Aiding and Abetting Anhedonia: Impact of Inflammation on the Brain and Pharmacological Implications

Pharmacological Reviews, Journal Year: 2021, Volume and Issue: 73(3), P. 1084 - 1117

Published: July 1, 2021

Exogenous administration of inflammatory stimuli to humans and laboratory animals chronic endogenous states lead motivational deficits ultimately anhedonia, a core disabling symptom depression present in multiple other psychiatric disorders. Inflammation impacts neurotransmitter systems neurocircuits subcortical brain regions including the ventral striatum, which serves as an integration point for reward processing decision-making. Many mechanisms contribute these effects inflammation, decreased synthesis, release reuptake dopamine, increased synaptic extrasynaptic glutamate, activation kynurenine pathway metabolites quinolinic acid. Neuroimaging data indicate that inflammation-induced manifest striatum functional connectivity circuitry involving ventromedial prefrontal cortex. Neurocircuitry changes turn mediate nuanced on motivation include willingness expend effort while maintaining ability experience reward. Taken together, reveal pathophysiologic phenotype is agnostic diagnosis. Given many involved, this represents opportunity development novel and/or repurposed pharmacological strategies target inflammation associated cellular systemic immunometabolic their downstream brain. To date, clinical trials have failed capitalize unique nature transdiagnostic phenotype, leaving field bereft interpretable meaningful application. However, trial designs incorporating established targets periphery using relevant outcome variables (e.g., anhedonia) are future targeted therapy psychiatry. SIGNIFICANCE STATEMENT: Emerging understanding by peripheral can affect behavior has created unprecedented opportunities treat well represented Mechanisms immunometabolism alterations metabolites, revealing target-rich environment nevertheless yet be fully exploited current drugs employed.

Language: Английский

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Adverse childhood events and cognitive function among young adults: Prospective results from the national longitudinal study of adolescent to adult health

Child Abuse & Neglect, Journal Year: 2021, Volume and Issue: 115, P. 105008 - 105008

Published: March 8, 2021

Language: Английский

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Adverse childhood experiences and severity levels of inflammation and depression from childhood to young adulthood: a longitudinal cohort study

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(4), P. 2255 - 2263

Published: March 3, 2022

Abstract Adverse childhood experiences (ACEs) are associated with depression and systemic inflammation in adults. However, limited longitudinal research has tested these relationships children young people, it is unclear whether an underlying mechanism through which ACEs influence depression. We examined the associations of several across different early-life periods patterns adulthood assessed mediating role inflammation. The data came from Avon Longitudinal Study Parents Children ( N = 3931). prenatal period to adolescence were operationalised using cumulative scores, single adversities, dimensions derived factor analysis. Inflammation (C-reactive protein) was measured on three occasions (9–18 years) depressive symptoms ascertained four (18–23 years). Latent class growth analysis employed delineate group-based trajectories between inflammation/depression multinomial logistic regression Most types all elevated trajectories, larger for threat-related adversities compared other ACEs. Bullying victimisation sexual abuse late childhood/adolescence CRP while unrelated also did not mediate These results suggest that consistently depression, whereas weak people. Interventions targeting this population might offer protection against

Language: Английский

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Adverse childhood experiences and premature mortality through mid-adulthood: A five-decade prospective study

The Lancet Regional Health - Americas, Journal Year: 2022, Volume and Issue: 15, P. 100349 - 100349

