Annual Research Review: Rethinking childhood trauma‐new research directions for measurement, study design and analytical strategies

Journal of Child Psychology and Psychiatry, Год журнала: 2019, Номер 61(3), С. 236 - 250

Опубликована: Ноя. 24, 2019

Childhood trauma is a key modifiable risk factor for psychopathology. Despite significant scientific advances, traumatised children still have poorer long‐term outcomes than nontraumatised children. New research paradigms are, thus, needed. To this end, the review examines three dominant assumptions about measurement, design and analytical strategies. Current warns against using prospective retrospective measures of childhood interchangeably; interpreting cross‐sectional differences in putative mediating mechanisms between adults with or without history as evidence longitudinal changes from pre‐trauma conditions; directly applying explanatory models resilience vulnerability to psychopathology forecast individual unseen cases. The warnings equally apply on broader adverse experiences (ACEs). Further examining these can generate new insights how prevent its detrimental effects.

Язык: Английский

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Longitudinal determination of resilience in humans to identify mechanisms of resilience to modern-life stressors: the longitudinal resilience assessment (LORA) study

European Archives of Psychiatry and Clinical Neuroscience, Год журнала: 2020, Номер 271(6), С. 1035 - 1051

Опубликована: Июль 18, 2020

Resilience is the maintenance and/or quick recovery of mental health during and after periods adversity. It conceptualized to result from a dynamic process successful adaptation stressors. Up now, large number resilience factors have been proposed, but mechanisms underlying are not yet understood. To shed light on complex time-varying processes that lead positive long-term outcome in face adversity, Longitudinal Assessment (LORA) study has established. In this study, 1191 healthy participants followed up at 3- 18-month intervals over course 4.5 years two centers Germany. Baseline visits entail multimodal phenotyping, including assessment status, sociodemographic lifestyle variables, factors, life history, neuropsychological assessments (of proposed mechanisms), biomaterials (blood for genetic epigenetic, stool microbiome, hair cortisol analysis). At 3-monthly online assessments, subjects monitored subsequent exposure stressors as well measures, which allows quantitative stressor-dependent changes main outcome. Descriptive analyses health, major events, daily hassles, perceived stress, ability recover stress here presented baseline sample. The LORA unique its design will pave way better understanding humans further development interventions successfully prevent stress-related disorder.

Язык: Английский

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High-throughput screening of glucocorticoid-induced enhancer activity reveals mechanisms of stress-related psychiatric disorders

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(49)

Опубликована: Ноя. 27, 2023

Exposure to stressful life events increases the risk for psychiatric disorders. Mechanistic insight into genetic factors moderating impact of stress can increase our understanding disease processes. Here, we test 3,662 single nucleotide polymorphisms (SNPs) from preselected expression quantitative trait loci in massively parallel reporter assays identify variants that modulate activity regulatory elements sensitive glucocorticoids, important mediators response. Of tested SNP sequences, 547 were located glucocorticoid-responsive which 233 showed allele-dependent activity. Transcripts regulated by these functional enriched those differentially expressed disorders postmortem brain. Phenome-wide Mendelian randomization analysis 4,439 phenotypes revealed potentially causal associations specifically neurobehavioral traits, including major depression and other Finally, a gene score derived was significantly associated with differences physiological response, suggesting may alter individual set point

Язык: Английский

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A Systematic Review of the Biological Correlates and Consequences of Childhood Maltreatment and Adverse Childhood Experiences

Trauma Violence & Abuse, Год журнала: 2021, Номер 24(1), С. 156 - 173

Опубликована: Июнь 9, 2021

Childhood maltreatment (CM) and adverse childhood experiences (ACEs) are two primary forms of interpersonal victimization that have been associated with a host deleterious health outcomes. Studies over the past decade begun to use range biologically informed methods better understand role biology plays in relationship between CM, ACEs, later life This line research has shown both occur at sensitive periods development, which can increase likelihood “getting under skin” influence behavior across course. review examines current state knowledge on this hypothesis. One hundred ninety-nine studies included systematic based criteria they be written English, method, conducted samples humans. Results reveal latent additive genetic influences, biological system functioning captured by biomarkers, polygenic risk scores, neurobiological factors commonly exposure response CM ACEs. The implication these findings for existing body early recommendations future policy discussed.

Язык: Английский

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Developmental Dyslexia: Environment Matters

Brain Sciences, Год журнала: 2021, Номер 11(6), С. 782 - 782

Опубликована: Июнь 13, 2021

Developmental dyslexia (DD) is a multifactorial, specific learning disorder. Susceptibility genes have been identified, but there growing evidence that environmental factors, and especially stress, may act as triggering factors determine an individual’s risk of developing DD. In DD, in most complex phenotypes, the presence genetic mutation fails to explain broad phenotypic spectrum observed. Early life stress has repeatedly associated with multifactorial disorders, due its effects on chromatin regulation, gene expression, HPA axis function long-term systemic response. Based recent evidence, we discuss potential role DD occurrence, putative epigenetic affected individuals, well necessity early appropriate intervention, based individual stress-associated (endo)phenotype.

