity individually (30,(49)(50)(51)(52)(53), and one derived latent classes of childhood adversity from multiple items (54). Component parts of adversity measures were heterogeneous across studies; most metrics included different sets of adverse events, relational, and socioeconomic factors. ...
... Component parts of adversity measures were heterogeneous across studies; most metrics included different sets of adverse events, relational, and socioeconomic factors. Just more than half (n = 23) included markers of extreme forms of adversity such as death of a parent, separation from a parent in wartime, and/or physical/sexual abuse (12,(14)(15)(16)(17)(22)(23)(24)26,27,(29)(30)(31)(32)(33)36,37,41,45,(48)(49)(50)(51). Fourteen studies (33%) included a marker of SES as part of an adversity assessment (e.g., household income, poverty, parental education; 13, [16][17][18]20,21,26,28,[31][32][33]35,37,53). ...
Objective:
Identifying the life course health effects of childhood adversity is a burgeoning area of research, particularly in relation to cardiovascular disease (CVD). However, adversity measurement varies widely across studies, which may hamper our ability to make comparisons across studies and identify mechanisms linking adversity to CVD. The purpose of this review is to summarize adversity measurement approaches in the context of CVD, identify gaps, and make recommendations for future research.
Methods:
PubMed and PsycINFO searches were conducted through June 2016. Studies were selected if CVD endpoint or pre-disease risk markers were investigated in association with a measure of childhood adversity. 43 studies were reviewed. A meta-analysis was not conducted due to the variation in exposures and outcomes assessed.
Results:
Adversity measurement was heterogeneous across studies. Metrics included different sets of adverse events, relational factors, and socioeconomic indicators. 37% measured childhood adversity prospectively, 23% examined a CVD endpoint, and 77% treated adversity as an unweighted summary score. Despite the heterogeneity in measurement, most studies found a positive association between childhood adversity and CVD risk, and the association appears to be dose-response.
Conclusions:
The literature on childhood adversity and CVD would benefit from improving consistency of measurement, using weighted adversity composites, modeling adversity trajectories over time, and considering socioeconomic status as an antecedent factor instead of a component part of an adversity score. We suggest conceptual and analytic strategies to enhance, refine and replicate the observed association between childhood adversity and CVD risk.
... First, many middle-aged adults might have lost or got separated from their parents during and after the Vietnam War . Previous studies have suggested that parental loss in childhood is associated with a worsening of cardiovascular health in adulthood [14][15][16]. Hence, those who experienced it during and after the war could be at a higher cardiometabolic risk. ...
Background
This study aimed to determine the association between parental absence during childhood and metabolic syndrome (MetS) in adulthood among middle-aged adults in rural Khanh Hoa province, Vietnam. Given that broader literature on adverse childhood experiences (ACEs) suggests a strong positive association between ACEs and cardiometabolic risk or diseases, we hypothesized that parental absence during childhood, which is a major component of ACEs, is more likely to cause MetS in adulthood.
Methods
Data were obtained from the baseline survey of the Khanh Hoa Cardiovascular Study, in which 3000 residents aged between 40 to 60 years participated. MetS was assessed using the modified Adult Treatment Panel III (ATP III) criteria. It was considered parental absence if the participants had experienced parental absence due to death, divorce, or out-migration before three or between three to 15 years. We used multiple logistic regression analyses to examine the association between parental absence during childhood and metabolic syndrome during adulthood.
Results
There was no significant association between parental absence and MetS; adjusted odds ratio [AOR] was 0.97 (95% confidence interval [CI] = 0.76–1.22) for those who experienced parental absence between three to 15 years and the corresponding figure for those who experienced it before three years was 0.93 (95% CI = 0.72–1.20). No significant associations were observed when these were examined for the causes of parental absence.
Conclusion
This study did not support our hypothesis of an association between parental absence during childhood and metabolic syndrome during adulthood. Parental absence may not be a predictor of MetS among Vietnamese people in rural communities.
... Emerging epidemiologic evidence strongly supports that ELS/CT is an independent albeit silent risk factor of future chronic cardiovascular risk through various systemic and molecular mechanisms (267)(268)(269)(270)(271)(272) and that its effect is particularly heightened among women (273). The recent American Heart Association scientific statement offers a comprehensive review of the literature on the influence of ELS/CT on cardiovascular outcomes (274). ...
Early life stressors display a high universal prevalence and constitute a major public health problem. Prolonged psychoneurobiological alterations as sequelae of early life stress (ELS) could represent a developmental risk factor and mediate risk for disease, leading to higher physical and mental morbidity rates in later life. ELS could exert a programming effect on sensitive neuronal brain networks related to the stress response during critical periods of development and thus lead to enduring hyper- or hypo-activation of the stress system and altered glucocorticoid signaling. In addition, alterations in emotional and autonomic reactivity, circadian rhythm disruption, functional and structural changes in the brain, as well as immune and metabolic dysregulation have been lately identified as important risk factors for a chronically impaired homeostatic balance after ELS. Furthermore, human genetic background and epigenetic modifications through stress-related gene expression could interact with these alterations and explain inter-individual variation in vulnerability or resilience to stress. This narrative review presents relevant evidence from mainly human research on the ten most acknowledged neurobiological allostatic pathways exerting enduring adverse effects of ELS even decades later (hypothalamic-pituitary-adrenal axis, autonomic nervous system, immune system and inflammation, oxidative stress, cardiovascular system, gut microbiome, sleep and circadian system, genetics, epigenetics, structural, and functional brain correlates). Although most findings back a causal relation between ELS and psychobiological maladjustment in later life, the precise developmental trajectories and their temporal coincidence has not been elucidated as yet. Future studies should prospectively investigate putative mediators and their temporal sequence, while considering the potentially delayed time-frame for their phenotypical expression. Better screening strategies for ELS are needed for a better individual prevention and treatment.
... Numerous clinical studies have shown a direct relationship between exposure to ELS and increased risk for hypertension, obesity, depression, and anxiety (1,56,57,60). All of these are important risk factors for CVD. ...
... This was illustrated in a cohort of older Finnish adults, where parental separation in early childhood was associated with the use of cardiovascular medication, but not cardiovascular mortality. 31 Our data indicate that suboptimal parenting style in childhood might be associated with mortality in old age via multiple mechanisms and pathways. Participants' affective and social problems and unhealthy behaviours appeared to be relevant. ...
Background:
Parenting style is associated with offspring health, but whether it is associated with offspring mortality at older ages remains unknown.
Aims:
We examined whether childhood experiences of suboptimal parenting style are associated with increased risk of death at older ages.
Method:
Longitudinal cohort study of 1964 community-dwelling adults aged 65-79 years.
Results:
The association between parenting style and mortality was inverse and graded. Participants in the poorest parenting style score quartile had increased risk of death (hazard ratio (HR) = 1.72, 95% CI 1.20-2.48) compared with those in the optimal parenting style score quartile after adjustment for age and gender. Full adjustment for covariates partially explained this association (HR = 1.49, 95% CI 1.02-2.18). Parenting style was inversely associated with cancer and other mortality, but not cardiovascular mortality. Maternal and paternal parenting styles were individually associated with mortality.
Conclusions:
Experiences of suboptimal parenting in childhood are associated with increased risk of death at older ages.
... This is the case largely because, until the last decade, the only non-social mode of inheritance from parents was believed to be genetic, which should be unchanged by experiences. However, non-genetic germ-line mechanisms for the transgenerational effects of early experiences have been recently identified [16,17]. Epigenetic changes to sperm DNA methylation patterns or micro-RNA expression, rather than changes to the genome sequence itself, have been observed in the sperm of fathers that experience temporary stress, coinciding with enhanced anxiety-related behavior in fathers [18][19][20][21][22][23][24]. ...
Early experiences influence the developing organism, with lifelong and potentially adaptive consequences. It has recently become clear that the effects of early experiences are not limited to the exposed generation, but can influence physiological and behavioral traits in the next generation. Mechanisms of transgenerational effects of parental early experiences on offspring development are often attributed to prenatal or postnatal parental influence, but recent data suggest that germ-line plasticity may also play a role in the transgenerational effects of early experiences. These non-genetic transgenerational effects are a potentially important developmental and evolutionary force, but the effects of parental experiences on behavior and physiology are not well understood in socially complex primates. In the non-human primate, the rhesus macaque, nursery rearing (NR) is an early life manipulation used for colony management purposes, and involves separating infants from parents early in life. We examined the effects of maternal and paternal early NR on infant rhesus macaque immunity, physiology, and behavior.
We theorized that differences in behavior or physiology in the absence of parent-offspring social contact would point to biological and perhaps germ-line, rather than social, mechanisms of effect. Thus, all subjects were themselves NR. Male and female infant rhesus macaques (N= 206) were separated from parents and social groups in the first four days of life to undergo NR. These infants differed only in their degree of NR ancestry – whether their dams or sires were themselves NR. At 3-4 months of age, infants underwent a standardized biobehavioral assessment. Factors describing immunity, plasma cortisol, and emotion regulation were generated from these data using factor analysis. Paternal, but not maternal, NR was associated with greater emotionality and higher plasma cortisol, compared with infants born to CONTROL reared fathers.
These data suggest that macaque biobehavioral makeup is strongly influenced by paternal experiences, and via non-social mechanisms.
... Exposure to low socioeconomic status, parental loss, sexual or physical abuse, and/or parental dysfunction during childhood, defined as early life stress (ELS), is associated with permanent changes in the adult health and behavior status (Alastalo et al. 2012;Low et al. 2009). For instance, exposure to ELS greatly increases the risk of developing chronic adult diseases, such as hypertension, ischemic heart disease, obesity, anxiety, and depression (Thomas et al. 2008). ...
