scholarly journals Brain mechanisms of insomnia: new perspectives on causes and consequences

2020 ◽  
Author(s):  
Eus J.W. Van Someren
Keyword(s):  
Mental Health ◽  
Life Stress ◽  
Animal Studies ◽  
Common Mental Disorder ◽  
Early Life Stress ◽  
Sleep Regulation ◽  
Major Life Events ◽  
Major Life ◽  
Brain Circuits ◽  
Brain Structure And Function

While insomnia is the second most common mental disorder, progress in our understanding of underlying neurobiological mechanisms has been limited. The present review addresses the definition and prevalence of insomnia and explores its subjective and objective characteristics across the 24-hour day. Subsequently, the review extensively addresses how the vulnerability to develop insomnia is affected by gene variants, early life stress and major life events and brain structure and function. Further supported by the clear mental health risks conveyed by insomnia, the integrated findings suggest that the vulnerability to develop insomnia could rather be found in brain circuits regulating emotion and arousal than in circuits involved in circadian and homeostatic sleep regulation. Finally, a testable model is presented. The model proposes that in people with a vulnerability to develop insomnia, the locus coeruleus is more sensitive to - or receives more input from - the salience network and related circuits, even during REM sleep, when it should normally be sound asleep. This vulnerability may ignite a downwards spiral of insufficient overnight adaptation to distress, resulting in accumulating hyperarousal which in turn impedes restful sleep and moreover increases the risk of other mental health adversity. Sensitized brain circuits are likely to be subjectively experienced as "sleeping with one eye open". The proposed model opens up the possibility for novel intervention studies and animal studies, thus accelerating the ignition of a neuroscience of insomnia, which is direly needed for better treatment.

Addressing Burgeoning Unmet Needs in College Mental Health (Preprint)

2021 ◽  
Author(s):  
Manpreet Kaur Singh ◽  
Alison Malmon ◽  
Obi Felten
Keyword(s):  
Mental Health ◽  
College Students ◽  
Life Stress ◽  
Early Life Stress ◽  
Health Resources ◽  
Integrated Approach ◽  
Support Network ◽  
Full Potential ◽  
Treatment Matching ◽  
Measurement Based Care

UNSTRUCTURED If we can measure the psychosocial impact of mental health challenges for college students, we can triage precious mental health resources through personalized measurement-based care, treatment matching, and a peer-support network. Thus, digitally derived measurement-based self-care, peer care, and clinician-delivered care can be deployed in a way that is meaningful to a student’s needs, preferences, and acceptability, and translated back for daily use and decision making. Indeed, if students can utilize a deeper understanding of behaviors to adopt or change, they can also make decisions about when to seek treatment. This ecological approach to the experience of students is advantageous not only for health promotion, but also better contextualizes symptoms to social determinants of health, early life stress exposure, adversity, and life events. While preliminary mental health digital applications and their uptake are encouraging, we have yet to tap the full potential of a more integrated approach to optimize mental health for all college students. Establishing the foundations of this path forward have never been more imperative.

scholarly journals Impaired developmental microglial pruning of excitatory synapses on CRH-expressing hypothalamic neurons exacerbates stress responses throughout life

2021 ◽  
Author(s):  
Jessica L Bolton ◽  
Annabel K Short ◽  
Shivashankar Othy ◽  
Cassandra L Kooiker ◽  
Manlin Shao ◽  
...  
Keyword(s):  
Stress Responses ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Mental Illnesses ◽  
Excitatory Synapses ◽  
Process Dynamics ◽  
Brain Circuits ◽  
Synapse Density ◽  
And Function

The developmental origins of stress-related mental illnesses are well-established, and early-life stress/adversity (ELA) is an important risk factor. However, it is unclear how ELA impacts the maturation of salient brain circuits, provoking enduring vulnerability to stress and stress-related disorders. Here we find that ELA increases the number and function of excitatory synapses onto stress-sensitive hypothalamic corticotropin-releasing hormone (CRH)-expressing neurons, and implicate disrupted synapse pruning by microglia as a key mechanism. Microglial process dynamics on live imaging, and engulfment of synaptic elements by microglia, were both attenuated in ELA mice, associated with deficient signaling of the microglial phagocytic receptor Mer. Accordingly, selective chemogenetic activation of ELA microglia increased microglial process dynamics and reduced excitatory synapse density to control levels. Selective early-life microglial activation also mitigated the adrenal hypertrophy and prolonged stress responses in adult ELA mice, establishing microglial actions during development as powerful contributors to experience-dependent sculpting of stress-related brain circuits.

