A perspective on epigenomic aging processes in the human brain and their plasticity in patients with mental disorders - a systematic review.

The debate surrounding nature versus nurture remains a central question in neuroscience, psychology, and in psychiatry, holding implications for both aging processes and the etiology of mental illness. Epigenetics can serve as a bridge between genetic predisposition and environmental influences, thus offering a potential avenue for addressing these questions. Epigenetic clocks, in particular, offer a theoretical framework for measuring biological age based on DNA methylation signatures, enabling the identification of disparities between biological and chronological age. This structured review seeks to consolidate current knowledge regarding the relationship between mental disorders and epigenetic age within the brain. Through a comprehensive literature search encompassing databases such as EBSCO, PubMed, and ClinicalTrials.gov, relevant studies were identified and analyzed. Studies that met inclusion criteria were scrutinized, focusing on those with large sample sizes, analyses of both brain tissue and blood samples, investigation of frontal cortex markers, and a specific emphasis on schizophrenia and depressive disorders. Our review revealed a paucity of significant findings, yet notable insights emerged from studies meeting specific criteria. Studies characterized by extensive sample sizes, analysis of brain tissue and blood samples, assessment of frontal cortex markers, and a focus on schizophrenia and depressive disorders yielded particularly noteworthy results. Despite the limited number of significant findings, these studies shed light on the complex interplay between epigenetic aging and mental illness. While the current body of literature on epigenetic aging in mental disorders presents limited significant findings, it underscores the importance of further research in this area. Future studies should prioritize large sample sizes, comprehensive analyses of brain tissue and blood samples, exploration of specific brain regions such as the frontal cortex, and a focus on key mental disorders. Such endeavors will contribute to a deeper understanding of the relationship between epigenetic aging and mental illness, potentially informing novel diagnostic and therapeutic approaches.

Temporal and spatial evolution of net primary productivity in the Three-River Headwaters Region under phenological changes and anthropogenic influence.

Understanding the spatiotemporal changes in net primary productivity (NPP) and the driving factors behind these changes in climate-vulnerable regions is crucial for ecological conservation. This study simulates the actual NPP (NPPA) and climate potential NPP (NPPC) in the Three-River Headwaters Region from 2000 to 2020. The Theil-Sen Median method and Mann-Kendall mutation analyses are employed to explore their spatiotemporal variation patterns, while geographic weighted regression and machine learning are used to investigate the influence of anthropogenic activities and climatic factors on NPPA, the results indicate that the average NPPA across the entire region over multiple years is 382.506 g C m - 2 yr - 1 , which is 0.132 times the average annual NPPC over the past 21 years, showing an overall distribution pattern of low in the northwest and high in the southeast. The annual increase in NPPA from 2000 to 2020 is approximately 1.034 g C m - 2 yr - 1 . The source region of the Yangtze River shows the largest improvement in vegetation, with 74.1% of the area showing improvement. Between 2002 and 2003, the annual NPPA in the Three-River Headwaters Region experienced a sudden change, lagging behind the NPPC change by 1 year, and after 2005, the upward trend in NPPA became more pronounced. The impact of anthropogenic activities on NPPA shifted from positive to negative to positive from 2000 to 2020, with significant impact areas mainly concentrated in the northeast and a few areas in the central and southern parts. The proportion of areas with extremely significant impact increased from 1.9% in 2000 to 3.7% in 2020. Over the past 21 years, the main factors influencing NPPA changes in the Three-River Headwaters Region have been soil moisture and precipitation, with the influence of different climate factors on NPP changing over time. Additionally, NPP is more sensitive to changes in altitude in low-altitude areas. This study can provide more accurate theoretical support for ecological environment assessment and subsequent protection efforts in the Three-River Headwaters Region.

Environmental and psychopathological predictors of clinical high-risk of psychosis in adolescence.

