Early Life Stress and Risks for Opioid Misuse: Review of Data Supporting Neurobiological Underpinnings

A robust body of research has shown that traumatic experiences occurring during critical developmental periods of childhood when neuronal plasticity is high increase risks for a spectrum of physical and mental health problems in adulthood, including substance use disorders. However, until recently, relatively few studies had specifically examined the relationships between early life stress (ELS) and opioid use disorder (OUD). Associations with opioid use initiation, injection drug use, overdose, and poor treatment outcome have now been demonstrated. In rodents, ELS has also been shown to increase the euphoric and decrease antinociceptive effects of opioids, but little is known about these processes in humans or about the neurobiological mechanisms that may underlie these relationships. This review aims to establish a theoretical model that highlights the mechanisms by which ELS may alter opioid sensitivity, thereby contributing to future risks for OUD. Alterations induced by ELS in mesocorticolimbic brain circuits, and endogenous opioid and dopamine neurotransmitter systems are described. The limited but provocative evidence linking these alterations with opioid sensitivity and risks for OUD is presented. Overall, the findings suggest that better understanding of these mechanisms holds promise for reducing vulnerability, improving prevention strategies, and prescribing guidelines for high-risk individuals.

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Early Life Stress and Pediatric Posttraumatic Stress Disorder

Brain Sciences ◽

10.3390/brainsci10030169 ◽

2020 ◽

Vol 10 (3) ◽

pp. 169 ◽

Cited By ~ 2

Author(s):

Panagiota Pervanidou ◽

Gerasimos Makris ◽

George Chrousos ◽

Agorastos Agorastos

Keyword(s):

Posttraumatic Stress Disorder ◽

Posttraumatic Stress ◽

Life Stress ◽

Early Life ◽

Stress Disorder ◽

Early Life Stress ◽

Traumatic Experiences ◽

Stress System ◽

Critical Periods ◽

Physical And Mental Health

Traumatic stress exposure during critical periods of development may have essential and long-lasting effects on the physical and mental health of individuals. Two thirds of youth are exposed to potentially traumatic experiences by the age of 17, and approximately 5% of adolescents meet lifetime criteria for posttraumatic stress disorder (PTSD). The role of the stress system is the maintenance of homeostasis in the presence of real/perceived and acute/chronic stressors. Early-life stress (ELS) has an impact on neuronal brain networks involved in stress reactions, and could exert a programming effect on glucocorticoid signaling. Studies on pediatric PTSD reveal diverse neuroendocrine responses to adverse events and related long-term neuroendocrine and epigenetic alterations. Neuroendocrine, neuroimaging, and genetic studies in children with PTSD and ELS experiences are crucial in understanding risk and resilience factors, and also the natural history of PTSD.

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Identifying Causative Mechanisms Linking Early-Life Stress to Psycho-Cardio-Metabolic Multi-Morbidity: The EarlyCause Project

10.1101/2020.07.08.181958 ◽

2020 ◽

Author(s):

Nicole Mariani ◽

Alessandra Borsini ◽

Charlotte A.M. Cecil ◽

Janine F. Felix ◽

Sylvain Sebert ◽

...

Keyword(s):

Life Stress ◽

Early Life ◽

Large Scale ◽

Early Life Stress ◽

Physical And Mental Health ◽

Cellular Models ◽

Causal Pathways ◽

Metabolic Systems ◽

Shared Risk ◽

The Impact

AbstractIntroductionDepression, cardiovascular diseases and diabetes are among the major non-communicable diseases, leading to significant disability and mortality worldwide. These diseases may share environmental and genetic determinants associated with multimorbid patterns. Stressful early-life events are among the primary factors associated with the development of mental and physical diseases. However, possible causative mechanisms linking early life stress (ELS) with psycho-cardio-metabolic (PCM) multi-morbidity are not well understood. This prevents a full understanding of causal pathways towards shared risk of these diseases and the development of coordinated preventive and therapeutic interventions.Methods and analysisThis paper describes the study protocol for EarlyCause, a large-scale and inter-disciplinary research project funded by the European Union’s Horizon 2020 research and innovation programme. The project takes advantage of human longitudinal birth cohort data, animal studies and cellular models to test the hypothesis of shared mechanisms and molecular pathways by which ELS shape an individual’s physical and mental health in adulthood. The study will research in detail how ELS converts into biological signals embedded simultaneously or sequentially in the brain, the cardiovascular and metabolic systems. The research will mainly focus on four biological processes including possible alterations of the epigenome, neuroendocrine system, inflammatome, and the gut microbiome. Life course models will integrate the role of modifying factors as sex, socioeconomics, and lifestyle with the goal to better identify groups at risk as well as inform promising strategies to reverse the possible mechanisms and/or reduce the impact of ELS on multi-morbidity development in high-risk individuals. These strategies will help better manage the impact of multi-morbidity on human health and the associated risk.Ethics and disseminationThe study has been approved by the Ethics Board of the European Commission. The results will be published in peer-reviewed academic journals, and disseminated to and communicated with clinicians, patient organisations and media.

