How adverse childhood experiences get under the skin: A systematic review, integration and methodological discussion on threat and reward learning mechanisms

eLife, Journal Year: 2024, Volume and Issue: 13

Published: July 16, 2024

Adverse childhood experiences (ACEs) are a major risk factor for the development of multiple psychopathological conditions, but mechanisms underlying this link poorly understood. Associative learning encompasses key through which individuals learn to important environmental inputs emotional and behavioral responses. ACEs may impact normative maturation associative processes, resulting in their enduring maladaptive expression manifesting psychopathology. In review, we lay out systematic methodological overview integration available evidence proposed association between threat reward processes. We summarize results from literature search (following PRISMA guidelines) yielded total 81 articles (threat: n=38, reward: n=43). Across fields, behaviorally, observed converging pattern aberrant with history ACEs, independent other sample characteristics, specific ACE types, outcome measures. Specifically, blunted was reflected reduced discrimination safety cues, primarily driven by diminished responding conditioned cues. Furthermore, attenuated manifested accuracy rate tasks involving acquisition contingencies. Importantly, emerged despite substantial heterogeneity assessment operationalization across both fields. conclude that represent mechanistic route become physiologically neurobiologically embedded ultimately confer greater closing, discuss potentially fruitful future directions research field, including considerations.

Language: Английский

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Neural and psychophysiological markers of intolerance of uncertainty

International Journal of Psychophysiology, Journal Year: 2023, Volume and Issue: 184, P. 94 - 99

Published: Jan. 4, 2023

Language: Английский

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Central amygdala CRF+ neurons promote heightened threat reactivity following early life adversity in mice

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 29, 2024

Abstract Failure to appropriately predict and titrate reactivity threat is a core feature of fear anxiety-related disorders common following early life adversity (ELA). A population neurons in the lateral central amygdala (CeAL) expressing corticotropin releasing factor (CRF) have been proposed be key processing different intensities mediate active expression. Here, we use vivo fiber photometry show that ELA results sex-specific changes activity CeAL CRF+ neurons, yielding divergent mechanisms underlying augmented startle mice, translationally relevant behavior indicative heightened hypervigilance. Further, chemogenic inhibition selectively diminishes produces long-lasting suppression reactivity. These findings identify mechanism for sex-differences susceptibility anxiety broad implications understanding neural circuitry encodes gates behavioral expression fear.

Language: Английский

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Reduced discrimination between signals of danger and safety but not overgeneralization is linked to exposure to childhood adversity in healthy adults

eLife, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 20, 2025

Childhood adversity is a strong predictor of developing psychopathological conditions. Multiple theories on the mechanisms underlying this association have been suggested which, however, differ in operationalization ‘exposure.’ Altered (threat) learning represent central by which environmental inputs shape emotional and cognitive processes ultimately behavior. 1402 healthy participants underwent fear conditioning paradigm (acquisition training, generalization), while acquiring skin conductance responses (SCRs) ratings (arousal, valence, contingency). was operationalized as (1) dichotomization, following (2) specificity model, (3) cumulative risk (4) dimensional model. Individuals exposed to childhood showed blunted physiological reactivity SCRs, but not ratings, reduced CS+/CS- discrimination during both phases, mainly driven attenuated CS+ responding. The latter evident across different operationalizations ‘exposure’ theories. None tested clear explanatory superiority. Notably, remarkably pattern increased responding CS- reported literature for anxiety patients, suggesting that individuals may specific sub-sample. We highlight linking (vulnerability to) psychopathology need refinement.

Language: Английский

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Fear-Conditioning to Unpredictable Threats Reveals Sex and Strain Differences in Rat Fear-Potentiated Startle (FPS)

Neuroscience, Journal Year: 2023, Volume and Issue: 530, P. 108 - 132

Published: Aug. 26, 2023

Language: Английский

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How adverse childhood experiences get under the skin: A systematic review, integration and methodological discussion on threat and reward learning mechanisms

Published: May 17, 2023

Adverse childhood experiences (ACEs) are a major risk factor for the development of multiple psychopathological conditions, but mechanisms underlying this link poorly understood. Associative learning encompasses key through which individuals learn to important environmental inputs emotional and behavioral responses. ACEs may impact normative maturation associative processes, resulting in their enduring maladaptive expression manifesting psychopathology. In review, we lay out systematic methodological overview integration available evidence proposed association between threat reward processes. We summarize results from literature search (following PRISMA guidelines) yielded total 81 articles (threat: n=38, reward: n=43). Across fields, behaviorally, observed converging pattern aberrant with history ACEs, independent other sample characteristics, specific ACE types, outcome measures. Specifically, blunted was reflected reduced discrimination safety cues, primarily driven by diminished responding conditioned cues. Furthermore, attenuated manifested accuracy rate tasks involving acquisition contingencies. Importantly, emerged despite substantial heterogeneity assessment operationalization across both fields. conclude that represent mechanistic route become physiologically neurobiologically embedded ultimately confer greater closing, discuss future directions research field, including considerations.

