The environment and schizophrenia

Childhood adversities and psychopathological outcomes

Adverse experiences over the lifespan can increase risk for poor health outcomes, likely operating in part through accelerated biological aging. From a life course perspective, the extent to which adverse experiences in adulthood predict biological aging will vary as a function of early life adversity, yet few studies have tested this. In this cross-sectional, pre-registered study, we examined associations of early life adversity and past-year potentially traumatic events and their interaction with telomere length in a sample of racially and ethnically diverse and predominantly low-income women (n = 127). We also tested hair cortisol as a potential pathway linking early life adversity and potentially traumatic events with telomere length. Women reported on experiences of early life adversity and the number and negative impact of past-year potentially traumatic events during interviews. Buccal cells and hair samples were collected to assess telomere length and cortisol, respectively. More negative impact of past-year potentially traumatic events was associated with shorter telomere length. However, the strength of this association was conditional on early life adversity and strongest at lower levels of early life adversity. Both greater early life adversity and more negative impact of potentially traumatic events were associated with higher hair cortisol, but hair cortisol was not associated with telomere length. Results suggest that early life adversity modifies the association between subsequent trauma and telomere length and advances understanding of how lifespan adversity shapes biological aging. These findings may inform future research to examine dynamic biological processes linking lifespan adverse experiences to health using longitudinal designs.

Early life adversity (ELA) is associated with diminished social cognition in populations with a neuropsychiatric diagnosis however less is known about general populations. Examining the association between ELA and social cognition in non-clinical populations allows determinants of social cognition to be explored in the absence of psychiatric classifications. The aim of this study was to examine the association between ELA and social cognition in the general adult population. The protocol for this study was preregistered on Prospero (preregistration-ID: CRD42023433358). Four databases and reverse citation searches were performed to identify relevant articles examining the relationship between social cognitive domains and ELA. Fisher’s r-to-z transformed correlation coefficients were synthesised using inverse variance weighted random effects modelling to provide a mean effect size estimate, with 95% confidence intervals. The limited number of included studies precluded subgroup, sensitivity and publication bias analysis. 1,314 articles were identified with 20 articles representing 18 study populations meeting the inclusion criteria. There is preliminary evidence that ELA is associated with diminished theory of mind (zr = -.247, p = .002) and emotion recognition (zr = -.121, p < .001) in the general adult population. Sexual abuse as a subdomain of ELA is also associated with diminished emotion recognition (zr = -.056, p < .001). Correlational findings on the association between retrospective accounts of ELA and social cognitive deficits during adulthood suggest a continuing impact of trauma in later life. Longitudinal research is best situated to further explore causative and mediating factors underlying this relationship. These results have helped to clarify the ELA-social cognition association without potential confounds of concurrent mental health status, and, further elucidate a possible risk mechanism for functional disability.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40653-025-00724-y.

Adverse experiences during early life exert important effects on development, health, reproduction, and social bonds, with consequences often persisting across generations. A mother’s early life experiences can impact her offspring’s development through a number of pathways, such as maternal care, physiological signaling through glucocorticoids, or even intergenerational effects like epigenetic inheritance. Early life adversity in female yellow baboons (Papio cynocephalus) predicts elevated glucocorticoids, reduced sociality, shortened lifespan, and higher offspring mortality. If baboon mothers with more early life adversity, experience poorer condition and struggle to provide for their offspring, this could contribute to the persisting transgenerational effects of adversity. Here, we examined the effects of mothers’ early life adversity on their maternal effort, physiology, and offspring survivability in a population of olive baboons, Papio anubis. Mothers who experienced more adversity in their own early development exerted greater maternal effort (i.e., spent more time nursing and carrying) and had higher levels of glucocorticoid metabolites than mothers with less early life adversity. Offspring of mothers with more early life adversity had reduced survivability compared to offspring of mothers with less early life adversity. There was no evidence that high maternal social rank buffered the effects of early life adversity. Our data suggest early life experiences can have lasting consequences on maternal effort and physiology, which may function as proximate mechanisms for intergenerational effects of maternal experience. Animals exposed to early life adversity experience both immediate and lasting consequences. If early life adversity exerts developmental constraints that affect a mother’s ability to provide for her offspring, this could explain the transgenerational effects of early life adversity. In our study of wild olive baboons, we examined how a mother’s own early life adversity predicts her maternal effort (i.e., nursing and carrying time), maternal fecal glucocorticoid levels, and offspring outcomes. We found that female baboons who experienced more early life adversity had higher glucocorticoid levels during pregnancy and lactation, exerted more maternal effort, and produced offspring with higher mortality risk than females with less early life adversity. Our results suggest that female baboons with more early life adversity experience developmental constraints and struggle to invest in offspring, which likely contributes to persisting effects of early life adversity across generations.