Published: Aug. 23, 2022

Adverse childhood experiences (ACEs) can have lasting effects on adult health and survival. In this study, we aimed to examine how the cumulative number clustering patterns of ACEs were related premature mortality.Participants (N=46 129; 45% White, 48% Black; 49·5% females) offspring (born in 1959-1966) participants enrolled Collaborative Perinatal Project (CPP). We conducted latent class analysis assessed between children's birth age seven. also calculated ACE scores 13 individual ACEs. Cox regression models used associations clusters with risk mortality from adolescence mid-adulthood.At start follow-up for 1979, 12-20 years old (Mean=15·99 years), within 38-year through 2016, 3 344 deaths observed among 46 129 CPP offspring. Five classes identified. Compared children Low Adversity (48% sample), Family Instability (9%, HR=1·28, 95%CI 1·07-1·53), Poverty & Crowded Housing (21%, HR=1·41, 1·24-1·62), Parental Separation (19%, HR=1·50, 1·33-1·68) had higher hazards mortality. addition, 2 (HR=1·27, 1·14-1·41), (HR=1·29, 1·15-1·45), 4+ (HR=1·45, 1·30-1·61) than those no ACE. The (HR=1·28, 1·10-1·49) (HR=1·23, 1·02-1·48) remained associated mortality, beyond (HR=1·05, 1·01-1·08).About half cohort experienced early life adversities that clustered into four distinct patterns, which different It is important deepen our understanding specific affect better inform approaches prevention interventions.

Language: Английский

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Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries

Physiological Reviews, Journal Year: 2023, Volume and Issue: 104(1), P. 473 - 532

Published: Sept. 21, 2023

The normal stress response in humans is governed by the hypothalamic-pituitary-adrenal (HPA) axis through heightened mechanisms during stress, raising blood levels of glucocorticoid hormone cortisol. Glucocorticoids are quintessential compounds that balance proper functioning numerous systems mammalian body. They also generated synthetically and preeminent therapy for inflammatory diseases. act binding to nuclear receptor transcription factor (GR), which has two main isoforms (GRα GRβ). Our classical understanding signaling from GRα isoform, binds hormone, whereas GRβ no known ligands. With glucocorticoids being involved many physiological cellular processes, even small disruptions their release via HPA axis, or changes GR isoform expression, can have dire ramifications on health. Long-term chronic lead a glucocorticoid-resistant state, we deliberate how this impacts disease treatment. Chronic treatment noticeable side effects such as weight gain, adiposity, diabetes, others discuss detail. There sexually dimorphic responses glucocorticoids, women tend more hyperresponsive than men. This review summarizes our critically analyzes beneficial deleterious sexual differences cause dichotomy responses. We future propose new concept dual agonist postulate why activating both may prevent resistance.

Language: Английский

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Inflammation as a mediator between adverse childhood experiences and adult depression: A meta-analytic structural equation model

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 357, P. 85 - 96

Published: April 25, 2024

Exposure to adverse childhood experiences (ACEs) confers a higher risk of developing depression in adulthood, yet the mediation inflammation remains under debate. To test this model, we conducted systematic review and two-stage structural equation modelling meta-analysis studies reporting correlations between ACEs before age 18, inflammatory markers severity adulthood. Scopus, Pubmed, Medline, PsycInfo, CINAHL were searched up 2 October 2023. Twenty-two data on C-reactive protein (CRP, n = 12,935), interleukin-6 (IL-6, 4108), tumour necrosis factor-α (TNF-α, 2256) composite measures (n 1674) included. Unadjusted models revealed that CRP (β 0.003, 95 % LBCI 0.0002 0.0068), IL-6 0.001 0.006), 0.009, 0.004 0.018) significantly mediated association adult depression. The effects no longer survived after adjusting for BMI; however, serial model BMI sequentially 0.002, 0.0005 0.0046), accounting 14.59 9.94 variance depressive symptoms, respectively. Due cross-sectional nature assessment findings should be approached with caution; results suggest complex interactions psychoneuroimmunological metabolic factors underlie adulthood

Language: Английский

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Family Socioeconomic Status and Exposure to Childhood Trauma: Racial Differences

