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Sleep's contribution to affective regulation is insufficiently understood. Previous human research has focused on memorizing or rating affective pictures and less on physiological affective responsivity. This may result in overlapping definitions of affective and declarative memories and inconsistent deductions for how rapid eye movement sleep (REMS) and slow-wave sleep (SWS) are involved. Literature associates REMS theta (4-8 Hz) activity with emotional memory processing, but its contribution to social stress habituation is unknown. Applying selective sleep stage suppression and oscillatory analyses, we investigated how sleep modulated affective adaptation toward social stress and retention of neutral declarative memories. Native Finnish participants ( N  = 29; age, M  = 25.8 years) were allocated to REMS or SWS suppression conditions. We measured physiological (skin conductance response, SCR) and subjective stress response and declarative memory retrieval thrice: before laboratory night, the next morning, and after 3 d. Linear mixed models were applied to test the effects of condition and sleep parameters on emotional responsivity and memory retrieval. Greater overnight increase in SCR toward the stressor emerged after suppressed SWS (intact REMS) relative to suppressed REMS (20.1% vs 6.1%; p  = 0.016). The overnight SCR increase was positively associated with accumulated REMS theta energy irrespective of the condition ( r  = 0.601; p  = 0.002). Subjectively rated affective response and declarative memory recall were comparable between the conditions. The contributions of REMS and SWS to habituation of social stress are distinct. REMS theta activity proposedly facilitates the consolidation of autonomic affective responses. Declarative memory consolidation may not have greater dependence on intact SWS relative to intact REMS., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Halonen et al.)

Early life stress (ELS) may increase the risk of anxiety throughout the life course. Whether this effect extends to late adulthood is poorly known. In our study comprising 1872 participants from the Helsinki Birth Cohort Study born in 1934-1944, we investigated the association of various forms of ELS and their accumulation with self-reported anxiety symptoms at the age of 65-77 years. Data on childhood socioeconomic status and separation from parents were based on national registers for all participants. Information on self-reported emotional and physical trauma, parental divorce, and death of a family member in childhood was obtained from 1277 participants. We found that experiencing emotional trauma, physical trauma, and low socioeconomic status in childhood were associated with increased anxiety symptoms in late adulthood [B = 0.44 (95% CI = 0.31-0.58); B = 0.33 (95% CI = 0.20-0.46); B = 0.10 (95% CI = 0.01-0.19), respectively]. These associations remained significant even after controlling for other forms of ELS. Accumulation of early life stress also increased the levels of late-adulthood anxiety symptoms and the risk of anxiety regarded as clinically significant. Screening for potentially stressful childhood experiences in elderly populations may help identifying individuals with increased anxiety symptoms and planning preventive and therapeutic interventions for those exposed to ELS.

Background: Evidence suggests that early life stress (ELS) may extend its effect into adulthood and predispose an individual to adverse health outcomes. We investigated whether wartime parental separation, an indicator of severe ELS, would be associated with frailty in old age., Methods: Of the 972 participants belonging to the present sub-study of the Helsinki Birth Cohort Study, 117 (12.0%) had been evacuated abroad unaccompanied by their parents in childhood during World War II. Frailty was assessed at a mean age of 71 years according to Fried's criteria., Results: Thirteen frail men (4 separated and 9 non-separated) and 20 frail women (2 separated and 18 non-separated) were identified. Compared to the non-separated men, men who had been separated had an increased relative risk ratio (RRR) of frailty (age-adjusted RRR 3.93, 95% CI 1.02, 15.11) that persisted after adjusting for several confounders. No associations were observed among women (RRR 0.62; 95% CI 0.13, 2.94)., Conclusions: These preliminary results suggest that ELS might extend its effects not just into adulthood but also into old age, and secondly, that men may be more vulnerable to the long-term effects of ELS.

