Early Adversity Research Articles

Annual Research Review: The power of predictability - patterns of signals in early life shape neurodevelopment and mental health trajectories.

The global burden of early life adversity (ELA) is profound. The World Health Organization has estimated that ELA accounts for almost 30% of all psychiatric cases. Yet, our ability to identify which individuals exposed to ELA will develop mental illness remains poor and there is a critical need to identify underlying pathways and mechanisms. This review proposes unpredictability as an understudied aspect of ELA that is tractable and presents a conceptual model that includes biologically plausible mechanistic pathways by which unpredictability impacts the developing brain. The model is supported by a synthesis of published and new data illustrating the significant impacts of patterns of signals on child development. We begin with an overview of the existing unpredictability literature, which has focused primarily on longer patterns of unpredictability (e.g. years, months, and days). We then describe our work testing the impact of patterns of parental signals on a moment-to-moment timescale, providing evidence that patterns of these signals during sensitive windows of development influence neurocircuit formation across species and thus may be an evolutionarily conserved process that shapes the developing brain. Next, attention is drawn to emerging themes which provide a framework for future directions of research including the evaluation of functions, such as effortful control, that may be particularly vulnerable to unpredictability, sensitive periods, sex differences, cross-cultural investigations, addressing causality, and unpredictability as a pathway by which other forms of ELA impact development. Finally, we provide suggestions for prevention and intervention, including the introduction of a screening instrument for the identification of children exposed to unpredictable experiences.

Family of Origin Stress, Posttraumatic Stress Symptoms, and Resource Loss for Couples During COVID-19: A Longitudinal Analysis

Few studies have addressed the influence of mass stressors in the context of couple relationships; therefore, understanding how unique constraints and stressors related to the COVID-19 pandemic influenced mental health distress and, in turn, loss in couple relationships is valuable. Because resource loss has been defined as the primary agent of stress, examining factors that may have shaped the degree of resource loss incurred during the pandemic will be vital. Previous research implies that early life adversity may be a form of resource loss and is linked to poorer mental health and relational outcomes in adulthood. Additionally, the stress sensitization hypothesis posits that childhood adversity may prime individuals to have a lower threshold for later life stress. As such, this study was designed to examine how family of origin stress (reported at the outset of pandemic related shutdowns in the US in April 2020) associated with posttraumatic stress (PTSS) 3 months later (July 2020) to, in turn, predict variation in resource losses associated with the COVID-19 pandemic reported 3 months later (October 2020) in 535 cisgender, heterosexual couples. Findings showed that individual’s higher family of origin stress predicted higher levels of their own PTSS at wave 2, and higher PTSS at wave 2 predicted higher levels of couples’ shared resource loss at wave 3. Additionally, family of origin stress is associated with higher levels of couples’ shared experience of loss via higher levels of their own PTSS.

Antecedents of maternal pregnancy-related anxiety trajectories: The FinnBrain birth cohort study.

Little is known about the normative courses of pregnancy-related anxiety throughout pregnancy and their antecedents. We examined in a large scale pregnancy cohort which potentially distinct trajectories of pregnancy-related anxiety across pregnancy can be identified, and which factors predict these trajectories. A general sample of pregnant women (n = 2928) from the FinnBrain Birth Cohort participated in this study. Several questionnaires were filled in at 14, 24, and 34 weeks of gestation, including the pregnancy-related anxiety questionnaire-revised as main outcome. Latent Growth Mixture Modeling was applied to identify the trajectories of pregnancy-related anxiety across pregnancy, and t-tests and chi-quare tests were conducted to find antecedents of these trajectories. Two distinct trajectories were identified: (1) a low symptoms group, N = 2594 (88.6%), with lower and slightly increasing levels of pregnancy-related anxiety (2) a moderately-high symptoms group, N = 334 (11.4%) reported higher and slightly decreasing levels of anxiety. Correlates of the moderately-high anxious group included a lower monthly income, drinking alcohol or smoking in early pregnancy, more daily hassles and less joy, more early life adversities, younger age, primiparity, single parenthood, using depression medication, and having higher scores on depression and general anxiety. Although the majority of pregnant women fall within a low risk trajectory of pregnancy-related anxiety, another group with consistently higher levels of pregnancy anxiety throughout pregnancy may need more clinical attention, as their high pregnancy-related anxiety scores may indicate a risk profile that includes a variety of general and more pregnancy-specific risk factors, which together can negatively affect fetal and infant development and behavior.