We previously reported that maternal separation, rat model of early life stress, enhances pressor responses to acute and chronic stressors. The aims of this study were to determine whether Dahl salt-sensitive (DS) rats subjected to maternal separation (MatSep-DS) as compared to normally reared DS (Ctl-DS) rats show exaggerated blood pressure responses to acute behavioral stressors, such as restraint stress or air jet stress (AJS), or, hypertensive stimuli including chronic high-salt diet (4% NaCl) and angiotensin II (AngII) infusion (200 ng/Kg/min) during 1 week. MatSep was performed in male DS rats for 3 h/day from postnatal days 2-14. At 8 weeks of age, rats were implanted with telemetry transmitters and allowed to recover. Mean arterial pressure (MAP) was not different between MatSep-DS and Ctl-DS rats at baseline (120 ± 2 mmHg vs. 118 ± 1 mmHg, n = 4-8). Blood pressure responses during AJS and restraint stress were not different between MatSep-DS and Ctl-DS at 3 min. However, blood pressure recovery from AJS was significantly impaired in MatSep-DS rats compared to Ctl-DS rats (P < 0.05). 3-h stress-induced similar responses in MatSep and Ctl-DS rats. Chronic blood pressure responses to AngII infusion in rats fed a high-salt diet displayed enhanced MAP in MatSep-DS when compared with Ctl-DS rats (167 ± 5 mmHg vs. 152 ± 2 mmHg, pinteraction <0.05). However, MAP increased similarly in both groups in response to AngII infusion or high-salt diet separately. Renal parameters such as proteinuria, urine flow rate, and urine electrolytes were not different between groups in response to each treatment. In summary, salt sensitivity induces exaggerated blood pressor responses only in presence of AngII due to early life stress.
© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
... 7 In men, separation associates with poorer cognitive performance 8 and with negative effects on physical and psychosocial functioning. 9 The consequences of separation were not limited to effects on mental health and the hypothalamic-pituitary-adrenal (HPA) axis, as cohort members who were separated from their parents in childhood also had a higher cardiovascular morbidity, including coronary artery disease, hypertension and type 2 diabetes, 10,11 with the highest prevalence of cardiovascular disease in those who were evacuated for the longest period. 11 Finally, early-life separation also associated with differences in reproductive and marital traits in both sexes. ...
Early-life stress (ELS) is known to be associated with an increased risk of neuropsychiatric and cardiometabolic disease in later life. One of the potential mechanisms underpinning this is through effects on the epigenome, particularly changes in DNA methylation. Using a well-phenotyped cohort of 83 men from the Helsinki Birth Cohort Study, who experienced ELS in the form of separation from their parents during childhood, and a group of 83 matched controls, we performed a genome-wide analysis of DNA methylation in peripheral blood. We found no differences in DNA methylation between men who were separated from their families and non-separated men; however, we did identify differences in DNA methylation in association with the development of at least mild depressive symptoms over the subsequent 5-10 years. Notably, hypomethylation was identified at a number of genes with roles in brain development and/or function in association with depressive symptoms. Pathway analysis revealed an enrichment of DNA methylation changes in pathways associated with development and morphogenesis, DNA and transcription factor binding and programmed cell death. Our results support the concept that DNA methylation differences may be important in the pathogenesis of psychiatric disease.
... A total of 1,327 articles were identified, 47 of which were extracted for full review. Twenty-six of these studies were excluded for one of the following reasons: the study was cross-sectional [10][11][12], the study was conducted in children [13,14], a psychosocial factor was not assessed [15], incident HTN/ sustained elevated BP was not the primary outcome [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32], or the stressor was induced in a laboratory setting [33][34][35]. Thus, 21 studies were included in this review. ...
A growing body of research demonstrates that psychosocial factors play an important role in the development of hypertension. Previous reviews have identified several key factors (i.e., occupational stress) that contribute to the onset of hypertension; however, they are now outdated. In this review, we provide an updated synthesis of the literature from 2010 to April 2014. We identified 21 articles for inclusion in the review, of which there were six categories of psychosocial stressors: occupational stress, personality, mental health, housing instability, social support/isolation, and sleep quality. Sixteen of the studies reported an association between the psychosocial stressor and blood pressure. While several findings were consistent with previous literature, new findings regarding mediating and moderating factors underlying the psychosocial-hypertension association help to untangle inconsistencies reported in the literature. Moreover, sleep quality is a novel additional factor that should undergo further exploration. Areas for future research based on these findings are discussed.
... The results of this study are at odds with those of Räsänen, 18 who documented lower adult CVD risk among evacuees originating from Kuopio county, Finland, as compared with a local comparison group, and with those of Alastalo et al., 16 who found significant elevated risks for hypertension and coronary heart disease while sampling evacuees from Helsinki Birth Cohort Study (1934---1944). Another study by Alastalo et al. 17 that also sampled child evacuees from the Helsinki Birth Cohort Study did not, however, find any association between evacuation and all-cause mortality and cardiovascular mortality in adulthood. Elevated mortality risk for the youngest male evacuees has not been documented before. ...
Objectives:
I examined associations between evacuation of Finnish children to temporary foster care in Sweden during World War II and all-cause mortality between ages 38 and 78 years.
Methods:
I used a Cox proportional hazards model to estimate mortality risk according to whether the individual was evacuated during childhood or not. I used within-sibling analysis to control for all unobserved socioeconomic and genetic characteristics shared among siblings. Individual-level data for Finnish cohorts born in 1933 to 1944 were derived from wartime government records, Finnish census data from 1950 and 1970, and death cause registry from 1971 to 2011.
Results:
I found no statistically significant association between evacuation and all-cause mortality when all exposed individuals were included in the analysis. However, subgroup analysis showed that men evacuated before age 4 years had a 1.31 higher mortality risk (95% confidence interval = 1.01, 1.69) than their nonevacuated counterparts.
Conclusions:
In the aggregate, individuals do not have elevated mortality risk as a consequence of foster care during early childhood owing to the onset of sudden external shocks (e.g., wars).
... For example, women with a history of child sexual abuse were approximately three times more likely to deliver preterm compared to women without histories of child sexual abuse (13). Childhood out-of-home placement (i.e., adoption or foster care) represents an extreme form of early life stress due to caregiver separation and instability (15) and is associated with a constellation of psychosocial and behavioral risk factors for PTB including lower socioeconomic position, emotional and behavioral difficulties, depression, and cigarette smoking (16)(17)(18). Therefore, there is reason to believe that childhood placement history may represent a risk factor for PTB. ...
To assess the impact of maternal history of adoption or foster care placement in childhood on risk for preterm birth (PTB), controlling for other known risk factors for PTB.
Participants were 302 pregnant women from a low-income, diverse sample drawn from two intensive prospective studies of maternal mood and behavior and fetal and infant development. Gestational age was determined by best obstetric estimate. Maternal history of adoption or foster care placement prior to age 18 was determined by maternal report. Other maternal characteristics, including maternal medical conditions, psychosocial characteristics, and health behaviors, were measured during second and third trimesters of pregnancy.
The odds of delivering preterm (GA<37 weeks) were approximately four times greater among women with a history of childhood adoption or foster care placement compared to women who were never placed out of the home during childhood. This association remained significant after adjusting for other known risk factors for PTB including maternal medical conditions, psychosocial characteristics, and negative health behaviors in pregnancy.
Findings suggest that history of adoption/foster care placement is an important risk factor for PTB and may be comparable to other established risk factors for PTB including prior history of PTB, body mass index, African-American race, and advanced maternal age. More studies are needed to understand why women with placement histories may be at increased risk to deliver preterm.
... The Finnish Government carried out evacuations to protect the children from the strains of war. We have shown in our previous reports based on findings from the Helsinki Birth Cohort Study (HBCS) that the effect of war-time separation experience during childhood increased the risk for health problems later in life including hypertension, coronary heart disease (CHD) and type 2 diabetes [17][18][19], as well as depressive symptoms and hospitalisation for mental disorders [20,21]. In the present study we hypothesize that, people who had experienced ELS have reduced physical and psychosocial functioning in later life. ...
Severe stress experienced in early life may have long-term effects on adult physiological and psychological health and well-being. We studied physical and psychosocial functioning in late adulthood in subjects separated temporarily from their parents in childhood during World War II.
The 1803 participants belong to the Helsinki Birth Cohort Study, born 1934-44. Of them, 267 (14.8%) had been evacuated abroad in childhood during WWII and the remaining subjects served as controls. Physical and psychosocial functioning was assessed with the Short Form 36 scale (SF-36) between 2001 and 2004. A test for trends was based on linear regression. All analyses were adjusted for age at clinical examination, social class in childhood and adulthood, smoking, alcohol intake, physical activity, body mass index, cardiovascular disease and diabetes.
Physical functioning in late adulthood was lower among the separated men compared to non-separated men (b = -0.40, 95% confidence interval [95% CI]: -0.71 to -0.08). Those men separated in school age (>7 years) and who were separated for a duration over 2 years had the highest risk for lower physical functioning (b = -0.89, 95% CI: -1.58 to -0.20) and (b = -0.65, 95% CI: -1.25 to -0.05), respectively). Men separated for a duration over 2 years also had lower psychosocial functioning (b = -0.70, 95% CI: -1.35 to -0.06). These differences in physical and psychosocial functioning were not observed among women.
Early life stress may increase the risk for impaired physical functioning in late adulthood among men. Timing and duration of the separation influenced the physical and psychosocial functioning in late adulthood.
