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The lifespan consequences of early life stress
Physiology & Behavior 106 (2012) 722–727
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The lifespan consequences of early life stress Anu-Katriina Pesonen, Katri Räikkönen ⁎ Institute of Behavioral Sciences, P.O. Box 9 00014 University of Helsinki, Finland
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Article history: Received 28 September 2011 Received in revised form 25 October 2011 Accepted 31 October 2011 Keywords: Early life stress WWII Lifespan Psychiatric disorders Intellectual ability Cortisol
a b s t r a c t Early life stress (ELS), an experience of severe stress due for example to parental loss, abuse or neglect during the childhood years, may have profound long-term effects on the individual's physiology and psychology. Here we review the findings of the Helsinki Birth Cohort Study 1934–44 (n= 13,345), of whom approximately 14% were temporarily separated from both their parents due to child evacuations in World War II. The children were evacuated from Finland, unaccompanied by their parents, to other countries in Scandinavia (Sweden and Denmark) at the average age of 4.7 years (SD = 2.4 years) and for an average period of 1.7 years (SD = 1.0 years). Information on these separations for each member of the HBCS was derived from the Finnish National Archives. We found significant effects of ELS on psychiatric morbidity and mortality, intellectual ability, stress reactivity, reproductive history, and inter-generational social mobility. © 2011 Published by Elsevier Inc.
1. Introduction Recent research has produced increasing evidence that early life stress (ELS), an experience of severe stress due for example to parental loss, abuse or neglect during the childhood years, may have profound long-term effects on the individual's physiology and psychology [1–4]. This evidence has confirmed observations from experimental animal models, in which ELS, usually defined as temporary maternal separation early in life, has shown to cause changes in gene expression that are manifest for instance, in the physiology of stress regulation [5,6]. However, compared to animal experiments, in which the nature and duration of ELS can be controlled by the experimenter, the research on ELS in humans is methodologically challenging. Most typically, children experience ELS in the form of abuse and neglect in their family environment, and it may be impossible to disentangle the effects of ELS from their shared genetic makeup with their parents. Secondly, the experience of ELS may be cumulative such that prenatal adversity, economical strains, learning difficulties, nutritional problems, parental mental health problems, lack of appropriate health care, child abuse and neglect accumulate in a manner that make it impossible to understand which characteristics of ELS may especially be harmful for later well-being. Finally, the major problem in the examination of ELS on later mental health is that most of the studies are conducted on samples in which participants are asked to report their experience of ELS retrospectively. In these studies there is always the possibility that the recall is biased by
⁎ Corresponding author. Tel.: + 358 919129501; fax: + 358 919129521. E-mail addresses: anukatriina.pesonen@helsinki.fi (A.-K. Pesonen), katri.raikkonen@helsinki.fi (K. Räikkönen). 0031-9384/$ – see front matter © 2011 Published by Elsevier Inc. doi:10.1016/j.physbeh.2011.10.030
the current mental health status, or by other life events that have occurred after the childhood years. Another prominent way to study the effects of ELS on later mental health across the life span is to profit from the opportunities provided by naturally occurring negative life events. These happen, when unfortunate circumstances cause ELS to some children, whereas their fellow peers remain intact. We are aware of three such studies, which have examined the effects of ELS on later mental health with relatively long follow-up periods. The first is a study that examined the mental health of individuals placed immediately after birth into a Christmas Seal Home for an average period of 7 months to avoid any contact with a mother with tuberculosis or any other family member. This public health policy program against morbidity and mortality for tuberculosis in children concerned all social groups in Finland during 1930s. In this register study, a heightened risks for depression [7] substance abuse [8] and criminal behavior [9] have been reported among the formerly institutionalized newborns. Noteworthy, the risk for schizophrenia or the risk for psychoses was not increased [10]. The second line of studies has followed the life of Holocaust survivors, although very rarely these studies have focused on the survivors that were children during the war. One such study showed that child survivors had higher PTSD symptom scores, higher depression, anxiety, somatization, and anger–hostility scores and lower quality of life [11,12]. Another study reported higher prevalence rates of anxiety disorders, sleep disturbances and emotional distress among a sample consisting mainly of child and adolescent survivors, the findings being independent of age during the Holocaust [13]. The third line of longitudinal research on ELS, which we have followed, is the examination the life course of children, who were
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evacuated during World War II (WW II) to live with foster families in safer environments. Large scale evacuations were organized in the United Kingdom (UK) and Finland, creating an exceptional opportunity to study the long-term lifespan outcomes related to parent–child separation in a natural setting. The results from the UK study are contradictory; one study found that former evacuees were more likely to have insecure attachment styles and lower levels of current psychological well-being than controls [14], and were in greater risk for depression and clinical anxiety [15]. Two other studies, however, found no effects of separation on adult mental health, depression and anxiety [16,17]. However, based on these studies, the evidence on the long-term consequences of parental separation is rather tenuous because separation was self-reported retrospectively, sample sizes have been small, participants were recruited through advertisement and word of mouth, ambiguity related to the age when the outcomes were measured, paternal death in the control group, and data being partly restricted to women [14–17]. Consequently, more research is needed to shed light on the life span consequences of ELS in humans. Here we review our findings regarding the Finnish experience of evacuations in World War II. 1.1. Child evacuations in the Helsinki Birth Cohort Study During WW II, Finland fought two wars with the Soviet Union in years 1939–40 and 1941–44. To protect Finnish children from the effects of these wars, children from various socioeconomic backgrounds were evacuated abroad, primarily to Sweden and Denmark, unaccompanied by their parents. It is also of note that siblings were usually placed in different foster families to promote faster learning of the new language. The evacuations had strong political support. Public criticism of the evacuations was discouraged by the government, and the media was used effectively to advocate the evacuations. Ultimately, the voluntary evacuations were seen as a positive opportunity in many families, particularly in 1942, when food shortages were severe and the war was expected to end soon [18,19]. However, the war continued, and altogether approximately 70,000 children were sent into foster care unaccompanied by their parents for an average of almost two years [18–21]. The Finnish National Archives preserve full documentation of the 48,628 children evacuated abroad by the Finnish Government. The Helsinki Birth Cohort Study (HBCS) comprises 13,345 women (n = 6370) and men (n= 6975) who were born as singletons in one of the two main maternity hospitals in Helsinki, Finland, between 1934 and 1944, and who were living in Finland in 1971 when a unique personal identification number was allocated to each member of the Finnish population [22]. From the documents retrieved from the Finnish National Archives' register, we identified 1781 (13.4% of the HBCS; n = 822, 46.2% women) participants who were evacuated through Ministry of Social Affairs and Health and thus separated temporarily from their parents as children. The age at the time of separation (M = 4.7 years, SD = 2.4 years) and the duration of the separation (M = 1.7 years, SD = 1.0 years) were also identified from the register. Note that the comparability between the studies reviewed in the following sections is compromised due to variation in the numbers of participants (N range 287–12,747) in each study, depending on the available data for the outcome in question. 2. Results 2.1. Findings on depressive symptoms One of our first studies was conducted in a randomly selected subsample (n= 1658) of the HBCS. They underwent detailed clinical examination on cardiometabolic and hormonal characteristics and filled in the Beck Depression Inventory twice, an average two years apart. We found that those who had been separated as children unaccompanied by either parent to temporary foster care reported, at the average age
