Stress induces behavioral abnormalities by increasing expression of phagocytic receptor MERTK in astrocytes to promote synapse phagocytosis.

Childhood neglect and/or abuse can induce mental health conditions with unknown mechanisms. Here, we identified stress hormones as strong inducers of astrocyte-mediated synapse phagocytosis. Using in vitro, in vivo, and human brain organoid experiments, we showed that stress hormones increased the expression of the Mertk phagocytic receptor in astrocytes through glucocorticoid receptor (GR). In post-natal mice, exposure to early social deprivation (ESD) specifically activated the GR-MERTK pathway in astrocytes, but not in microglia. The excitatory post-synaptic density in cortical regions was reduced in ESD mice, and there was an increase in the astrocytic engulfment of these synapses. The loss of excitatory synapses, abnormal neuronal network activities, and behavioral abnormalities in ESD mice were largely prevented by ablating GR or MERTK in astrocytes. Our work reveals the critical roles of astrocytic GR-MERTK activation in evoking stress-induced abnormal behaviors in mice, suggesting GR-MERTK signaling as a therapeutic target for stress-induced mental health conditions.

Stressful life events and prenatal representations of the child.

Caregivers' mental representations of their children can be assessed prenatally and are prospectively associated with later caregiving quality and caregiver-child attachment. Compared to balanced, distorted or disengaged representations are linked to insecure caregiver-child attachments. The present study explored factors (i.e. stressful life experiences and positive experiences) that may be linked to risk for distorted and disengaged representations. We used a brief version of the Prenatal Working Model of the Child Interview in a sample of 298 pregnant people (ages 19 to 45 years; M = 30.83, SD = 5.00) between gestational age 11-38 weeks (M = 23.49, SD = 5.70). A greater number of stressful events across three developmental periods (i.e., lifespan, childhood, and pregnancy) were related to increased odds of distorted, compared to balanced classification. Pregnancy stress had the largest association. Positive experiences from childhood did not buffer the association between stress and representations. Findings highlight the importance of stress on prenatal representations of one's child.

Integrating the pattern of negative emotion processing and acute stress response with childhood stress among healthy young adults.

Childhood adversity might impair corticolimbic brain regions, which play a crucial role in emotion processing and the acute stress response. The dimensional model of childhood adversity proposed that deprivation and threat dimensions might associated with individuals' development through different mechanisms. However, few studies have explored the relationship between different dimensions of childhood stress, emotion processing, and acute stress reactivity despite the overlapping brain regions of the last two. With the aid of the event-related potentials technique, we explore whether negative emotion processing, which might be particularly relevant for adaptive stress responding among individuals with adverse childhood experience, mediates the relationship between dimensional childhood stress and acute stress response. Fifty-one young adults completed a free-viewing task to evaluate neural response to negative stimuli measured by late positive potential (LPP) of ERPs (Event-related potentials). On a separate day, heart rate and salivary cortisol were collected during a social-evaluative stress challenge (i.e. TSST, Trier Social Stress Test). After the TSST, the childhood trauma questionnaire was measured to indicate the level of abuse (as a proxy of threat) and neglect (as a proxy of deprivation) dimensions. Multiple linear regression and mediation analysis were used to explore the relationship among childhood stress, emotion processing, and acute stress response. Higher level of childhood abuse (but not neglect) was distinctly related to smaller LPP amplitudes to negative stimuli, as well as smaller heart rate reactivity to acute stress. For these participants, smaller LPP amplitudes were linked with smaller heart rate reactivity to acute stress. Furthermore, decreased LPP amplitudes to negative stimuli mediated the relationship between higher level of childhood abuse and blunted heart rate reactivity to stress. Consistent with the dimensional model of childhood stress, our study showed that childhood abuse is distinctly associated with neural as well as physiological response to threat. Furthermore, the blunted neural response to negative stimuli might be the underlying mechanism in which childhood abuse leads to the blunted acute stress response. Considering that all the participants are healthy in the present study, the blunted processing of negative stimuli might rather reflect adaptation instead of vulnerability, in order to prevent stress overshooting in the face of early-life threatening experiences.