scholarly journals The Dual Impact of Early and Concurrent Life Stress on Adults’ Diurnal Cortisol Patterns: A Prospective Study

2019 ◽  
Vol 30 (5) ◽  
pp. 739-747 ◽  
Author(s):  
Ethan S. Young ◽  
Allison K. Farrell ◽  
Elizabeth A. Carlson ◽  
Michelle M. Englund ◽  
Gregory E. Miller ◽  
...  
Keyword(s):  
Life Stress ◽  
High Stress ◽  
Early Life Stress ◽  
Stress Exposure ◽  
Childhood Stress ◽  
Major Life ◽  
Diurnal Cortisol ◽  
A Prospective Study ◽  
Cumulative Model

Major life stress often produces a flat diurnal cortisol slope, an indicator of potential long-term health problems. Exposure to stress early in childhood or the accumulation of stress across the life span may be responsible for this pattern. However, the relative impact of life stress at different life stages on diurnal cortisol is unknown. Using a longitudinal sample of adults followed from birth, we examined three models of the effect of stress exposure on diurnal cortisol: the cumulative model, the biological-embedding model, and the sensitization model. As its name implies, the cumulative model focuses on cumulative life stress. In contrast, the biological-embedding model implicates early childhood stress, and the sensitization model posits that current life stress interacts with early life stress to produce flat diurnal cortisol slopes. Our analyses are consistent with the sensitization model, as they indicate that the combination of high stress exposure early in life and high current stress predict flat diurnal cortisol slopes. These novel findings advance understanding of diurnal cortisol patterns and point to avenues for intervention.

scholarly journals Influence of early life stress on later hypothalamic–pituitary–adrenal axis functioning and its covariation with mental health symptoms: A study of the allostatic process from childhood into adolescence

2011 ◽  
Vol 23 (4) ◽  
pp. 1039-1058 ◽  
Author(s):  
Marilyn J. Essex ◽  
Elizabeth A. Shirtcliff ◽  
Linnea R. Burk ◽  
Paula L. Ruttle ◽  
Marjorie H. Klein ◽  
...  
Keyword(s):  
Mental Health ◽  
Hpa Axis ◽  
Life Stress ◽  
Early Life ◽  
Specific Activity ◽  
Early Life Stress ◽  
Hierarchical Linear Model ◽  
Mental Health Symptoms ◽  
Health Symptoms ◽  
Hypothalamic Pituitary Adrenal

AbstractThe hypothalamic–pituitary–adrenal (HPA) axis is a primary mechanism in the allostatic process through which early life stress (ELS) contributes to disease. Studies of the influence of ELS on children's HPA axis functioning have yielded inconsistent findings. To address this issue, the present study considers multiple types of ELS (maternal depression, paternal depression, and family expressed anger), mental health symptoms, and two components of HPA functioning (traitlike and epoch-specific activity) in a long-term prospective community study of 357 children. ELS was assessed during the infancy and preschool periods; mental health symptoms and cortisol were assessed at child ages 9, 11, 13, and 15 years. A three-level hierarchical linear model addressed questions regarding the influences of ELS on HPA functioning and its covariation with mental health symptoms. ELS influenced traitlike cortisol level and slope, with both hyper- and hypoarousal evident depending on type of ELS. Further, type(s) of ELS influenced covariation of epoch-specific HPA functioning and mental health symptoms, with a tighter coupling of HPA alterations with symptom severity among children exposed previously to ELS. Results highlight the importance of examining multiple types of ELS and dynamic HPA functioning in order to capture the allostatic process unfolding across the transition into adolescence.

scholarly journals The effect of mindfulness-based stress intervention on neurobiological and symptom measures in adolescents with early life stress: A feasibility randomized controlled trial