How do family adversity and youth stressful experiences lead to adult economic adversity? An integration of multiple life course mechanisms

ABSTRACT The primary objective of the present study was to apply multiple life course mechanisms, drawn from the life course epidemiological perspective, to explain the long-term influence of family socioeconomic adversity and adolescent stressful life events on adult economic adversity. The study used prospective data over 13 years from 11,075 adolescents from the Adolescent to Adult Health Study (Add Health). First, we developed a comprehensive life course model by integrating causal and temporal relationships among different life course processes and pathways discussed in previous research. Specifically, the findings provided evidence for the long-term influence of family socioeconomic adversity on adult economic adversity through life-stage specific stressful life events and depressive symptoms. This connection occurred through various risk pathways such as the clustering of risk, risk cascading, and cumulative exposure. Such integrated models are well suited to investigate life course stressors and can be used as broad analytical frameworks for life course developmental studies. Thus, the present study has served substantive, illustrative, and methodological purposes. The study findings suggest that to improve adult wellbeing, programmes and policies focusing on early life adversities and stressors are important.

Impact of poverty and adversity on perceived family support in adolescence: findings from the UK Millennium Cohort Study

Emotional support from family members may have an important effect on adolescent health outcomes, and has been identified as a target for policy to protect against the impacts of poverty and other early life adversities. However, few studies have assessed the extent to which poverty and adversity themselves influence the nature of emotional support that parents can provide to adolescents. We, therefore, aimed to investigate the impact of trajectories of income poverty and family adversities, including parental mental ill health, alcohol misuse and domestic violence across childhood developmental stages on young people’s relationships with their families and perceived emotional support received. We analysed longitudinal data on 10,976 children from the nationally representative UK Millennium Cohort study. Exposure trajectories of poverty and family adversities were characterised using group-based multi-trajectory models (age 9 months–14 years). The outcomes were perceived emotional support and quality of family relationships, measured by the three-item Short Social Provisions Scale (SPS-3) and levels of parent–adolescent closeness and conflict, measured at age 14. ORs and 95% CIs were estimated using multivariable logistic regression models, adjusting for potential confounding factors. At age 14, the overall prevalence of low perceived emotional support was 13% (95% CI: 12, 14). Children of mothers with lower socioeconomic status (SES) were more likely to report low emotional support, with a clear social gradient (education—degree plus: 10.3% vs. no qualifications: 15.4%). Compared with children exposed to low levels of poverty and adversity, children in the persistent adversity trajectory groups experienced higher odds of low emotional support and low-quality parent–adolescent relationship; those exposed to both persistent poverty and poor parental mental health were particularly at increased risk of experiencing poor family relationships and low perceived emotional support (adjusted odds ratio 2·2; 95% CI 1·7–2·9). Low perceived emotional support and poor family relationships in adolescence are more prevalent among socially disadvantaged children and adolescents and those experiencing social adversity. Policies to improve levels of family support for UK adolescents should focus on improving modifiable determinants such as child poverty and family mental health.

Heightened response to positive facial cues as a potential marker of resilience following childhood adversity

ABSTRACT Background: Childhood maltreatment profoundly influences social and emotional development, increasing psychiatric risk. Alterations in the implicit processing of threat-related cues following early abuse and neglect represent a marker of mental health vulnerability. Less is known about how early adversity influences the perception of positive social cues, despite their central role in establishing and maintaining social interactions and their association with better mental health outcomes. Methods: The sample consisted of 42 children and adolescents with substantiated childhood maltreatment experiences and 32 peers (mean age 13.3), matched on age, pubertal status, gender, socioeconomic status, ethnicity, and cognitive ability. A computerised experimental task assessed the perceived emotional intensity of positive (happy) and negative (fearful) facial expressions. Mental health symptoms were measured via self- and parental reports, and perceived social support was self-reported. Results: The experience of abuse and neglect was associated with heightened perceived intensity of positive facial cues. Cross-sectional post-hoc moderation and mediation analyses, employing a model-building approach, revealed that in maltreatment-exposed participants: (i) their increased response to positive facial cues was associated with lower symptoms; (ii) the presence of social support accounted for their heightened perceived intensity of positive facial cues; (iii) the presence of social support putatively contributed to lower symptoms by increasing the perceived intensity of positive facial cues. No group differences in perceived intensity of negative expressions were observed. Conclusions: These findings provide fresh insight into how positive faces are processed following maltreatment experience in childhood. Maltreatment experience was found to be associated with heightened perceived intensity of happy faces, which in turn was associated with better mental health and greater levels of social support. This suggests that heightened saliency of positive emotions acts protectively in children with maltreatment experience.