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of approximately 60 years, 20%more severe depressive symptoms than did those who did not experience any parental separation in times of war. Furthermore, they were almost twice as likely to remain at least mild in severity in depressive symptoms over two consecutive measurement occasions in late adulthood. Moreover, separation that lasted more than 3 years had the largest effect, being associated with over 33%more severe depressive symptoms, with an odds ratio of 4.4 for belonging to the group who reported depressive symptoms remaining at least mild in severity over time. In addition, those separated in infancy or at the school-age were the most affected. 2.2. Findings on psychiatric morbidity and mortality Our next study on the effects of ELS on mental health was based on the Finnish Hospital Discharge Register (HDR), and the Finnish Causes of Death Register (CDR) between years 1969 and 2004, and it examined the cumulative incidence of psychiatric disorders from early to late adulthood severe enough to require hospital treatment or cause death in the separated and the non-separated participants of the HBCS. This study involved 12747 participants (96% of the initial cohort), of whom 1719 had been separated according to the register information [23]. Compared to the non-separated, the separated had significantly higher risks for psychiatric morbidity due to substance use disorder (OR 1.3) and personality disorder (OR 1.6). The odds for any mental disorder (including psychotic, substance use, mood, anxiety and personality disorders) was equally heightened (OR 1.2). However, when we stratified the study population according to childhood socioeconomic status (SES), we observed that individuals with an upper childhood socioeconomic background were particularly sensitive to the temporary separations as they showed the highest risk of any mental, substance use mood, psychotic, and personality disorders (ORs 2.1–3.0). In individuals with a lower childhood socioeconomic background, the temporary separations did not add to the increased risk already associated with a lower SES. These associations were not confounded by factors that were associated with a higher likelihood of being temporarily separated from the parents and/or that may pose a risk of mental disorders. When we further narrowed our analyses to the participants who had some form of psychiatric disorder, we observed that the risk was heightened specifically for personality disorders among the separated, and of the different personality disorders, the risk for dramatic personality disorder was especially heightened among the separated men [24]. Separation under the age 5 increased the risk for personality disorders further [24]. The findings linking temporary separation from the parents specifically with substance use and personality disorders, but not with psychoses (in the entire study population) are, thus, in agreement with the previous findings [8,9,25–28], but fewer findings with mood disorders and null findings with anxiety disorders were discordant with past reports [8,27,29,30]. 2.3. Findings on stress reactivity Animal models have demonstrated that consequences of ELS may lead to physiological changes in the central nervous system that may be permanent. Among the plausible physiological mechanisms behind the associations is of ELS and later psychiatric morbidity is stress-related hypothalamic-pituitary-adrenal (HPA) axis functioning that shows associations with a number of psychiatric disorders [31]. Animals who have experienced ELS show increased corticotrophin-releasing hormone expression and decreased numbers of glucocorticoid receptors in the hippocampus, hypothalamus, and frontal cortex [32] and methylation of hippocampal glucocorticoid receptor genes [33], all reflecting altered neural plasticity at multiple levels of the central nervous system. At a behavioral level, lower levels of glucocorticoid receptors have been associated with poorer stress regulation capacity and more prolonged
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stress reactions [34]. Consequently, early separated animals exhibit greater startle responses, greater freezing and anxiety responses, and two- to three-fold greater hormonal responses to stress as adults [35]. We had the opportunity to study the hormonal stress reactivity of a subsample of the HBCS (n = 282), using the Trier Social Stress Test (TSST) [36], which is a well-validated psychosocial stress test. We found that ELS was associated with altered responsiveness of the HPA axis more than 60 years after childhood separation [36]. In comparison to non-separated, separated individual displayed 20–25%higher salivary cortisol and plasma ACTH levels across the time points during the TSST, and higher salivary cortisol reactivity in response to the TSST, more than 60 years later. Importantly, altered stress reactivity can be due to current depressive symptoms, and not to initial ELS. Therefore, we controlled for the current depressive symptoms in our analyses, and found that the association between ELS and HPA axis function is not explained by the presence of symptoms of depression [36]. This suggests that the interrelations between early life stress, stress physiology, and mental health are not merely due to symptoms of depression. In addition, we observed an inverse u-shaped relationship between age at separation and both salivary or plasma cortisol and plasma ACTH reactivity. The highest concentrations were observed in the middle of the age range, i.e., among those separated as toddlers and in early childhood (4–7 year olds). Comparison of this observation to earlier observations is difficult, since the specific age period of ELS due to abusive experiences can rarely be identified retrospectively. Studies of parental loss or divorce, on the other hand, have not been able to specify age periods with such accuracy [37–39]. It might have been that the children in the middle of the age range might have perceived the social and cultural upheavals of separation (foreign language and customs, new peers) as more difficult to cope with owing to their undeveloped self-regulative capacities, and this uncontrollability is associated with higher HPA axis responses later on. 2.4. Findings on cognitive ability Importantly, the neural circuitry of stress involves several brain structures, including the hippocampus, amygdala, and prefrontal cortex, all of which are vital to cognitive function. Indeed, animal research has suggested that ELS may also accelerate late-onset progressive impairment of the hippocampus and cognitive function [40,41]. The human evidence, however, is scarce. It shows that institutionalized children, in comparison to their siblings or peers who were adopted from these institutions, obtained lower scores on tests of intellectual ability at an average age of 54 months [42]. When compared to peers in their new homeland, inter-country adoptees scored