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At least 19 recordsLinked to original sources
PubMed2026

Can Psychiatric Genetics Advance Without Incorporating a Life Course Perspective?

Psychiatric disorders unfold over the life course; however, genomic studies of these conditions overwhelmingly rely on phenotypes collected at a single time point, often in adulthood. Therefore, genome-wide association studies (GWASs) of psychiatric conditions may miss genetic variants with time-varying relevance to etiology, prevention, and treatment, such as those that influence trajectories of symptoms and behaviors, age at onset, course of treatment response, and the co-evolution of comorbidities. With recent advances in longitudinal biobanks and analytic tools, we posit that incorporating a life course perspective in psychiatric genetics will enable critically relevant insights into each of these areas of investigation. We propose that the current inconsistent portability of polygenic scores across age groups can be reconciled through the design of carefully considered longitudinal GWASs in age-diverse samples. Pioneering longitudinal GWASs in psychiatry have revealed novel genomic signals associated with time-dependent phenotypes that are distinct from those influencing lifetime diagnosis, suggesting that the study of longitudinal phenotypes will complement cross-sectional approaches and empower biological and therapeutic discoveries. Advances in post-GWAS functional annotation resources and analytic approaches now enable us to contextualize the genetic contributions to psychiatric disorders as dynamic age- and exposure-dependent processes. Although longitudinal GWASs pose unique challenges with regard to data availability, selection bias, and missing data, integrating temporality into psychiatric genetics at scale is now attainable and promises to reveal novel biology and therapeutic opportunities for psychiatric conditions.

Cohort study↗
PubMed2026

Life-course stress exposure and cognitive decline in middle-aged and older Chinese adults: The role of sex differences and educational protection.

BACKGROUND: Stressful life events (SLEs) across the life course have been associated with cognitive decline, but evidence on their cumulative impact and potential modifiers remains limited. We aimed to examine the associations between SLE exposure in childhood, adulthood, or both life stages and cognitive trajectories, and to investigate whether these associations vary by sex and education. METHODS: We used data from the China Health and Retirement Longitudinal Study, a nationally representative cohort of adults aged ≥45 years. Participants with complete data on SLEs, cognition, and covariates were included (n = 5922). SLEs were retrospectively assessed for childhood and adulthood. Cognitive function was measured using a composite score (range 0-21) across three waves (2011-2015). Linear mixed-effects models examined longitudinal associations, adjusting for sociodemographic factors, health behaviors, and chronic conditions, with interaction analyses for sex and education. RESULTS: Compared with participants reporting no SLEs, cumulative exposure showed the strongest association with cognitive decline (β = -0.52, 95% CI -0.69 to -0.35), followed by childhood-only (β = -0.34, -0.48 to -0.20) and adulthood-only exposure (β = -0.22, -0.37 to -0.07). Sex significantly moderated the associations for childhood and cumulative exposure, with women exhibiting greater cognitive vulnerability. Higher educational attainment attenuated the associations between single-period stress and cognitive decline, with only partial protection observed against cumulative adversity. CONCLUSION: Cumulative life-course stress is associated with accelerated cognitive decline in Chinese middle-aged and older adults. Women appear more vulnerable to stress-related cognitive effects, whereas higher education confers partial resilience, highlighting the need for sex-sensitive and education-informed prevention strategies.

Humans↗
PubMed2024

Depressive symptoms in adolescence and adult educational and employment outcomes: a structured life course analysis.

BACKGROUND: Depression is a common mental health disorder that often starts during adolescence, with potentially important future consequences including 'Not in Education, Employment or Training' (NEET) status. METHODS: We took a structured life course modeling approach to examine how depressive symptoms during adolescence might be associated with later NEET status, using a high-quality longitudinal data resource. We considered four plausible life course models: (1) an early adolescent sensitive period model where depressive symptoms in early adolescence are more associated with later NEET status relative to exposure at other stages; (2) a mid adolescent sensitive period model where depressive symptoms during the transition from compulsory education to adult life might be more deleterious regarding NEET status; (3) a late adolescent sensitive period model, meaning that depressive symptoms around the time when most adults have completed their education and started their careers are the most strongly associated with NEET status; and (4) an accumulation of risk model which highlights the importance of chronicity of symptoms. RESULTS: Our analysis sample included participants with full information on NEET status (N = 3951), and the results supported the accumulation of risk model, showing that the odds of NEET increase by 1.015 (95% CI 1.012-1.019) for an increase of 1 unit in depression at any age between 11 and 24 years. CONCLUSIONS: Given the adverse implications of NEET status, our results emphasize the importance of supporting mental health during adolescence and early adulthood, as well as considering specific needs of young people with re-occurring depressed mood.