Long-Term Impact of Early-Life Stress on Serotonin Connectivity

BackgroundChronic childhood stress is a prominent risk factor for developing affective disorders, yet mechanisms underlying this association remain unclear. Maintenance of optimal serotonin (5-HT) levels during early postnatal development is critical for the maturation of brain circuits. Understanding the long-lasting effects of early-life stress (ELS) on serotonin-modulated brain connectivity is crucial to develop treatments for affective disorders arising from childhood stress. MethodsUsing a mouse model of chronic developmental stress, we determined the long-lasting consequences of ELS on 5-HT circuits and behavior in females and males. Using FosTRAP mice, we cross-correlated regional c-Fos density to determine brain-wide functional connectivity of the raphe nucleus. We next performed in vivo fiber photometry to establish ELS-induced deficits in 5-HT dynamics and optogenetics to stimulate 5-HT release to improve behavior. ResultsAdult female and male mice exposed to ELS showed heightened anxiety-like behavior. ELS further enhanced susceptibility to acute stress by disrupting the brain-wide functional connectivity of the raphe nucleus and the activity of 5-HT neuron population, in conjunction with increased orbitofrontal cortex (OFC) activity and disrupted 5-HT release in medial OFC. Optogenetic stimulation of 5-HT terminals in the medial OFC elicited an anxiolytic effect in ELS mice in a sex-dependent manner. ConclusionsThese findings suggest a significant disruption in 5-HT–modulated brain connectivity in response to ELS, with implications for sex-dependent vulnerability. The anxiolytic effect of the raphe–medial OFC circuit stimulation has potential implications for developing targeted stimulation-based treatments for affective disorders that arise from early life adversities.

Prevalence of Technology-Facilitated Abuse Among Sexual and Gender Minority Youths

Digital communication and imaging technologies have created new opportunities for technology-facilitated abuse (TFA) and necessitate a better understanding of how and why the risk for TFA varies across different groups of youths. To compare the prevalence of TFA among youths across 5 different sexual and gender identity groups, and to identify risk factors that may explain variations in TFA risk. A US nationally representative online survey was conducted among 2639 young adults recruited from the KnowledgePanel online panel from November 19 to December 29, 2021. Individuals aged 18 to 28 years were asked retrospectively about TFA and a variety of other youth experiences in childhood (aged <18 years). Participants were asked about their sexual and gender identities, 11 types of TFA occurring before the age of 18 years, and several potential risk factors. Prevalence rates of any TFA were compared across sexual and gender identity groups, and analyses were conducted to identify risk factors that help explain group differences. Weights were developed to compensate for gender, education, race and ethnicity, household income, census region, and metropolitan status disproportions. Among the 2510 respondents (mean [SD] age, 24.8 [2.8] years) who provided gender and sexual identity information, 46.5% (95% CI, 41.9%-51.1%) were cisgender heterosexual females, 25.2% (95% CI, 21.6%-29.1%) were cisgender sexual minority females, 18.3% (95% CI, 14.4%-22.9%) were cisgender heterosexual males, 6.8% (95% CI, 4.6%-9.9%) were cisgender sexual minority males, and 3.3% (95% CI, 2.0%-5.4%) were gender minority individuals. The prevalence of TFA occurring before the age of 18 years was highest among sexual minority females (55.3%; 95% CI, 48.0%-62.4%) and gender minority individuals (53.4%; 95% CI, 33.5%-72.2%). Rates of sexting were highest among cisgender sexual minority females (38.8%; 95% CI, 19.1%-58.8%) and gender minority individuals (36.7%; 95% CI, 19.1%-58.8%) and represented the strongest risk factor for TFA exposure (odds ratio, 5.7; 95% CI, 4.0-8.0). However, it explained little variation in TFA across groups once early in-person adversity, sexual abuse, bullying, and maltreatment were taken into account. This study demonstrates the risk of TFA among sexual and gender minority youths and the need to target prevention efforts toward these vulnerable groups. In addition to strategies to reduce risky behavior, efforts to lower the risk of early sexual abuse, bullying, and maltreatment are likely to also be effective in decreasing TFA among these marginalized groups.