lower on tests of intellectual ability in young adulthood [42–44]. Further, a recent study demonstrated that elderly Holocaust survivors had a greater age-related decline in explicit memory compared to their non-exposed peers [45]. These studies can, however, rarely distinguish other factors accompanied by early stress, such as impaired nutrition. Our study provided further prospective evidence on the long-term intellectual outcomes of ELS among 2725 men of the HBCS [46]. Data on verbal, arithmetic and visuospatial intellectual abilities of the young adults of the HBCS was retrieved from the archives of the Finnish Defence Forces: since 1950s, every Finnish man has undergone this test in conjunction with his compulsory military service. This obligatory test is given to all new recruits during the first two weeks of their military service and is used when the conscripts are selected for leadership training. The test battery and its psychometric properties are described in detail elsewhere [47]. It is designed to measure general ability and logical thinking, is composed of verbal, visuospatial, and arithmetic reasoning subtests. Each subtest is timed and consists of 40 multiple-choice questions that are ordered by difficulty. Correct answers are summed to yield a test score. We also used a composite
score of intellectual ability, analyzed as the mean of the three individual subtests. We found that the separated had −0.28 SD units lower verbal ability, − 0.13 SD units lower visuospatial ability, −0.18 SD units lower arithmetic ability scores as compared to non-separated [46]. Interestingly and consistent to previous retrospective and scant prospective evidence, we found the strongest relationship between ELS and lower scores on verbal reasoning [48–50]. The associations were not confounded by childhood social class, birth order, birth weight, parity, nor by age or height at time of intellectual assessment, factors that previous research has found as predictors of intellectual development. In addition to showing considerable main effects of ELS, we were able to demonstrate a threshold effect between duration of stress exposure and impairment of intellectual ability. A separation lasting for one year or less was not associated with worse intellectual performance. Secondly, we were able to specify an age period when the child is probably most vulnerable to ELS. The most widely affected children were aged from two to seven years, when first separated, whereas separation in infancy or at school-age had fewer effects on the test scores, except for the verbal ability score. Our finding corresponds to our previous observation, that the highest HPA axis reactivity to stress in adults occurs within this same group of separation age [36]. These findings showing that infancy may be a period of lesser vulnerability parallels findings showing that adoption during infancy may buffer the potentially compromised cognitive development following institutionalization [42,51]. 2.5. Findings on life history Targeting solely on mental health outcomes, stress reactivity, or cognitive ability, may not effectively describe the long-term consequences of ELS. Therefore, we also examined whether the separations were associated with reproductive and marital traits among a subsample of 1704 former evacuees [52]. According to the life history theory and its variations [53,54], a risky and uncertain environment during childhood may lead to reproducing early in life in order to maximize the probability of leaving descents. Among humans, this theory is supported by fairly rich retrospective evidence associating general childhood family adversities, or the father's absence, with an earlier onset of menarche [55]. Among the few existing prospective studies, a recent large-scale one showed that children who were adopted in Denmark had a 10–20-times risk for developing a precocious puberty compared to inhabitants of Danish origin [56]. While most of the existing evidence points to earlier rather than later pubertal development, there are data from the former Yugoslavia [57], suggesting delayed pubertal development in times of the war, at least in girls exposed to stressful conditions during or shortly before their menarcheal age. Our aim was to test whether a separation in childhood was associated with reproductive traits later in life, measured by age at onset of menarche. We also explored the associations between a separation and age at first childbirth, number of children by late adulthood and their interbirth intervals, all issues which have not been prospectively tested against ELS in an epidemiological cohort [52]. In accordance with earlier studies, we found that the separated women had an earlier onset of menarche than non-separated women, independent of the year of birth, mothers' age at menarche, childhood SES, and BMI at age 7 [52]. Compared to the non-separated girls, the separated girls were 2.1 times more likely to have their menarche before or at the age of 12 than after the age of 13. An adjustment for general parental quality during, measured by a retrospective report childhood did not affect the results, further emphasizing the role of separation in explaining the results. We also found that the separated women were 2.3-times more likely to have four or more children, and 1.9-times more likely to have 3 children, than to have a single child, when compared to non-separated. The findings concerned also men:
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relative to non-separated, the separated men had their first child at a younger age, and subsequent children at shorter interbirth intervals. Based on these observations, we hypothesized that a traumatic experience may lead to a need to start a family at an earlier age in order to overcome the instability derived from the ELS. Even though the effects were relatively weak, they were theoretically-based and delineated a consistent tendency to maximize early reproduction in uncertain times, such as following ELS. In agreement with recent theorizing [53], instead of emphasizing non-optimal, development disruptions, the results concerning family development may challenge to put more emphasis on considering whether these processes function as adaptive life-solutions and coping processes following ELS. 2.6. Findings on inter-generational social mobility Inter-generational social mobility refers to transition of an individual from the parental social position to another social position in adult life. Socioeconomic position (SEP) and inter-generational social mobility are known to be powerful determinants of health, illness, and mortality. However, relative to the wealth of studies showing how SEP may function either as the source or the consequence of health inequality [58–62]; far less attention has been paid to the early life determinants of adult SEP and inter-generational social mobility. On our recent study [63], we explored whether ELS plays a role in these processes. This life-course study, spanning from birth across the entire work career in adulthood, showed that ELS is associated with socioeconomic disadvantage in adult life. Firstly, the separated attained a lower SEP in adulthood, as indicated by their own highest attained occupational status, educational level and taxable incomes, compared to the nonseparated. These associations persisted after controlling for SES in childhood, sex, year of birth, and birth order. Secondly, we found that the inter-generational social mobility was associated with the separation. Compared to the non-separated participants, the separated participants whose fathers had a manual worker occupation were less likely to be upwardly mobile, and those who had fathers in junior clerical and senior clerical occupations were more likely to be downwardly mobile. The income trajectories across the working career in adulthood, from year 1970 to year 2000, showed that the differences between the separated and non-separated participants were evident throughout adulthood, such that the group differences grew larger with years passing by, with the separated displaying a decrease in the taxable incomes. When stratified according to the initial childhood SES, the difference was most marked among participants in the lowest SES. However, also separated participants with fathers in junior and senior clerical occupations had different income trajectories; whereas in the first 15 years there were no marked differences, the separated having even higher incomes in the highest childhood SEP group, the income differences enlarged thereafter in favour of the non-separated. 