Objective: Adults born preterm at very low birthweight (VLBW; ≤ 1500 g) have high levels of cardiovascular risk factors and altered responses to psychosocial stress including higher blood pressure and lower cortisol. Our aim was to investigate adrenalin (A), noradrenalin (NA) and heart rate (HR) responses to psychosocial stress in adults born preterm at VLBW., Design and Participants: We studied 50 young adults, aged 19-27 years, born at VLBW and 39 term-born controls, group-matched for age, sex and birth hospital. They underwent a standardized psychosocial stress test, the Trier Social Stress Test (TSST)., Measurements: During TSST, A, NA (baseline and 0, 10 and 90 min after stress) and HR were measured. Data were analysed with mixed-effects and linear regression models, adjusted for age, sex, body mass index, hormonal contraception, time of day and highest parental educational attainment., Results: Baseline concentrations, peak after stress, increments and area under the curve for A and NA were similar in VLBW and control groups. In women, NA concentrations were 27.7% lower (95% CI; 3.1-52.2) in VLBW compared with control women; in men, there was no significant difference. A concentrations were similar for VLBW and control groups in both sexes. Mean HR at baseline, task and HR reactivity was also similar in VLBW and control groups., Conclusions: Very low-birthweight women seem to have a lower NA response to stress compared with term-born peers. If replicated, this could be a protective characteristic for cardiovascular diseases., (© 2014 John Wiley & Sons Ltd.)

Early life stress (ELS) poses a risk for mental disorders and aging-related diseases. Accelerated biological aging, reflected in shorter leukocyte telomere length (LTL), may underlie these risks. We examined whether objectively recorded ELS and retrospectively self-reported traumatic experiences across the lifespan are associated with LTL in later adulthood. Of 1486 participants, 215 had been exposed to ELS, namely to temporary separation from both parents in childhood. Participants self-reported emotionally or physically traumatic experiences across the lifespan at a mean age of 63.2 years. LTL was measured using a quantitative PCR method at a mean age of 61.5 years. Separation or self-reported traumatic experiences were not associated with LTL. However, separated participants who self-reported traumatic experiences had shorter LTL. Our results suggest that while ELS or self-reported traumatic experiences are not per se associated with LTL measured decades later, ELS may in combination with self-reported traumatic events be associated with accelerated biological aging., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Young adults born preterm at very low birth weight (VLBW, ≤1500 g) have higher levels of cardiovascular risk factors, including impaired glucose regulation, than their term-born peers. This could be mediated through altered hypothalamic-pituitary-adrenal axis (HPAA) response to stress., Objective: To compare HPAA, glucose and insulin responses provoked by psychosocial stress in VLBW subjects versus a comparison group of term-born controls., Design and Participants: We studied 54 unimpaired young adults, aged 19-27 years, born at VLBW and a comparison group of 40 adults born at term, group-matched for age, sex and birth hospital, from one regional centre in southern Finland. The participants underwent a standardized psychosocial stress test (Trier Social Stress Test, TSST)., Measurements: In conjunction with TSST, we measured salivary cortisol, plasma ACTH, cortisol, glucose and insulin. Data were analysed with mixed-effects model and multiple linear regression analyses., Results: Baseline concentrations for cortisol, ACTH, insulin and glucose were similar in VLBW and comparison groups. During TSST, analysed with mixed-effects model, overall concentrations of plasma cortisol were 17·2% lower (95% CI; 3·5 to 28·9) in the VLBW group. The VLBW group also had lower salivary (P = 0·04) and plasma cortisol (P = 0·02) responses to TSST. Insulin and glucose concentrations correlated with changes in cortisol concentrations. Accordingly, VLBW subjects had 26·5% lower increment in insulin (95% CI; 9·8-40·1). Analyses were adjusted for age, sex, body mass index, hormonal contraception, menstrual cycle phase, time of day and parental education., Conclusions: VLBW adults have lower HPAA responses to psychosocial stress than term-born controls. This is accompanied by a lower insulin response., (© 2013 John Wiley & Sons Ltd.)

Objective: To assess the associations of sleep problems with 24-hour ambulatory blood pressure and cardiovascular reactivity in children., Methods: Sleep problems in 285 term-born, healthy 8-year-olds (mean [standard deviation] = 8.1 [0.3] years) were measured with a parent-rated Sleep Disturbance Scale for Children. Ambulatory blood pressure (n = 241) was measured for 24 hours (41% nonschool days) with an oscillometric device. The children (n = 274) underwent the Trier Social Stress Test for Children during which blood pressure, electrocardiography, and thoracic impedance were recorded and processed offline to give measures of cardiovascular and autonomic function., Results: No associations were found between sleep problems and 24-hour ambulatory blood pressure. Children with sleep breathing disorders (n = 5) had higher baseline sympathetic vascular activity (p = .014) and higher heart rate (p = .044) and sympathetic cardiac activity (p = .031) in reaction to stress. Children with disorders of excessive somnolence (n = 55) had higher baseline parasympathetic activity (p = .016). None of the associations remained significant after controlling for multiple testing., Conclusions: Our results suggest that in a healthy community sample of prepubertal children, sleep problems are not associated with an unhealthy cardiovascular phenotype at this age. However, associations may be underestimated because of the low prevalence of sleep breathing disorders in this sample and may not generalize to older populations.