OBJECTIVES: Clinical high-risk psychosis (CHRp) samples can be heterogeneous, consisting essentially of people with not only psychotic-like experiences but also nonspecific symptoms that may reflect common mental disorders such as depression, anxiety, or substance abuse pathologies. Few studies have attempted to analyze and understand psychosis risk in relation to both environmental (ER) and psychopathological risk (PsR) factors. This study aimed to determine the clinical risk of psychosis in adolescents. METHODS: A representative sample of 1824 Spanish adolescents from the general population was evaluated using different scales to thoroughly examine the possible interaction of CHRp with various ER and PsR factors. Partial correlations were calculated to assess the relationships between the variables. A series of hierarchical linear regression models were then used to obtain a CHRp predictor model. RESULTS: The CHRp predictor model indicated that PsR was the most significant determining factor, explaining 22% of the total associated variance of CHRp. However, the ER factor also emerged as a significant predictor of high-risk psychosis (accounting for 9% of the variance). CONCLUSIONS: A predictive model for CHRp in adolescents was found, in which common psychological problems were presented as more determinant risk factors than ER disruptors. Furthermore, certain transdiagnostic processes, such as psychological inflexibility, may play a central role in the development of mental health problems, including psychosis. Specifying the mechanisms underlying the emergence of CHRp in adolescence is the key to optimizing the focus of preventive therapeutic interventions in these early stages.

Genetic and Environmental Influences on Perceived Stress in South Korean Twins.

Researchers have proposed that culture significantly influences perceived stress (PS). To date, however, twin studies on PS have been conducted mostly in western, individualistic cultures, which demonstrate that PS due to controllable (personal) life events is more heritable than PS due to uncontrollable (network) life events. This study aimed to investigate genetic and environmental influences on PS in South Korean twins. South Korea practices a dominant collectivist culture. In total, 1372 twin individuals (mean age = 22.4 ± 2.5 years) completed an online survey on PS, which consisted of the scales, Friendship, Academic Stress, Future Career, Family Conflicts, and Family Financial Difficulties (FFD). Friendship, Academic Stress, and Future Career can be considered PS due to personal life events, and Family Conflict and FFD, PS due to network life events. The general sex-limitation model-fitting analysis revealed the absence of qualitative or quantitative sex differences in genetic and environmental influences. Specifically, additive genetic influences were predominant for Friendship (63%), Academic Stress (67%), and Future Career (57%) for both sexes, with the remaining variance attributable to nonshared environmental influences. In contrast, shared environmental influences were largest for Family Conflict (47% for both genders) and FFD (64% for males, 63% for females) with no significant genetic effects. Despite known cultural differences in the means and variances of PS, South Korean twins exhibited significant genetic effects in PS due to personal life events and large shared environmental effects in PS due to network life events, which is similar to western samples.

[New aspects in etiology and treatment of adolescent anorexia nervosa-a postulated bio-psycho-social model and the impact of the COVID-19 pandemic]. / Neue Aspekte in der Ätiologie und Therapie der jugendlichen Anorexia nervosa ­ ein postuliertes biopsychosoziales Modell und die Auswirkungen der COVID-19-Pandemie.

Anorexia nervosa is one of the most frequent chronic disorders of adolescence associated with a high mortality. During the COVID-19-pandemic, the number of hospitalized children and adolescents with anorexia nervosa significantly increased. This article outlines new research findings to decode the etiology of this serious disorder, especially a genetic disposition and changes of metabolism. Against the background of increasing rates during the COVID-19 pandemic, the importance of the gene-environment interaction is discussed, and new treatment forms are described. Besides the development of new biological treatment strategies, there is also some important progress in psychotherapeutic interventions. Carers should always be integrated when treating children and adolescents with anorexia nervosa, which is especially emphasized in the new "home treatment" setting. The new concept of anorexia nervosa as a metabo-psychiatric disorder gives us hope for new research ideas and treatment strategies in this often-debilitating disorder of childhood and adolescence.

Genetic Correlates of Biological Aging and the Influence on Prediction of Mortality.

Longevity and disease-free survival are influenced by a combination of genetics and lifestyle. Biological age (BioAge), a measure of aging based on composite biomarkers, may outperform chronological age in predicting health and longevity. This study investigated the relationship between genetic risks, lifestyle factors, and delta age (Δage), estimated as the difference between biological and chronological age. BioAge and Δage were calculated for 52 418 participants from the population-based Lifelines cohort. We computed 2 independent polygenic risk scores (PRS) for health span and DNA methylation-based aging clock to characterize genetic risks. The capacity of BioAge to predict all-cause mortality when adjusted for chronological age and genetic risks for aging, was assessed. Obesity, lifestyle, socioeconomic status, sex, and genetic variations in a population contributed to the differences in the rates of accelerated aging. The overall risk of death for a 1-year increase in BioAge for a given chronological age and sex among the genotyped participants was 11% (HR = 1.11; 95% CI: 1.09, 1.13). After adjusting for genetic factors, BioAge maintained its sensitivity for predicting mortality. Findings from this study ascertain that BioAge can be a useful tool for risk stratification in research and aging interventions.