3. General comments As summarized [64], the major challenges in human studies on ELS are to get as close as possible to experimental conditions, and to obtain more information on the timing of trauma. Our study in the HBSC unique prospective setting, of which approximately 14%were exposed to a specific form of ELS, parental separation, has allowed us to overcome some of the challenges relating to human studies on ELS. Even contemporary child mental health professionals in Finland advocated the evacuations, creating the sense that this was an opportunity for children, as Finnish child psychiatrist T. Brander pertinently remarked in 1943 [65, p. 314]: “Not a single case has come to my attention in which a child suffered psychological injury from this voluntary evacuation. Quite the contrary: such a stay proved to be an instructive and refreshing experience, from which the children returned with heightened
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vitality. This was due to the excellent care and attention bestowed on our children by our western neighbors”. These kinds of exceptional conditions are particularly significant to potential natural experiments because the confounders are assumed to be randomly distributed across the groups under investigation. We have previously argued that the likelihood of a Finnish child being evacuated was to some extent random, influenced by an unpredictable interplay between political and intrafamilial factors, such as the parents generally choosing to send only one or some children away. However, several methodological considerations should be taken account when interpreting the findings. In the studies among subsamples of the HBCS, the differences in the socioeconomic background of the separated and non-separated were not statistically significant. However, in studies involving more subjects, we observed a statistically significant difference in childhood SES: the separated originated more frequently from lower socioeconomic background. Although we have adjusted for childhood SES in all our studies, the role of childhood SES on later outcomes may have been more complex, thus acting as a potential confounder in our studies. On the other hand, when we examined the role of ELS in later psychiatric morbidity and mortality, it was especially those participants who originated from upper socioeconomic position that were in increased risk for later psychiatric disorders, whereas the temporary separations did not add to the risk otherwise associated with a lower childhood socioeconomic background. In this sense, preponderance of separation in the lowest category of childhood SES may have even masked the effects of ELS in our studies. In addition, our findings suggested that an upper childhood socioeconomic background may not buffer from severe ELS, such as that arising from temporary separations from parents. Another challenge in the longitudinal studies is the sampling bias. This kind of sampling bias concerned only these two studies based on voluntary participation. Those who responded to the depression questionnaire may have been healthier than those who did not, and those who attended the stressful stress test may have been more adventurous and less depressed than those who refused. A second source of sampling bias is related to the migration processes and childhood mortality, thus concerning all our studies. Approximately 11%of the separated were adopted in Sweden as child. However, a previous study [66] found no significant differences in mental health status between the adopted and returned former child evacuees. In addition to adoptions, the migration processes between Sweden and Finland have been relatively complex, some adopted children moving back to Finland as they grew up, and some former evacuees moving back to Sweden as young adults. Noteworthy, the emigration in adulthood was more likely for former child evacuees than for non-separated in the HBCS [23]. The mortality of evacuated children was 0.6%over the whole evacuation period (mean: 2.1 years), slightly lower than the mortality among Finnish children aged 1–9 years, which ranged annually from 0.4%to 0.5%during 1941–1945 [20].We also acknowledge that the parents may have generally chosen the weakest child(ren), causing potential bias. However, the original governmental policy aimed at excluding unhealthy children. Later in the war, sick children (11%of registered evacuations, 3.5%mortality) were also considered eligible for evacuation [20]. Finally, we are aware that evacuated children may have experienced other adversities during their foreign stay, making it difficult to isolate the effect of separation from other influences. However, we definitely know that the children lost their secure base with the unpredictable evacuation and, thus, also lost the parental assistance needed in regulating emotions, especially under serious stress. As a subjective case report describes [67], the separation trauma evoked both dissociative memory function and uncontrollable anxiety, which characterized individual emotion regulation even 50 years after evacuation. In conclusion, our study presents evidence of long-term disadvantage for physiology, psychology and mental health following experience of
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ELS. Although the historical circumstances in this study were particular, the developmental significance of ELS is not bound to this study. According to data reported by the United Nations Refugee Agency (UNHCR) in 2008, there were 42 million displaced individuals worldwide, including 15.2 refugees, of which 44%are children (http://www. unhcr.org/4a375c426.html). Even without displacement, an experience of ELS for various reasons, parental loss or family disruption, child abuse and neglect, traumatizing events, illness, poverty, institutionalization, or war concerns children everywhere in the contemporary world. References [1] Alastalo H, Räikkönen K, Pesonen AK, Osmond C, Barker DJ, Kajantie E, et al. Cardiovascular health of Finnish war evacuees 60 years later. Ann Med 2009;41: 66–72. [2] Danese A, Moffitt TE, Pariante CM, Ambler A, Poulton R, Caspi A. Elevated inflammation levels in depressed adults with a history of childhood maltreatment. Arch Gen Psychiatry 2008;65:409–15. 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The lifespan consequences of early life stress Anu-Katriina Pesonen, Katri Räikkönen ⁎ Institute of Behavioral Sciences, P.O. Box 9 00014 University of Helsinki, Finland
a r t i c l e
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Article history: Received 28 September 2011 Received in revised form 25 October 2011 Accepted 31 October 2011 Keywords: Early life stress WWII Lifespan Psychiatric disorders Intellectual ability Cortisol
a b s t r a c t Early life stress (ELS), an experience of severe stress due for example to parental loss, abuse or neglect during the childhood years, may have profound long-term effects on the individual's physiology and psychology. Here we review the findings of the Helsinki Birth Cohort Study 1934–44 (n= 13,345), of whom approximately 14% were temporarily separated from both their parents due to child evacuations in World War II. The children were evacuated from Finland, unaccompanied by their parents, to other countries in Scandinavia (Sweden and Denmark) at the average age of 4.7 years (SD = 2.4 years) and for an average period of 1.7 years (SD = 1.0 years). Information on these separations for each member of the HBCS was derived from the Finnish National Archives. We found significant effects of ELS on psychiatric morbidity and mortality, intellectual ability, stress reactivity, reproductive history, and inter-generational social mobility. © 2011 Published by Elsevier Inc.