Background: 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., Methods: 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., Results: 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., Conclusion: 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.

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Context: Children who undertake more physical activity (PA) not only have more optimal physical health but also enjoy better mental health. However, the pathways by which PA affects well-being remain unclear., Objective: To address this question, we examined whether objectively measured daytime PA was associated with diurnal hypothalamic-pituitary-adrenocortical axis (HPAA) activity and HPAA responses to psychosocial stress., Design and Setting: We conducted a cross-sectional study in a birth cohort in Helsinki, Finland., Participants: We studied 258 8-year-old children., Main Outcome Measures: PA was assessed with wrist-worn accelerometers. Overall PA and percentage of time spent in vigorous PA (VPA) were categorized by sex into thirds. Salivary cortisol was measured diurnally and in response to the Trier Social Stress Test for Children., Results: The children in different PA groups did not show differences in diurnal salivary cortisol (P > .10 for overall PA and VPA). Children with the highest levels of overall PA or VPA showed no, or only small, increases over time in salivary cortisol after stress (P = .10 and P =.03 for time in analyses of PA and VPA, respectively), whereas children belonging to the lowest and intermediate thirds showed significant increases over time in salivary cortisol after stress (P ≤ .002 for time in the analyses of overall PA and VPA)., Conclusions: These results suggest that children with lower levels of daytime PA have higher HPAA activity in response to stress. These findings may offer insight into the pathways of PA on physical and mental well-being.

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.

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., (Copyright © 2011. Published by Elsevier Inc.)

We tested associations of diurnal hypothalamic-pituitary adrenal axis (HPAA) activity and its response to stress with behavioral symptoms of Attention Deficit Hyperactivity Disorder (ADHD) among 272 eight-year-old children. We measured their diurnal salivary cortisol and salivary cortisol responses to the Trier Social Stress Test for Children (TSST-C). Mothers rated their child's behavior with the ADHD-IV Rating Scale and the Child Behavior Checklist (CBCL). There were no significant associations between ADHD symptoms and diurnal cortisol concentrations. The boys with predominantly inattentive symptoms of ADHD (ADHD-I; scores at or above the 90th percentile) had 26% lower mean salivary cortisol levels during the TSST-C than the boys with scores below this cutoff. In the girls with symptoms of ADHD-I, initial salivary cortisol levels prior to the TSST-C were higher and fell more rapidly during and after the TSST-C, which was not seen in the remaining girls (P = 0.007 for interaction 'ADHD-I × sampling time'). Controlling for Oppositional Defiant Disorder/Conduct Disorder and Anxiety Disorder or excluding children with these comorbid problems did not substantially affect these findings. We conclude that the boys and the girls with behavioral symptoms of ADHD-I had reduced HPAA responsiveness to stress, which is also seen in people after traumatic events or with chronic stress. Their diurnal cortisol rhythm was not affected. Thus, ADHD-I may be associated with dysregulation of the HPAA or reduced engagement with stressful stimuli., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A suboptimal prenatal environment may induce permanent changes in cells, organs and physiology that alter social, emotional and cognitive functioning, and increase the risk of cardiometabolic and mental disorders in subsequent life ("developmental programming"). Although animal studies have provided a wealth of data on programming and its mechanisms, including on the role of stress and its glucocorticoid mediators, empirical evidence of these mechanisms in humans is still scanty. We review the existing human evidence on the effects of prenatal maternal stress, anxiety and depression, glucocorticoids and intake of liquorice (which inhibits the placental barrier to maternal glucocorticoids) on offspring developmental outcomes including, for instance, alterations in psychophysiological and neurocognitive functioning and mental health. This work lays the foundations for biomarker discovery and affords opportunities for prevention and interventions to ameliorate adverse outcomes in humans.

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.