Background: Although research suggests that early-life adversity (ELA) and cannabis use are linked, researchers have not established factors that mediate or modify this relationship. Identifying such factors could help in developing targeted interventions. We explored chronic pain as a potential mediator or moderator of this relationship. Methods: Using an online study, we collected cross-sectional data about ELA, cannabis use, and chronic pain to test whether ELA (adverse childhood experiences total score) is associated with cannabis use, and to examine pain as a potential mediator or moderator. Cannabis use was examined two ways: times used per day, and categorized as non-, some, or regular use. Chronic pain was measured as present/absent and as the number of painful body locations (0-8). Analyses used linear and multinomial regression. Results: ELA, chronic pain, and cannabis use were common among respondents. ELA was strongly associated with both measures of cannabis use. The number of painful body locations modestly mediated the association of ELA with cannabis use, reducing the magnitude of regression coefficients by about 1/7. The number of painful body locations modified the association between ELA and cannabis use (p≤0.006), while chronic pain presence/absence (a less-informative measure) had only a nonsignificant modification effect (p≥0.10). When either ELA or pain was high, the other was not associated with cannabis use; when either ELA or pain was low, more painful locations or higher ELA (respectively) was associated with more intense cannabis use. Conclusion: These exploratory findings suggest the importance of ELA and chronic pain as factors contributing to cannabis use, and of accounting for these factors in developing treatment and prevention strategies addressing cannabis use.

Do measures of healthy eating differ in survivors of early adversity?

Early life adversity (ELA) is a major risk factor for mental illness, but the neurobiological mechanisms by which ELA increases the risk for future psychopathology are still poorly understood. Brain development is particularly malleable during prenatal and early postnatal life, when complex neural circuits are being formed and refined through an interplay of excitatory and inhibitory neural input, synaptogenesis, synaptic pruning, myelination, and neurogenesis. Adversity that influences these processes during sensitive periods of development can thus have long-lasting and pervasive effects on neural circuit maturation. In this review, we will discuss clinical and preclinical evidence for the impact of ELA on neural circuit formation with a focus on the early postnatal period, and how long-lasting impairments in these circuits can affect future behavior. We provide converging evidence from human and animal studies on how ELA alters the functional development of brain regions, neural circuits, and neurotransmitter systems that are crucial for cognition and affective behavior, including the hippocampus, the hypothalamus-pituitary-adrenal (HPA) axis, neural networks of fear responses and cognition, and the serotonin (5-HT) system. We also discuss how gene-by-environment (GxE) interactions can determine individual differences in susceptibility and resilience to ELA, as well as molecular pathways by which ELA regulates neural circuit development, for which we emphasize epigenetic mechanisms. Understanding the molecular and neurobiological mechanisms underlying ELA effects on brain function and psychopathology during early postnatal sensitive periods may have great potential to advance strategies to better treat or prevent psychiatric disorders that have their origin early in life.

Background and objectivesIndividuals who experience early life adversity are at an increased risk for chronic disease later in life. Less is known about how early life factors are associated with cancer susceptibility. Here, we use a life history framework to test whether early life adversity increases the risk of breast cancer. We predict that early life adversity can shift investment in somatic maintenance and accelerate the timing of reproduction, which may mediate or interact with the risk of breast cancer.MethodologyWe use population-wide data from the Utah Population Database (UPDB) and Utah Cancer Registry, leading to 24 957 cases of women diagnosed with breast cancer spanning 20 years (1990–2010) and 124 785 age-matched controls. We generated a cumulative early life adversity summation score to evaluate the interaction (moderation) and mediation between early life adversity, reproductive history and their association with breast cancer risk.ResultsOur analyses led to three key findings: (i) more early life adversity, when considered as a main effect, accelerates the time to first birth and death, (ii) early age at first birth and high parity decreases the risk of breast cancer and (iii) we find no association between early adversity and breast cancer risk either as a main effect or in its interaction with reproductive history.Conclusion and implicationsEarly adversity elevates the risk of overall mortality through mechanisms other than breast cancer risk. This suggests early life factors can generate different effects on health. Future work should incorporate more complex view of life history patterns, including multiple life stages, when making predictions about cancer susceptibility.

Maladaptive anger and aggression are common in US military veterans and increase risk for impaired social relationships and functioning, justice-involvement and violence. Early life (before age 18) adversity predisposes veterans to later life psychopathology, though the link to increased later life anger is unclear. We analysed cross-sectional data of 158 post-9/11 veterans from the Translational Research Center for Traumatic Brain Injury and Stress Disorders study with and without a history of early life adversity (ns = 109 and 49, respectively). We explored the relationship among major clinical variables and current veteran anger (Dimensions of Anger Reactions) and whether the associations with these variables differed among participants with and without a history of retrospective self-reported early life adversity (Childhood Trauma Questionnaire). In the overall sample, posttraumatic stress disorder (PTSD) and depression severities had the strongest associations with current veteran anger (βs = 0.261 and 0.263; p-values = 0.0022 and 0.0103, respectively). In the subsample without early life adversity, only PTSD severity was significantly associated with anger (β = 0.577, p = 0.0004). In the early life adversity subsample, this strong association weakened and was no longer significant (β = 0.168, p = 0.1007); instead, anxiety and depression severities showed moderate associations with anger (βs = 0.243 and 0.287, p-values = 0.0274 and 0.0130, respectively). Findings suggest that clinicians should screen veterans with history of early life adversity for depression and anxiety when anger is present.