1. Introduction Recent research has produced increasing evidence that early life stress (ELS), an experience of severe stress due for example to parental loss, abuse or neglect during the childhood years, may have profound long-term effects on the individual's physiology and psychology [1–4]. This evidence has confirmed observations from experimental animal models, in which ELS, usually defined as temporary maternal separation early in life, has shown to cause changes in gene expression that are manifest for instance, in the physiology of stress regulation [5,6]. However, compared to animal experiments, in which the nature and duration of ELS can be controlled by the experimenter, the research on ELS in humans is methodologically challenging. Most typically, children experience ELS in the form of abuse and neglect in their family environment, and it may be impossible to disentangle the effects of ELS from their shared genetic makeup with their parents. Secondly, the experience of ELS may be cumulative such that prenatal adversity, economical strains, learning difficulties, nutritional problems, parental mental health problems, lack of appropriate health care, child abuse and neglect accumulate in a manner that make it impossible to understand which characteristics of ELS may especially be harmful for later well-being. Finally, the major problem in the examination of ELS on later mental health is that most of the studies are conducted on samples in which participants are asked to report their experience of ELS retrospectively. In these studies there is always the possibility that the recall is biased by
⁎ Corresponding author. Tel.: + 358 919129501; fax: + 358 919129521. E-mail addresses: anukatriina.pesonen@helsinki.fi (A.-K. Pesonen), katri.raikkonen@helsinki.fi (K. Räikkönen). 0031-9384/$ – see front matter © 2011 Published by Elsevier Inc. doi:10.1016/j.physbeh.2011.10.030
the current mental health status, or by other life events that have occurred after the childhood years. Another prominent way to study the effects of ELS on later mental health across the life span is to profit from the opportunities provided by naturally occurring negative life events. These happen, when unfortunate circumstances cause ELS to some children, whereas their fellow peers remain intact. We are aware of three such studies, which have examined the effects of ELS on later mental health with relatively long follow-up periods. The first is a study that examined the mental health of individuals placed immediately after birth into a Christmas Seal Home for an average period of 7 months to avoid any contact with a mother with tuberculosis or any other family member. This public health policy program against morbidity and mortality for tuberculosis in children concerned all social groups in Finland during 1930s. In this register study, a heightened risks for depression [7] substance abuse [8] and criminal behavior [9] have been reported among the formerly institutionalized newborns. Noteworthy, the risk for schizophrenia or the risk for psychoses was not increased [10]. The second line of studies has followed the life of Holocaust survivors, although very rarely these studies have focused on the survivors that were children during the war. One such study showed that child survivors had higher PTSD symptom scores, higher depression, anxiety, somatization, and anger–hostility scores and lower quality of life [11,12]. Another study reported higher prevalence rates of anxiety disorders, sleep disturbances and emotional distress among a sample consisting mainly of child and adolescent survivors, the findings being independent of age during the Holocaust [13]. The third line of longitudinal research on ELS, which we have followed, is the examination the life course of children, who were
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evacuated during World War II (WW II) to live with foster families in safer environments. Large scale evacuations were organized in the United Kingdom (UK) and Finland, creating an exceptional opportunity to study the long-term lifespan outcomes related to parent–child separation in a natural setting. The results from the UK study are contradictory; one study found that former evacuees were more likely to have insecure attachment styles and lower levels of current psychological well-being than controls [14], and were in greater risk for depression and clinical anxiety [15]. Two other studies, however, found no effects of separation on adult mental health, depression and anxiety [16,17]. However, based on these studies, the evidence on the long-term consequences of parental separation is rather tenuous because separation was self-reported retrospectively, sample sizes have been small, participants were recruited through advertisement and word of mouth, ambiguity related to the age when the outcomes were measured, paternal death in the control group, and data being partly restricted to women [14–17]. Consequently, more research is needed to shed light on the life span consequences of ELS in humans. Here we review our findings regarding the Finnish experience of evacuations in World War II. 1.1. Child evacuations in the Helsinki Birth Cohort Study During WW II, Finland fought two wars with the Soviet Union in years 1939–40 and 1941–44. To protect Finnish children from the effects of these wars, children from various socioeconomic backgrounds were evacuated abroad, primarily to Sweden and Denmark, unaccompanied by their parents. It is also of note that siblings were usually placed in different foster families to promote faster learning of the new language. The evacuations had strong political support. Public criticism of the evacuations was discouraged by the government, and the media was used effectively to advocate the evacuations. Ultimately, the voluntary evacuations were seen as a positive opportunity in many families, particularly in 1942, when food shortages were severe and the war was expected to end soon [18,19]. However, the war continued, and altogether approximately 70,000 children were sent into foster care unaccompanied by their parents for an average of almost two years [18–21]. The Finnish National Archives preserve full documentation of the 48,628 children evacuated abroad by the Finnish Government. The Helsinki Birth Cohort Study (HBCS) comprises 13,345 women (n = 6370) and men (n= 6975) who were born as singletons in one of the two main maternity hospitals in Helsinki, Finland, between 1934 and 1944, and who were living in Finland in 1971 when a unique personal identification number was allocated to each member of the Finnish population [22]. From the documents retrieved from the Finnish National Archives' register, we identified 1781 (13.4% of the HBCS; n = 822, 46.2% women) participants who were evacuated through Ministry of Social Affairs and Health and thus separated temporarily from their parents as children. The age at the time of separation (M = 4.7 years, SD = 2.4 years) and the duration of the separation (M = 1.7 years, SD = 1.0 years) were also identified from the register. Note that the comparability between the studies reviewed in the following sections is compromised due to variation in the numbers of participants (N range 287–12,747) in each study, depending on the available data for the outcome in question. 2. Results 2.1. Findings on depressive symptoms One of our first studies was conducted in a randomly selected subsample (n= 1658) of the HBCS. They underwent detailed clinical examination on cardiometabolic and hormonal characteristics and filled in the Beck Depression Inventory twice, an average two years apart. We found that those who had been separated as children unaccompanied by either parent to temporary foster care reported, at the average age