Atypical Interpersonal Problem-Solving and Resting-state Functional Connectivity in Adolescents with Maltreatment Experience.

Childhood maltreatment is associated with altered neurocognitive functioning, which is thought to reflect, in part, adaptation to early adverse environmental experiences. However, we continue to lack a precise mechanistic understanding linking atypical neurocognitive processing with social functioning and psychiatric outcomes following early adversity. The present work investigated interpersonal problem-solving, resting-state functional connectivity (rsFC), and mental health symptoms in adolescents with documented maltreatment experience and explored whether altered neural function contributes in part to poorer social functioning. Forty adolescents (aged 12-17) with documented experiences of abuse or neglect and a carefully matched group of 42 non-maltreated peers participated in this study that measured task-based interpersonal problem-solving skills and rsFC. Adolescents with maltreatment experience showed poorer interpersonal problem-solving performance, which partly accounted for their elevated mental health symptoms. Resting-state seed-based analyses revealed that adolescents with maltreatment experience showed a significant increase in rsFC between medial Default Mode Network (DMN) hubs, the medial prefrontal cortex (mPFC), with a posterior cluster, including the posterior cingulate cortex (PCC), precuneus (PCu), retrosplenial cortex (RSC), and lingual gyrus (LG). Moderation analyses revealed that maltreatment-related increased DMN rsFC partly accounted for poorer performance in interpersonal problem-solving. Poorer interpersonal problem-solving, partly accounted for by atypical coupling between DMN medial hubs, was associated with maltreatment exposure. Interventions tailored to enhance interpersonal problem-solving represents a promising avenue to promote resilience and reduce the likelihood of mental health disorder following maltreatment experience.

A longitudinal analysis of health inequalities from adolescence to young adulthood and their underlying causes

Research suggests that children of low-educated parents face greater health burdens during the passage from adolescence to young adulthood, as they are more likely to become low-educated themselves, establish behavioural and psychosocial disadvantages, or being exposed to unhealthy working conditions. However, studies examining the development and drivers of health inequalities during this particular life stage are limited in number and have produced varied results. This study investigates trajectories of self-rated health and overweight from 14 to 25 years of age, stratified by parental education, and explores the role of potential mediators (educational achievement, health behaviours, psychosocial factors, working conditions). We rely on prospective cohort data from the National Educational Panel Study (NEPS), a representative sample of 14,981 German ninth graders interviewed yearly from 2011 to 2021 (n = 90,096 person-years). First, we estimated random-effects growth curves for self-rated health and overweight over participants’ age and calculated the average marginal effect of high versus low parental education. Second, a series of simulation-based mediation analyses were performed to test how much of health inequalities were explained by children’s educational attainment (years of school education, years in university), health behaviours (smoking, alcohol, physical inactivity), psychosocial factors (number of grade repetitions, years in unemployment, chronic stress, self-esteem) and working conditions (physical and psychosocial job demands). We accounted for potential confounding by controlling for age, sex, migration background, residential area, household composition, and interview mode. Results show that higher parental education was related to higher self-rated health and lower probabilities of being overweight. Interaction between parental education and age indicated that, after some equalisation in late adolescence, health inequalities increased in young adulthood. Furthermore, educational attainment, health behaviours, psychosocial factors, and early-career working conditions played a significant role in mediating health inequalities. Of the variables examined, the level of school education and years spent in university were particular strong mediating factors. School education accounted for around one-third of the inequalities in self-rated health and one-fifth of the differences in overweight among individuals. Results support the idea that the transition to adulthood is a sensitive period in life and that early socio-economic adversity increases the likelihood to accumulate health disadvantages in multiple dimensions. In Germany, a country with comparatively low educational mobility, intergenerational continuities in class location seem to play a key role in the explanation of health inequalities in youth.

Cuidándome: A trauma-informed and cultural adaptation of a chronic disease self-management program for Latina immigrant survivors with a history of adverse childhood experiences and depression or anxiety symptoms.