Childhood stress and midlife depression in women: the influence of diet quality.

OBJECTIVE: How does diet quality (DQ) moderate associations between serious childhood stress exposures and adult depression? METHODS: We analyzed a cohort of Californian women at midlife (N=382; age 36-42). Serious childhood stress was defined as high perceived stress during childhood or adverse childhood experiences (ACEs) of physical abuse, sexual abuse, and/or household substance abuse. Women were dichotomized by current depression risk (high/low). The Healthy Eating Index (HEI)-2015 and Alternate Healthy Eating Index (AHEI)-2010 measured current DQ from 3-day food records. Interactions between childhood stress exposures and DQ indices were tested one-by-one in multivariable Poisson regression models. RESULTS: Depression risks associated with endorsing all 3 ACEs differed by HEI and AHEI scores, as did risks associated with endorsing high perceived stress, physical abuse, and sexual abuse by AHEI. Where DQ moderated stress-depression associations, predicted prevalences of high depression risk did not vary with DQ among women endorsing the particular childhood stressors. However, among non-endorsing women, predicted high depression risk prevalences were significantly lower with higher DQ compared to in their stress-exposed counterparts - e.g. at the 90th AHEI percentile, depression prevalences were ∼20% among 'non-childhood-stressed' women versus 48.8% (high perceived stress, sexual abuse), 52.0% (physical abuse), and 73.0% (3 ACEs) in 'childhood-stressed' women. CONCLUSIONS: Higher current DQ, particularly as aligned with chronic disease prevention guidelines, predicts lower depression risk in women with low childhood adversity. DQ did not buffer depression risk in women with high childhood stress. Further research is warranted to examine persistent pathways of depression risk and diet's role within.

RPS6KA5 methylation predict response to 6-week treatment for adolescent MDD patients.

OBJECTIVE: We aimed to investigate the effect of differentially methylated genes and chronic childhood stress on the development of depressive symptoms in Chinese adolescents, as well as to test whether methylation at baseline can be used as a predictor of remission at follow-up after six weeks of treatment. METHODS: After recruiting 87 MDD patients and 53 healthy controls, we compared demographic and baseline clinical characteristics. The Childhood Chronic Stress Questionnaire was used to assess stress caused by early-life events. MDD patients underwent six weeks of treatment, and response to treatment was assessed using the Beck Depression Inventory-II. In addition, four MDD patients and five controls were randomly chosen for genome-wide methylation analysis. RESULTS: The gene RPS6KA5 showed significant methylation differences between the two groups. Severity of chronic childhood stress was significantly associated with increased risk of depression in adolescents, but not with treatment response. Baseline RPS6KA5 methylation can predict remission after six weeks of treatment. We did not observe any interaction between RPS6KA5 methylation and chronic childhood stress. CONCLUSIONS: Our results suggest that RPS6KA5 methylation can be used as a predictor of response to treatment in adolescent MDD patients. Here we offer new evidence for the role of epigenetics in early response to treatment of depression. TRIAL REGISTRATION: ChiCTR, ChiCTR2000033402, 31/05/2020, http://www.chictr.org.cn/index.aspx.

Developmental Adaptation to Stress: An Evolutionary Perspective.

The assumption that early stress leads to dysregulation and impairment is widespread in developmental science and informs prevailing models (e.g., toxic stress). An alternative evolutionary-developmental approach, which complements the standard emphasis on dysregulation, proposes that early stress may prompt the development of costly but adaptive strategies that promote survival and reproduction under adverse conditions. In this review, we survey this growing theoretical and empirical literature, highlighting recent developments and outstanding questions. We review concepts of adaptive plasticity and conditional adaptation, introduce the life history framework and the adaptive calibration model, and consider how physiological stress response systems and related neuroendocrine processes may function as plasticity mechanisms. We then address the evolution of individual differences in susceptibility to the environment, which engenders systematic person-environment interactions in the effects of stress on development. Finally, we discuss stress-mediated regulation of pubertal development as a case study of how an evolutionary-developmental approach can foster theoretical integration.

