Predicting susceptibility and resilience in an animal model of post-traumatic stress disorder (PTSD)

Translational Psychiatry, Год журнала: 2020, Номер 10(1)

Опубликована: Июль 21, 2020

Post-traumatic stress disorder (PTSD) is a psychiatric whose pathogenesis relies on maladaptive expression of the memory for life-threatening experience, characterized by over-consolidation, generalization, and impaired extinction, which are responsible dramatic changes in arousal, mood, anxiety, social behavior. Even if subjects experiencing traumatic event during lifetime all show an acute response to trauma, only subset them (susceptible) ultimately develops PTSD, meanwhile others (resilient) fully recover after first response. However, dynamic relationships between interacting brain circuits that might potentially link trauma-related experiences emergence susceptible resilient PTSD phenotypes individuals not well understood. Toward step reach this goal, we have implemented our experimental model previously developed, making it suitable differentiate (high responders, HR) (low LR) rats terms impairment long trauma. Rats were exposed five footshocks paired with isolation. One week trauma but before animals tested Open Field Social Interaction tasks identification predictive variable identify possible appearance PTSD-like phenotype. Our findings exploratory activity novel environment very robust predict susceptibility towards This thus able screen differentiate, extinction learning potential therapeutic intervention, rats.

Язык: Английский

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The effect of SSRIs on fear learning: a systematic review and meta-analysis

Psychopharmacology, Год журнала: 2023, Номер 240(11), С. 2335 - 2359

Опубликована: Фев. 27, 2023

Abstract Rationale Selective serotonin reuptake inhibitors (SSRIs) are considered first-line medication for anxiety-like disorders such as panic disorder, generalized anxiety and post-traumatic stress disorder. Fear learning plays an important role in the development treatment of these disorders. Yet, effect SSRIs on fear not well known. Objective We aimed to systematically review six clinically effective acquisition, expression, extinction cued contextual conditioned fear. Methods searched Medline Embase databases, which yielded 128 articles that met inclusion criteria reported 9 human 275 animal experiments. Results Meta-analysis showed significantly reduced expression facilitated cue. Bayesian-regularized meta-regression further suggested chronic exerts a stronger anxiolytic than acute treatment. Type SSRI, species, disease-induction model, type test used did seem moderate SSRIs. The number studies was relatively small, level heterogeneity high, publication bias has likely occurred may have resulted overestimation overall sizes. Conclusions This suggests efficacy be related their effects cue, rather acquisition. However, due more general inhibition fear-related emotions. Therefore, additional meta-analyses unconditioned responses provide insight into actions

Язык: Английский

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Watching with Argus eyes: Characterization of emotional and physiological responding in adults exposed to childhood maltreatment and/or recent adversity

Psychophysiology, Год журнала: 2023, Номер 60(7)

Опубликована: Фев. 2, 2023

Abstract Exposure to adverse experiences is a well‐established major risk factor for affective psychopathology. The vulnerability of deleterious sequelae assumed in maladaptive processes the defensive system, particularly emotional processing. More specifically, childhood maltreatment has been suggested be associated with recruitment specific and distinct response profiles. To date, it remains unclear whether these are or generalizable recent adversity adulthood. This pre‐registered study aimed investigate impact exposure on processing 685 healthy adults “Affective Startle Modulation” Paradigm (ASM). First, we replicated higher trait anxiety depression levels individuals exposed both types adversity. Second, observed increased general skin conductance reactivity Third, showed reduced, while discrimination between pictures negative neutral valence, compared non‐exposed SCR. No association fear potentiated startle was observed. Furthermore, explorative analyses revealed moderate dimensional categorical agreement two questionnaires provide insight into potential adversity‐type effects. Our results support experience‐dependent plasticity sympathetic nervous system suggest profiles modulation early versus We emphasize need further explore our understanding psychophysiological their implication prevention intervention.