Associations between distinct dimensions of early life adversity and accelerated reproductive strategy among middle-aged women in China

Social anxiety disorder (SAD) is a psychiatric disorder characterized by extensive fear in social situations. Multiple genetic and environmental factors are known to contribute to its pathogenesis. One of the main environmental risk factors is early life adversity (ELA). Evidence is emerging that epigenetic mechanisms such as DNA methylation might play an important role in the biological mechanisms underlying SAD and ELA. To investigate the relationship between ELA, DNA methylation, and SAD, we performed an epigenome-wide association study for SAD and ELA examining DNA from whole blood of a cohort of 143 individuals using DNA methylation arrays. We identified two differentially methylated regions (DMRs) associated with SAD located within the genes SLC43A2 and TNXB. As this was the first epigenome-wide association study for SAD, it is worth noting that both genes have previously been associated with panic disorder. Further, we identified two DMRs associated with ELA within the SLC17A3 promoter region and the SIAH3 gene and several DMRs that were associated with the interaction of SAD and ELA. Of these, the regions within C2CD2L and MRPL28 showed the largest difference in DNA methylation. Lastly, we found that two DMRs were associated with both the severity of social anxiety and ELA, however, neither of them was found to mediate the contribution of ELA to SAD later in life. Future studies are needed to replicate our findings in independent cohorts and to investigate the biological pathways underlying these effects.

Early life adversity exposure and circulating markers of inflammation in children and adolescents: A systematic review and meta-analysis

Evidence suggests that exposure to early life adversity (ELA) programs the hypothalamic-pituitary-adrenal (HPA) axis to influence responses to later adversity and predisposes women to depression. However, few studies have examined whether ELA moderates the HPA cortisol response to adulthood adversity and depressive symptoms in pregnant women. The aims of this study were to determine (a) whether ELA, adulthood adversity, and depressive symptoms differentially predict patterns of cortisol and (b) whether ELA moderates the relationship of adulthood adversity or depressive symptoms to cortisol. This was a descriptive, cross-sectional study of pregnant women (N = 58, mean = 26.5weeks gestation). Participants completed the Stress and Adversity Inventory and Edinburgh Depression Scale and collected salivary cortisol five times per day for 3days to assess cortisol awakening response (CAR), diurnal cortisol slope, and cortisol area under the curve (AUC). ELA predicted a larger CAR, while depressive symptoms predicted a blunted CAR and higher cortisol AUC. Adulthood adversity predicted a blunted CAR and steeper diurnal slope, but only in women with high ELA. ELA also moderated the effect of depressive symptoms on diurnal slope. Early adversity and depressive symptoms appear to have significant effects on the HPA axis during pregnancy, with early adversity also moderating effects of depressive symptoms and adulthood adversity on cortisol regulation. Early adversity may be an important factor in identifying unique HPA phenotypes and risk for HPA axis dysregulation in pregnancy.

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Early life adversity is associated with both persistent disruptions in the hypothalamic-pituitary-adrenal (HPA) axis and psychiatric symptoms. Glucocorticoid receptors (GRs), which are encoded by the NR3C1 gene, bind to cortisol and other glucocorticoids to create a negative feedback loop within the HPA axis to regulate the body’s neuroendocrine response to stress. Excess methylation of a promoter sequence within NR3C1 that attenuates GR expression, however, has been associated with both early life adversity and psychopathology. As critical regulators within the HPA axis, GRs and their epigenetic regulation may mediate the link between early life adversity and the onset of psychopathology. The present review discusses this work as one mechanism by which stress may get under the skin to disrupt HPA functioning at an epigenetic level and create long-lasting vulnerabilities in the stress regulatory system that subsequently predispose individuals to psychopathology. Spanning prenatal influences to critical periods of early life and adolescence, we detail the impact that early adversity has on GR expression, physiological responses to stress, and their implications for long-term stress management. We next propose a dual transmission hypothesis regarding both genomic and non-genomic mechanisms by which chronic and acute stress propagate through numerous generations. Lastly, we outline several directions for future research, including potential reversibility of methylation patterns and its functional implications, variation in behavior determined solely by NR3C1, and consensus on which specific promoter regions should be studied.