Background
Electronic health records (EHRs) of mothers and children provide an opportunity to identify adverse childhood experiences (ACEs) during crucial periods of childhood development, yet well developed indicators of ACEs remain scarce. We aimed to develop clinically relevant indicators of ACEs for linked EHRs of mothers and children using a multistage prediction model of child maltreatment and maternal intimate partner violence (IPV).
Methods
In this multistage development and validation study, we developed a representative population-based birth cohort of mothers and children in England, followed from up to 2 years before birth to up to 5 years after birth across the Clinical Practice Research Datalink (CPRD) GOLD (primary care), Hospital Episode Statistics (secondary care), and the Office for National Statistics mortality register. We included livebirths in England between July 1, 2004, and June 30, 2016, to mothers aged 16–55 years, who had registered with a general practitioner (GP) that met CPRD quality standards before 21 weeks of gestation. The primary outcome (reference standard) was any child maltreatment or maternal IPV in either the mother's or child's record from 2 years before birth (maternal IPV only) to 5 years after birth. We used seven prediction models, combined with expert ratings, to systematically develop indicators. We validated the final indicators by integrating results from machine learning models, survival analyses, and clustering analyses in the validation cohort.
Findings
We included data collected between July 1, 2002, and June 27, 2018. Of 376 006 eligible births, we included 211 393 mother–child pairs (422 786 patients) from 400 practices, of whom 126 837 mother–child pairs (60·0%; 240 practices) were randomly assigned to a derivation cohort and 84 556 pairs (40·0%; 160 practices) to a validation cohort. We included 63 indicators in six ACE domains: maternal mental health problems, maternal substance misuse, adverse family environments, child maltreatment, maternal IPV, and high-risk presentations of child maltreatment. Excluding the seven indicators in the reference standard, 56 indicators showed high discriminative validity for the reference standard of any child maltreatment or maternal IPV between 2 years before and 5 years after birth (validation cohort, area under the receiver operating characteristic curve 0·85 [95% CI 0·84–0·86]). During the 2 years before birth and 5 years after birth, the overall period prevalence of maternal IPV and child maltreatment (reference standard) was 2·3% (2876 of 126 837 pairs) in the derivation cohort and 2·3% (1916 of 84 556 pairs) in the validation cohort. During the 2 years before and after birth, the period prevalence was 39·1% (95% CI 38·7–39·5; 34 773 pairs) for any of the 63 ACE indicators, 22·2% (21·8–22·5%; 20 122 pairs) for maternal mental health problems, 15·7% (15·4–16·0%; 14 549 pairs) for adverse family environments, 8·1% (7·8–8·3%; 6808 pairs) for high-risk presentations of child maltreatment, 6·9% (6·7–7·2%; 7856 pairs) for maternal substance misuse, and 3·0% (2·9–3·2%; 2540 pairs) for any child maltreatment (2·4% [2·3–5·6%; 2051 pairs]) and maternal IPV (1·0% [0·8–1·0%; 875 pairs]). 62·6% (21 785 of 34 773 pairs) of ACEs were recorded in primary care only, and 72·3% (25 140 cases) were recorded in the maternal record only.
Interpretation
We developed clinically relevant indicators for identifying ACEs using the EHRs of mothers and children presenting to general practices and hospital admissions. Over 70% of ACEs were identified via maternal records and were recorded in primary care by GPs within 2 years of birth, reinforcing the importance of reviewing parental and carer records to inform clinical responses to children. ACE indicators can contribute to longitudinal surveillance informing public health policy and resource allocation. Further evaluation is required to determine how ACE indicators can be used in clinical practice.
Funding
None.
Background
Parent-child separation has been shown to increase the risk of a range of mental and physical health conditions later in life. Hypothalamic-pituitary-adrenal axis (HPA) dysregulation may help to explain this association. However, few studies have examined the effect of maternal separation on cortisol in late adulthood.
Methods
We examined the relationship between maternal separation in childhood and hair cortisol concentrations in late adulthood, using data from the Whitehall II study (n=3969, mean age: 70 y, range: 60-83 y). Additionally, the role of childhood (adverse childhood experiences (ACEs), material disadvantage, and parenting), adult (marital status and social position), and health measures (health behaviors, cardiovascular health and medication, and depression) in this association were examined. Finally, we examined age of separation and reason for separation. Analysis was carried out using linear regression.
Results
Hair cortisol concentrations (pg/mg) among participants who reported maternal separation during childhood were higher (B=0.179, 95% CI 0.041-0.317, p=0.01) compared to those who did not report separation. This effect was robust to adjustment by childhood, adult, and health measures. Among participants who reported separation, age at onset and reason for separation were not significantly associated with hair cortisol concentrations.
Conclusion
In older age individuals, hair cortisol concentrations were higher in those who reported maternal separation during childhood. This effect was independent of a wide variety of factors suggesting that there are lifelong pathways between early life separation and HPA functioning in old age.
Epidemiological and experimental observations tend to prove that environment, lifestyle or nutritional challenges influence heart functions together with genetic factors. Furthermore, when occurring during sensitive windows of heart development, these environmental challenges can induce an ‘altered programming’ of heart development and shape the future heart disease risk. In the etiology of heart diseases driven by environmental challenges, epigenetics has been highlighted as an underlying mechanism, constituting a bridge between environment and heart health. In particular, micro-RNAs which are involved in each step of heart development and functions seem to play a crucial role in the unfavorable programming of heart diseases. This review describes the latest advances in micro-RNA research in heart diseases driven by early exposure to challenges and discusses the use of micro-RNAs as potential targets in the reversal of the pathophysiology.
It is well established that factors active during prenatal life and early childhood largely influence later health outcomes. Slow rates of growth during prenatal and postnatal life increase the later risk for coronary heart disease, type 2 diabetes and hypertension. Lifestyle is closely associated with these non-communicable disease outcomes. The programming of food choices and exercise habits seems to take place early in life and could be one factor explaining the association between early growth and later health outcomes.
Objectives:
We studied the long-term effects of early separation among aging Finnish evacuees and non-evacuees. A broad set of outcome variables reflecting the psychosocial well-being of both groups in 2005 was analyzed. The role of resilience was also analyzed.
Method:
To identify persons with similar patterns of psychosocial well-being among both evacuated (n = 887) and non-evacuated persons (n = 1748), a cluster analysis was conducted, using the mixture model of latent class analysis/latent profile analysis method. The psychosocial well-being of the evacuees and non-evacuees in 2005 was predicted by multinomial logistic regression analysis, with the nominal cluster variable as the dependent variable.
Results:
Although the evacuees had experienced early separation trauma, they were not faring worse than the non-evacuees regarding psychosocial well-being in 2005. Favorable rearing home circumstances are a protective factor during the entire life span, when the psychosocial well-being of both groups was predicted in 2005. Sense of coherence was a significant predictor of psychosocial well-being. To rejoin the rearing family was stressful for many evacuees.
Conclusion:
The results show that even long-term separation from one's parents during childhood must be understood as representing a developmental context which makes the emergence of problems either less likely or more likely, depending on other risk and protective factors in both the rearing home and the foster family. After the war, when the evacuees returned home the families should have received help and support to amend the reunion.
Severe early life stress (ELS) is a well-known risk factor for mental health disorders later in life. Not only mental health disorders are affected by ELS but early life stressors can also induce physical and biological changes increasing the risk for several noncommunicable diseases including type 2 diabetes and cardiovascular disease.
This review focuses on the cohesive studies of individuals from the Helsinki Birth Cohort Study born 1934-1944 who were sent abroad from Finland during World War II as "war children."
The review encompasses both epidemiological and clinical studies ranging from mental health disorders to type 2 diabetes and cardiovascular disease as well as potential underlying mechanisms explaining the association between ELS and later health.
ELS is capable of causing changes that alter the normal physiological responses and thereby increase later disease risk, including cardiometabolic disorders. Am. J. Hum. Biol., 2013. © 2013 Wiley Periodicals, Inc.
Early origins of adult disease may be defined as adversity or challenges during early life that alter physiological responses and prime the organism to chronic disease in adult life. Adverse childhood experiences or early life stress (ELS) may be considered a silent independent risk factor capable of predicting future cardiovascular disease risk. Maternal separation (MatSep) provides a suitable model to elucidate the underlying molecular mechanisms by which ELS increases the risk to develop cardiovascular disease in adulthood. The aim of this review is to describe the links between behavioural stress early in life and chronic cardiovascular disease risk in adulthood. We will discuss the following: (i) adult cardiovascular outcomes in humans subjected to ELS, (ii) MatSep as an animal model of ELS as well as the limitations and advantages of this model in rodents and (iii) possible ELS-induced mechanisms that predispose individuals to greater cardiovascular risk. Overall, exposure to a behavioural stressor early in life sensitizes the response to a second stressor later in life, thus unmasking an exaggerated cardiovascular dysfunction that may influence quality of life and life expectancy in adulthood.
Human growth data from Guatemalan school children were analyzed to test the hypothesis that the degree of sexual size dimorphism (SSD) in height is reduced for people living under more adverse environmental quality.
The sample consists of 2,560 girls and 3,262 boys, 6-16.99 years of age, from the two major Guatemalan ethnic groups, Maya of very low socioeconomic status (SES) and Ladino of high, middle, and low SES. SES was estimated by questionnaire and ethnographic observation. All data are from the Longitudinal Study of Child Development of the Universidad del Valle de Guatemala. Significance of SSD was tested within each whole year age category (e.g., 6.0-6.9 years) by SES for Ladinos and Maya. Ethnic groups were then compared for each age category to determine whether the SSD values were significantly different between groups.