Язык: Английский

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Early-life stress induces persistent astrocyte dysfunction associated with fear generalisation

Опубликована: Янв. 15, 2025

Early-life stress can have lifelong consequences, enhancing susceptibility and resulting in behavioural cognitive deficits. While the effects of early-life on neuronal function been well-described, we still know very little about contribution non-neuronal brain cells. Investigating complex interactions between distinct cell types is critical to fully understand how cellular changes manifest as deficits following stress. Here, using male female mice report that induces anxiety-like behaviour fear generalisation an amygdala-dependent learning memory task. These were associated with impaired synaptic plasticity, increased neural excitability, astrocyte hypofunction. Genetic perturbation amygdala by either reducing calcium activity or network was sufficient replicate cellular, synaptic, Our data reveal a role astrocytes tuning emotionally salient provide mechanistic links stress, hypofunction,

Язык: Английский

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Anxiety and Trauma-Related Disorders

Oxford University Press eBooks, Год журнала: 2025, Номер unknown, С. 523 - 540

Опубликована: Янв. 1, 2025

Abstract Despite the pervasiveness of anxiety and trauma-related disorders, there is no mechanistic explanation for their causes, search ongoing therapeutic interventions that are effective do not cause undesirable side effects. Given evolutionarily advantageous function fear responses, multiple redundant circuits. However, robustness this redundancy provides also represents a challenge targeted anxiolytic therapies to penetrate layers circuitry. To find new targets, preclinical models required delve into neural underpinnings anxiety. The most utilized have historically been demonstrated various degrees face, predictive, construct validity but only assess limited range behaviors. Broader use assays combined with unsupervised machine learning discovery behavioral motifs using computer vision tools will allow researchers parse phenotyping greater granularity.

Язык: Английский

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Early-life stress induces persistent astrocyte dysfunction associated with fear generalisation

eLife, Год журнала: 2025, Номер 13

Опубликована: Фев. 5, 2025

Early-life stress can have lifelong consequences, enhancing susceptibility and resulting in behavioural cognitive deficits. While the effects of early-life on neuronal function been well-described, we still know very little about contribution non-neuronal brain cells. Investigating complex interactions between distinct cell types is critical to fully understand how cellular changes manifest as deficits following stress. Here, using male female mice report that induces anxiety-like behaviour fear generalisation an amygdala-dependent learning memory task. These were associated with impaired synaptic plasticity, increased neural excitability, astrocyte hypofunction. Genetic perturbation amygdala by either reducing calcium activity or network was sufficient replicate cellular, synaptic, Our data reveal a role astrocytes tuning emotionally salient provide mechanistic links stress, hypofunction,

Язык: 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, Год журнала: 2025, Номер 12

Опубликована: Фев. 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.

Язык: Английский

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Dopamine modulation of basolateral amygdala activity and function

Journal of Computational Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 19, 2025

Язык: Английский

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Reward Processing and Circuit Dysregulation in Posttraumatic Stress Disorder

Frontiers in Psychiatry, Год журнала: 2021, Номер 12

Опубликована: Май 28, 2021

Past decades have witnessed substantial progress in understanding of neurobiological mechanisms that contribute to generation various PTSD symptoms, including intrusive memories, physiological arousal and avoidance trauma reminders. However, the neurobiology anhedonia emotional numbing PTSD, been conceptualized as reward processing deficits - wanting (anticipation reward) liking (satisfaction with outcome), respectively, remains largely unexplored. Empirical evidence on is rather limited, no studies examined association abnormalities neurocircuitry-based models pathophysiology. The manuscript briefly summarizes “state science” both human processing, implicated neurocircuitry, well empirical PTSD. We then summarize current gaps literature outline key future directions, further illustrating it by example two alternative explanations pathophysiology potentially affecting via different pathways. Studying will not only advance their link, but also could enhance treatment approaches specifically targeting symptoms patients.

Язык: Английский

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

Neuroscience, Год журнала: 2023, Номер 530, С. 108 - 132

Опубликована: Авг. 26, 2023

Язык: Английский

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