Humans↗
PubMed2026

Life-course influence of birthweight and subsequent pathways on healthy aging: a Mendelian randomization study.

BACKGROUND: Birthweight readily measurable marker of fetal growth that may influence health across the lifespan. We aimed to investigate the potential causal association between birthweight and healthy aging and to identify the mediating roles of subsequent socioeconomic, behavioral, functional, and disease-related factors to inform life-course strategies to promote healthy aging and reduce health inequities. METHODS: We performed two-sample Mendelian randomization analyses in European-ancestry participants to estimate the effect of birthweight (n = 298,142-423,683) on two robust, composite healthy aging phenotypes (genetically independent phenotype of aging (aging-GIP) and multivariate aging-related genetic factor (mvAge)) and six individual aging phenotypes, including healthspan, resilience, parental lifespan, self-rated health, phenotypic age deceleration, and 90th percentile self-longevity (n = 34,710-1,958,774), and screened for 100 candidate mediators (n = 14,267-1,812,017) using a two-step mediation analysis. RESULTS: Genetically determined each 1-SD higher birthweight was associated with higher aging-GIP (β [95% CI] in different models ranging from 0.131 [0.066-0.196] to 0.162 [0.089-0.235] SDs) and mvAge (0.036 [0.010-0.063] to 0.045 [0.024-0.067]), independent of later-life obesity indicators; also with more interpretable benefits, including 12%-16% higher odds of longer healthspan, a 0.079-0.089 SD improvement in resilience, and a 1.22-1.74 year increase in parental lifespan. Of 100 candidates, 26 and 25 mediated the effect of birthweight on aging-GIP and mvAge, respectively, including socioeconomic indicators (education, household income, occupational attainment; individual mediation proportion: 12.72%-27.79%); behaviors (e.g., cheese intake, age at first sex; 10.38%-29.56%); physical functions (e.g., blood pressure, grip strength; 7.57%-42.65%); and cardiometabolic diseases (e.g., type 2 diabetes, cardiovascular diseases; 25.02%-70.11%). CONCLUSIONS: Higher birthweight within the normal range directly promotes healthy aging, mediated by multifaceted modifiable factors. Our findings advocate adopting a life-course approach to foster healthy aging, starting with optimal birthweight and extending to interventions that enhance socioeconomic status, promote healthy behaviors, strengthen physical functions, and prevent cardiometabolic diseases.

Mendelian Randomization Analysis↗
PubMed1978

Evaluated time: a life course perspective.

Evaluated time is a dimension of time perspective which has received minimal attention from researchers; it subsumes those constructs dealing with the affective tone, or feelings, placed upon different points of the life cycle. Using data from a cross-sectional study of 216 men and women aged 16 to 67, a variety of approaches to the study of evaluated time were examined. Evaluations were found to differ by the respondents' stage of life and by sex, with older respondents and women generally being more optimistic in their perceptions of later life. For example, while all the younger respondents viewed old age more negatively than other periods, older respondents drew a distinction between the young old and the old old. The former period was protrayed as a time of continued satisfaction.

Adaptation, Psychological↗
PubMed2025

Polygenic prediction of body mass index and obesity through the life course and across ancestries.

Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.6% African ancestry, 14.4% American ancestry, 8.4% East Asian ancestry, 71.1% European ancestry and 1.5% South Asian ancestry) from the GIANT consortium and 23andMe, Inc., we developed ancestry-specific and multi-ancestry PGSs. The multi-ancestry score explained 17.6% of BMI variation among UK Biobank participants of European ancestry. For other populations, this ranged from 16% in East Asian-Americans to 2.2% in rural Ugandans. In the ALSPAC study, children with higher PGSs showed accelerated BMI gain from age 2.5 years to adolescence, with earlier adiposity rebound. Adding the PGS to predictors available at birth nearly doubled explained variance for BMI from age 5 onward (for example, from 11% to 21% at age 8). Up to age 5, adding the PGS to early-life BMI improved prediction of BMI at age 18 (for example, from 22% to 35% at age 5). Higher PGSs were associated with greater adult weight gain. In intensive lifestyle intervention trials, individuals with higher PGSs lost modestly more weight in the first year (0.55 kg per s.d.) but were more likely to regain it. Overall, these data show that PGSs have the potential to improve obesity prediction, particularly when implemented early in life.

Adolescent↗
PubMed2026

Cardiovascular Health Across the Life Course for Individuals With Breast Cancer: A Review.

