Neurobiology and systems biology of stress resilience

Physiological Reviews, Journal Year: 2024, Volume and Issue: 104(3), P. 1205 - 1263

Published: March 14, 2024

Stress resilience is the phenomenon that some people maintain their mental health despite exposure to adversity or show only temporary impairments followed by quick recovery. Resilience research attempts unravel factors and mechanisms make possible harness its insights for development of preventative interventions in individuals at risk acquiring stress-related dysfunctions. Biological has been lagging behind psychological social sciences but seen a massive surge recent years. At same time, progress this field hampered methodological challenges related finding suitable operationalizations study designs, replicating findings, modeling animals. We embed review behavioral, neuroimaging, neurobiological, systems biological findings adults critical methods discussion. find preliminary evidence hippocampus-based pattern separation prefrontal-based cognitive control functions protect against pathological fears aftermath singular, event-type stressors [as found fear-related disorders, including simpler forms posttraumatic stress disorder (PTSD)] facilitating perception safety. Reward system-based pursuit savoring positive reinforcers appear more generalized dysfunctions anxious-depressive spectrum resulting from severe longer-lasting (as depression, comorbid anxiety, PTSD). Links between preserved functioning these neural under neuroplasticity, immunoregulation, gut microbiome composition, integrity barrier blood-brain are beginning emerge. On basis, avenues pointed out.

Language: Английский

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Reactivation of Early-Life Stress-Sensitive Neuronal Ensembles Contributes to Lifelong Stress Hypersensitivity

Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 43(34), P. 5996 - 6009

Published: July 10, 2023

Early-life stress (ELS) is one of the strongest lifetime risk factors for depression, anxiety, suicide, and other psychiatric disorders, particularly after facing additional stressful events later in life. Human animal studies demonstrate that ELS sensitizes individuals to subsequent stress. However, neurobiological basis such sensitization remains largely unexplored. We hypothesized ELS-induced would be detectable at level neuronal ensembles, cells activated by more reactive adult To test this, we leveraged transgenic mice genetically tag, track, manipulate experience-activated neurons. found both male female mice, ELS-activated neurons within nucleus accumbens (NAc), a lesser extent medial prefrontal cortex, were preferentially reactivated whether reactivation ensembles NAc contributes hypersensitivity, expressed hM4Dis receptor control or pups chemogenetically inhibited their activity during experience Inhibition neurons, but not control-tagged ameliorated social avoidance behavior following chronic defeat males. These data provide evidence hypersensitivity encoded corticolimbic ensembles. SIGNIFICANCE STATEMENT enhances sensitivity life, yet mechanisms are unknown. Here, show brain regions remain hypersensitive across life span, quieting these rescues hypersensitivity.

Language: Английский

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Neuroendocrine mechanisms in the links between early life stress, affect, and youth substance use: A conceptual model for the study of sex and gender differences

Frontiers in Neuroendocrinology, Journal Year: 2024, Volume and Issue: 73, P. 101121 - 101121

Published: Jan. 20, 2024

Language: Английский

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

Translational Psychiatry, Journal Year: 2022, Volume and Issue: 12(1)

Published: June 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.

Language: Английский

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Characterizing the mechanisms of social connection

Neuron, Journal Year: 2023, Volume and Issue: 111(24), P. 3911 - 3925

Published: Oct. 6, 2023

Understanding how individuals form and maintain strong social networks has emerged as a significant public health priority result of the increased focus on epidemic loneliness myriad protective benefits conferred by connection. In this review, we highlight psychological neural mechanisms that enable us to connect with others, which in turn help buffer against consequences stress isolation. Central process is experience rewards derived from positive interactions, encourage sharing perspectives preferences unite individuals. Sharing affective states others helps align our understanding world another's, thereby continuing reinforce bonds strengthen relationships. These processes depend systems supporting reward cognitive function. Lastly, also consider limitations associated pursuing healthy connections outline potential avenues future research.

Language: Английский

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The Stress Phenotyping Framework: A multidisciplinary biobehavioral approach for assessing and therapeutically targeting maladaptive stress physiology

Stress, Journal Year: 2024, Volume and Issue: 27(1)

Published: May 6, 2024

Although dysregulated stress biology is becoming increasingly recognized as a key driver of lifelong disparities in chronic disease, we presently have no validated biomarkers toxic physiology; biological, behavioral, or cognitive treatments specifically focused on normalizing processes; and agreed-upon guidelines for treating the clinic evaluating efficacy interventions that seek to reduce improve human functioning. We address these critical issues by (a) systematically describing systems mechanisms are stress; (b) summarizing indicators, biomarkers, instruments assessing response systems; (c) highlighting therapeutic approaches can be used normalize stress-related biopsychosocial also present novel multidisciplinary Stress Phenotyping Framework bring researchers clinicians one step closer realizing goal using precision medicine-based prevent treat stress-associated health problems.

Language: Английский

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Stress and substance use disorders: risk, relapse, and treatment outcomes

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(16)

Published: Aug. 14, 2024

Stress has long been associated with substance misuse and use disorders (SUDs). The past two decades have seen a surge in research aimed at understanding the underlying mechanisms driving this association. This Review introduces multilevel "adaptive stress response" framework, encompassing baseline, acute reaction, recovery return-to-homeostasis phase that occurs varying response times across domains of analysis. It also discusses evidence showing disruption adaptive context chronic repeated stressors, trauma, adverse social drug-related environments, as well drug withdrawal abstinence sequelae. Subjective, cognitive, peripheral, neurobiological disruptions phases their link to inflexible, maladaptive coping; increased craving; relapse risk; maintenance intake are presented. Finally, prevention treatment implications targeting "stress pathophysiology addiction" discussed, along specific aspects may be targeted intervention development rescue stress-related alterations motivation improve SUD outcomes.

Language: Английский

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The VTA dopaminergic system as diagnostic and therapeutical target for Alzheimer's disease

Frontiers in Psychiatry, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 17, 2022

Neuropsychiatric symptoms (NPS) occur in nearly all patients with Alzheimer's Disease (AD). Most frequently they appear since the mild cognitive impairment (MCI) stage preceding clinical AD, and have a prognostic importance. Unfortunately, these also worsen daily functioning of patients, increase caregiver stress accelerate disease progression from MCI to AD. Apathy depression are most common NPS, much attention has been given recent years understand biological mechanisms related their appearance Although for many decades known be abnormalities dopaminergic ventral tegmental area (VTA), direct association between deficits VTA NPS AD never investigated. Fortunately, this scenario is changing studies using preclinical models demonstrated number functional, structural metabolic alterations affecting neurons mesocorticolimbic targets. These findings early, stage, seem correlate NPS. Here, we provide an overview evidence directly linking propose setting which precocious identification can helpful biomarker early diagnosis. In scenario, treatments drugs might slow down delay living activities.

Language: Английский

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Plasticity of synapses and reward circuit function in the genesis and treatment of depression

Neuropsychopharmacology, Journal Year: 2022, Volume and Issue: 48(1), P. 90 - 103

Published: Sept. 3, 2022

Language: Английский

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

Addiction Neuroscience, Journal Year: 2023, Volume and Issue: 6, P. 100067 - 100067

Published: Jan. 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.

Language: Английский

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