To develop a cultural and trauma-informed mental health self-management program for immigrant Latina survivors of adverse childhood experiences with depression or anxiety symptoms. Guided by Barrera's five-stage process for cultural adaptation, we collaborated with multiple stakeholders including clinical psychologists, community health workers, and Latina immigrant women with a history of adverse childhood experiences and depression or anxiety to transform a chronic disease self-management program to be trauma informed, culturally appropriate, and focus on self-management of depression and anxiety symptoms. Adaptations included translating program materials to Spanish, education on how early life adversity and trauma may impact mental health, virtual delivery, more frequent and shorter sessions, and addition of graphics and written prompts in workbook materials. For the facilitator's manual, culturally relevant vignettes and guidance were added to guide participants through activities and adapt sessions based on participant needs. Barrera's five-stage process was useful for adapting a program to be both trauma and culturally informed for an underserved population disproportionately affected by trauma and limited access to mental health services. The adaptation demonstrated acceptability with Latina immigrant women and the promise of utilizing unlicensed personnel and technology for increasing the reach of mental health support. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Association of early life adversity with cardiovascular disease and its potential mechanisms: a narrative review.

Strong epidemiological evidence has shown that early life adversity (ELA) has a profound negative impact on health in adulthood, including an increased risk of cardiovascular disease, the leading cause of death worldwide. Here, we review cohort studies on the effects of ELA on cardiovascular outcomes and the possible underlying mechanisms. In addition, we summarize relevant studies in rodent models of ELA. This review reveals that the prevalence of ELA varies between regions, time periods, and sexes. ELA increases cardiovascular health risk behaviors, susceptibility to mental illnesses, and neuroendocrine and immune system dysfunction in humans. Rodent models of ELA have been developed and show similar cardiovascular outcomes to those in humans but cannot fully replicate all ELA subtypes. Therefore, combining cohort and rodent studies to further investigate the mechanisms underlying the association between ELA and cardiovascular diseases may be a feasible future research strategy.

Early life adversity and obesity risk in adolescence: a 9-year population-based prospective cohort study.

There are few prospective studies of factors that mediate the association between exposure to adverse childhood experiences (ACEs) and obesity in adolescence. Our aim was to address this limitation. We used prospective data from the Growing up in Ireland cohort study, with measurements at 9, 13, and 18 years old. The exposures were 14 adverse experiences before age 9. The mainoutcome was body mass index (BMI) at 18 years. Mediators were daily activity, diet quality, self-image and behavioural difficulties at 13 years. Among the 4561 adolescentsin the final cohort, 77.2% experienced any adversity, 50.5% were female and 26.7% were overweight/obese at 18 years. BMI Z was higher at ages 9 (0.54 vs 0.43, p < 0.05, 95% CI of difference: -0.22, -0.01) and 13 years (0.50 vs 0.35, p < 0.05, 95% CI of difference: -0.25, -0.06), in those exposed to an ACE, compared to those unexposed. Structural equation models revealed that behavioural difficulties (β = 0.01; 95% CI: 0.007-0.018, p < 0.001) and self-concept (β = 0.0027; 95% CI: 0.0004-0.0050, p = 0.026) indirectly mediate the association between exposure to ACEs and BMI at 18 years. The association between ACEs and BMI in adolescence is mediated by behavioural difficulties and self-concept. In a previous study, we found modest associations between exposure to a range of adverse childhood experiences and weight gain at 13 years of age. The strength of the association between adverse childhood experiences and weight gain was lower at 18 years of age compared to the association observed at 13 years and was no longer significant after controlling for confounding and including possible mediators. The association between adverse childhood experiences and BMI in adolescence is indirectlymediated by behavioural difficulties and self-concept.

Harsh, unpredictable childhood environments are associated with inferior frontal gyrus connectivity and binge eating tendencies in late adolescents