Cardiovascular (CV) response to mental stress, a predictor of CV disease risk, may be determined already in utero. However, the underlying mechanisms remain unclear, and previous studies have used adult subjects and neglected CV recovery. We investigated 147 girls and 136 boys aged 8 years who underwent the Trier Social Stress Test for children to determine whether body size at birth is associated with CV activity. Blood pressure (BP), electrocardiogram and impedance-derived indices were recorded and analyzed from continuous measurements using Vasotrac APM205A and Biopac MP150 systems. Among girls, lower birth weight was associated with lower baseline systolic BP (SBP) and diastolic BP (DBP) values (1.9 mm Hg and 1.5 mm Hg per 1 s.d. birth weight for gestational age, respectively), higher SBP and DBP response to mental stress (1.6 mm Hg and 1.1 mm Hg per 1 s.d. birth weight for gestational age, respectively), slower BP recovery and overall higher cardiac sympathetic activity. In contrast, among boys lower birth weight was associated with higher baseline levels of SBP (2.1 mm Hg per 1 s.d. birth weight for gestational age) and total peripheral resistance (TPR), overall lower cardiac sympathetic activity, lower TPR response to mental stress and a more rapid BP and cardiac sympathetic recovery. In boys, the associations with baseline levels and cardiac sympathetic activity became significant only after adjusting for current body size. These sex-specific results suggest that individual differences in childhood CV response to and recovery from mental stress may have prenatal origins. This phenomenon may be important in linking smaller body size at birth to adult CV disease.

Given the ethical limitations of exposing children to experimentally manipulated adverse experiences, evidence of the effects of childhood traumas on subsequent life history are based mostly on women's retrospective reports and animal studies. Only a few prospective studies have assessed the life-long consequences of childhood trauma. We asked whether a traumatic separation from both parents during childhood is associated with reproductive and marital traits later in life, measured by age of onset of menarche, timing of menopause, period of fertile years, age at first childbirth, birth spacing, number of children, and history of divorce. We studied members of the 1934-1944 Helsinki Birth Cohort, including 396 former war evacuees from varying socioeconomic backgrounds, who were sent unaccompanied by their parents to temporary foster families in Sweden and Denmark, and 503 participants who had no separation experiences. Data on separation experiences, number of children, and divorces experienced came from national registers, and the remaining data from a survey among the participants aged 61.6 years (SD = 2.9). Former evacuees had earlier menarche, earlier first childbirth (men), more children by late adulthood (women), and shorter interbirth intervals (men), than the non-separated. A traumatic experience in childhood is associated with significant alterations in reproductive and marital traits, which characterize both women and men. The implications are relevant to the 9.2 million child refugees living throughout the world today.

Background: Studies in humans and animals have suggested intrauterine programming of hypothalamic-pituitary-adrenal axis (HPAA) function as an important mechanism in linking fetal life conditions with adult disease., Objective: Our aim was to assess how body size at birth, a marker of intrauterine conditions, is associated with hypothalamic-pituitary-adrenal axis response to psychosocial stress in late adulthood., Design and Setting: We conducted a clinical study in the Helsinki Birth Cohort., Participants: Two hundred eighty-seven men and women born between 1934 and 1944 whose birth measurements and gestational age came from hospital records participated in the study., Measurements: We measured salivary cortisol and, for 215 individuals, plasma cortisol and ACTH concentrations in conjunction with a standardized psychosocial stressor (Trier Social Stress Test)., Results: There was a linear relationship between low birth weight and low plasma ACTH but no linear relationship with cortisol. There were, however, quadratic relationships between birth weight and salivary (mixed model P = 0.001) and plasma cortisol (P = 0.005) but not with plasma ACTH (P = 0.1). The lowest peak salivary cortisol concentrations were seen in the lowest third of birth weights (adjusted for gestational age and sex): 12.9 nmol/liter (95% confidence interval of mean 11.2-15.0), compared with 17.1 nmol/liter (14.8-19.8) in the middle and 14.1 nmol/liter (12.6-15.7) in the highest third of birth weights. Corresponding figures for plasma cortisol were 418 nmol/liter (380-459), 498 nmol/liter (455-545), and 454 nmol/liter (428-482), and for plasma ACTH 8.17 pmol/liter (6.98-9.57), 12.42 pmol/liter (10.64-14.51), and 11.50 (10.06-13.14), respectively. Results for areas under the curve were similar., Conclusions: We found an inverse U-shaped relationship between birth weight and cortisol concentrations during psychosocial stress. The lowest cortisol and ACTH concentrations were seen in subjects with the lowest birth weights. These results support the hypothesis that both hyper- and hypocortisolism may be programmed during the fetal period.