Statistically significant height SSD was found for 10 of the 11 age categories for the high SES Ladinos, 8 of the 11 age categories for middle SES Ladinos, 3 of the 11 low SES Ladino age categories, and 0 of the 11 very low SES Maya age categories. For all SES and ethnic groups SSD tended to decrease between 6 and 11 years of age and then increase after age 12 years.
A poor quality environment for growth and development, as estimated by SES, was found to reduce or eliminate statistically significant SSD. Patterns of biological maturation before and after puberty also seem to contribute to age changes in SSD. Am. J. Hum. Biol., 2013. © 2013 Wiley Periodicals, Inc.
We examined the effects of early life stress on cognitive ability and decline among men of the Helsinki Birth Cohort Study, 10% of whom were separated temporarily (mean age at separation = 4.1 years) from their parent(s) during World War II. The men underwent the Finnish Defense Forces Basic Intellectual Ability Test twice, at 20 years and retest at 70 years. Compared with the men without childhood separation and matched for year of birth (n = 186), men separated from their parents (n = 93) scored lower by 5.5 (95% confidence interval [CI], -9.2 to -1.7), 4.2 (95% CI, -8.1 to -0.3), 3.1 (95% CI, -7.0 to 0.8), and 4.5 (95% CI, -10.5 to -1.4) standardized points (SD = 15) on verbal, visuospatial, arithmetic, and general cognitive ability, respectively, at 70 years. Longer duration of separation was associated with lower test scores. Though early life stress was also associated significantly with weaker cognitive performance at the ages 20 and 70 years, it was not associated with cognitive decline over the 50-year period within this sample.
Severe stress experienced in early life may have long-term consequences on adult physiological functions. We studied the long-term effects of separation on blood pressure levels in non-obese subjects who were separated temporarily in childhood from their parents during World War II (WWII). The original clinical study cohort consists of people born during 1934-1944 in Helsinki, Finland. This substudy includes 1361 non-obese subjects (body mass index <30 kg m(-2)). Of these, 192 (14.1%) had been evacuated abroad during WWII. The remaining subjects served as controls. Blood pressure levels and use of blood pressure medication were studied. The separated subjects had significantly higher systolic blood pressure values than the non-separated (148.6+21.5 vs 142.2+19.6 mm Hg, P<0.0001) in adult life. Those subjects separated in early childhood had markedly higher systolic and diastolic blood pressure values in adult life compared with the non-separated (154.6 vs 142.5 mm Hg; 95% confidence interval (CI) 2.6-14.7; P<0.005 and 90.8 vs 87.7 mm Hg; 95% CI 1.0-7.3; P<0.02, respectively). Systolic blood pressure was also higher in the group separated for a duration of <1 year (151.7 vs 142.2 mm Hg; 95% CI 0.0-12.4; P<0.05) compared with the non-separated. Besides being separated, age at separation and duration of separation also influenced blood pressure levels in adult life. This could be due to early hormonal and metabolic programming, during plastic periods in early life, influencing blood pressure levels in adult life.Journal of Human Hypertension advance online publication, 16 February 2012; doi:10.1038/jhh.2012.6.
In a large, prospective epidemiological study we tested whether exposure to severe early life stress increases the risk of severe mental disorders in adulthood, and whether childhood socioeconomic background and sex modify these associations. Among the 12,747 participants of the Helsinki Birth Cohort Study, born 1934-1944, 1719 were recorded as separated temporarily from their parents in childhood. The separations took place during World War II when Finnish children were voluntarily evacuated unaccompanied by their parents to temporary foster care abroad (mean age at and length of separation 4.6 and 1.7 years, respectively). Severe mental disorders were identified from the Finnish Hospital Discharge and Causes of Death Registers between years 1969 and 2004. Compared to the non-separated, the separated had higher risks of mental, substance use and personality disorder (P-values ≤ 0.05). The risk of any mental and substance use disorder was, however, highest in the separated and lowest in the non-separated with an upper childhood socioeconomic background; individuals with a lower childhood socioeconomic background showed an intermediate risk regardless of their separation status (P-values for interactions ≤ 0.05). Temporary separation from parents poses a risk of severe mental disorders later in life. Children with an upper childhood socioeconomic background may be particularly sensitive to this type of early life stress, while for children with a lower childhood socioeconomic background it may not add to the risk already associated with lower socioeconomic position in childhood.
Studies suggest that childhood adversities are important determinants of various types of later illnesses as well as poor health behaviour. However, few large-scale prospective studies have examined the associations between childhood adversities and cardiovascular disease.
To investigate whether childhood adversities are associated with increased risk of incident cardiovascular disease.
Participants were 23 916 men and women in four age groups (20-24, 30-34, 40-44, and 50-54 years) from the Health and Social Support study, a longitudinal study on a random sample representative of the Finnish population. Data from national health registers on coronary heart disease and cerebrovascular disease during a mean follow-up of 6.9 years were linked to survey responses on childhood adversities. Cox proportional hazard models were adjusted for age group and potential mediators (education, health risk behaviours, diabetes and depression).
There was a significant linear trend between the number of childhood adversities and disease end points in women. The risk of incident cardiovascular disease was threefold among women exposed concurrently to three types of childhood adversities (financial difficulties, interpersonal conflicts and longstanding illness of a family member). Among men, increased risk was observed only among those with longstanding illness of a family member (HR=1.44; 95% CI 1.06 to 1.96).
In this prospective population-based sample, childhood adversities were associated with a significantly increased risk of objectively verified cardiovascular disease, especially among women but to a lesser extent among men. More studies with prospective settings are needed to confirm the association and possible mechanisms.
Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment
To understand why children exposed to adverse psychosocial experiences are at elevated risk for age-related disease, such as cardiovascular disease, by testing whether adverse childhood experiences predict enduring abnormalities in stress-sensitive biological systems, namely, the nervous, immune, and endocrine/metabolic systems.
A 32-year prospective longitudinal study of a representative birth cohort.
New Zealand.
A total of 1037 members of the Dunedin Multidisciplinary Health and Development Study. Main Exposures During their first decade of life, study members were assessed for exposure to 3 adverse psychosocial experiences: socioeconomic disadvantage, maltreatment, and social isolation.
At age 32 years, study members were assessed for the presence of 3 age-related-disease risks: major depression, high inflammation levels (high-sensitivity C-reactive protein level >3 mg/L), and the clustering of metabolic risk biomarkers (overweight, high blood pressure, high total cholesterol, low high-density lipoprotein cholesterol, high glycated hemoglobin, and low maximum oxygen consumption levels.
Children exposed to adverse psychosocial experiences were at elevated risk of depression, high inflammation levels, and clustering of metabolic risk markers. Children who had experienced socioeconomic disadvantage (incidence rate ratio, 1.89; 95% confidence interval, 1.36-2.62), maltreatment (1.81; 1.38-2.38), or social isolation (1.87; 1.38-2.51) had elevated age-related-disease risks in adulthood. The effects of adverse childhood experiences on age-related-disease risks in adulthood were nonredundant, cumulative, and independent of the influence of established developmental and concurrent risk factors.
Children exposed to adverse psychosocial experiences have enduring emotional, immune, and metabolic abnormalities that contribute to explaining their elevated risk for age-related disease. The promotion of healthy psychosocial experiences for children is a necessary and potentially cost-effective target for the prevention of age-related disease.
Much remains to be understood about how low socioeconomic status (SES) increases cardiovascular disease and mortality risk. Data from the Kuopio Ischemic Heart Disease Risk Factor Study (1984–1993) were used to estimate the associations between acute myocardial infarction and income, all-cause mortality, and cardiovascular mortality in a population-based sample of 2, 272 Finnish men, with adjustment for 23 biologic, behavioral, psychologic, and social risk factors. Compared with the highest income quintile, those in the bottom quintile had age-adjusted relative hazards of 3.14 (95% confidence interval (Cl) 1.77–5.56), 2.66 (95% Cl 1.25–5.66), and 4.34 (95% Cl 1.95–9.66) for all-cause mortality, cardiovascular mortality, and AMI, respectively. After adjustment for risk factors, the relative hazards for the same comparisons were 1.32 (95% Cl 0.70–2.49), 0.70 (95% Cl 0.29–1.69), and 2.83 (95% Cl 1.14–7.00). In the lowest income quintile, adjustment for risk factors reduced the excess relative risk of all-cause mortality by 85%, that of cardiovascular mortality by 118%, and that of acute myocardial infarction by 45%. These data show how the association between SES and cardiovascular mortality and all-cause mortality is mediated by known risk factor pathways, but full “explanations” for these associations will need to encompass why these biologic, behavioral, psychologic, and social risk factors are differentially distributed by SES. Am J Epidemiol 1996; 144: 934-42.
Child abuse is associated with markedly elevated rates of major depression and other psychiatric disorders in adulthood. This article reviews preclinical studies examining the effects of early stress, factors that modify the impact of these experiences, and neurobiological changes associated with major depression. Preclinical studies demonstrate that early stress can alter the development of the hypothalamic-pituitary-adrenal axis, hypothalamic and extrahypothalamic corticotropin releasing hormone, monoaminergic, and gamma-aminobutyric acid/benzodiazepine systems. Stress has also been shown to promote structural and functional alterations in brain regions similar to those seen in adults with depression. Emerging data suggest, however, that the long-term effects of early stress can be moderated by genetic factors and the quality of the subsequent caregiving environment. These effects also can be prevented or reversed with various pharmacologic interventions. Preclinical studies of early stress can provide valuable insights in understanding the pathophysiology and treatment of major depression. They also can provide an important tool to use to investigate interactions between genes and environments in determining an individual's sensitivity to stress. More research is needed to understand how inherent factors interact with experiences of abuse and other psychosocial factors to confer vulnerability to develop depression.
