Annual Research Review: The power of predictability – patterns of signals in early life shape neurodevelopment and mental health trajectories

Journal of Child Psychology and Psychiatry, Год журнала: 2024, Номер 65(4), С. 508 - 534

Опубликована: Фев. 20, 2024

The global burden of early life adversity (ELA) is profound. World Health Organization has estimated that ELA accounts for almost 30% all psychiatric cases. Yet, our ability to identify which individuals exposed will develop mental illness remains poor and there a critical need underlying pathways mechanisms. This review proposes unpredictability as an understudied aspect tractable presents conceptual model includes biologically plausible mechanistic by impacts the developing brain. supported synthesis published new data illustrating significant patterns signals on child development. We begin with overview existing literature, focused primarily longer (e.g. years, months, days). then describe work testing impact parental moment‐to‐moment timescale, providing evidence these during sensitive windows development influence neurocircuit formation across species thus may be evolutionarily conserved process shapes Next, attention drawn emerging themes provide framework future directions research including evaluation functions, such effortful control, particularly vulnerable unpredictability, periods, sex differences, cross‐cultural investigations, addressing causality, pathway other forms Finally, we suggestions prevention intervention, introduction screening instrument identification children unpredictable experiences.

Язык: Английский

---

Early life adversity as a risk factor for cognitive impairment and Alzheimer’s disease

Translational Neurodegeneration, Год журнала: 2023, Номер 12(1)

Опубликована: Май 12, 2023

Abstract Neurological conditions, including cognitive impairment and Alzheimer’s disease (AD), impose a huge burden on society, affecting millions of people globally. In addition to genetic factors, recent studies indicate that environmental experiential factors may contribute the pathogenesis these diseases. Early life adversity (ELA) has profound impact brain function health later in life. rodent models, exposure ELA results specific deficits aggravated AD pathology. Extensive concerns have been raised regarding higher risk developing impairments with history ELA. this review, we scrutinize findings from human animal focusing connection AD. These discoveries suggest ELA, especially at early postnatal stages, increases susceptibility terms mechanisms, could lead dysregulation hypothalamus-pituitary-adrenal axis, altered gut microbiome, persistent inflammation, oligodendrocyte dysfunction, hypomyelination, aberrant adult hippocampal neurogenesis. Crosstalks among events synergistically Additionally, discuss several interventions alleviate adverse consequences Further investigation into crucial area will help improve management reduce related neurological conditions.

Язык: Английский

---

Enduring disruption of reward and stress circuit activities by early-life adversity in male rats

Translational Psychiatry, Год журнала: 2022, Номер 12(1)

Опубликована: Июнь 16, 2022

Abstract In humans, early-life adversity (ELA) such as trauma, poverty, and chaotic environment is linked to increased risk of later-life emotional disorders including depression substance abuse. These involve underlying disruption reward circuits likely vary by sex. Accordingly, we previously found that ELA leads anhedonia for natural rewards cocaine in male rodents, whereas females instead increases vulnerability addiction-like use opioid drugs palatable food. While these findings suggest ELA-induced circuitry may differ between the sexes, specific circuit nodes are influenced either sex remain poorly understood. Here, adult Sprague-Dawley rats, ask how impacts addiction-relevant behaviors tested after females. We probe potential mechanisms males assessing opioid-associated neuronal activation stress nucleus accumbens (NAc), amygdala, medial prefrontal cortex (mPFC), paraventricular thalamus. find diminishes opioid-seeking males, alters heroin-induced NAc, PFC, suggesting a circuit-based mechanism. studies demonstrate behavioral neurobiological disruptions consistent with unlike seeking saw Our findings, taken together our prior work, men women could face qualitatively different mental health consequences ELA, which be essential individually tailoring future intervention strategies.