Transgenerational associations between maternal childhood stress exposure and profiles of infant emotional reactivity.

Childhood exposure to stress can induce prolonged negative effects on health, which in turn confer risks for the next generation, but greater specificity is needed to inform intervention. A first step is to measure individual differences in emotional reactivity to stress early in life in ways that can account for heterogeneity in child exposure. The present study tested the hypothesis that mothers' childhood exposure to stress would be differentially associated with patterns of positive and negative emotional reactivity in their offspring, suggesting transmission of stress response across generations. Participants were 268 young mothers (age 14-23 years) followed longitudinally since childhood, and their infants aged 3-9 months. Latent class analysis of infant emotions expressed before and during the still-face paradigm yielded five subgroups that varied in valence, intensity, and reactivity. After accounting for sociodemographic factors, infant temperament, and postpartum depression, multinomial regression models showed that, relative to an emotionally regulated still-face response, infants showing low negative reactivity were more likely to have mothers exposed to childhood emotional abuse, and infants showing high and increasing negative reactivity were more likely to have mothers exposed to childhood emotional neglect. Mechanisms by which early maternal stress exposure influences emotional reactivity in offspring are discussed.

The Development of Future Orientation is Associated with Faster Decline in Hopelessness during Adolescence.

Hopelessness is implicated in multiple psychological disorders. Little is known, however, about the trajectory of hopelessness during adolescence or how emergent future orientation may influence its trajectory. Parallel process latent growth curve modelling tested whether (i) trajectories of future orientation and hopelessness and (ii) within-individual change in future orientation and hopelessness were related. The study was comprised of 472 adolescents [52% female, 47% Caucasian, 47% received free lunch] recruited at ages 12-13 who completed measures of future orientation and hopelessness at five annual assessments. The results indicate that a general decline in hopelessness across adolescence occurs quicker for those experiencing faster development of future orientation, when controlling for age, sex, low socio-economic status in addition to stressful life events in childhood and adolescence. Stressful childhood life events were associated with worse future orientation at baseline and negative life events experienced during adolescence were associated with both an increase in the trajectory of hopelessness as well as a decrease in the trajectory of future orientation. This study provides compelling evidence that the development of future orientation during adolescence is associated with a faster decline in hopelessness.

Stress in childhood, adolescence and early adulthood, and cortisol levels in older age.

The glucocorticoid hypothesis suggests that overexposure to stress may cause permanent upregulation of cortisol. Stress in youth may therefore influence cortisol levels even in older age. Using data from the 6-Day Sample, we investigated the effects of high stress in childhood, adolescence and early adulthood - as well as individual variables contributing to these measures; parental loss, social deprivation, school and home moves, illness, divorce and job instability - upon cortisol levels at age 77 years. Waking, waking +45 min (peak) and evening salivary cortisol samples were collected from 159 participants, and the 150 who were not using steroid medications were included in this study. After correcting for multiple comparisons, the only significant association was between early-adulthood job instability and later-life peak cortisol levels. After excluding participants with dementia or possible mild cognitive impairment, early-adulthood high stress showed significant associations with lower evening and mean cortisol levels, suggesting downregulation by stress, but these results did not survive correction for multiple comparisons. Overall, our results do not provide strong evidence of a relationship between stress in youth and later-life cortisol levels, but do suggest that some more long-term stressors, such as job instability, may indeed produce lasting upregulation of cortisol, persisting into the mid-to-late seventies.

Indirect effect of corticotropin-releasing hormone receptor 1 gene variation on negative emotionality and alcohol use via right ventrolateral prefrontal cortex.