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of approximately 60 years, 20%more severe depressive symptoms than did those who did not experience any parental separation in times of war. Furthermore, they were almost twice as likely to remain at least mild in severity in depressive symptoms over two consecutive measurement occasions in late adulthood. Moreover, separation that lasted more than 3 years had the largest effect, being associated with over 33%more severe depressive symptoms, with an odds ratio of 4.4 for belonging to the group who reported depressive symptoms remaining at least mild in severity over time. In addition, those separated in infancy or at the school-age were the most affected. 2.2. Findings on psychiatric morbidity and mortality Our next study on the effects of ELS on mental health was based on the Finnish Hospital Discharge Register (HDR), and the Finnish Causes of Death Register (CDR) between years 1969 and 2004, and it examined the cumulative incidence of psychiatric disorders from early to late adulthood severe enough to require hospital treatment or cause death in the separated and the non-separated participants of the HBCS. This study involved 12747 participants (96% of the initial cohort), of whom 1719 had been separated according to the register information [23]. Compared to the non-separated, the separated had significantly higher risks for psychiatric morbidity due to substance use disorder (OR 1.3) and personality disorder (OR 1.6). The odds for any mental disorder (including psychotic, substance use, mood, anxiety and personality disorders) was equally heightened (OR 1.2). However, when we stratified the study population according to childhood socioeconomic status (SES), we observed that individuals with an upper childhood socioeconomic background were particularly sensitive to the temporary separations as they showed the highest risk of any mental, substance use mood, psychotic, and personality disorders (ORs 2.1–3.0). In individuals with a lower childhood socioeconomic background, the temporary separations did not add to the increased risk already associated with a lower SES. These associations were not confounded by factors that were associated with a higher likelihood of being temporarily separated from the parents and/or that may pose a risk of mental disorders. When we further narrowed our analyses to the participants who had some form of psychiatric disorder, we observed that the risk was heightened specifically for personality disorders among the separated, and of the different personality disorders, the risk for dramatic personality disorder was especially heightened among the separated men [24]. Separation under the age 5 increased the risk for personality disorders further [24]. The findings linking temporary separation from the parents specifically with substance use and personality disorders, but not with psychoses (in the entire study population) are, thus, in agreement with the previous findings [8,9,25–28], but fewer findings with mood disorders and null findings with anxiety disorders were discordant with past reports [8,27,29,30]. 2.3. Findings on stress reactivity Animal models have demonstrated that consequences of ELS may lead to physiological changes in the central nervous system that may be permanent. Among the plausible physiological mechanisms behind the associations is of ELS and later psychiatric morbidity is stress-related hypothalamic-pituitary-adrenal (HPA) axis functioning that shows associations with a number of psychiatric disorders [31]. Animals who have experienced ELS show increased corticotrophin-releasing hormone expression and decreased numbers of glucocorticoid receptors in the hippocampus, hypothalamus, and frontal cortex [32] and methylation of hippocampal glucocorticoid receptor genes [33], all reflecting altered neural plasticity at multiple levels of the central nervous system. At a behavioral level, lower levels of glucocorticoid receptors have been associated with poorer stress regulation capacity and more prolonged
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stress reactions [34]. Consequently, early separated animals exhibit greater startle responses, greater freezing and anxiety responses, and two- to three-fold greater hormonal responses to stress as adults [35]. We had the opportunity to study the hormonal stress reactivity of a subsample of the HBCS (n = 282), using the Trier Social Stress Test (TSST) [36], which is a well-validated psychosocial stress test. We found that ELS was associated with altered responsiveness of the HPA axis more than 60 years after childhood separation [36]. In comparison to non-separated, separated individual displayed 20–25%higher salivary cortisol and plasma ACTH levels across the time points during the TSST, and higher salivary cortisol reactivity in response to the TSST, more than 60 years later. Importantly, altered stress reactivity can be due to current depressive symptoms, and not to initial ELS. Therefore, we controlled for the current depressive symptoms in our analyses, and found that the association between ELS and HPA axis function is not explained by the presence of symptoms of depression [36]. This suggests that the interrelations between early life stress, stress physiology, and mental health are not merely due to symptoms of depression. In addition, we observed an inverse u-shaped relationship between age at separation and both salivary or plasma cortisol and plasma ACTH reactivity. The highest concentrations were observed in the middle of the age range, i.e., among those separated as toddlers and in early childhood (4–7 year olds). Comparison of this observation to earlier observations is difficult, since the specific age period of ELS due to abusive experiences can rarely be identified retrospectively. Studies of parental loss or divorce, on the other hand, have not been able to specify age periods with such accuracy [37–39]. It might have been that the children in the middle of the age range might have perceived the social and cultural upheavals of separation (foreign language and customs, new peers) as more difficult to cope with owing to their undeveloped self-regulative capacities, and this uncontrollability is associated with higher HPA axis responses later on. 2.4. Findings on cognitive ability Importantly, the neural circuitry of stress involves several brain structures, including the hippocampus, amygdala, and prefrontal cortex, all of which are vital to cognitive function. Indeed, animal research has suggested that ELS may also accelerate late-onset progressive impairment of the hippocampus and cognitive function [40,41]. The human evidence, however, is scarce. It shows that institutionalized children, in comparison to their siblings or peers who were adopted from these institutions, obtained lower scores on tests of intellectual ability at an average age of 54 months [42]. When compared to peers in their new homeland, inter-country adoptees scored lower on tests of intellectual ability in young adulthood [42–44]. Further, a recent study