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Functional Alterations and Cerebral Variations in Humans Exposed to Early Life Stress

Frontiers in Public Health ◽

10.3389/fpubh.2020.536188 ◽

2021 ◽

Vol 8 ◽

Author(s):

Carlos A. González-Acosta ◽

Christian A. Rojas-Cerón ◽

Efraín Buriticá

Keyword(s):

Psychiatric Disorders ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Anterior Cingulate ◽

Brain Anatomy ◽

Physical And Mental Health ◽

Post Traumatic Stress ◽

Early Stress ◽

The Impact

Early life stress can be caused by acute or chronic exposure to childhood events, such as emotional, physical, sexual abuse, and neglect. Early stress is associated with subsequent alterations in physical and mental health, which can extend into adolescence, adulthood, and even old age. The effects of early stress exposure include alterations in cognitive, neuropsychological, and behavioral functions, and can even lead to the development of psychiatric disorders and changes in brain anatomy. The present manuscript provides a review of the main findings on these effects reported in the scientific literature in recent decades. Early life stress is associated with the presence of psychiatric disorders, mainly mood disorders such as depression and risk of suicide, as well as with the presence of post-traumatic stress disorder. At the neuropsychological level, the involvement of different mental processes such as executive functions, abstract reasoning, certain memory modalities, and poor school-skill performance has been reported. In addition, we identified reports of alterations of different subdomains of each of these processes. Regarding neuroanatomical effects, the involvement of cortical regions, subcortical nuclei, and the subcortical white matter has been documented. Among the telencephalic regions most affected and studied are the prefrontal cortex, the hippocampus, the amygdala, and the anterior cingulate cortex. Understanding the impact of early life stress on postnatal brain development is very important for the orientation of therapeutic intervention programs and could help in the formulation and implementation of preventive measures as well as in the reorientation of research targets.

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Associations between early life stress, self-reported traumatic experiences across the lifespan and leukocyte telomere length in elderly adults

Biological Psychology ◽

10.1016/j.biopsycho.2014.02.002 ◽

2014 ◽

Vol 97 ◽

pp. 35-42 ◽

Cited By ~ 49

Author(s):

Katri Savolainen ◽

Johan G. Eriksson ◽

Laura Kananen ◽

Eero Kajantie ◽

Anu-Katriina Pesonen ◽

...

Keyword(s):

Telomere Length ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Traumatic Experiences ◽

Leukocyte Telomere Length ◽

Elderly Adults

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Combination of early life stress and traumatic experiences across the lifespan are associated with shorter leukocyte telomere length in later adulthood: the Helsinki Birth Cohort Study

European Journal of Psychotraumatology ◽

10.3402/ejpt.v3i0.19366 ◽

2012 ◽

Vol 3 (0) ◽

Author(s):

Katri Savolainen ◽

Johan G. Eriksson ◽

Laura Kananen ◽

Eero Kajantie ◽

Iiris Hovatta ◽

...

Keyword(s):

Cohort Study ◽

Telomere Length ◽

Birth Cohort ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Traumatic Experiences ◽

Birth Cohort Study ◽

Leukocyte Telomere Length

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Identifying causative mechanisms linking early-life stress to psycho-cardio-metabolic multi-morbidity: The EarlyCause project

PLoS ONE ◽

10.1371/journal.pone.0245475 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0245475

Author(s):

Nicole Mariani ◽

Alessandra Borsini ◽

Charlotte A. M. Cecil ◽

Janine F. Felix ◽

Sylvain Sebert ◽

...

Keyword(s):

Life Stress ◽

Early Life ◽

Large Scale ◽

Early Life Stress ◽

Physical And Mental Health ◽

Cellular Models ◽

Causal Pathways ◽

Metabolic Systems ◽

Shared Risk ◽

The Impact

Introduction Depression, cardiovascular diseases and diabetes are among the major non-communicable diseases, leading to significant disability and mortality worldwide. These diseases may share environmental and genetic determinants associated with multimorbid patterns. Stressful early-life events are among the primary factors associated with the development of mental and physical diseases. However, possible causative mechanisms linking early life stress (ELS) with psycho-cardio-metabolic (PCM) multi-morbidity are not well understood. This prevents a full understanding of causal pathways towards the shared risk of these diseases and the development of coordinated preventive and therapeutic interventions. Methods and analysis This paper describes the study protocol for EarlyCause, a large-scale and inter-disciplinary research project funded by the European Union’s Horizon 2020 research and innovation programme. The project takes advantage of human longitudinal birth cohort data, animal studies and cellular models to test the hypothesis of shared mechanisms and molecular pathways by which ELS shapes an individual’s physical and mental health in adulthood. The study will research in detail how ELS converts into biological signals embedded simultaneously or sequentially in the brain, the cardiovascular and metabolic systems. The research will mainly focus on four biological processes including possible alterations of the epigenome, neuroendocrine system, inflammatome, and the gut microbiome. Life-course models will integrate the role of modifying factors as sex, socioeconomics, and lifestyle with the goal to better identify groups at risk as well as inform promising strategies to reverse the possible mechanisms and/or reduce the impact of ELS on multi-morbidity development in high-risk individuals. These strategies will help better manage the impact of multi-morbidity on human health and the associated risk.

Download Full-text