Язык: Английский

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Interaction of Cigarette Smoking and Polygenic Risk Score on Reduced Lung Function

JAMA Network Open, Год журнала: 2021, Номер 4(12), С. e2139525 - e2139525

Опубликована: Дек. 16, 2021

Importance

The risk of airflow limitation and chronic obstructive pulmonary disease (COPD) is influenced by combinations cigarette smoking genetic susceptibility, yet it remains unclear whether gene-by-smoking interactions are associated with quantitative measures lung function.

Objective

To assess the interaction polygenic score in association reduced

Design, Setting, Participants

This UK Biobank cohort study included citizens European ancestry aged 40 to 69 years spirometry data passing quality control metrics. Data was analyzed from July 2020 March 2021.

Exposures

PRS combined forced expiratory volume 1 second (FEV₁) percent vital capacity exhaled first (FEV1/FVC), self-reported pack-years smoking, ever- vs never-smoking status, current- former- or status.

Main Outcomes Measures

FEV₁/FVC primary outcome. Models were used test for models, including main effects PRS, different variables, their cross-product terms. between compared those highest lowest decile estimated low

Results

We 319 730 individuals, whom 24 915 (8%) had moderate-to-severe COPD cases, 44.4% men. Participants a mean (SD) age 56.5 (8.02) years. significantly lower (PRS: β, −0.03; 95% CI, −0.031 pack-years: −0.0064; −0.0064 −0.0063) term (β, −0.0028; −0.0029 −0.0026). A stepwise increment effect sizes these terms observed per 10 exposure. 11 20, 31 40, more than 50 categories β (interaction) −0.0038 (95% −0.0046 −0.0031); −0.013 −0.014 −0.012); −0.017 −0.019 −0.016), respectively. There evidence significant never- status interaction; −0.0068 −0.0060) current not-current −0.0091; −0.0097 −0.0084). For any given level exposure, individuals tenth (ie, risk) risk. every 20 showed nearly 2-fold reduction FEV₁/FVC.

Conclusions Relevance

characterized diminished function, our analyses suggest there substantial genome-wide exposures. While decreased function across all categories, associations strongest higher

Язык: Английский

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Biological Mechanisms of Stress Resilience

Oxford University Press eBooks, Год журнала: 2025, Номер unknown, С. 553 - 570

Опубликована: Янв. 1, 2025

Abstract Abstract: Resilience is the ability to adapt successfully in face of severe stress, trauma, or adversity. Best conceptualized as existing on a continuum, resilience shaped by genetic makeup and environmental factors. The developmental years are critical for shaping stress response systems brain circuits underlying emotion regulation, yet can also be enhanced throughout an individual’s lifetime. This chapter presents overview complex interactions between neurotransmitters, neuropeptides, hormones, other biological that mediate resilience, well functional differences neural circuitry function key resilience-promoting psychological growing understanding genetic, epigenetic, developmental, psychological, neurobiological factors continues lead development interventions enhance resilience. Examples preventive treatment discussed, along with recent developments field.

Язык: Английский

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Neuroendocrine Mechanisms of Depression

Oxford University Press eBooks, Год журнала: 2025, Номер unknown, С. 435 - 448

Опубликована: Янв. 1, 2025

Abstract Major depressive disorder (MDD) is among the most common psychiatric disorders. This chapter summarized evidence for neuroendocrine changes in pathophysiology of MDD from both human and animal studies. The focus lies on hypothalamus–pituitary–adrenal (HPA) axis, which central response to stress adversity. Altered function HPA axis has been linked at different levels, measured endocrine altered receptor function. Moderation by genetic variants epigenetic mechanisms are discussed. Finally, using measures as biomarkers presented, pharmacological studies targeting this system summarized.

Язык: Английский

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Transcriptional Profiling of Primate Central Nucleus of the Amygdala Neurons to Understand the Molecular Underpinnings of Early-Life Anxious Temperament

Biological Psychiatry, Год журнала: 2020, Номер 88(8), С. 638 - 648

Опубликована: Май 19, 2020

Язык: Английский

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Familial and socioeconomic contributions to premorbid functioning in psychosis: Impact on age at onset and treatment response

European Psychiatry, Год журнала: 2020, Номер 63(1)

Опубликована: Янв. 1, 2020

Premorbid adjustment (PA) abnormalities in psychotic disorders are associated with an earlier age at onset (AAO) and unfavorable clinical outcomes, including treatment resistance. Prior family studies suggest that familial liability, likely reflecting increased genetic risk, socioeconomic status (SES) contribute to premorbid maladjustment. However, their joint effect possibly indicating gene-environment interaction has not been evaluated.We examined whether history of psychosis (FHP) parental SES may predict PA AAO unrelated cases first-episode (n = 108) schizophrenia 104). academic social functioning domains during childhood early adolescence were retrospectively assessed. Regression analyses performed investigate main effects FHP SES, as well interaction. The relationships between PA, AAO, response antipsychotic medication also explored.Positive difficulties importantly interacted moderate (interaction p 0.024). Positive did differences AAO. Nevertheless, was observed among worse (β -0.20; 0.005) -0.19; 0.007). Further, confirming evidence emerged for association deficient poor (p 0.04).Familial risk interact position influencing childhood. In addition, this study supports the link deviations, onset, resistance, which highlights a promising indicator.

Язык: Английский

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