Язык: Английский

---

Ventral pallidal regulation of motivated behaviors and reinforcement

Frontiers in Neural Circuits, Год журнала: 2023, Номер 17

Опубликована: Фев. 2, 2023

The interconnected nuclei of the ventral basal ganglia have long been identified as key regulators motivated behavior, and dysfunction this circuit is strongly implicated in mood substance use disorders. pallidum (VP) a central node ganglia, recent studies revealed complex VP cellular heterogeneity cell- circuit-specific regulation reward, aversion, motivation, drug-seeking behaviors. Although canonically considered relay output structure for circuit, emerging data indicate that hub an extensive network reward processing motivation extends beyond classically defined borders. neurons respond temporally faster show more advanced coding prediction error than upstream nucleus accumbens, regulate activity mesencephalon dopamine system. This review will summarize findings literature provide update on behaviors reinforcement by with specific focus In addition, we discuss mechanisms which stress drug exposure alter functioning produce susceptibility to neuropsychiatric Lastly, outline unanswered questions identify future directions necessary further clarify role Significance: Research last decade has Novel insights obtained using interrogation strategies led major shift our understanding region. Here, comprehensive integrate novel existing highlight linchpin neural systems aversion. animal models

Язык: Английский

---

Enduring Neurobiological Consequences of Early-Life Stress: Insights from Rodent Behavioral Paradigms

Biomedicines, Год журнала: 2024, Номер 12(9), С. 1978 - 1978

Опубликована: Сен. 2, 2024

Stress profoundly affects physical and mental health, particularly when experienced early in life. Early-life stress (ELS) encompasses adverse childhood experiences such as abuse, neglect, violence, or chronic poverty. These stressors can induce long-lasting changes brain structure function, impacting areas involved emotion regulation, cognition, response. Consequently, individuals exposed to high levels of ELS are at an increased risk for health disorders like depression, anxiety, post-traumatic disorders, well issues, including metabolic cardiovascular disease, cancer. This review explores the biological psychological consequences early-life adversity paradigms rodents, maternal separation deprivation limited bedding nesting. The study these experimental models have revealed that organism’s response is complex, involving genetic epigenetic mechanisms, associated with dysregulation physiological systems nervous, neuroendocrine, immune systems, a sex-dependent fashion. Understanding impact crucial developing effective interventions preventive strategies humans stressful traumatic childhood.

Язык: Английский

---

The Protective Effect of Social Reward on Opioid and Psychostimulant Reward and Relapse: Behavior, Pharmacology, and Brain Regions

Journal of Neuroscience, Год журнала: 2022, Номер 42(50), С. 9298 - 9314

Опубликована: Дек. 14, 2022

Until recently, most modern neuroscience research on addiction using animal models did not incorporate manipulations of social factors. Social factors play a critical role in human addiction: isolation and exclusion can promote drug use relapse, while connections inclusion tend to be protective. Here, we discuss the state literature opioid psychostimulant preference, self-administration, relapse. We first summarize results from rodent studies behavioral, pharmacological, circuit mechanisms protective effect traditional experimenter-controlled interaction procedures conditioned place Next, behavioral brain-mechanism newer operant social-interaction that inhibit self-administration conclude by discussing how reviewed point future directions for field other psychiatric fields, their implications mechanistic understanding development new treatments. SIGNIFICANCE STATEMENT In this review, propose incorporating into could improve accounts help close gaps translating discovery treatment. both procedures. then potential clinical implications.

Язык: Английский

---

Sex differences in addiction-relevant behavioral outcomes in rodents following early life stress

Addiction Neuroscience, Год журнала: 2023, Номер 6, С. 100067 - 100067

Опубликована: Янв. 26, 2023

In humans, exposure to early life stress (ELS) is an established risk factor for the development of substance use disorders (SUDs) during later life. Similarly, rodents exposed ELS involving disrupted mother-infant interactions, such as maternal separation (MS) or adverse caregiving due scarcity-adversity induced by limited bedding and nesting (LBN) conditions, also exhibit long-term alterations in alcohol drug consumption. both humans rodents, there a range addiction-related behaviors that are associated with even predictive subsequent SUDs. these include increased anxiety-like behavior, impulsivity, novelty-seeking, altered intake patterns, well reward-related processes consummatory social behaviors. Importantly, expression often varies throughout lifespan. Moreover, preclinical studies suggest sex differences play role how impacts reward phenotypes underlying brain circuitry. Here, addiction-relevant behavioral outcomes mesolimbic dopamine (DA) dysfunction resulting from form MS LBN discussed focus on age- sex-dependent effects. Overall, findings may increase susceptibility SUDs interfering normal maturation function.