Variations in the corticotropin-releasing hormone receptor 1 (CRHR1) gene have been found to interact with stress in modulating excessive alcohol consumption. However, the neural mechanisms through which CRHR1 influences this risk in humans is largely unknown. This study examined the influence of an intronic CRHR1 gene variant, rs110402, on brain responses to negative emotional words, negative emotional traits, and alcohol use in adolescents and young adults at high risk for alcoholism. Childhood stress was investigated as a potential moderator. Using functional magnetic resonance imaging, we found that a region in the right ventrolateral prefrontal cortex (rVLPFC) was more engaged during negative emotional word processing in G homozygotes than in A allele carriers (p(FWE corrected) < 0.01, N = 77). Moreover, an indirect effect of genotype on negative emotionality via rVLPFC activation (p < 0.05, N = 69) was observed, which was further moderated by childhood stress (p < 0.05, N = 63). Specifically, with low childhood stress, G homozygotes exhibited lower levels of negative emotionality associated with greater rVLPFC activation, suggesting that the rVLPFC is involved in reappraisal that neutralizes negative emotional responses. In addition, we found that genotype indirectly modulated excessive alcohol consumption (p < 0.05, N = 69). Specifically, G homozygotes showed greater rVLPFC activation and had lower levels of negative emotionality, which were associated with fewer binge-drinking days and fewer alcohol related problems. This work provides support for a model in which CRHR1 gene variation modulates the risk of problem drinking via an internalizing/negative affect pathway involving rVLPFC and reappraisal of negative emotion.

Childhood maltreatment modifies the relationship of depression with hippocampal volume.

BACKGROUND: Childhood maltreatment (CM) may modify the relationship between major depressive disorder (MDD) and hippocampal volume reduction. To disentangle the impact of MDD and CM on hippocampal volume we investigated the association between MDD and hippocampal volume in persons with and without a history of CM in two independent cohorts. METHOD: We used data of 262 participants from the Netherlands Study of Depression and Anxiety (NESDA) (mean age 37 years, 32% male) and 636 participants from the SMART-Medea study (mean age 61 years, 81% male). In both studies a 12-month diagnosis of MDD and CM were assessed using a diagnostic interview. Hippocampal volume was measured in NESDA using FreeSurfer software on 3-T magnetic resonance (MR) images and in SMART it was manually outlined on 1.5-T MR images. With analysis of covariance adjusted for intracranial volume, age, gender and lifestyle factors we estimated the effects of MDD and CM on hippocampal volume. RESULTS: In both cohorts CM was not significantly associated with hippocampal volume. After pooling the data MDD was associated with smaller hippocampal volume (B = -138.90 mm(3), p = 0.05) and the interaction between MDD and CM reached significance (p = 0.04); in participants with CM, MDD was related to smaller hippocampal volume (NESDA: B = -316.8 mm(3), p = 0.02; SMART: B = -407.6, p = 0.046), but not in participants without CM (p > 0.05). CONCLUSIONS: Our study shows that in two independent cohorts, particularly in individuals with CM, a diagnosis of MDD is related to smaller hippocampal volume. Prospective studies are needed to further determine through which mechanism CM may amplify the relationship between MDD and hippocampal volume.

Paradox and promise: research on the role of recent advances in paleodemography and paleoepidemiology to the study of "health" in Precolumbian societies.

Bioarcheology has made tremendous strides since the subdiscipline's inception, subsequent syntheses, the standardization of data collection methods, and analytical advances ranging from molecular analyses through age-estimation and biodistance. Concurrently, health and the adaptive success of past populations have remained primary concerns. However, questions are routinely raised about lesions and whether or not changing frequencies are synonymous with increases or decreases in stress, morbidity, and overall health. These include how and why healed lesions can simultaneously represent stress and survival, demanding that researchers understand how population dynamics influence skeletal sample formation. In this study, methods to analyze age- and sex-specific mortality patterns prior to, and in conjunction with, the analysis of linear enamel hypoplasias are demonstrated. Paleodemographic and paleoepidemiological models are presented for late Pre-Columbian skeletal samples from the Eastern Woodlands. Results of hazard modeling demonstrate that elevated mortality rates were commonplace during the latter half of the Mississippian period (AD 1200-1450) with reproductive-age females experiencing high age-specific risk of death attributed to the development of fortified villages and novel environments for increased pathogen loads. Corollary results are presented for the age-specificity of linear enamel hypoplasias in the central Illinois River valley. The epidemiological models demonstrate that the relationship between adult mortality and early childhood stress varied through space, culture, and time. These findings highlight the need to effectively operationalize measurements related to health and stress in past populations and support the adoption of selective mortality and heterogeneity in frailty as key concepts in bioarcheological research. Am J Phys Anthropol 155:268-280, 2014. © 2014 Wiley Periodicals, Inc.