demonstrated that elderly Holocaust survivors had a greater age-related decline in explicit memory compared to their non-exposed peers [45]. These studies can, however, rarely distinguish other factors accompanied by early stress, such as impaired nutrition. Our study provided further prospective evidence on the long-term intellectual outcomes of ELS among 2725 men of the HBCS [46]. Data on verbal, arithmetic and visuospatial intellectual abilities of the young adults of the HBCS was retrieved from the archives of the Finnish Defence Forces: since 1950s, every Finnish man has undergone this test in conjunction with his compulsory military service. This obligatory test is given to all new recruits during the first two weeks of their military service and is used when the conscripts are selected for leadership training. The test battery and its psychometric properties are described in detail elsewhere [47]. It is designed to measure general ability and logical thinking, is composed of verbal, visuospatial, and arithmetic reasoning subtests. Each subtest is timed and consists of 40 multiple-choice questions that are ordered by difficulty. Correct answers are summed to yield a test score. We also used a composite
score of intellectual ability, analyzed as the mean of the three individual subtests. We found that the separated had −0.28 SD units lower verbal ability, − 0.13 SD units lower visuospatial ability, −0.18 SD units lower arithmetic ability scores as compared to non-separated [46]. Interestingly and consistent to previous retrospective and scant prospective evidence, we found the strongest relationship between ELS and lower scores on verbal reasoning [48–50]. The associations were not confounded by childhood social class, birth order, birth weight, parity, nor by age or height at time of intellectual assessment, factors that previous research has found as predictors of intellectual development. In addition to showing considerable main effects of ELS, we were able to demonstrate a threshold effect between duration of stress exposure and impairment of intellectual ability. A separation lasting for one year or less was not associated with worse intellectual performance. Secondly, we were able to specify an age period when the child is probably most vulnerable to ELS. The most widely affected children were aged from two to seven years, when first separated, whereas separation in infancy or at school-age had fewer effects on the test scores, except for the verbal ability score. Our finding corresponds to our previous observation, that the highest HPA axis reactivity to stress in adults occurs within this same group of separation age [36]. These findings showing that infancy may be a period of lesser vulnerability parallels findings showing that adoption during infancy may buffer the potentially compromised cognitive development following institutionalization [42,51]. 2.5. Findings on life history Targeting solely on mental health outcomes, stress reactivity, or cognitive ability, may not effectively describe the long-term consequences of ELS. Therefore, we also examined whether the separations were associated with reproductive and marital traits among a subsample of 1704 former evacuees [52]. According to the life history theory and its variations [53,54], a risky and uncertain environment during childhood may lead to reproducing early in life in order to maximize the probability of leaving descents. Among humans, this theory is supported by fairly rich retrospective evidence associating general childhood family adversities, or the father's absence, with an earlier onset of menarche [55]. Among the few existing prospective studies, a recent large-scale one showed that children who were adopted in Denmark had a 10–20-times risk for developing a precocious puberty compared to inhabitants of Danish origin [56]. While most of the existing evidence points to earlier rather than later pubertal development, there are data from the former Yugoslavia [57], suggesting delayed pubertal development in times of the war, at least in girls exposed to stressful conditions during or shortly before their menarcheal age. Our aim was to test whether a separation in childhood was associated with reproductive traits later in life, measured by age at onset of menarche. We also explored the associations between a separation and age at first childbirth, number of children by late adulthood and their interbirth intervals, all issues which have not been prospectively tested against ELS in an epidemiological cohort [52]. In accordance with earlier studies, we found that the separated women had an earlier onset of menarche than non-separated women, independent of the year of birth, mothers' age at menarche, childhood SES, and BMI at age 7 [52]. Compared to the non-separated girls, the separated girls were 2.1 times more likely to have their menarche before or at the age of 12 than after the age of 13. An adjustment for general parental quality during, measured by a retrospective report childhood did not affect the results, further emphasizing the role of separation in explaining the results. We also found that the separated women were 2.3-times more likely to have four or more children, and 1.9-times more likely to have 3 children, than to have a single child, when compared to non-separated. The findings concerned also men:
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relative to non-separated, the separated men had their first child at a younger age, and subsequent children at shorter interbirth intervals. Based on these observations, we hypothesized that a traumatic experience may lead to a need to start a family at an earlier age in order to overcome the instability derived from the ELS. Even though the effects were relatively weak, they were theoretically-based and delineated a consistent tendency to maximize early reproduction in uncertain times, such as following ELS. In agreement with recent theorizing [53], instead of emphasizing non-optimal, development disruptions, the results concerning family development may challenge to put more emphasis on considering whether these processes function as adaptive life-solutions and coping processes following ELS. 2.6. Findings on inter-generational social mobility Inter-generational social mobility refers to transition of an individual from the parental social position to another social position in adult life. Socioeconomic position (SEP) and inter-generational social mobility are known to be powerful determinants of health, illness, and mortality. However, relative to the wealth of studies showing how SEP may function either as the source or the consequence of health inequality [58–62]; far less attention has been paid to the early life determinants of adult SEP and inter-generational social mobility. On our recent study [63], we explored whether ELS plays a role in these processes. This life-course study, spanning from birth across the entire work career in adulthood, showed that ELS is associated with socioeconomic disadvantage in adult life. Firstly, the separated attained a lower SEP in adulthood, as indicated by their own highest attained occupational status, educational level and taxable incomes, compared to the nonseparated. These associations persisted after controlling for SES in childhood, sex, year of birth, and birth order. Secondly, we found that the inter-generational social mobility was associated with the separation. Compared to the non-separated participants, the separated participants whose fathers had a manual worker occupation were less likely to be upwardly mobile, and those who had fathers in junior clerical and senior clerical occupations were more likely to be downwardly mobile. The income trajectories across the working career in adulthood, from year 1970 to year 2000, showed that the differences between the separated and non-separated participants were evident throughout adulthood, such that the group differences grew larger with years passing by, with the separated displaying a decrease in the taxable incomes. When stratified according to the initial childhood SES, the difference was most marked among participants in the lowest SES. However, also separated participants with fathers in junior and senior clerical occupations had different income trajectories; whereas in the first 15 years there were no marked differences, the separated having even higher incomes in the highest childhood SEP group, the income differences enlarged thereafter in favour of the non-separated. 