Язык: Английский

---

Individual longitudinal changes in DNA-methylome identify signatures of early-life adversity and correlate with later outcome

Neurobiology of Stress, Год журнала: 2024, Номер 31, С. 100652 - 100652

Опубликована: Май 31, 2024

Adverse early-life experiences (ELA) affect a majority of the world's children. Whereas enduring impact ELA on cognitive and emotional health is established, there are no tools to predict vulnerability consequences in an individual child. Epigenetic markers including peripheral-cell DNA-methylation profiles may encode provide predictive outcome markers, yet interindividual variance human genome rapid changes DNA methylation childhood pose significant challenges. Hoping mitigate these challenges we examined relation several dimensions using within-subject longitudinal design high methylation-change threshold. was analyzed buccal swab / saliva samples collected twice (neonatally at 12 months) 110 infants. We identified CpGs differentially methylated across time for each child determined whether they associated with indicators executive function age 5. assessed sex differences derived sex-dependent 'impact score' based sites that most contributed changes. Changes between two reflected age-related trends correlated years later. Among tested life factors income needs ratios, maternal sensitivity, body mass index infant sex, unpredictability parental household signals strongest predictor function. In girls, interacted presage Thus, longitudinal, signature potential marker outcome.

Язык: Английский

---

Early Life Social Stress Causes Sex- and Region-Dependent Dopaminergic Changes that Are Prevented by Minocycline

Molecular Neurobiology, Год журнала: 2022, Номер 59(6), С. 3913 - 3932

Опубликована: Апрель 18, 2022

Early life stress (ELS) is known to modify trajectories of brain dopaminergic development, but the mechanisms underlying have not been determined. ELS perturbs immune system and microglia reactivity, inflammation influence transmission development. Whether mediate effects on dopamine (DA) development still unknown. We explored repeated early social in male female mice through histological, electrophysiological, transcriptomic analyses. Furthermore, we tested whether these could be mediated by ELS-induced altered microglia/immune activity a pharmacological approach. found that DA neurons morphology, reduced transporter (DAT) tyrosine hydroxylase expression, lowered DAT-mediated currents ventral tegmental area substantia nigra only. Notably, stress-induced alterations were prevented minocycline, an inhibitor activation. Transcriptome analysis developing revealed caused downregulation alteration hormonal peptide signaling pathways. Results from this study offer new insight into response maturation after ELS, providing evidence neuroimmune interaction, sex differences, regional specificity.

Язык: Английский

---

“I Grew Up Amidst Alcohol and Drugs:” a Qualitative Study on the Lived Experiences of Parental Substance Use Among Adults Who Developed Substance Use Disorders Themselves

Frontiers in Psychiatry, Год журнала: 2022, Номер 13

Опубликована: Фев. 2, 2022

Experiencing parental substance use (PSU) has been associated with a heightened risk of developing disorders (SUDs) in offspring. The primary goal this study was to explore perspectives adult children lived experience PSU who also developed SUDs themselves through first-hand experience. This conducted Flanders (Belgium). A qualitative exploratory research design applied. Seventeen semi-structured interviews were parents (range: 29-48 years) had SUDs. All audio-taped and transcribed verbatim. Three overarching themes emerged thematic analysis: 1) loneliness neglect childhood; 2) stigma the self; 3) role social connection recovery. narratives highlighted central feelings loneliness, isolation belonging among childhood adulthood. Increasing public awareness on impact accessible support is needed overcome remove barriers inclusion for Findings may prove valuable informing policy, program treatment development aimed at breaking maladaptive intergenerational cycles.

Язык: Английский

---