To determine how growth during infancy and childhood modifies the increased risk of coronary heart disease associated with small body size at birth.
Longitudinal study.
Helsinki, Finland.
4630 men who were born in the Helsinki University Hospital during 1934-44 and who attended child welfare clinics in the city. Each man had on average 18.0 (SD 9.5) measurements of height and weight between birth and age 12 years.
Hospital admission or death from coronary heart disease.
Low birth weight and low ponderal index (birth weight/length(3)) were associated with increased risk of coronary heart disease. Low height, weight, and body mass index (weight/height(2)) at age 1 year also increased the risk. Hazard ratios fell progressively from 1.83 (95% confidence interval 1.28 to 2.60) in men whose body mass index at age 1 year was below 16 kg/m(2) to 1.00 in those whose body mass index was >19 (P for trend=0.0004). After age 1 year, rapid gain in weight and body mass index increased the risk of coronary heart disease. This effect was confined, however, to men with a ponderal index <26 at birth. In these men the hazard ratio associated with a one unit increase in standard deviation score for body mass index between ages 1 and 12 years was 1.27 (1.10 to 1.47; P=0.001).
Irrespective of size at birth, low weight gain during infancy is associated with increased risk of coronary heart disease. After age 1 year, rapid weight gain is associated with further increase in risk, but only among boys who were thin at birth. In these boys the adverse effects of rapid weight gain on later coronary heart disease are already apparent at age 3 years. Improvements in fetal, infant, and child growth could lead to substantial reductions in the incidence of coronary heart disease.
Risky families are characterized by conflict and aggression and by relationships that are cold, unsupportive, and neglectful. These family characteristics create vulnerabilities and/or interact with genetically based vulnerabilities in offspring that produce disruptions in psychosocial functioning (specifically emotion processing and social competence), disruptions in stress-responsive biological regulatory systems, including sympathetic-adrenomedullary and hypothalamic-pituitary-adrenocortical functioning, and poor health behaviors, especially substance abuse. This integrated biobehavioral profile leads to consequent accumulating risk for mental health disorders, major chronic diseases, and early mortality. We conclude that childhood family environments represent vital links for understanding mental and physical health across the life span.
Stress in early life has been associated with insufficient glucocorticoid signaling in adulthood, possibly affecting inflammation processes. Childhood maltreatment has been linked to increased risk of adult disease with potential inflammatory origin. However, the impact of early life stress on adult inflammation is not known in humans. We tested the life-course association between childhood maltreatment and adult inflammation in a birth cohort followed to age 32 years as part of the Dunedin Multidisciplinary Health and Development Study. Regression models were used to estimate the effect of maltreatment on inflammation, adjusting for co-occurring risk factors and potential mediating variables. Maltreated children showed a significant and graded increase in the risk for clinically relevant C-reactive protein levels 20 years later, in adulthood [risk ratio (RR) = 1.80, 95% confidence interval (CI) = 1.26–2.58]. The effect of childhood maltreatment on adult inflammation was independent of the influence of co-occurring early life risks (RR = 1.58, 95% CI = 1.08–2.31), stress in adulthood (RR = 1.64, 95% CI = 1.12–2.39), and adult health and health behavior (RR = 1.76, 95% CI = 1.23–2.51). More than 10% of cases of low-grade inflammation in the population, as indexed by high C-reactive protein, may be attributable to childhood maltreatment. The association between maltreatment and adult inflammation also generalizes to fibrinogen and white blood cell count. Childhood maltreatment is a previously undescribed, independent, and preventable risk factor for inflammation in adulthood. Inflammation may be an important developmental mediator linking adverse experiences in early life to poor adult health.
• C-reactive protein
• development
• epidemiology
• risk factor
• stress
Several decades of research link childhood parental loss with risk for major depression and other forms of psychopathology. A large body of preclinical work on maternal separation and some recent studies of humans with childhood parental loss have demonstrated alterations of hypothalamic-pituitary-adrenal (HPA) axis function that could predispose to the development of psychiatric disorders.
Eighty-eight healthy adults with no current Axis I psychiatric disorder participated in this study. Forty-four participants experienced parental loss during childhood, including 19 with a history of parental death and 25 with a history of prolonged parental separation. The loss group was compared with a matched group of individuals who reported no history of childhood parental separation or childhood maltreatment. Participants completed diagnostic interviews and questionnaires and the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Repeated measures general linear models were used to test the effects of parental loss, parental care, gender, and age on the hormone responses to the Dex/CRH test.
Parental loss was associated with increased cortisol responses to the test, particularly in men. The effect of loss was moderated by levels of parental care; participants with parental desertion and very low levels of care had attenuated cortisol responses. Adrenocorticotropic hormone responses to the Dex/CRH test did not differ significantly as a function of parental loss.
These findings are consistent with the hypothesis that early parental loss induces enduring changes in neuroendocrine function.
We validated diagnoses of acute myocardial infarction (AMI) and death from coronary heart disease (CHD) found in the Finnish National Hospital Discharge Register and the Register of Causes of Death from a sample of the 29,133 men participating in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The cases were traced to hospitals and institutes performing medico-legal death cause examinations and all relevant information was collected. The cardiac events were re-evaluated according to the diagnostic criteria of the Finnish contribution to the WHO MONICA project, i.e. the FINMONICA criteria. Altogether 408 cases of non-fatal AMI (n = 217) and death from CHD (n = 191) were reviewed. In the re-evaluation 94% of them (95% confidence interval 92--96%) were diagnosed as either definite (57%) or possible (37%) AMI. Non-fatal cases were more often classified definite AMI in the review, whereas fatal cases were more often classified possible AMI. Age or trial supplementation group did not affect classification, and no secular trend was observed. In conclusion, the diagnoses of AMI and death from CHD in the registers were highly predictive of a true major coronary event defined by strict criteria, thus their use in endpoint assessment in epidemiological studies and clinical trials is justified.
The validity of stroke diagnosis in the National Hospital Discharge Register and the Register of Causes of Death was examined among 546 middle-aged men in Finland. The subjects were cases of cerebrovascular diseases of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and identified by record linkage to the registers. In all, 375 events with cerebrovascular disease as hospital discharge diagnosis and 218 events with cerebrovascular disease as the underlying cause of death were reviewed using specific criteria modified from the classifications of the National Survey of Stroke and the WHO MONICA Study. For hospital stroke diagnoses, there was agreement on diagnosis for all strokes in 90%, for subarachnoid hemorrhage in 79%, intracerebral hemorrhage in 82%, and cerebral infarction in 90%. The respective agreement rates for stroke as the underlying cause of death were 97%, 95%, 91%, and 92%. The data were insufficient for review in 1% and 3% of the stroke events, respectively. Age, observation year and trial supplementation with alpha-tocopherol or beta-carotene had no effect on validity. In conclusion, the validity of stroke diagnosis was good in registers of hospital diagnoses and causes of death justifying their use for endpoint assessment in epidemiological studies.
INTRODUCTION. Socio-economic position (SEP) is a powerful source of health inequality. Less is known of early life conditions that may determine the course of adult SEP. We tested if early life stress (ELS) due to a separation from the parents during World War II predicts adult SEP, trajectories of incomes across the entire working career, and inter-generational social mobility. MATERIALS AND METHODS. Participants (n = 10,702) were from the Helsinki Birth Cohort Study 1934-44. Compared to the non-separated, the separated individuals attained a lower SEP in adulthood. The separated whose fathers were manual workers were less likely to be upwardly mobile from paternal occupation category to higher categories of own occupation, education, and incomes. The separated whose fathers had junior and senior clerical occupations were more likely to be downwardly mobile. Comparison of trajectories of incomes across adulthood showed that the difference between the separated and the non-separated grew larger across time, such that among the separated the incomes decreased. CONCLUSIONS. This life-course study shows that severe ELS due to a separation from parents in childhood is associated with socio-economic disadvantage in adult life. Even high initial SEP in childhood may not protect from the negative effects of ELS.
The role of childhood adversities in predicting adulthood depression has been suggested to be complex and in need of additional comprehensive studies.
This investigation set out to examine whether increased exposure to life events (LEs) in adulthood mediates the association between childhood adversities and adulthood depression.
This study is based on a random health survey sample from the Finnish working-aged population (n=16,877) with a follow-up of up to 7 years. Depression was identified by Beck Depression Inventory, records of antidepressant prescriptions and hospitalization due to depression obtained from national health registers.
Childhood adversities were associated with an increased likelihood of experiencing a high number of LEs in adulthood and their perceived burdensomeness. The mean number of new LEs correlated significantly (P<0.001) in a dose-response relationship with the number of childhood adversities. Reporting childhood adversities was associated with a 1.28-2.70-fold increase in the odds of depression as indicated by BDI score, a 1.29-1.94-fold increase in the rate of antidepressant prescriptions and a 1.17-4.04-fold increase in the risk of hospitalization due to depression. Adjustment for new LE attenuated these associations by 21-24%, but did not render them insignificant.
Increased exposure to adult negative life events proximal to adult depression may partially explain the association between childhood adversities and adult depression.
Animal models have linked early maternal separation with lifelong changes in hypothalamic-pituitary-adrenocortical (HPA) axis activity. Although this is paralleled in human studies, this is often in the context of other life adversities, for example, divorce or adoption, and it is not known whether early separation in the absence of these factors has long term effects on the HPA axis.
The Finnish experience in World War II created a natural experiment to test whether separation from a father serving in the armed forces or from both parents due to war evacuation are associated with alterations in HPA axis response to psychosocial stress in late adulthood.