Genotype-Environment Interaction in ADHD: Genetic Predisposition Determines the Extent to Which Environmental Influences Explain Variability in the Symptom Dimensions Hyperactivity and Inattention.

Although earlier research has shown that individual differences on the spectrum of attention deficit hyperactivity disorder (ADHD) are highly heritable, emerging evidence suggests that symptoms are associated with complex interactions between genes and environmental influences. This study investigated whether a genetic predisposition [Note that the term 'genetic predisposition' was used in this manuscript to refer to an estimate based on twin modeling (an individual's score on the latent trait that resembles additive genetic influences) in the particular population being examined.] for the symptom dimensions hyperactivity and inattention determines the extent to which unique-environmental influences explain variability in these symptoms. To this purpose, we analysed a sample drawn from the Twins Early Development Study (TEDS) that consisted of item-level scores of 2168 16-year-old twin pairs who completed both the Strengths and Difficulties Questionnaire (SDQ; Goodman, in J Child Psychol Psychiatry 38:581-586, 1997) and the Strength and Weaknesses of ADHD Symptoms and Normal Behavior (SWAN; Swanson, in Paper presented at the meeting of the American Psychological Association, Los Angeles, 1981) questionnaire. To maximize the psychometric information to measure ADHD symptoms, psychometric analyses were performed to investigate whether the items from the two questionnaires could be combined to form two longer subscales. In the estimation of genotype-environment interaction, we corrected for error variance heterogeneity in the measurement of ADHD symptoms through the application of item response theory (IRT) measurement models. A positive interaction was found for both hyperactivity (e.g., [Formula: see text] = 2.20 with 95% highest posterior density interval equal to [1.79;2.65] and effect size equal to 3.00) and inattention (e.g., [Formula: see text] = 2.16 with 95% highest posterior density interval equal to [1.56;2.79] and effect size equal to 3.07). These results indicate that unique-environmental influences were more important in creating individual differences in both hyperactivity and inattention for twins with a genetic predisposition for these symptoms than for twins without such a predisposition.

Explicating narrow and broad conceptualizations of environmental influences on personality.

BACKGROUND: A surge of studies aims to identify environmental factors that explain individual differences, personality stability, and personality development. This special issue builds on this large interest and solicited articles on broad and narrow environmental factors of personality. OBJECTIVE: We provide an overview of the motivations behind the special issue, review each of the articles, and present data on researchers' perceptions of environmental factors contributing to personality expression and development. METHOD: We review 16 special issue articles, thematically grouped into seven topics-culture and race, genes and environment, geography and habitat, major/minor life events, social relationships, socioeconomic status and economic inequality, and work. We also present data on researchers' (N = 223) responses and ratings of environmental influences on personality expression and development. RESULTS: In the open-ended responses, the most important environmental influences were family, culture, peers, relationships, and trauma. Among the least important were weather, birth order, geography, climate, and shared environment. Nearly all the environmental influences featured in this special issue were considered at least somewhat important; however, there was considerable heterogeneity in how important researchers found each topic. CONCLUSIONS: There is no perfect consensus among researchers as to which environmental factors contribute most to personality expression and development. We hope that there is a larger surge of studies on personality constructs beyond traits, that contextualize concepts within a cultural and historical framework and develop more stringent theories to hypothesize about the environmental influences on personality.

Spatiotemporal distribution and environmental influences of severe fever with thrombocytopenia syndrome in Shandong Province, China.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease discovered in China in 2009. The purpose of this study was to describe the spatiotemporal distribution of SFTS and to identify its environmental influencing factors and potential high-risk areas in Shandong Province, China. METHODS: Data on the SFTS incidence from 2010 to 2021 were collected. Spatiotemporal scan statistics were used to identify the time and area of SFTS clustering. The maximum entropy (MaxEnt) model was used to analyse environmental influences and predict high-risk areas. RESULTS: From 2010 to 2021, a total of 5705 cases of SFTS were reported in Shandong. The number of SFTS cases increased yearly, with a peak incidence from April to October each year. Spatiotemporal scan statistics showed the existence of one most likely cluster and two secondary likely clusters in Shandong. The most likely cluster was in the eastern region, from May to October 2021. The first secondary cluster was in the central region, from May to October 2021. The second secondary cluster was in the southeastern region, from May to September 2020. The MaxEnt model showed that the mean annual wind speed, NDVI, cattle density and annual cumulative precipitation were the key factors influencing the occurrence of SFTS. The predicted risk map showed that the area of high prevalence was 28,120 km2, accounting for 18.05% of the total area of the province. CONCLUSIONS: The spatiotemporal distribution of SFTS was heterogeneous and influenced by multidimensional environmental factors. This should be considered as a basis for delineating SFTS risk areas and developing SFTS prevention and control measures.