IMPORTANCE: Breast cancer is the most common cancer diagnosed in women. Therapies for breast cancer are evolving rapidly, and several are associated with cardiovascular adverse effects, can exacerbate cardiovascular risk factors, or can increase the risk of cardiovascular disease. OBSERVATIONS: Advances in screening and treatment have led to earlier diagnosis and improved disease-free survival. For long-term survivors of breast cancer, cardiovascular adverse effects can pose a greater threat to overall long-term health than the cancer itself. Additionally, the increasing incidence of breast cancer in younger, premenopausal women has created a distinct demographic with unique medical needs. CONCLUSIONS AND RELEVANCE: Cardiology practitioners need to remain updated on rapidly evolving breast cancer therapies to care for this growing, unique patient population. The field of cardio-oncology has evolved to address the cardiovascular needs of patients and survivors.

Humans↗
PubMed2024

Prenatal cannabis exposure is associated with alterations in offspring DNA methylation at genes involved in neurodevelopment, across the life course.

Prenatal cannabis exposure (PCE) is of increasing concern globally, due to the potential impact on offspring neurodevelopment, and its association with childhood and adolescent brain development and cognitive function. However, there is currently a lack of research addressing the molecular impact of PCE, that may help to clarify the association between PCE and neurodevelopment. To address this knowledge gap, here we present epigenome-wide association study data across multiple time points, examining the effect of PCE and co-exposure with tobacco using two longitudinal studies, the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Christchurch Health and Development Study (CHDS) at birth (0 y), 7 y and 15-17 y (ALSPAC), and ~27 y (CHDS). Our findings reveal genome-wide significant DNA methylation differences in offspring at 0 y, 7 y, 15-17 y, and 27 y associated with PCE alone, and co-exposure with tobacco. Importantly, we identified significantly differentially methylated CpG sites within the genes LZTS2, NPSR1, NT5E, CRIP2, DOCK8, COQ5, and LRP5 that are shared between different time points throughout development in offspring. Notably, functional pathway analysis showed enrichment for differential DNA methylation in neurodevelopment, neurotransmission, and neuronal structure pathways, and this was consistent across all timepoints in both cohorts. Given the increasing volume of epidemiological evidence that suggests a link between PCE and adverse neurodevelopmental outcomes in exposed offspring, this work highlights the need for further investigation into PCE, particularly in larger cohorts.

DNA Methylation↗
PubMed2025

Methylome profiling of cell-free DNA during the early life course in (un)complicated pregnancies using MeD-seq: Protocol for a cohort study embedded in the prospective Rotterdam periconception cohort.

INTRODUCTION: Placental DNA methylation differences have been associated with timing in gestation and pregnancy complications. Maternal cell-free DNA (cfDNA) partly originates from the placenta and could enable the minimally invasive study of placental DNA methylation dynamics. We will for the first time longitudinally investigate cfDNA methylation during pregnancy by using Methylated DNA Sequencing (MeD-seq), which is compatible with low cfDNA levels and has an extensive genome-wide coverage. We aim to investigate DNA methylation in placental tissues and cfDNA during different trimesters in uncomplicated pregnancies, and in pregnancies with placental-related complications, including preeclampsia and fetal growth restriction. Identified gestational-age and disease-specific differentially methylated regions (DMRs) could lead to numerous applications including biomarker development. METHODS AND ANALYSIS: Our study design involves three sub-studies. Sub-study 1 is a single-centre prospective, observational subcohort embedded within the Rotterdam Periconception cohort (Predict study). We will longitudinally collect maternal plasma in each trimester and during delivery, and sample postpartum placentas (n = 300). In sub-study 2, we will prospectively collect first and second trimester placental tissues (n = 10 per trimester). In sub-study 3 we will retrospectively collect plasma after non-invasive prenatal testing (NIPT) in an independent validation case-control cohort (n = 30-60). A methylation-dependent restriction enzyme (LpnPI) will be used to generate DNA fragments followed by sequencing on the Illumina NextSeq2000 platform. DMRs will be identified in placental tissues and cell types, and in cfDNA related to gestational-age or placental-related complications. (Paired) placental methylation profiles will be correlated to DMRs in cfDNA to aid tissue-of-origin analysis. We will establish a methylation score to predict associated diseases. DISCUSSION: This study will provide insights in placental DNA methylation dynamics in health and disease, and could lead to clinical relevant biomarkers.

Humans↗
PubMed1978

[Contribution to wet and dry weights of mesenchymal and parenchymatous organs of humans and rats during the course of life (author's transl)].