2020 ◽  
Author(s):  
Zsofia Cohen ◽  
Kelly T. Cosgrove ◽  
Elisabeth Akeman ◽  
Sara Coffey ◽  
Kent Teague ◽  
...  
Keyword(s):  
Mental Health ◽  
Stress Reduction ◽  
Life Stress ◽  
Early Life ◽  
Controlled Trial ◽  
Early Life Stress ◽  
Medium Effect ◽  
Mental Health Symptoms ◽  
Health Symptoms ◽  
Symptom Level

Background Early life stress (ELS) has been linked to poor mental and physical health outcomes in adolescence and adulthood. Mindfulness reduces symptoms of depression and anxiety and improves cognitive and social outcomes in both youth and adults. However, little is known whether mindfulness can mitigate against the adverse neurobiological and psychological effects of ELS. This study aimed to examine the feasibility of conducting a group mindfulness intervention in adolescents with ELS and provide preliminary indication of potential effects on stress-related biomarkers and mental health symptoms. Methods Forty adolescents were randomized to receive either eight sessions of Mindfulness-Based Stress Reduction for Teens in group format (MBSR-T; n = 21) or Control (CTRL; n = 17). Outcomes were assessed at baseline and follow-up and included measures associated with neurobiological functioning (immune and endocrine biomarkers) and self-reported mental health symptoms. Linear mixed effects models were used to assess the effects of group and time on these outcome measures. ResultsSixteen of the 21 adolescents completed the intervention, attending an average of 6.5 sessions. The model examining depressive symptoms revealed a medium effect for symptom reduction [Cohen’s d = .69] in the MBSR-T relateive to CTRL groups.ConclusionsThis study demonstrated feasibilility of conducting a group-based MBSR intervention for adolescents with ELS. There was some evidence for efficacy on a symptom level with potential subtle changes on a biological level. Future larger studies are needed to determine the efficacy of group-based mindfulness interventions in this population.

Major Life Events

2019 ◽  
pp. 6-26
Author(s):  
Scott M. Monroe ◽  
George M. Slavich
Keyword(s):  
Life Events ◽  
Life Stress ◽  
Major Life Events ◽  
Major Life ◽  
Future Directions ◽  
Wide Range ◽  
Key Issues ◽  
Health And Disease ◽  
Human Disorder

The purpose of the present chapter is to provide an overview of key issues involving the definition and assessment of major life events for researchers interested in the effects of life stress on a wide range of disorders. General conceptual and definitional issues are addressed initially, and a conceptual heuristic is proposed for guiding inquiry on major life stress and human disorder. This heuristic is drawn upon to develop principled practices for assessing, operationalizing, and finally quantifying major life events. Throughout the chapter, contemporary approaches for research on major life events are evaluated, their relative merits and shortcomings discussed, and their psychometric credentials formally compared. In closing, we consider future directions for research on major life events and their implications for health and disease.

Stress and the Brain

2018 ◽  
pp. 434-462
Author(s):  
Deanna M. Barch ◽  
David Pagliaccio
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Life Stress ◽  
Early Life ◽  
Diffusion Imaging ◽  
Early Life Stress ◽  
Resting State Functional Connectivity ◽  
Major Depressive ◽  
Brain Structure And Function ◽  
And Function

This chapter reviews associations between early life stress and brain structure and function as assessed by structural and functional magnetic resonance imaging. Particularly, this chapter focuses on structural associations in children and adults and the regional overlap with neural alterations observed in major depressive disorder, though we also more briefly cover diffusion imaging, task-based imaging, and resting-state functional connectivity. Major depressive disorder is highlighted given that early life stress is a critical risk factor for depression and the neural alterations observed with stress and depression may serve as key mediating factors of this association. A brief methodological overview is provided for each neuroimaging domain as well as a discussion of limitations and future directions for this field.