Association between adverse childhood experiences and bodily pain in early adolescence.

We aimed to examine the relationship between lifetime exposure to adverse childhood experiences (ACEs) during the first decade of life and recent pain features reported in early adolescence. We conducted a prospective study using data from 4564 adolescent Generation XXI birth cohort participants recruited in 2005-2006. Adverse childhood experiences were reported by children at ages 10 and 13 years using a 15-item questionnaire. Recent pain features (e.g., any pain, pain sites, recurrent pain intensity, and recurrent pain duration) were measured using structured questionnaires, including the Luebeck pain screening questionnaire at age 13. Using hierarchical binary and multinomial logistic regression analyses with progressive adjustments for confounders, we estimated the associations [adjused odds ratios (aOR) with their 95% confidence intervals (95% CI)] between exposure to ACEs at 10 and pain features at 13 years. The study revealed a statistically significant association between exposure to ACEs reported at age 10 and any pain experienced at age 13 (OR = 1.09; 95% CI [1.07, 1.12]). Even after accounting for the newly reported ACEs at age 13, the association with ACEs at age 10, remained significant (aOR = 1.11 [95% CI, 1.08-1.14]). Consistent patterns were observed when the number of pain sites, recurrent pain intensity, or recurrent pain duration were used as outcome variables instead of any pain at age 13. Adverse childhood experiences occurring during the first decade of life predict the onset of pain features during early adolescence. Consequently, childhood exposure to adversity should be considered a pivotal initial exposure in a pathway leading to chronic pain later in life.

Impact of gene-by-trauma interaction in MDD-related multimorbidity clusters.

BACKGROUND: Major depressive disorder (MDD) is considerably heterogeneous in terms of comorbidities, which may hamper the disentanglement of its biological mechanism. In a previous study, we classified the lifetime trajectories of MDD-related multimorbidities into seven distinct clusters, each characterized by unique genetic and environmental risk-factor profiles. The current objective was to investigate genome-wide gene-by-environment (G × E) interactions with childhood trauma burden, within the context of these clusters. METHODS: We analyzed 77,519 participants and 6,266,189 single-nucleotide polymorphisms (SNPs) of the UK Biobank database. Childhood trauma burden was assessed using the Childhood Trauma Screener (CTS). For each cluster, Plink 2.0 was used to calculate SNP × CTS interaction effects on the participants' cluster membership probabilities. We especially focused on the effects of 31 candidate genes and associated SNPs selected from previous G × E studies for childhood maltreatment's association with depression. RESULTS: At SNP-level, only the high-multimorbidity Cluster 6 revealed a genome-wide significant SNP rs145772219. At gene-level, MPST and PRH2 were genome-wide significant for the low-multimorbidity Clusters 1 and 3, respectively. Regarding candidate SNPs for G × E interactions, individual SNP results could be replicated for specific clusters. The candidate genes CREB1, DBH, and MTHFR (Cluster 5) as well as TPH1 (Cluster 6) survived multiple testing correction. LIMITATIONS: CTS is a short retrospective self-reported measurement. Clusters could be influenced by genetics of individual disorders. CONCLUSIONS: The first G × E GWAS for MDD-related multimorbidity trajectories successfully replicated findings from previous G × E studies related to depression, and revealed risk clusters for the contribution of childhood trauma.

A history of asthma may be associated with grandparents' exposures to stress and cigarette smoking.