282 subjects (M=63.5 years, SD=2.5), of whom 85 were non-separated, 129 were separated from their father, and 68 were separated from both their caregivers during WWII, were enlisted to participate in a Trier Social Stress Test (TSST), during which we measured salivary cortisol and, for 215 individuals, plasma cortisol and ACTH concentrations. We used mixed models to study whether parental separation is associated with salivary and plasma cortisol or plasma ACTH reactivity, and linear regressions to analyse differences in the baseline, or incremental area under the cortisol or ACTH curves.
Participants separated from their father did not differ significantly from non-separated participants. However, those separated from both parents had higher average salivary cortisol and plasma ACTH concentrations across all time points compared to the non-separated group. They also had higher salivary cortisol reactivity to the TSST. Separated women had higher baselines in plasma cortisol and ACTH, whereas men had higher reactivity in response to stress during the TSST. Participants who had experienced the separation in early childhood were more affected than children separated during infancy or school age.
Separation from parents during childhood may alter an individual's stress physiology much later in adult life.
This study of 870 respondents aged 62-72 years investigates possible long-term effects on adult mental health due to temporary childhood separation by evacuation in the United Kingdom during World War 2.
Using univariate and multivariate analyses associations were examined between upbringing, evacuation experience and certain life-course variables with the lifetime incidence of depression and clinical anxiety, and also with the dependency and self-critical factors of the Depressive Experiences Questionnaire (DEQ) (Blatt, S.J., D'Affitti, J.P., & Quinlan, D.M. (1976). Experiences of depression in normal young adults. Journal of Abnormal Psychology, 85, 383-389.) were examined by univariate and multivariate analyses.
Those evacuated at a young age, 4-6 years, or who received poor foster care, were found to be at a greater risk of depression and clinical anxiety, with high levels of self-criticism. Compared to other groups respondents evacuated at 13-15 years age, who received good care, had reduced incidences of both affective disorders, comparable to those who were not evacuated. The quality of home nurture was also found to be significantly associated with both disorders. Structural equation models for each sex based on those variables significantly associated with depression explained 45% of the variance of the incidence of depression for males and 25% for females. The models also confirmed the relatively high levels of dependency for females and their vulnerability to these levels in terms of depression.
The study demonstrated significant associations between childhood experiences and lifespan mental health, reinforcing the importance of knowledge of childhood history in the clinical treatment of older adults.
Early life experiences might have long-term effects on health.
To assess prevalence of cardiovascular disease and diabetes in later life among individuals exposed to traumatic separation in early childhood due to World War II.
Of the participants of the Helsinki Birth Cohort 1934-44 Study (n=2003), 320 had been evacuated abroad to temporary foster care in childhood. The remaining participants served as controls. The mean age at evacuation was 4.8 (SD=2.4) years and the mean duration of the evacuation was 1.7 (SD=1.0) years.
Cardiovascular morbidity was higher among the former war evacuees (14.7% versus 7.9%; odds ratio (OR)=2.0, 95% confidence interval (95% CI) 1.4-2.9; P<0.001). A similar difference in prevalence of type 2 diabetes was observed (19.7% versus 14.8%; OR=1.4, 95% CI 1.1-1.9, P=0.025). The former war evacuees were also more likely to be hypertensive (P<0.05). The effects on morbidity were not explained by age at testing or socio-economic circumstances in childhood or adulthood.
Early life traumatic events may extend lifelong effects on health. This study is among the first to show that early life trauma predicts higher prevalence of cardiovascular disease and type 2 diabetes in late adulthood, in a longitudinal clinical study setting.
Inflammation may be important in the pathogenesis of atherothrombosis. We studied whether inflammation increases the risk of a first thrombotic event and whether treatment with aspirin decreases the risk.
We measured plasma C-reactive protein, a marker for systemic inflammation, in 543 apparently healthy men participating in the Physicians' Health Study in whom myocardial infarction, stroke, or venous thrombosis subsequently developed, and in 543 study participants who did not report vascular disease during a follow-up period exceeding eight years. Subjects were randomly assigned to receive aspirin or placebo at the beginning of the trial.
Base-line plasma C-reactive protein concentrations were higher among men who went on to have myocardial infarction (1.51 vs. 1.13 mg per liter, P<0.001) or ischemic stroke (1.38 vs. 1.13 mg per liter, P=0.02), but not venous thrombosis (1.26 vs. 1.13 mg per liter, P=0.34), than among men without vascular events. The men in the quartile with the highest levels of C-reactive protein values had three times the risk of myocardial infarction (relative risk, 2.9; P<0.001) and two times the risk of ischemic stroke (relative risk, 1.9; P=0.02) of the men in the lowest quartile. Risks were stable over long periods, were not modified by smoking, and were independent of other lipid-related and non-lipid-related risk factors. The use of aspirin was associated with significant reductions in the risk of myocardial infarction (55.7 percent reduction, P=0.02) among men in the highest quartile but with only small, nonsignificant reductions among those in the lowest quartile (13.9 percent, P=0.77).
The base-line plasma concentration of C-reactive protein predicts the risk of future myocardial infarction and stroke. Moreover, the reduction associated with the use of aspirin in the risk of a first myocardial infarction appears to be directly related to the level of C-reactive protein, raising the possibility that antiinflammatory agents may have clinical benefits in preventing cardiovascular disease.
To investigate the association between social circumstances in childhood and mortality from various causes of death in adulthood.
Prospective observational study.
27 workplaces in the west of Scotland.
5645 men aged 35-64 years at the time of examination.
Death from various causes.
Men whose fathers had manual occupations when they were children were more likely as adults to have manual jobs and be living in deprived areas. Gradients in mortality from coronary heart disease, stroke, lung cancer, stomach cancer, and respiratory disease were seen (all P<0.05), generally increasing from men whose fathers had professional and managerial occupations (social class I and II) to those whose fathers had semiskilled and unskilled manual occupations (social class IV and V). Relative rates of mortality adjusted for age for men with fathers in manual versus non-manual occupations were 1.52 (95% confidence interval 1.24 to 1.87) for coronary heart disease, 1.83 (1.13 to 2. 94) for stroke, 1.65 (1.12 to 2.43) for lung cancer, 2.06 (0.93 to 4. 57) for stomach cancer, and 2.01 (1.17 to 3.48) for respiratory disease. Mortality from other cancers and accidental and violent death showed no association with fathers' social class. Adjustment for adult socioeconomic circumstances and risk factors did not alter results for mortality from stroke and stomach cancer, attenuated the increased risk of coronary heart disease and respiratory disease, and essentially eliminated the association with lung cancer.
Adverse socioeconomic circumstances in childhood have a specific influence on mortality from stroke and stomach cancer in adulthood, which is not due to the continuity of social disadvantage throughout life. Deprivation in childhood influences risk of mortality from coronary heart disease and respiratory disease in adulthood, although an additive influence of adulthood circumstances is seen in these cases. Mortality from lung cancer, other cancer, and accidents and violence is predominantly influenced by risk factors that are related to social circumstances in adulthood.
The relationship of health risk behavior and disease in adulthood to the breadth of exposure to childhood emotional, physical, or sexual abuse, and household dysfunction during childhood has not previously been described.
A questionnaire about adverse childhood experiences was mailed to 13,494 adults who had completed a standardized medical evaluation at a large HMO; 9,508 (70.5%) responded. Seven categories of adverse childhood experiences were studied: psychological, physical, or sexual abuse; violence against mother; or living with household members who were substance abusers, mentally ill or suicidal, or ever imprisoned. The number of categories of these adverse childhood experiences was then compared to measures of adult risk behavior, health status, and disease. Logistic regression was used to adjust for effects of demographic factors on the association between the cumulative number of categories of childhood exposures (range: 0-7) and risk factors for the leading causes of death in adult life.
More than half of respondents reported at least one, and one-fourth reported > or = 2 categories of childhood exposures. We found a graded relationship between the number of categories of childhood exposure and each of the adult health risk behaviors and diseases that were studied (P < .001). Persons who had experienced four or more categories of childhood exposure, compared to those who had experienced none, had 4- to 12-fold increased health risks for alcoholism, drug abuse, depression, and suicide attempt; a 2- to 4-fold increase in smoking, poor self-rated health, > or = 50 sexual intercourse partners, and sexually transmitted disease; and 1.4- to 1.6-fold increase in physical inactivity and severe obesity. The number of categories of adverse childhood exposures showed a graded relationship to the presence of adult diseases including ischemic heart disease, cancer, chronic lung disease, skeletal fractures, and liver disease. The seven categories of adverse childhood experiences were strongly interrelated and persons with multiple categories of childhood exposure were likely to have multiple health risk factors later in life.
We found a strong graded relationship between the breadth of exposure to abuse or household dysfunction during childhood and multiple risk factors for several of the leading causes of death in adults.
The hypothalamic-pituitary-adrenal (HPA) axis, the mediator of cortisol, plays a central role in the homeostatic processes. In this study, we addressed the potential impact of HPA axis activity on established anthropometric, metabolic and haemodynamic risk factors for cardiovascular disease (CVD), type 2 diabetes mellitus and stroke.
A cross-sectional study.
A subgroup of 284 men from a population sample of 1040 at the age of 51 years.
Anthropometric measurements included body mass index (BMI, kg m-2), waist/hip circumference ratio (WHR) and abdominal sagittal diameter (D). Overnight fasting values of blood glucose, serum insulin, triglycerides, total, low (LDL) and high density (HDL) lipoprotein cholesterol, as well as resting heart rate and blood pressure, were also determined. By using repeated diurnal salivary cortisol measurements during everyday conditions, methods were developed to characterize the status of the HPA axis, and set in relation to the anthropometric, metabolic and haemodynamic measurements.