scholarly journals The effect of a mindfulness-based stress intervention on neurobiological and symptom measures in adolescents with early life stress: a randomized feasibility study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zsofia P. Cohen ◽  
Kelly T. Cosgrove ◽  
Elisabeth Akeman ◽  
Sara Coffey ◽  
Kent Teague ◽  
...  
Keyword(s):  
Mental Health ◽  
Depressive Symptoms ◽  
Stress Reduction ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Medium Effect ◽  
Control Group ◽  
Treatment As Usual ◽  
Symptom Level

Abstract Background Early life stress (ELS) has been linked to poor mental and physical health outcomes in adolescence and adulthood. Mindfulness reduces symptoms of depression and anxiety and improves cognitive and social outcomes in both youth and adults. However, little is known whether mindfulness can mitigate against the adverse neurobiological and psychological effects of ELS. This study aimed to examine the feasibility of conducting a group mindfulness intervention in adolescents with ELS and provide preliminary indication of potential effects on stress-related biomarkers and mental health symptoms. Methods Forty adolescents were randomized to receive either eight sessions of Mindfulness-Based Stress Reduction for Teens in group format (MBSR-T; n = 21) or Treatment as Usual Control group (CTRL; n = 17). Outcomes were assessed at baseline and follow-up and included measures associated with neurobiological functioning (immune and endocrine biomarkers) and self-reported mental health (depressive) symptoms. Linear mixed effects models were used to assess the effects of group and time on these outcome measures. Results Sixteen of the 21 adolescents completed the intervention, attending an average of 6.5 sessions. The model examining cortisol responses to stress induction revealed medium effects trending toward significance (Cohen’s d = .56) for anticipatory cortisol levels in the MBSR-T relative to CTRL groups. No significant effects were found in models examining C-reactive protein or interleukin 6 inflammatory markers. The model examining depressive symptoms revealed a medium effect for symptom reduction (Cohen’s d = .69) in the MBSR-T relative to CTRL groups. Conclusions This study demonstrated feasibility of conducting a group-based MBSR-T intervention for adolescents with ELS. There was some evidence for efficacy on a symptom level with potential subtle changes on a biological level. Future larger studies are needed to determine the efficacy of group-based mindfulness interventions in this population. Trial registration Identifier #NCT03633903, registered 16/08/2018.

scholarly journals A Polygenic Score for Body Mass Index is Associated with Depressive Symptoms via Early Life Stress: Evidence for gene-environment correlation

2019 ◽  
Author(s):  
Reut Avinun ◽  
Ahmad R. Hariri
Keyword(s):  
Mental Health ◽  
Body Mass Index ◽  
Depressive Symptoms ◽  
Body Mass ◽  
Indirect Effect ◽  
Genetic Risk ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Gene Environment

ABSTRACTBackgroundIncreasing childhood overweight and obesity rates are associated with not only adverse physical, but also mental health outcomes, including depression. These negative outcomes may be caused and/or exacerbated by the bullying and shaming overweight individuals experience. As body mass index (BMI) can be highly heritable, we hypothesized that a genetic risk toward higher BMI, will predict higher early life stress (ELS), which in turn will predict higher depressive symptoms in adulthood. Such a process will reflect an evocative gene-environment correlation (rGE) wherein an individual’s genetically influenced phenotype evokes a reaction from the environment that subsequently shapes the individual’s health.MethodsWe modeled genetic risk using a polygenic score of BMI derived from a recent large GWAS meta-analysis. Self-reports were used for the assessment of ELS and depressive symptoms in adulthood. The discovery sample consisted of 524 non-Hispanic Caucasian university students from the Duke Neurogenetics Study (DNS; 278 women, mean age 19.78±1.23 years) and the independent replication sample consisted of 5 930 white British individuals from the UK biobank (UKB; 3 128 women, mean age 62.66±7.38 years).ResultsA significant mediation effect was found in the DNS (indirect effect=.207, bootstrapped SE=.10, 95% CI: .014 to .421), and then replicated in the UKB (indirect effect=.04, bootstrapped SE=.01, 95% CI: .018 to .066). Higher BMI polygenic scores were associated with higher depressive symptoms through the experience of higher ELS.ConclusionsOur findings suggest that evocative rGE may contribute to weight-related mental health problems and stress the need for interventions that aim to reduce weight bias, specifically during childhood.

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