Harsh, unpredictable childhood environments (HUCE) are associated with obesity older in life, but knowledge of how HUCE affect binge eating tendencies is lacking. Five hundred and one late adolescents aged 16–22 were recruited to finish resting state functional magnetic resonance imaging scan, behavioral measures including retrospective recall of childhood environmental harshness and unpredictability, binge eating tendencies and demographics. Three hundred and seventy-six of participants further completed the computerized visual probe task designed to evaluate attentional engagement towards high and low calorie food. As right inferior frontal gyrus (IFG) was the key nodes that related to both early life adversity and binge eating tendencies, it was treated as the interest region in the dynamic functional connectivity analyses. Results found that HUCE are associated with significant but modest decreases in connectivity of right inferior frontal gyrus (IFG)– bilateral medial frontal gyrus, right IFG – bilateral inferior parietal lobule (IPL), and right IFG – left superior frontal gyrus connectivity, as well as attentional engagement to high-calorie food and binge eating tendencies. A machine-learning method named linear support vector regression (SVR) and leave one out cross-validation (LOOCV) procedure used to examine the robustness of the brain-behavior relationship further confirm the findings. Mediation analyses suggested that right IFG – left IPL connectivity mediates the association of HUCE and binge eating tendencies. Findings suggest right IFG – left IPL connectivity may serve as a crucial neurobiological underpinning of HUCE to regulate binge eating behaviors. As such, these results contribute to a novel perspective and hypotheses in elucidating developmental neuro-mechanisms related to binge eating.

Major stress in early childhood strengthens the association between peripheral inflammatory activity and corticostriatal responsivity to reward

BackgroundSevere, chronic stress during childhood accentuates vulnerability to mental and physical health problems across the lifespan. To explain this phenomenon, the neuroimmune network hypothesis proposes that childhood stressors amplify signaling between peripheral inflammatory cells and developing brain circuits that support processing of rewards and threats. Here, we conducted a preliminary test of the basic premises of this hypothesis. Methods180 adolescents (mean age = 19.1 years; 68.9 % female) with diverse racial and ethnic identities (56.1 % White; 28.3 % Hispanic; 26.1 % Asian) participated. The Childhood Trauma Interview was administered to quantify early adversity. Five inflammatory biomarkers were assayed in antecubital blood — C-reactive protein, tumor necrosis factor-a, and interleukins-6, −8, and −10 — and were averaged to form a composite score. Participants also completed a functional MRI task to measure corticostriatal responsivity to the anticipation and acquisition of monetary rewards. ResultsStress exposure and corticostriatal responsivity interacted statistically to predict the inflammation composite. Among participants who experienced major stressors in the first decade of life, higher inflammatory activity covaried with lower corticostriatal responsivity during acquisition of monetary rewards. This relationship was specific to participants who experienced major stress in early childhood, implying a sensitive period for exposure, and were evident in both the orbitofrontal cortex and the ventral striatum, suggesting the broad involvement of corticostriatal regions. The findings were independent of participants’ age, sex, racial and ethnic identity, family income, and depressive symptoms. ConclusionsCollectively, the results are consistent with hypotheses suggesting that major stress in childhood alters brain-immune signaling.

Relationships between early life adversity and depressive symptoms in adolescents: a network analysis

Relationships between early life adversity and depressive symptoms in adolescents: a network analysis

The Continuity of Adversity: Negative Emotionality Links Early Life Adversity With Adult Stressful Life Events

Adversity that exhibits continuity across the life course has long-term detrimental effects on physical and mental health. Using 920 participants from the Dunedin Study, we tested the following hypotheses: (a) Children (ages 3–15) who experienced adversity would also tend to experience adversity in adulthood (ages 32–45), and (2) interim personality traits in young adulthood (ages 18–26) would help account for this longitudinal association. Children who experienced more adversity tended to also experience more stressful life events as adults, β = 0.11, 95% confidence interval [CI] = [0.04, 0.18], p = .002. Negative emotionality—particularly its subfacet alienation, characterized by mistrust of others—helped explain this childhood-to-midlife association (indirect effect: β = 0.06, 95% CI = [0.04, 0.09], p &lt; .001). Results were robust to adjustment for sex, socioeconomic origins, childhood IQ, preschool temperament, and other young-adult personality traits. Prevention of early life adversity and treatment of young-adult negative emotionality may reduce vulnerability to later life stress and thereby promote the health of aging adults.

Embers of the Past: Early Childhood Traumas Interact with Variation in P2RX7 Gene Implicated in Neuroinflammation on Markers of Current Suicide Risk.

