Volume 58, August 2024, 101403Author links open overlay panel, , , Highlights•

Behavioral profiling enables unveiling changes specific to resilience.

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Resilient individuals differ from unexposed ones, indicating an active response.

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Resilience mechanisms may differ between males and females.

Individual variability in response to stress highlights the importance of behavioral profiling to unveil changes specific to resilience. Emphasizing distinct mechanisms, this review reveals resilience as an active coping response that differs from the unexposed healthy population. Individual differences add complexity to stress-related outcomes and are essential for tailoring effective interventions. The data highlight resilience promotion through maintaining blood–brain barrier integrity and modulating inflammatory responses. Epigenetic findings implicate multiple processes, such as immune function, cell proliferation, and synaptic transmission. Disruptions in neuronal excitation and inhibition equilibrium significantly impact the resilience-vulnerability balance. Understanding the neural circuit interplay and sex-specific responses offers a comprehensive perspective on the multifaceted nature of resilience and provides potential avenues for preventive and therapeutic strategies.

Section snippetsIndividual variability in response to stress

The interplay between stress and human behavior constitutes a dynamic field of study. Stress, as an omnipresent aspect of life, impacts individuals in multifaceted ways, and the diversity in these responses underscores the complex relationship between genetic, environmental, and personal factors. Stress-related disorders manifest as maladaptive biological and psychological responses to short- or long-term exposure to physical or emotional stressors. Stress resilience is an emerging field in

Inflammation

Several studies highlight the relationship between stress, inflammatory responses, and blood–brain barrier (BBB) integrity [10]. Stress-vulnerable mice exhibited increased BBB permeability, while resilient mice maintained their integrity. Another study links tumor necrosis factor alpha (TNFα)/nuclear factor kappa B (NFκB) signaling to vulnerability, identifying inflammation as a factor leading to BBB permeability and abnormal behaviors [11]. Astrocytes play a crucial role in maintaining BBB

Behavioral profiling

As indicated above, not all individuals exposed to trauma develop pathology. However, numerous animal studies overlook this variability by relying on limited tests with single time points. They often label the stress-exposed group as presenting pathology, obscuring individual differences, and hindering the identification of neurobiological mechanisms specifically linked to resilience or vulnerability [53]. It is crucial that animal models of PTSD, aiming to elucidate differences between

Potential key points for intervention

The data shown here offers three main fields where potential key points for intervention in the context of either prevention or treatment can be further examined. With regard to inflammation, chronic treatment with fluoxetine inhibits the activation of specific inflammatory phenotypes in the hippocampus and cortex, offering relief from abnormal behaviors [59]. Another avenue involves reducing circulating TNFα to prevent stress-induced BBB integrity loss, suggesting inflammation reduction as a

Discussion

The studies above paint a complex picture of stress responsivity, revealing a diverse pattern of alterations influencing resilience and vulnerability across regions and subregions and involving various molecular pathways and mechanisms. The interconnectedness and reciprocal interactions among the discussed prominent brain regions suggest a ripple effect, potentially involving metaplasticity, which affects the ability of a region to respond to subsequent challenges 66, 67.

The findings show the

Declaration of Competing Interest

The authors declare that they have no conflict of interest.

Acknowledgements

This work was supported by the Israel Science Foundation (ISF) (Grant no: 814/21) to GRL.

References and recommended reading (67)View full text

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