[The exposome in the context of preventive measures for Alzheimer's and Parkinson's diseases]. / Das Exposom im Fokus präventiver Maßnahmen für die Alzheimer- und Parkinson-Erkrankung.

BACKGROUND: Preventive measures addressing the exposome can counteract neurodegenerative diseases. OBJECTIVE: This article gives an overview on the influence of general and individual exogenous factors (environmental influences and lifestyle changes) as well as endogenous factors (e.g. metabolic alterations) on the development and progression of Alzheimer's disease (AD) and Parkinson's disease (PD). METHODS: Summary and evaluation of current scientific studies and evidence regarding the exposome and prevention of AD and PD. RESULTS: Numerous studies could demonstrate a potential influence of environmental influences associated with industrialization (general exogenous factors), such as pesticides, solvents or air pollution on the development of AD and PD. Additionally, individually addressable changes of lifestyle (individual exogenous factors, e.g. physical activity, cognitive stimulation, nutrition and sleep) contribute to disease protection and modification and are becoming increasingly more important in light of still limited therapeutic interventions. Moreover, other exogenous factors (medication, noise pollution, head trauma and heavy metals) are discussed as risk factors for AD and/or PD. Endogenous factors (e.g., changes of the enteral microbiome, systemic inflammation and neuroinflammation, metabolic changes) can contribute to disease development by a higher potential for interacting with exogenous factors. CONCLUSION: Despite the comprehensive scientific evidence confirming the significance of the exposome for the pathogenesis of AD and PD, the great potential of preventive measures has not yet been exploited. A clarification of the high potential of lifestyle changes should be a therapeutic standard not only for individuals with manifest PD/AD but also for individuals with a risk profile or with suspected prodromal disease. Further investigations on the influence of environmental factors and the implementation of preventive strategies to avoid exposure should be the focus of international efforts.

Patterns of Eating Behavior among 13-Year-Old Adolescents and Associated Factors: Findings from the Generation XXI Birth Cohort.

Eating behavior adopted during adolescence may persist into adulthood. The aims of this study were to identify eating behavior patterns among Portuguese adolescents and to explore whether groups differ in terms of early life and family characteristics, severity of depressive symptoms, and body mass index (BMI) z-score. Participants were 3601 13-year-olds enrolled in the birth cohort Generation XXI. Eating behavior was assessed using the self-reported Adult Eating Behavior Questionnaire (AEBQ), validated in this sample. The severity of depressive symptoms was measured through the Beck Depression Inventory (BDI-II), and data on sociodemographic and anthropometrics were collected at birth and 13-years-old. Latent class analysis was conducted, and associations were estimated using multinomial logistic regression models. Five patterns of individuals were identified: "Picky eating", "Disinterest towards food", "Food neophilia", "Emotional eating", and "Food attractiveness". The adolescents' sex, maternal education, BMI z-score, and severity of depressive symptoms were significantly associated with the identified patterns. In particular, adolescents with a higher BMI z-score were more likely in "Food neophilia" while individuals with more severe depressive symptoms were in the "Picky eating", "Emotional eating", and "Food attractiveness" patterns. These findings suggest a starting point for the development and planning of targeted public health interventions.

Increased consumption despite fewer occasions: A longitudinal analysis of COVID-19 lockdown effects on soft drink consumption in England.

We examined the impact of a COVID-19 lockdown in England on the frequency of consumption occasions and amount of soft drinks consumed. Beverage consumption is strongly associated with specific, often social, consumption situations (e.g., going out). We reasoned that lockdown would affect consumption behaviour because it removed typical soft drink consumption situations. Specifically, we hypothesised that soft drink consumption occasions and amount would be reduced during lockdown compared to before and after lockdown, especially in typical soft drink consumption situations. In two surveys (Dec. 2020 and May 2021) among the same participants (N = 211, N = 160; consuming soft drinks at least once/week), we assessed the frequency of soft drink and water consumption occasions before, during, and after the Nov./Dec. 2020 lockdown, across typical soft drink and water drinking situations. This presents a detailed picture of the situations in which participants drink soft drinks and water, and how this was affected by a lockdown. We also assessed the daily amount of soft drinks and water consumed in each period, and perceived habitualness of drinking soft drinks and water. As predicted, participants reported fewer occasions of drinking soft drinks during lockdown compared to before and after, especially in typical soft drink consumption situations. Unexpectedly, however, the daily amount of soft drinks consumed increased during lockdown, compared to before and after, especially among participants with stronger perceived habitualness of soft drink consumption. Exploratory analyses suggest that during lockdown, participants increased their soft drink consumption at home. Water consumption, on the other hand, was not systematically affected by the lockdown. These findings suggest that even if some typical consumption situations disappear, consumption may be hard to disrupt if the behaviour is rewarding.