Both early childhood traumatic experiences and current stress increase the risk of suicidal behaviour, in which immune activation might play a role. Previous research suggests an association between mood disorders and P2RX7 gene encoding P2X7 receptors, which stimulate neuroinflammation. We investigated the effect of P2RX7 variation in interaction with early childhood adversities and traumas and recent stressors on lifetime suicide attempts and current suicide risk markers. Overall, 1644 participants completed questionnaires assessing childhood adversities, recent negative life events, and provided information about previous suicide attempts and current suicide risk-related markers, including thoughts of ending their life, death, and hopelessness. Subjects were genotyped for 681 SNPs in the P2RX7 gene, 335 of which passed quality control and were entered into logistic and linear regression models, followed by a clumping procedure to identify clumps of SNPs with a significant main and interaction effect. We identified two significant clumps with a main effect on current suicidal ideation with top SNPs rs641940 and rs1653613. In interaction with childhood trauma, we identified a clump with top SNP psy_rs11615992 and another clump on hopelessness containing rs78473339 as index SNP. Our results suggest that P2RX7 variation may mediate the effect of early childhood adversities and traumas on later emergence of suicide risk.

Early life adversity in primates: Behavioral, endocrine, and neural effects

BackgroundEvidence suggests that early life adversity is associated with maladaptive behaviors and is commonly an antecedent of stress-related psychopathology. This is particularly relevant to rearing in primate species as infant primates depend on prolonged, nurturant rearing by caregivers for normal development. To further understand the consequences of early life rearing adversity, and the relation among alterations in behavior, physiology and brain function, we assessed young monkeys that had experienced maternal separation followed by peer rearing with behavioral, endocrine and multimodal neuroimaging measures. Methods50 young rhesus monkeys were studied, half of which were rejected by their mothers and peer reared, and the other half were reared by their mothers. Assessments were performed at approximately 1.8 years of age and included: threat related behavioral and cortisol responses, cerebrospinal fluid (CSF) measurements of oxytocin and corticotropin releasing hormone (CRH), and multimodal neuroimaging measures (anatomical scans, resting functional connectivity, diffusion tensor imaging, and threat-related regional glucose metabolism). ResultsThe results demonstrated alterations across behavioral, endocrine, and neuroimaging measures in young monkeys that were reared without their mothers. At a behavioral level in response to a potential threat, peer reared animals engaged in significantly less freezing behavior (p = 0.022) along with increased self-directed behaviors (p < 0.012). Levels of oxytocin in the CSF, but not plasma, were significantly reduced in the peer reared animals (p = 0.019). No differences in plasma cortisol or CSF CRH were observed. Diffusion tensor imaging revealed significantly decreased white matter density across the brain. Exploratory correlational and permutation analyses suggest that the impact of peer rearing on behavior, endocrine and brain structural alterations are mediated by separate parallel mechanisms. ConclusionsTaken together, these results demonstrate in NHPs the importance of maternal rearing on the development of brain, behavior and hormonal systems that are linked to social functioning and adaptive responses. The findings suggest that the effects of maternal deprivation are mediated via multiple independent pathways which may account for the heterogeneity in behavioral and biological alterations observed in individuals that have experienced this early life adversity.

Behavior, synaptic mitochondria, and microglia are differentially impacted by chronic adolescent stress and repeated endotoxin exposure in male and female rats

Early life adversity and chronic inflammation have both been associated with cognitive impairment and neural compromise. In this study, we investigated the interactions between a history of chronic adolescent stress (CAS) and repeated endotoxin exposure on behavior, synaptic mitochondria, and microglia in adult male and female Wistar rats. Adult rats from chronic stress and control conditions were exposed to either repeated endotoxin (lipopolysaccharide; LPS) or saline injections every 3 days for 9 weeks. In both sexes, repeated LPS, regardless of stress history, impaired working memory in the Y maze. Regarding spatial memory, LPS impaired function for females; whereas, CAS altered function in males. Although males had an increase in anxiety-like behavior shortly after CAS, there were no long-term effects on anxiety-like behavior or social interaction observed in males or females. Stress did not alter synaptic mitochondrial function in either sex. Repeated LPS altered synaptic mitochondrial function such that ATP production was increased in females only. There were no observed increases in IBA-1 positive cells within the hippocampus for either sex. However, LPS and CAS altered microglia morphology in females. Impact of repeated LPS was evident at the terminal endpoint with increased spleen weight in both sexes and decreased adrenal weight in males only. Circulating cytokines were not impacted by repeated LPS at the terminal endpoint, but evidence of CAS effects on cytokines in females were evident. These data suggest a long-term impact of chronic stress and an impact of repeated endotoxin challenge in adulthood; however, not all physiological and behavioral metrics examined were impacted by the paradigm employed in this study and the two environmental challenges rarely interacted.