Impact of life adversity and gene expression on psychiatric symptoms in children and adolescents: findings from the Brazilian high risk cohort study

Frontiers in Psychiatry, Год журнала: 2025, Номер 16

Опубликована: Фев. 13, 2025

Introduction While the influence of both genetic and environmental factors on development psychiatric symptoms is well-recognized, precise nature their interaction throughout remains a subject ongoing debate. This study investigated association between expression 78 candidate genes, previously associated with phenotypes, in peripheral blood adversity psychopathology sample 298 young individuals assessed at two time points from Brazilian High Risk Cohort Study for Mental Conditions (BHRCS). Methods Psychopathology was using Child Behavior Checklist (CBCL), considering total CBCL, p-factor (i.e. general factor psychopathology), internalizing externalizing as clinical variables. The life adversities considered this includes four composite variables: child maltreatment, stressful events, threat deprivation. Gene measured next-generation sequencing target genes differential gene analyzed DESeq2 package. Results Mixed models revealed six symptoms: NR3C1, HSPBP1, SIN3A, SMAD4, CRLF3 exhibited negative correlation these symptoms, while FAR1 showed positive correlation. Additionally, we also found USP38 symptoms. Finally, DENND11 PRRC1 were negatively deprivation, latent characterized by neglect, parental absence, measures material forms No mediation or moderation effect observed meaning that they might distinct pathways. Discussion Among nine which encodes glucocorticoid receptor, far most investigated, being depressive early adversity, stress. further research needed to fully understand complex relationship expression, adversities, psychopathology, our findings provide valuable insights into molecular mechanisms underlying mental disorders.

Язык: Английский

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Intervening After Trauma: Child–Parent Psychotherapy Treatment Is Associated With Lower Pediatric Epigenetic Age Acceleration

Psychological Science, Год журнала: 2024, Номер 35(9), С. 1062 - 1073

Опубликована: Авг. 14, 2024

Early-life adversity increases the risk of health problems. Interventions supporting protective and responsive caregiving offer a promising approach to attenuating adversity-induced changes in stress-sensitive biomarkers. This study tested whether participation an evidence-based dyadic psychosocial intervention, child-parent psychotherapy (CPP), was related lower epigenetic age acceleration, trauma-sensitive biomarker accelerated biological aging that is associated with later impairment, sample children trauma histories. Within this quasi-experimental, repeated-measures study, we examined acceleration at baseline postintervention low-income receiving CPP treatment (

Язык: Английский

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The body keeps the score: The neurobiological profile of traumatized adolescents

Neuroscience & Biobehavioral Reviews, Год журнала: 2023, Номер 145, С. 105033 - 105033

Опубликована: Янв. 4, 2023

Trauma-related disorders are debilitating psychiatric conditions that affect people who have directly or indirectly witnessed adversities. Experiencing multiple types of traumas appears to be common during childhood, and even more so adolescence. Dramatic brain/body transformations occurring adolescence may provide a highly responsive substrate external stimuli lead trauma-related vulnerability conditions, such as internalizing (anxiety, depression, anhedonia, withdrawal) externalizing (aggression, delinquency, conduct disorders) problems. Analyzing relations among neuronal, endocrine, immune, biochemical signatures trauma behaviors, including the role personality traits in shaping these conducts, this review highlights marked effects traumatic experience on involve changes at nearly every level analysis, from brain structure, function connectivity endocrine immune systems, gene expression (including gut) development personality.

Язык: Английский

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Telehealth Parenting Program and Salivary Epigenetic Biomarkers in Preschool Children With Developmental Delay

JAMA Network Open, Год журнала: 2024, Номер 7(7), С. e2424815 - e2424815

Опубликована: Июль 29, 2024

Children with developmental delays are at a heightened risk of experiencing mental health challenges, and this is exacerbated among racially minoritized children who face disproportionate adversity. Understanding the impact parenting interventions on biological markers associated these risks crucial for mitigating long-term disparities. To examine effect 20 weeks an internet-based parent-child interaction training (iPCIT) program biomarkers aging chronic inflammation preschoolers delay 12-month follow-up. An observational secondary analysis data from randomized clinical trial conducted March 17, 2016, to December 15, 2020, assess changes in salivary DNA methylation (DNAm)-derived following iPCIT intervention. Participants were recruited 3 Part C early intervention sites large southeastern US city. Eligible participants included within months their third birthday had Child Behavior Checklist Externalizing Problems T score greater than 60 provided saliva least 1 study wave. Data was May 2023 April 2024. received either (a telehealth therapeutic focused enhancing relationship addressing behavioral challenges young children) or referrals as usual. DNAm follow-up assessed using Infinium HumanMethylationEPIC Bead Chip Assay derive DunedinPACE, C-reactive protein (CRP), interleukin-6 (IL-6). Analyses intent-to-treat used path analysis. A total 71 (mean [SD] age, 36.27 [0.61] 51 male [71.8%] female [28.2%]) analyzed, whom 34 37 The group slower pace (β = 0.26; 95% CI, 0.06 0.50; P .03) less DNAm-derived CRP 0.27; 0.05 0.49; .01) relative control condition These associations remained significant after accounting baseline score, child demographics, symptom severity, independent predicted buccal epithelial cell proportion both DunedinPACE CRP. There no association IL-6 0.14; -0.08 0.36; .21). In intervention, iPCIT, decreased molecular suggests potential modify aspects embedding stress. systemic such offers insights into disparities promoting resilience vulnerable populations. ClinicalTrials.gov Identifier: NCT03260816.