Introduction: Within human epidemiological studies, associations have been demonstrated between grandparental exposures during childhood and grandchildren's outcomes. A few studies have assessed whether asthma has ancestral associations with exposure to cigarette smoking, but results have been mixed so far. Material and methods: In this study we used four generations: (F0 great-grandparents, F1 grandparents, F2 parents, F3 study children) of the Avon Longitudinal Study of Parents and Children (ALSPAC) to determine whether there is evidence of associations between asthma in generations F2 or F3 and exposures to severe trauma in childhood and/or active cigarette smoking during the adolescence of grandmothers and grandfathers in generations F0 and F1 respectively, or of a history of a F0 or F1 grandmother smoking during pregnancy. Results: We have shown that: a) stress exemplified by the death of a F1 grandparent's parent during the grandparents' childhood was associated with increased risk of asthma in generation F3, especially if the grandparent involved was the paternal grandmother; b) if the grandparents of generations F0 or F1 smoked during adolescence (i.e. < 17 years), their grandchildren in generations F2 and F3 were more likely to have a history of asthma; c) paternal F1 grandmother's smoking in pregnancy was associated with her F3 grandchild's asthma at age 7; d) There were differences between the results for the grandsons and granddaughters of the paternal grandmother with exposure to smoking in adolescence and with smoking in pregnancy. e) The addition of all of the individual exposure variables to the different analyses often provided a considerable increase in goodness of fit compared with only adding demographic factors associated with asthma at P < 0.10 such as social class; this was particularly true when all four exposure variables were combined in one model, suggesting possible synergistic effects between them. Discussion: We have shown associations between all four types of exposure to the grandparents to be associated with asthma in the grandchildren, such that the results both depended on whether the male or female line was involved, and the sex of the grandchildren. It was notable that the paternal grandmother was particularly involved in many of the associations. We emphasize that these are exploratory analyses, that asthma diagnostic criteria likely changed over time and may not be consistent between generations, and that the results should be tested in other cohorts.

Adverse childhood experiences in early life increase the odds of depression among adults with multiple sclerosis.

Background: Adverse childhood experiences are demonstrated risk factors for depression, a common co-morbidity of multiple sclerosis, but are understudied among people with multiple sclerosis. Objective: Estimate the association between adverse childhood experiences and depression among 1,990 adults with multiple sclerosis. Methods: Participants were members of Kaiser Permanente Northern California from two studies between 2006 and 2021 and were diagnosed with multiple sclerosis by a neurologist. Adverse childhood experiences were assessed using two instruments, including the Behavioral Risk Factor Surveillance System. Participants self-reported ever experiencing a major depressive episode. Meta-analysis random effects models and logistic regression were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationship between adverse childhood experiences and a history of depression across study samples. Adverse childhood experiences were expressed as any/none, individual events, and counts. Models adjusted for sex, birth year, race, and ethnicity. Results: Exposure to any adverse childhood experiences increased the odds of depression in people with multiple sclerosis (OR: 1.71, 95% CI: 1.21-2.42). Several individual adverse childhood experiences were also strongly associated with depression, including "significant abuse or neglect" (OR: 2.79, 95% CI: 2.11-3.68). Conclusion: Findings suggest that adverse childhood experiences are associated with depression among people with multiple sclerosis. Screening for depression should be done regularly, especially among people with multiple sclerosis with a history of adverse childhood experiences.

Epigenetic Changes Associated with Different Types of Stressors and Suicide.

Stress is associated with various epigenetic changes. Some stress-induced epigenetic changes are highly dynamic, whereas others are associated with lasting marks on the epigenome. In our study, a comprehensive narrative review of the literature was performed by investigating the epigenetic changes that occur with acute stress, chronic stress, early childhood stress, and traumatic stress exposures, along with examining those observed in post-mortem brains or blood samples of suicide completers and attempters. In addition, the transgenerational effects of these changes are reported. For all types of stress studies examined, the genes Nr3c1, OXTR, SLC6A4, and BDNF reproducibly showed epigenetic changes, with some modifications observed to be passed down to subsequent generations following stress exposures. The aforementioned genes are known to be involved in neuronal development and hormonal regulation and are all associated with susceptibility to mental health disorders including depression, anxiety, personality disorders, and PTSD (post-traumatic stress disorder). Further research is warranted in order to determine the scope of epigenetic actionable targets in individuals suffering from the long-lasting effects of stressful experiences.

The mediating role of allostatic load in the relationship between early life adversity and cognitive function across the adult lifespan.