Children, Journal Year: 2020, Volume and Issue: 7(6), P. 57 - 57

Published: June 3, 2020

Minorities' diminished returns (MDRs) refer to weaker effects of socioeconomic status (SES) indicators such as parental educational attainment and family income in generating tangible childhood outcomes for racial ethnic minorities compared the majority group, a pattern prevalent US. Our existing knowledge is minimal, however, about SES on reducing exposure trauma.To determine if there was difference between non-Hispanic whites (NHW) blacks (NHB) effect trauma among children ages 8-11 years old.In this cross-sectional study, we analyzed data from 4696 NHW or NHB American 8-11-year-old who were participants Adolescent Brain Cognitive Development (ABCD) Study. The independent variables income. primary outcome 1 2+ traumas, measured by Kiddie Schedule Affective Disorders Schizophrenia (K-SADS) semi-structured interview. Polynomial regression used analysis.Parental education had statistically significant protective (negative) trauma, indicating high highly educated families exposed lower level trauma. However, race/ethnicity showed interactions with children. Race-specific models but not children.The against are systematically NHBs NHWs. To minimize racial/ethnic health gaps, should be addressed. There need programs interventions that equalize only also marginal groups. Such efforts require addressing structural societal barriers hinder translating their resources into outcomes. studies can MDRs families, similarly secure presence resources.

Language: Английский

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Inflammation and early life stress: An updated review of childhood trauma and inflammatory markers in adulthood

Pharmacology Biochemistry and Behavior, Journal Year: 2021, Volume and Issue: 211, P. 173291 - 173291

Published: Oct. 22, 2021

Language: Английский

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The association of child maltreatment and systemic inflammation in adulthood: A systematic review

PLoS ONE, Journal Year: 2021, Volume and Issue: 16(4), P. e0243685 - e0243685

Published: April 8, 2021

Introduction Child maltreatment (CM) is associated with mental and physical health disorders in adulthood. Some studies have identified elevated markers of systemic inflammation adult survivors CM, may mediate the association between CM later problems. However, there are methodological inconsistencies findings conflicting. We performed a systematic review to examine adults. Methods A pre-registered was following PRISMA guidelines. Medline, Embase, Scopus PsychInfo were searched for blood Quality assessed using Crowe Critical Appraisal Tool. had intended perform meta-analysis, but this not possible due variation study design reporting. Results Forty-four articles met criteria inclusion review. The most widely reported biomarkers C-Reactive Protein (CRP) (n = 27), interleukin-6 (IL-6) 24) Tumour Necrosis Factor-alpha (TNF-a) 17). Three prospective (all relating CRP) remainder retrospective. 86% based high income countries. In studies, CRP retrospective Methodological issues construct methods analysis, accounting confounding or mediating variables (particularly Body Mass Index) contribute uncertainty field. Conclusions There some robust evidence from that significant literature proposed measures future researchers could employ improve consistency across studies. Further prospective, longitudinal, research comparable careful consideration required bring clarity

Language: Английский

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A Scoping Review on Adverse Childhood Experiences Studies Using Latent Class Analysis: Strengths and Challenges

Trauma Violence & Abuse, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 18, 2023

Adverse childhood experiences (ACEs) studies reveal the profound impacts of experiencing trauma and hardships in childhood. However, cumulative risk approach treating ACEs obscures heterogeneity their consequences, making actionable interventions impossible. latent class analysis (LCA) has increasingly been used to address these concerns by identifying underlying subgroups people who experience distinctive patterns co-occurring ACEs. Though LCA its strengths, existing research produces few comparable findings because results are dependent on measures indicators, which vary widely study. Therefore, a scoping review using that focuses measures, is needed inform field. Following Arksey O'Malley's five-stage methodological framework, we first identified 211 articles from databases EBSCOhost, PubMed, Scopus "adverse experiences" for title search "latent analysis" abstract search. Based inclusion criteria peer-reviewed written English published 2012 2022 exclusion nonempirical not analyzing ACEs, finally selected 58 this review. Results showed endorsed community examine associations between human health well-being across culturally diverse populations. overcame limitations traditional methods revealing specific clusters exert potent effects certain outcomes. arbitrary nature selecting limited use theory impedes field moving forward.

Language: Английский

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