The wet and dry weights of parenchymatous (lung, heart, liver, kidney) and of mesenchymal organs (aorta, skin, xiphoid cartilage) of humans and rats (both sexes) were investigated during the course of life. Furthermore, these investigations were done on the following rat organs: brain (divided in cerebrum as well as in cerebellum plus pons), spleen, rib cartilage, testis and ovar. The water content of these tissues and organs of both species was calculated by means of their wet and dry weights. The dry weights of the investigated parenchymal and mesenchymal organs of both species remain constant during the whole course of life (pastly until the high senile age)--using freeze-drying. The same is true for the water content: constancy without significant decrease during the investigated life periods and without sex dependent differences.

Aging↗
PubMed2026

Timing of adverse childhood experiences shapes epigenetic ageing and life-history outcomes.

Early-life adversity is widely linked to accelerated biological ageing, yet it remains unclear whether such associations reflect exposure during sensitive developmental periods, the cumulative burden of exposures, or temporal proximity to later outcomes. Here, we leverage life-history theory and a life course framework to nuance how the timing of adverse childhood experiences (ACEs) becomes biologically embedded through epigenetic ageing. Using longitudinal data from the Future of Families and Child Wellbeing Study (N=1,974), we apply statistical learning and structured life course modelling to test sensitive period, cumulative risk, and recency hypotheses across multiple domains of adversity (poverty, instability, deprivation, and maltreatment). We find that adversity exposure during specific developmental periods, rather than cumulative burden or recent exposure, are most strongly associated with epigenetic age acceleration in late childhood ([Formula: see text]=0.003). Moreover, the timing and direction of these effects vary by adversity type. Epigenetic ageing is in turn associated with later health-related risks ([Formula: see text]=0.29, SE=0.06; [Formula: see text]=1.62, SE=0.27) and demographic behaviour ([Formula: see text]=0.21, SE=0.08; [Formula: see text]=0.22, SE=0.11), and further mediates the association between ACEs and outcomes in young adulthood, particularly for BMI ([Formula: see text]=0.003, SE=0.002, [Formula: see text]=11%). These findings demonstrate that childhood adversity may be linked to biological ageing in developmentally specific and domain-dependent ways, with certain developmental periods appearing more sensitive to adversity exposure than others.

Humans↗
PubMed1978

The hypothalamo-hypophysial system in acipenseridae. VII. The functional morphology of the peptidergic neurosecretory cells in the preoptic nucleus of the sturgeon, Acipenser güldenstädti Brandt. A quantitative study.

The peptidergic neurosecretory cells (NSC) of the nucleus praeopticus (NP) of male and female sturgeons, A. güldenstädti Brandt, were studied light microscopically at different stages of their life cycle and under experimental conditions. Four main NSC types reflecting different phases of secretory cycle and life course of the cell have been tentatively distinguished. The maximum percentage of the high and moderate active NSC are found in juvenile animals in the sea (stages I and I-II of gonadal maturity, sgm), in upstream migrating fish in spring before spawning, in down-stream migrating fish 1-1.5 months after spawning, and in experimental fish kept for 8.5 hours in a 32% sodium chloride solution. The least active NSC accumulating neurosecretory material (NSM) are characteristic of juvenile fish (sgm II) in the sea, sturgeons maintained in a sodium chloride solution for 3.5 or 6 hours and fish which remained in a net, thrown to the sea, for some hours before fixation. The lowest percentage of these cells is observed in autumn migrants, in females soon after spawning (sgm VI) and in fish kept for 8.5 hours in a sodium chloride solution. Cells rich in basophilic substance and poor in NSM occur in juvenile and in down-stream migrating fish. Cells reflecting the state of exhaustion after hyperactivity and "ageing" cells are seen in adults, expecially in sgm VI fish, and in autumn migrants. Pyknomorphous NSC are constantly present in all fish; they are most numerous in sturgeons found in a net. A diagram demonstrating the life course and the secretory cycle of the NSC is presented and the role of the hypothalamo-hypophysial neurosecretory system (HHNS) under stress conditions is discussed.

Aging↗
PubMed1977

Life graphs and life events.

The present study investigates changes in personal satisfaction over the whole life course by means of life graphs and their determinants. The life graphs were administered within a 4-year interval to 371 individuals (age 45-70). A modified version of the Holmes and Rahe life events scale, administered in the second interview, was used to ascertain the occurrence of four kinds of events: (1) children leaving home, (2) ill health, (3) death of family or friends, and (4) changes in work. Differences in height between the peak of the graph and the height at the current age is the measurement technique used with the life graphs. Events are found to play a different role at different stages of life and seem to be measured against an implicit schedule according to which the events are seen as traumatic or acceptable. Thus, the same event has different effects on perception of emotional state according to age.

Age Factors↗