In bivariate analyses, risk factors intercorrelated in clusters of anthropometric (BMI, WHR, D), metabolic (insulin, glucose and their ratio, triglycerides, cholesterol [total and LDL], HDL cholesterol [negative]) and haemodynamic (systolic and diastolic blood pressure and heart rate) measurements. This was also the case in the two-dimensional scaling analysis, where, however, HDL separated out. A normal HPA axis status, characterized by high variability and morning cortisol values, as well as a clear response to a standardized lunch and dexamethasone suppression test, was then introduced by a statistical weighting procedure. This did not essentially change the results of either the bivariate correlation matrix or the two-dimensional scaling analysis. A similar introduction of a pathological HPA axis, characterized by low variability and morning cortisol values, a poor lunch-induced cortisol response and a blunted dexamethasone suppression of cortisol, changed the results markedly. Now strong and consistent correlations were found not only within but also between different clusters of risk factors, which also congregated into one distinct cluster, again except for HDL cholesterol.
These results disclose the prospect of an overriding function of a pathological HPA axis on other, established risk factors for CVD, type 2 diabetes and stroke. Its close association to HPA axis dysfunction may explain the previously reported powerful risk indication of abdominal obesity for the diseases mentioned. The HPA axis abnormality has been reported to be a characteristic consequence of frequently repeated or chronic environmental stress challenges.
Since inflammation is believed to have a role in the pathogenesis of cardiovascular events, measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events.
We conducted a prospective, nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation. The markers included high-sensitivity C-reactive protein (hs-CRP), serum amyloid A, interleukin-6, and soluble intercellular adhesion molecule type 1 (sICAM-1). We also studied homocysteine and a variety of lipid and lipoprotein measurements. Cardiovascular events were defined as death from coronary heart disease, nonfatal myocardial infarction or stroke, or the need for coronary-revascularization procedures.
Of the 12 markers measured, hs-CRP was the strongest univariate predictor of the risk of cardiovascular events; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 (95 percent confidence interval, 2.2 to 8.9). Other markers significantly associated with the risk of cardiovascular events were serum amyloid A (relative risk for the highest as compared with the lowest quartile, 3.0), sICAM-1 (2.6), interleukin-6 (2.2), homocysteine (2.0), total cholesterol (2.4), LDL cholesterol (2.4), apolipoprotein B-100 (3.4), HDL cholesterol (0.3), and the ratio of total cholesterol to HDL cholesterol (3.4). Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone (P<0.001). The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter (3.4 mmol per liter), the target for primary prevention established by the National Cholesterol Education Program. In multivariate analyses, the only plasma markers that independently predicted risk were hs-CRP (relative risk for the highest as compared with the lowest quartile, 1.5; 95 percent confidence interval, 1.1 to 2.1) and the ratio of total cholesterol to HDL cholesterol (relative risk, 1.4; 95 percent confidence interval, 1.1 to 1.9).
The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events.
The 3478 death certificates (7.1% of all annual death certificates) of this study comprise those national death certificates in 1995 submitted for validation to the panel representing both medical and nosological expertise. As such, it is highly selected and represents, from the nosological point of view, the most inconsistently filled-in portion of Finnish death certificates. The routine validation procedure is essentially based on exploitation of the extra medical information, i.e. the case history, on the Finnish death certificate form. Altogether, 2813 (80.9%) out of 3478 certificates could be adjusted at the primary panel session; the rest required further clarification. The re-assignment of cause of death by the panel and the impact of panel adjustments on the national mortality statistics is assessed here by comparing the initial death certification and the finally registered underlying cause of death grouped into ICD-9 major categories with special reference to the subcategories of neoplasm, cardiovascular disease (HVD) and unnatural death. A statistically significant decline (p<0.0001) in deaths, both in the category of symptoms, signs and ill-defined conditions and in the pulmonary circulation disease subcategory of HVD with 37.6 and 35.1%, respectively, was observed. The decrease of 11.1% in the benign or NUD neoplasm subcategory and the increase of 8.6 and 7.0% in the categories of endocrine disease, and musculo-skeletal and connective tissue disease, respectively, are essential observations as to the quality of the cause of death register. The effect on the HVD major category was practically nil. At the HVD-subcategorial level, a decrease of 14.0% for diseases of the veins and lymphatics and other circulatory diseases and an increase of 3.5% for hypertensive diseases (HYP) were the two next most obvious alterations to the diseases of the pulmonary circulation, but were without statistical significance. For ischaemic heart disease and other subcategories, the effects were minor. The unnatural deaths as a whole increased in the final statistics with only 0.9%. In the study data, categorial changes ranged from the decrease of 75.2% for symptoms, signs and ill-defined conditions to the increase of 77.3% for endocrine diseases. In conclusion, the Finnish death certificate form, death certification practices and cause of death validation procedure seem to serve the coding of causes of death for mortality statistics appropriately. The results of the study form a relevant reference background to evaluation of epidemiological studies on mortality.
Epidemiologic studies indicate that children exposed to early adverse experiences are at increased risk for the development of depression, anxiety disorders, or both. Persistent sensitization of central nervous system (CNS) circuits as a consequence of early life stress, which are integrally involved in the regulation of stress and emotion, may represent the underlying biological substrate of an increased vulnerability to subsequent stress as well as to the development of depression and anxiety. A number of preclinical studies suggest that early life stress induces long-lived hyper(re)activity of corticotropin-releasing factor (CRF) systems as well as alterations in other neurotransmitter systems, resulting in increased stress responsiveness. Many of the findings from these preclinical studies are comparable to findings in adult patients with mood and anxiety disorders. Emerging evidence from clinical studies suggests that exposure to early life stress is associated with neurobiological changes in children and adults, which may underlie the increased risk of psychopathology. Current research is focused on strategies to prevent or reverse the detrimental effects of early life stress on the CNS. The identification of the neurobiological substrates of early adverse experience is of paramount importance for the development of novel treatments for children, adolescents, and adults.
There is considerable evidence to suggest that adverse early-life experiences have a profound effect on the developing brain. Neurobiological changes that occur in response to untoward early-life stress can lead to lifelong psychiatric sequelae. Children who are exposed to sexual or physical abuse or the death of a parent are at higher risk for development of depressive and anxiety disorders later in life. Preclinical and clinical studies have shown that repeated early-life stress leads to alterations in central neurobiological systems, particularly in the corticotropin-releasing factor system, leading to increased responsiveness to stress. Clearly, exposure to early-life stressors leads to neurobiological changes that increase the risk of psychopathology in both children and adults. Identification of the neurobiological substrates that are affected by adverse experiences in early life should lead to the development of more effective treatments for these disorders. The preclinical and clinical studies evaluating the consequences of early-life stress are reviewed.
Children in foster care face a challenging journey through childhood. In addition to the troubling family circumstances that bring them into state care, they face additional difficulties within the child welfare system that may further compromise their healthy development. This article discusses the importance of safety and stability to healthy child development and reviews the research on the risks associated with maltreatment and the foster care experience. It finds: Family stability is best viewed as a process of caregiving practices that, when present, can greatly facilitate healthy child development. Children in foster care, as a result of exposure to risk factors such as poverty, maltreatment, and the foster care experience, face multiple threats to their healthy development, including poor physical health, attachment disorders, compromised brain functioning, inadequate social skills, and mental health difficulties. Providing stable and nurturing families can bolster the resilience of children in care and ameliorate negative impacts on their developmental outcomes. The author concludes that developmentally-sensitive child welfare policies and practices designed to promote the well-being of the whole child, such as ongoing screening and assessment and coordinated systems of care, are needed to facilitate the healthy development of children in foster care.
The purpose of this study was to assess the relation of adverse childhood experiences (ACEs), including abuse, neglect, and household dysfunction, to the risk of ischemic heart disease (IHD) and to examine the mediating impact on this relation of both traditional IHD risk factors and psychological factors that are associated with ACEs.
Retrospective cohort survey data were collected from 17,337 adult health plan members from 1995 to 1997. Logistic regression adjusted for age, sex, race, and education was used to estimate the strength of the ACE-IHD relation and the mediating impact of IHD risk factors in this relation. Nine of 10 categories of ACEs significantly increased the risk of IHD by 1.3- to 1.7-fold versus persons with no ACEs. The adjusted odds ratios for IHD among persons with > or =7 ACEs was 3.6 (95% CI, 2.4 to 5.3). The ACE-IHD relation was mediated more strongly by individual psychological risk factors commonly associated with ACEs than by traditional IHD risk factors. We observed significant association between increased likelihood of reported IHD (adjusted ORs) and depressed affect (2.1, 1.9 to 2.4) and anger (2.5, 2.1 to 3.0) as well as traditional risk factors (smoking, physical inactivity, obesity, diabetes and hypertension), with ORs ranging from 1.2 to 2.7.
We found a dose-response relation of ACEs to IHD and a relation between almost all individual ACEs and IHD. Psychological factors appear to be more important than traditional risk factors in mediating the relation of ACEs to the risk of IHD. These findings provide further insights into the potential pathways by which stressful childhood experiences may increase the risk of IHD in adulthood.
The recent introduction of sensitive markers of myocardial injury is likely to affect the epidemiology of coronary heart disease (CHD). The American Heart Association together with other societies and research agencies have recently published a new definition on acute CHD to improve consistency in epidemiological and clinical studies (referred here as the '2003 definition').
In this study we compare the data on CHD events in the Finnish National Hospital Discharge Register (HDR) and the Causes of Death Register (CDR) with the population-based myocardial infarction (MI) register, FINMONICA/FINAMI. The FINMONICA/FINAMI events were classified according to the 2003 definition. The relevant International Classification of Diseases (ICD) codes from the HDR and CDR were used.