Translation and Cultural Adaptation of the StimQ for Use with Italian Children from Kindergartens.

The StimQ questionnaire is used to assess the home environment of children. The questionnaire is comprised of four subscales, and it was completed by the main caregiver. The items were different considering the band ages of the children: infants (5-12 months), toddlers (12-36 months), and preschoolers (36-72 months). The aim of the study was to translate, transculturally adapt, and evaluate the psychometric characteristics of the Italian version of the StimQ. To achieve this goal, a sample of 142 children was recruited from different kindergartens. The mean age of the group was 30.63 (SD 19.56), and 112 of them were female. The main caregiver was the mother in 95% of the cases. The Cronbach's alfa was excellent, considering the total score (0.82 for infants, 0.85 for toddlers, and 0.86 for preschoolers). Intrarater reliability was performed by administering the questionnaire after 48 h and by two different researchers. Both analyses showed an excellent reliability for the total score and all the subscales. The intrarater reliability was 0.99 for the infant, 1 for the toddler and 0.99 for the preschooler age groups. The interrater reliability was 0.95 for the infant, 0.93 for the toddler, and 0.97 for the preschooler age groups. The StimQ is a reliable questionnaire that could be helpful for clinicians and researchers who work with children in Italy.

Charge transfer as a mechanism for chlorophyll fluorescence concentration quenching.

Highly concentrated solutions of chlorophyll display rapid fluorescence quenching. The same devastating energy loss is not seen in photosynthetic light-harvesting antenna complexes, despite the need for chromophores to be in close proximity to facilitate energy transfer. A promising, though unconfirmed mechanism for the observed quenching is energy transfer from an excited chlorophyll monomer to a closely associated chlorophyll pair that subsequently undergoes rapid nonradiative decay to the ground state via a short-lived intermediate charge-transfer state. In this work, we make use of newly emerging fast methods in quantum chemistry to assess the feasibility of this proposed mechanism. We calculate rate constants for the initial charge separation, based on Marcus free-energy surfaces extracted from molecular dynamics simulations of solvated chlorophyll pairs, demonstrating that this pathway will compete with fluorescence (i.e., drive quenching) at experimentally measured quenching concentrations. We show that the rate of charge separation is highly sensitive to interchlorophyll distance and the relative orientations of chromophores within a quenching pair. We discuss possible solvent effects on the rate of charge separation (and consequently the degree of quenching), using the light-harvesting complex II (LH2) protein from rps. acidophila as a specific example of how this process might be controlled in a protein environment. Crucially, we reveal that the LH2 antenna protein prevents quenching, even at the high chlorophyll concentrations required for efficient energy transfer, by restricting the range of orientations that neighboring chlorophyll pairs can adopt.

The relative and interactive impact of multiple risk factors in schizophrenia spectrum disorders: a combined register-based and clinical twin study.

BACKGROUND: Research has yielded evidence for genetic and environmental factors influencing the risk of schizophrenia. Numerous environmental factors have been identified; however, the individual effects are small. The additive and interactive effects of multiple risk factors are not well elucidated. Twin pairs discordant for schizophrenia offer a unique opportunity to identify factors that differ between patients and unaffected co-twins, who are perfectly matched for age, sex and genetic background. METHODS: Register data were combined with clinical data for 216 twins including monozygotic (MZ) and dizygotic (DZ) proband pairs (one or both twins having a schizophrenia spectrum diagnosis) and MZ/DZ healthy control (HC) pairs. Logistic regression models were applied to predict (1) illness vulnerability (being a proband v. HC pair) and (2) illness status (being the patient v. unaffected co-twin). Risk factors included: A polygenic risk score (PRS) for schizophrenia, birth complications, birth weight, Apgar scores, paternal age, maternal smoking, season of birth, parental socioeconomic status, urbanicity, childhood trauma, estimated premorbid intelligence and cannabis. RESULTS: The PRS [odds ratio (OR) 1.6 (1.1-2.3)], childhood trauma [OR 4.5 (2.3-8.8)], and regular cannabis use [OR 8.3 (2.1-32.7)] independently predicted illness vulnerability as did an interaction between childhood trauma and cannabis use [OR 0.17 (0.03-0.9)]. Only regular cannabis use predicted having a schizophrenia spectrum diagnosis between patients and unaffected co-twins [OR 3.3 (1.1-10.4)]. CONCLUSION: The findings suggest that several risk factors contribute to increasing schizophrenia spectrum vulnerability. Moreover, cannabis, a potentially completely avoidable environmental risk factor, seems to play a substantial role in schizophrenia pathology.