Язык: Английский

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Patterns of childhood trauma co-occurrence and its predictivity for suicidality: A machine learning approach

iScience, Год журнала: 2025, Номер unknown, С. 111877 - 111877

Опубликована: Янв. 1, 2025

Язык: Английский

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Human genomic regions of systemic interindividual epigenetic variation are implicated in neurodevelopmental and metabolic disorders

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

Epigenome-wide association studies (EWAS) profile DNA methylation across the human genome to identify associations with diseases and exposures. Most employ Illumina arrays; this platform, however, under-samples interindividual epigenetic variation. The systemic stable nature of variation at correlated regions (CoRSIVs) should be advantageous EWAS. Here, we analyze 2,203 published EWAS determine whether probes within CoRSIVs are over-represented in literature. Enrichment CoRSIV-overlapping was observed for most classes disease, particularly neurodevelopmental disorders type 2 diabetes, indicating an opportunity improve power by over 200- 100-fold, respectively. targeting all known accelerate discovery between individual risk disease.

Язык: Английский

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Epigenetic Echoes: Bridging Nature, Nurture, and Healing Across Generations

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3075 - 3075

Опубликована: Март 27, 2025

Trauma can impact individuals within a generation (intragenerational) and future generations (transgenerational) through complex interplay of biological environmental factors. This review explores the epigenetic mechanisms that have been correlated with effects trauma across generations, including DNA methylation, histone modifications, non-coding RNAs. These regulate expression stress-related genes (such as glucocorticoid receptor (NR3C1) FK506 binding protein 5 (FKBP5) gene), linking to pathways may affect long-term stress regulation health outcomes. Although research using model organisms has elucidated potential underlying intergenerational trauma, applying these findings human populations remains challenging due confounding variables, methodological limitations, ethical considerations. complexity is compounded by difficulties in establishing causality disentangling influences from shared Emerging therapies, such psychedelic-assisted treatments mind-body interventions, offer promising avenues address both psychological aspects trauma. However, translating into effective interventions will require interdisciplinary methods culturally sensitive approaches. Enriched environments, cultural reconnection, psychosocial shown mitigate trauma's impacts generations. By integrating biological, social, perspectives, this highlights critical importance frameworks breaking cycles fostering resilience, advancing comprehensive healing

Язык: Английский

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Strengthening Rigor and Reproducibility in Epigenome-Wide Association Studies of Social Exposures and Brain-Based Health Outcomes

Current Environmental Health Reports, Год журнала: 2025, Номер 12(1)

Опубликована: Апрель 21, 2025

Studies examining the effects of social factors on epigenome have proliferated over last two decades. Social epigenetics research to date has broadly demonstrated that spanning childhood adversity, neighborhood disadvantage, educational attainment, and economic instability are associated with alterations DNA methylation may a functional impact health. These relationships particularly relevant brain-based health outcomes such as psychiatric disorders, which strongly influenced by exposures also leading cause disability worldwide. However, studies limited many challenges faced both epigenome-wide association (EWAS) study factors. In this manuscript, we provide framework achieve greater rigor reproducibility in research. We discuss current limitations field, well existing new solutions improve reproducibility. Readers will gain better understanding considerations processes could maximize when conducting research, technologies approaches merit attention investment propel continued discovery into future.

Язык: Английский

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Different epistemic stances for different traumatic experiences: implications for mentalization

Research in Psychotherapy Psychopathology Process and Outcome, Год журнала: 2023, Номер 26(3)

Опубликована: Дек. 20, 2023

Traumatic experiences may impair reflective functioning (RF), making it difficult for individuals to understand their own and others' mental states. Epistemic trust (ET), which enables evaluating social information as reliable relevant, vary in association with RF. In this study, we explored the implications of different ET stances (i.e., trust, mistrust, credulity) relation between childhood traumatic emotional abuse, physical sexual neglect, neglect) types RF impairments (uncertainty certainty about states). A non-clinical community sample 496 cisgender emerging adults (mage = 24.91, standard deviation 2.66, 71.85% assigned female at birth, 63.63% heterosexual) reported on experiences, ET, We used structural equation models examine direct indirect associations. The results showed significant effects abuse uncertainty states through credibility. also observed mistrust findings suggest that a lack discrimination when knowledge from others might promote increased have experienced childhood. Conversely, tendency view all sources unreliable or ill-intentioned mistrust) foster greater protective mechanism against an potentially harmful world combined abuse. clinical practice intervention are discussed.

Язык: Английский

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A lifetime perspective on risk factors for cognitive decline with a special focus on early events

Cerebral Circulation - Cognition and Behavior, Год журнала: 2024, Номер 6, С. 100217 - 100217

Опубликована: Янв. 1, 2024

Both Alzheimer's disease and vascular dementia are the result of processes that typically develop over several decades. Population studies have estimated more than half risk for is preventable or at least modifiable through behavioral adaptations. The association between these lifestyle factors most evident exposure in midlife. However, habits formed middle age often reflect a lifetime behavior patterns living conditions. Therefore, individuals who, example, able to maintain healthy diets regular exercise during their years likely benefit from cognition-protective they practiced throughout lives. For numerous adult diseases, significant risks can be traced back early childhood. Suboptimal conditions perinatal period, childhood adolescence increase including stroke, heart disease, insulin resistance, hypertension dementia. This review aims summarizing some evidence life-time perspective with goal raising awareness prevention successful aging.

Язык: Английский

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