Early life adversity is consequential for poor cognitive health in mid to late-life. Early life adversity is associated with higher allostatic load, a biological indicator of physiological dysregulation due to cumulative wear-and-tear from chronic stress. Higher allostatic load is also associated with poorer cognitive function across the lifespan. To date, a paucity of research has examined allostatic load as a mechanism through which early life adversity impacts cognition in adulthood. Using cross-sectional data from the Midlife in the United States (MIDUS) Study, the objective of the current study was to investigate the mediating role of allostatic load in the relationship between early life adversity and cognitive performance (global cognition, episodic memory, executive function) among middle-aged and older adults without cognitive impairment (n = 1541, Mage=53 ± 12, 53% female). Early life adversity was measured retrospectively using the Childhood Trauma Questionnaire. Allostatic load was composed of 20 biomarker proxies of neuroendocrine, metabolic, inflammatory, and cardiovascular systems, stratified by sex. Cognitive performance was evaluated using a battery of standardized neuropsychological tests. Controlling for age, education, and race, allostatic load significantly mediated the relationship between early life adversity and global cognition (ß=-0.01, 95%CI [-0.01,-0.001]), and early life adversity and executive function (ß=-0.01, 95%CI [-0.01,-0.001]), but not episodic memory. Findings did not change after controlling for lifestyle behaviours and current depression. Consistent with the biopsychosocial lifespan model of cognitive aging, findings suggest that early life adversity may become biologically embedded over time to negatively impact cognitive function in later adulthood in a domain-specific manner.

ALSPAC parents' descriptions of childhood stresses in their parents and grandparents.

Background: There is evidence that childhood stresses or traumas influence individuals' descendants' health and wellbeing through epigenetic mechanisms. However, few longitudinal studies have details of such ancestral data. Methods: Nearly 7,000 parents of the original Avon Longitudinal Study of Parents and Children (ALSPAC) cohort completed questionnaires concerning their parents' and grandparents' childhoods. As part of a questionnaire validation exercise  we conducted recorded interviews with 100 of these parents. Here we describe some of the vivid accounts from these interviews of stresses encountered by the parents' ancestors. Results: The interviews provided insights into the childhoods of two previous generations of this cohort, most of whom had lived through one, if not two, World Wars. Many children were brought up, not by their parents but by relatives or acquaintances and/or left home very young to 'go into service' or start work. A few interviewees had wealthy relatives with nannies and governesses and attended expensive boarding schools but by far the most frequent accounts were of poverty, often severe, with related lack of education and illiteracy, alcoholism and violence, alongside devastating effects of the World Wars. Conclusions: Although the interviews focussed on stresses in childhood and therefore the accounts seemed somewhat negative, many interviewees described their relatives as having secure, stable childhoods. Of the many struggling families though, the predominant impression was their remarkable resilience; all went on to have children or grandchildren who are stable enough to participate for three decades, entirely altruistically, in ALSPAC.

Meta-Analysis of Direct and Indirect Effects of Father Absence on Menarcheal Timing.

Despite extensive evidence of the association between father absence and early onset of menarche, whether father absence directly accelerates the onset of menarche or the association is mediated by other negative family psychosocial processes remains unclear. Reliable theories on the basis of which father absence has been investigated also vary. Within the life history (LH) theoretical framework, we conducted a meta-analysis of studies that investigated father absence, menarcheal timing, and various family disturbances that cause stress in children. We tested the hypothesis that father absence exerts a direct effect on menarcheal timing and an indirect effect on menarcheal timing mediated by integrated childhood stress. Quantitative synthesis using a two-stage meta-analytic structural equation modeling approach was applied to test our hypothesis. Based on seven research articles (N = 4,619) that include at least one form of family stressor as well as father absence and menarcheal timing, integrated childhood stress emerged as a robust mediator of the association between father absence and early menarcheal timing, and the total effect of father absence on menarcheal timing had reduced in size after accounting for the mediating effect of childhood stress. The findings emphasize the importance of a father figure in regulating a child's LH, including menarcheal timing.