Using the 2003 definition as the reference, the overall sensitivity of the ICD codes for MI in the combined HDR and CDR was 83% and the positive predictive value (PPV) was 90%. When the ICD codes for unstable angina were added to the analyses, the sensitivity improved to 85% and the PPV declined to 83%. In the age group 35-74 the sensitivity of the MI codes improved over time, in men from 64% in 1988-1992 to 81% in 1998-2002, and in women from 61 to 78%, respectively. The oldest age group, 75 years or older, had sensitivity and PPV values comparable to those of the younger.
Diagnoses of fatal and non-fatal CHD events in the Finnish HDR and Causes of Death register were reasonably valid indicators for hard CHD events when compared with the FINMONICA/FINAMI register data.
We sought to establish whether women's childhood socioeconomic position influenced their risk of mortality separately from the effects of adult socioeconomic position.
We examined 11855 British women aged 14 to 49 years, with mortality follow-up over a 45-year period.
Trends according to childhood social class were observed for all-cause mortality, circulatory disease, coronary heart disease, respiratory disease, chronic obstructive pulmonary disease, stroke, lung cancer, and stomach cancer, with higher death rates among members of unskilled manual groups. Associations attenuated after adjustment for adult social class, smoking, and body mass index. No trend was seen for breast cancer or accidents and violence. Adverse social conditions in both childhood and adulthood were associated with higher death rates from coronary heart disease and respiratory disease. Stomach cancer was influenced primarily by childhood conditions and lung cancer by factors in adult life.
Socioeconomic position in childhood was associated with adult mortality in a large sample of British women.
This article examines how processes of cumulative adversity shape heart attack risk trajectories across the life course.
Our sample includes 9,760 Health and Retirement Study respondents born between 1931 and 1941. Using self-reported retrospective measures of respondents' early background, we first identify three latent classes with differential exposure to childhood disadvantage. Intervening covariates associated with educational attainment, employment status, income attainment, marital history, and health behaviors are added to capture sequential processes of adversity. Final latent-class cluster models estimate the cumulative impact of these covariates on three different heart attack risk trajectories between 1992 and 2002: high, increasing, and low.
Early disadvantage and childhood illness have severe enduring effects and increase the risk for heart attack. Adult pathways, however, differentially influence trajectories of heart attack risk and mediate the effects of early disadvantage.
Findings suggest that future research should consider how processes of cumulative adversity initiated in childhood influence health outcomes in older ages.
The aim of this study is to investigate associations between childhood adversities and coronary heart disease (CHD).
This was a case-control study based on a postal questionnaire addressed to randomly selected working-aged Finns, and response rate was 39% (N = 15,477). The sample comprised 319 CHD patients. Four age- and gender-matched controls were selected for every patient. The participants were asked in six questions to think about their childhood adversities.
Fear of some family member and someone in the family being seriously or chronically ill were more common during childhood among working-aged CHD patients than among controls. Likewise, among female CHD patients, serious conflicts in the family and someone in the family having had alcohol problems and, among male CHD patients, long-lasting financial problems were more common than among controls. Odds ratios (OR) varied between 1.27 and 2.66. Adjustment for education had no influence among women, but it had an influence among men. Upon adjustment for conventional risk factors (smoking, obesity, and hypertension), the association mostly disappeared. A family member having been seriously or chronically ill was statistically significant after full adjustment among both genders.
Working-aged CHD patients have experienced more dramatic events during their childhood than did the control population. This issue cannot be solved in doctors' offices. Health-promoting social policies are of vital importance.
Administrative registers, like hospital discharge registers and causes of death registers are used for the monitoring of disease incidences and in the follow-up studies. Obtaining reliable results requires that the diagnoses in these registers are correct and the coverage of the registers is high. The purpose of this study was to evaluate the validity of the Finnish hospital discharge registers and causes of death registers stroke diagnoses against the population-based FINSTROKE register.
All first stroke events from the hospital discharge registers and causes of death registers from the areas covered by the FINSTROKE register were obtained for years 1993-1998 and linked to the FINSTROKE register. The sensitivity and positive predictive values were calculated.
A total of 3633 stroke events, 767 fatal and 2866 non-fatal strokes, were included in the registers. The sensitivity for all first stroke events was 85%, for fatal strokes 86% and for non-fatal strokes 85%. The positive predictive values for all first strokes was 86%, for fatal strokes 92% and for non-fatal strokes 85%. The sensitivity as well as the positive predictive values for subarachnoid haemorrhage and intracerebral haemorrhage was higher than for cerebral infarctions. There were no marked differences in the sensitivity or positive predictive values between men and women.
The sensitivity and the positive predictive values of the Finnish hospital discharge registers and causes of death registers are fairly good. Finnish administrative registers can be used for the monitoring of stroke incidence, but the number of cerebral infarctions should be interpreted with caution.
Preclinical research findings suggest that exposure to stress and concomitant hypothalamus-pituitary-adrenal (HPA) axis activation during early development can have permanent and potentially deleterious effects. A history of early-life abuse or neglect appears to increase risk for mood and anxiety disorders. Abnormal HPA response to stress challenge has been reported in adult patients with major depressive disorder and posttraumatic stress disorder.
Plasma adrenocorticotropin hormone (ACTH) and cortisol reactivity to the Trier Social Stress Test were examined in healthy adults (n = 50) without current psychopathology. Subjects with a self-reported history of moderate to severe childhood maltreatment (MAL) (n = 23) as measured by the Childhood Trauma Questionnaire were compared with subjects without such a history (CTL) (n = 27).
Compared with CTLs, MAL subjects exhibited significantly lower cortisol and ACTH baseline-to-peak deltas. A significant group effect was seen in the (repeated measures) cortisol response to the stress challenge, reflecting lower concentrations among MAL subjects. A significant group x time effect characterized the relatively blunted ACTH response of the MAL group. Emotional neglect (-.34, p = .02) and sexual abuse (.31, p = .03) strongly predicted maximal cortisol release.
In adults without diagnosable psychopathology, childhood maltreatment is associated with diminished HPA axis response to a psychosocial stressor. Possible explanations for the finding are discussed.
Despite the significance of childhood trauma for later life, there is little evidence on the long-term consequences of parent-child
separation. World War II created a unique natural experiment that allowed the authors to test whether 1) evacuation to temporary
foster care unaccompanied by either parent and 2) separation from the father because of his military service predicted depressive
symptoms later on. Members of the Helsinki 1934–1944 Birth Cohort (n = 1,658) filled out the Beck Depression Inventory (BDI) at the ages of 61.6 (standard deviation: 2.9) and 63.4 (standard
deviation: 2.9) years. The mean of the two BDI scores was used as the dependent variable. The data on separation experiences
were extracted from the Finnish National Archives and from a survey among the participants. Former evacuees (n = 410) reported 20% (95% confidence interval: 8.7, 33.1) more severe depressive symptoms, and the odds ratio was 1.7 (95%
confidence interval: 1.1, 2.6) for having at least mild (BDI score: ≥10) symptoms over time compared with those who were not
separated. Those separated from their father because of the father's military assignment (n = 744) did not differ from those who were not separated.
Animal and human studies have found that prior stressful events can result in an altered reactivity in the HPA axis. The aim of the present study was to investigate the role of adverse events in childhood on cortisol reactivity to psychosocial stress in young healthy subjects (n=80).
Salivary cortisol levels were measured before, during and after exposure to a psychosocial stress task in healthy men and women with high (n=33) and low (n=47) exposure to adverse childhood events.
A significant blunted cortisol response was found in individuals with a history of adverse events compared to individuals with no adverse life events, with no differences in baseline cortisol levels. This finding appeared to be primarily driven by men. The groups did not differ on any other physiological or subjective stress measure, including heart rate, blood pressure, and subjective tension.
These findings suggest that, at least in healthy young males, adverse childhood events are associated with changes in HPA-axis functioning. Longitudinal studies are needed to investigate whether the blunted cortisol response is a risk factor in the etiology of psychiatric disorders or rather reflects resiliency with regard to the development of psychopathology.
Poliittiset tekijät lastensiirroissa Ruotsiin sotiemme aikana ja niiden jälkeen. Helsinki, Finland: Faculty of Arts, Department of Philosophy, History, Culture and Art Studies, University of Helsinki
- P Kavén
- Humanitaarisuuden
Kavén P. Humanitaarisuuden varjossa: Poliittiset tekijät lastensiirroissa
Ruotsiin sotiemme aikana ja niiden jälkeen. Helsinki, Finland: Faculty of
Arts, Department of Philosophy, History, Culture and Art Studies, University of Helsinki; 2010 (English summary available at: http://urn.fi/
URN:ISBN:978-952-10-6722-8).
Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men
- P M Ridker
- M Cushman
- M J Stampfer
- R P Tracy
- C H Hennekens
Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy
men. N Engl J Med 1997;336:973Y9.
C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women
- P M Ridker
- C H Hennekens
- J E Buring
- N Rifai
Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and
other markers of inflammation in the prediction of cardiovascular disease
in women. N Engl J Med 2000;342:836Y43.
Global Trends: Refugees, Asylum-seekers, Returnees, Internally Displaced and Stateless Persons
- Unhcr
UNHCR. 2009 Global Trends: Refugees, Asylum-seekers, Returnees, Internally Displaced and Stateless Persons. 2010 Available at: http://www.unhcr.org/
4c11f0be9.html. Accessed January 27, 2011.
Effects of early adverse experiences on brain structure and function: clinical implications.
- Kaufman
Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men.
- Ridker
C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women.
- Ridker
Risky families: family social environments and the mental and physical health of offspring.
- Repetti