Language: Английский

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Reduced discrimination between signals of danger and safety but not overgeneralization is linked to exposure to childhood adversity in healthy adults

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Dec. 20, 2023

Childhood adversity is a strong predictor of developing psychopathological conditions. Multiple theories on the mechanisms underlying this association have been suggested which, however, differ in operationalization 'exposure.' Altered (threat) learning represent central by which environmental inputs shape emotional and cognitive processes ultimately behavior. 1402 healthy participants underwent fear conditioning paradigm (acquisition training, generalization), while acquiring skin conductance responses (SCRs) ratings (arousal, valence, contingency). was operationalized as (1) dichotomization, following (2) specificity model, (3) cumulative risk (4) dimensional model. Individuals exposed to childhood showed blunted physiological reactivity SCRs, but not ratings, reduced CS+/CS- discrimination during both phases, mainly driven attenuated CS+ responding. The latter evident across different operationalizations 'exposure' theories. None tested clear explanatory superiority. Notably, remarkably pattern increased responding CS- reported literature for anxiety patients, suggesting that individuals may specific sub-sample. We highlight linking (vulnerability to) psychopathology need refinement.

Language: Английский

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Fear-conditioning to unpredictable threats reveals sex differences in rat fear-potentiated startle (FPS)

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 8, 2023

Fear-potentiated startle (FPS) has been widely used to study fear processing in humans and rodents. Human studies have shown higher amplitudes exaggerated reactivity unpredictable vs. predictable threats individuals suffering from post-traumatic stress disorder (PTSD). Although human FPS often use both sexes, a surprisingly limited number of rodent females. Here we investigate the effects signal-threat contingency, order threat predictability on sexes. We classic fear-conditioning protocol (100% contingency cue shock pairings, with forward conditioning such that co-terminates shock) compare it modified protocols (70% contingency; backward conditioning; or unpaired). there are no sex differences when corrected for body weight, females demonstrate during fear-conditioning. Both sexes comparable levels cued, non-cued, contextual but show reduced discrimination males. Fear-conditioning 70% (cue co-starts induces similar they differ extinction. Lastly, prominent difference is uncovered following un-paired), showing significantly overall recall, regardless trial type, than This striking might help understand mechanisms underlying incidence PTSD women.Male female rats weightFemale foot-shock males fear-conditioningFemale FPSReversed increases sexesExposure general only

Language: Английский

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Extinction Learning Across Development: Neurodevelopmental Changes and Implications for Pediatric Anxiety Disorders

Current topics in behavioral neurosciences, Journal Year: 2023, Volume and Issue: unknown, P. 237 - 256

Published: Jan. 1, 2023

Language: Английский

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Reduced discrimination between signals of danger and safety but not overgeneralization is linked to exposure to childhood adversity in healthy adults

Published: Oct. 16, 2024

Childhood adversity is a strong predictor for developing psychopathological conditions. Exposure to threat-related childhood has been suggested be specifically linked altered emotional learning as well changes in neural circuits involved responding and fear. Learning mechanisms are particularly interesting they central through which environmental inputs shape cognitive processes ultimately behavior. Multiple theories on the underlying this association have which, however, differ operationalization of “exposure”. In current study, 1,402 physically mentally healthy participants underwent differential fear conditioning paradigm including acquisition generalization phase while skin conductance responses (SCRs) different subjective ratings were acquired. was retrospectively assessed trauma questionnaire (CTQ) classified individuals exposed or unexposed at least moderate according established cut-off criteria. addition, we provide exploratory analyses aiming translate (verbal) how exposure related from threat into statistical models. During training generalization, reduced discrimination SCRs between stimuli signaling danger vs. safety, primarily due cues. no differences degree observed but generally blunted occurred individuals. No groups any experimental phases. The signals safety evident across operationalizations “exposure” guided by theories. Of note, none these tested showed clear explanatory superiority. Our results stand stark contrast typical patterns patients suffering anxiety stress-related disorders (i.e., cues increased signals). However, CS - albeit CS+ also patient risk samples reporting adversity, suggesting that pattern may specific with history adversity. conclude linking psychopathology need refinement.

Language: Английский

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