3. General comments As summarized [64], the major challenges in human studies on ELS are to get as close as possible to experimental conditions, and to obtain more information on the timing of trauma. Our study in the HBSC unique prospective setting, of which approximately 14%were exposed to a specific form of ELS, parental separation, has allowed us to overcome some of the challenges relating to human studies on ELS. Even contemporary child mental health professionals in Finland advocated the evacuations, creating the sense that this was an opportunity for children, as Finnish child psychiatrist T. Brander pertinently remarked in 1943 [65, p. 314]: “Not a single case has come to my attention in which a child suffered psychological injury from this voluntary evacuation. Quite the contrary: such a stay proved to be an instructive and refreshing experience, from which the children returned with heightened
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vitality. This was due to the excellent care and attention bestowed on our children by our western neighbors”. These kinds of exceptional conditions are particularly significant to potential natural experiments because the confounders are assumed to be randomly distributed across the groups under investigation. We have previously argued that the likelihood of a Finnish child being evacuated was to some extent random, influenced by an unpredictable interplay between political and intrafamilial factors, such as the parents generally choosing to send only one or some children away. However, several methodological considerations should be taken account when interpreting the findings. In the studies among subsamples of the HBCS, the differences in the socioeconomic background of the separated and non-separated were not statistically significant. However, in studies involving more subjects, we observed a statistically significant difference in childhood SES: the separated originated more frequently from lower socioeconomic background. Although we have adjusted for childhood SES in all our studies, the role of childhood SES on later outcomes may have been more complex, thus acting as a potential confounder in our studies. On the other hand, when we examined the role of ELS in later psychiatric morbidity and mortality, it was especially those participants who originated from upper socioeconomic position that were in increased risk for later psychiatric disorders, whereas the temporary separations did not add to the risk otherwise associated with a lower childhood socioeconomic background. In this sense, preponderance of separation in the lowest category of childhood SES may have even masked the effects of ELS in our studies. In addition, our findings suggested that an upper childhood socioeconomic background may not buffer from severe ELS, such as that arising from temporary separations from parents. Another challenge in the longitudinal studies is the sampling bias. This kind of sampling bias concerned only these two studies based on voluntary participation. Those who responded to the depression questionnaire may have been healthier than those who did not, and those who attended the stressful stress test may have been more adventurous and less depressed than those who refused. A second source of sampling bias is related to the migration processes and childhood mortality, thus concerning all our studies. Approximately 11%of the separated were adopted in Sweden as child. However, a previous study [66] found no significant differences in mental health status between the adopted and returned former child evacuees. In addition to adoptions, the migration processes between Sweden and Finland have been relatively complex, some adopted children moving back to Finland as they grew up, and some former evacuees moving back to Sweden as young adults. Noteworthy, the emigration in adulthood was more likely for former child evacuees than for non-separated in the HBCS [23]. The mortality of evacuated children was 0.6%over the whole evacuation period (mean: 2.1 years), slightly lower than the mortality among Finnish children aged 1–9 years, which ranged annually from 0.4%to 0.5%during 1941–1945 [20].We also acknowledge that the parents may have generally chosen the weakest child(ren), causing potential bias. However, the original governmental policy aimed at excluding unhealthy children. Later in the war, sick children (11%of registered evacuations, 3.5%mortality) were also considered eligible for evacuation [20]. Finally, we are aware that evacuated children may have experienced other adversities during their foreign stay, making it difficult to isolate the effect of separation from other influences. However, we definitely know that the children lost their secure base with the unpredictable evacuation and, thus, also lost the parental assistance needed in regulating emotions, especially under serious stress. As a subjective case report describes [67], the separation trauma evoked both dissociative memory function and uncontrollable anxiety, which characterized individual emotion regulation even 50 years after evacuation. In conclusion, our study presents evidence of long-term disadvantage for physiology, psychology and mental health following experience of
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ELS. Although the historical circumstances in this study were particular, the developmental significance of ELS is not bound to this study. According to data reported by the United Nations Refugee Agency (UNHCR) in 2008, there were 42 million displaced individuals worldwide, including 15.2 refugees, of which 44%are children (http://www. unhcr.org/4a375c426.html). Even without displacement, an experience of ELS for various reasons, parental loss or family disruption, child abuse and neglect, traumatizing events, illness, poverty, institutionalization, or war concerns children everywhere in the contemporary world. References [1] Alastalo H, Räikkönen K, Pesonen AK, Osmond C, Barker DJ, Kajantie E, et al. Cardiovascular health of Finnish war evacuees 60 years later. Ann Med 2009;41: 66–72. [2] Danese A, Moffitt TE, Pariante CM, Ambler A, Poulton R, Caspi A. Elevated inflammation levels in depressed adults with a history of childhood maltreatment. Arch Gen Psychiatry 2008;65:409–15. 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