Personality and peer groups in adolescence: Reciprocal associations and shared genetic and environmental influences.

OBJECTIVE: Peer groups represent a critical developmental context in adolescence, and there are many well-documented associations between personality and peer behavior at this age. However, the precise nature and direction of these associations are difficult to determine as youth both select into, and are influenced by, their peers. METHOD: We thus examined the phenotypic, genetic, and environmental links between antisocial and prosocial peer characteristics and several personality traits from middle childhood to late adolescence (ages 11, 14, and 17 years) in a longitudinal twin sample (N = 3762) using teacher ratings of personality and self-reports of peer characteristics. RESULTS: Less adaptive trait profiles (i.e., high negative emotionality, low conscientiousness, and low agreeableness) were associated with more antisocial and fewer prosocial peer characteristics across time. Associations between personality traits related to emotionality (negative emotionality and extraversion) and peer behavior were largely attributable to shared genetic influences, while associations between personality traits related to behavioral control (conscientiousness and agreeableness) and peer behavior were due to overlapping genetic and shared environmental influences. CONCLUSIONS: Overall, results suggest a set of environmental presses that push youth toward both behavioral undercontrol and antisocial peer affiliations, making the identification of such influences and their relative importance a critical avenue of future work.

Joint Consideration of Means and Variances Might Change the Understanding of Etiology.

Twin and adoption studies compare the similarities of people with differing degrees of relatedness to estimate genetic and environmental contributions to trait population variance. The analytic workhorse of these kinds of variance-focused designs is the intraclass correlation, which estimates similarity between pairs of individuals. Group means, by contrast, play no overt role in estimating genetic and environmental influences. Although this focus on variance has made very important contributions to understanding psychological characteristics, we contend that the exclusion of mean effects from behavioral genetic designs may have obscured key environmental influences and impeded full appreciation of the ubiquity and nature of gene-environment interplay in human outcomes. We provide empirical examples already in the literature and a theoretical framework for thinking through the incorporation of mean effects using largely forgotten, non-Mendelian theory regarding how genes influence human outcomes. We conclude that the field needs to develop models capable of fully incorporating mean effects into twin and adoption studies.

Intergenerational transmission of lifetime stressor exposure in adolescent girls at differential maternal risk for depression.

OBJECTIVE: Adolescent girls who grow up with mothers who are depressed are themselves highly vulnerable to developing depression (i.e., "intergenerational transmission of depression"). Stressor exposure is a strong risk factor for depression, and the transmission of depression risk from mothers to daughters is partly due to mothers experiencing more stressors, increasing daughters' stressor burden. However, research in this area has only assessed recent stressors, making the role of cumulative lifetime stressors unclear. METHOD: To address this issue, we recruited 52 dyads of mothers and adolescent daughters, of which 22 daughters were at high maternal risk for depression. Participants completed diagnostic interviews, and daughters additionally self-reported their depressive symptoms. Participants also completed the Stress and Adversity Inventory, a new-generation instrument for assessing cumulative lifetime history of acute and chronic stressors based on the contextual threat approach. We tested moderated mediation models evaluating the conditional indirect effects of mothers' lifetime stressors on high- versus low-risk daughters' depressive symptoms through daughters' lifetime stressors. RESULTS: As hypothesized, mothers of high-risk (but not low-risk) adolescent daughters who reported more lifetime acute stressors had daughters who reported more lifetime acute stressors and current depressive symptoms. Moreover, this finding was driven specifically by mothers' stressors occurring after their daughters' births. There was also tentative evidence that high-risk daughters' lifetime chronic stressors potentiated the impact of daughters' acute stressors on their depressive symptoms. CONCLUSION: These findings provide new insights into how stressful contexts are transmitted intergenerationally.