Cited by 297Resilience and Mental HealthStress Responses and CortisolNeurotransmitter Receptor Influence on Behavior

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Neurobiology of Resilience: Interface Between Mind and Body

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Cathomas, Flurin, Murrough, James W., Nestler, Eric J., Han, Ming-Hu, Russo, Scott J.·2019·Biological Psychiatry

DOI 10.1016/j.biopsych.2019.04.011PMC PMC6717018

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Abstract

Stress-related neuropsychiatric disorders, such as major depressive disorder and posttraumatic stress disorder, exact enormous socioeconomic and individual consequences. Resilience, the process of adaptation in the face of adversity, is an important concept that is enabling the field to understand individual differences in stress responses, with the hope of harnessing this information for the development of novel therapeutics that mimic the body's natural resilience mechanisms. This review provides an update on the current state of research of the neurobiological mechanisms of stress resilience. We focus on physiological and transcriptional adaptations of specific brain circuits, the role of cellular and humoral factors of the immune system, the gut microbiota, and changes at the interface between the brain and the periphery, the blood-brain barrier. We propose viewing resilience as a process that requires the integration of multiple central and peripheral systems and that elucidating the underlying neurobiological mechanisms will ultimately lead to novel therapeutic options.

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“Further testing and validation of this assessment battery will help move the field of developmental psychology forward, especially in light of growing effort to characterize the biological substrates of risk and resilience (Cathomas et al., 2019).”
Background
Neurobiological mechanisms of mood disorders: Stress vulnerability and resilience
Pereira, C. M., Castro, F. C. D. A. Q., Barcelos, R. M., Chiepe, K. C. M. B., Rossoni, J. V., Ambrósio, R. P., Chiarelli-Neto, O., & Pesarico, A. P. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.1006836 · Cited by 36
“Resilience can be viewed as an active process that implies continuous adaptation without external intervention (Russo et al., 2012; Cathomas et al., 2019).”
Background
Resilience to Stress and Resilience to Pain: Lessons from Molecular Neurobiology and Genetics
Nestler, E. J., & Waxman, S. G. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.03.007 · Cited by 33
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Sex and region-specific effects of variable stress on microglia morphology
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“Specifically, there is significant overlap in sex specifically regulated immune associated genes between women and female mice in the NAc, an area of the brain that integrates hedonic experience and emotional processing (Cathomas et al., 2019; Christoffel et al., 2015; Menard et al., 2017; Wang et al., 2018).”
Background
Prediction of Learned Resistance or Helplessness by Hippocampal-Prefrontal Cortical Network Activity during Stress
Marques, D. B., Ruggiero, R. N., Bueno-Júnior, L. S., Rossignoli, M. T., & Leite, J. P. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.0128-21.2021 · Cited by 31
Hippocampal Over-Expression of Cyclooxygenase-2 (COX-2) Is Associated with Susceptibility to Stress-Induced Anhedonia in Mice
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“These studies found similar increases in corticosterone blood levels, an important indicator of hyperactivity of the HPA axis in depressed patients [104,106] that in the context of the results reported here may be interpreted as a sign of dysregulation of COX-2 expression by glucocorticoids in a susceptible cohort of…”
Background
Pharmaco-Multiomics: A New Frontier in Precision Psychiatry
Dhieb, D., & Bastaki, K. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26031082 · Cited by 34
Gut microbiota regulate stress resistance by influencing microglia-neuron interactions in the hippocampus
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“Individuals differ substantially in their resilience to stress (Cathomas et al., 2019; Dion-Albert et al., 2022; Fleshner et al., 2011), and the same is true of laboratory animals (Dudek et al., 2020; Menard et al., 2017; Zhang et al., 2021).”
Background
Stress and Feline Health
Buffington, C. A. T., & Bain, M. J. (2020) · Veterinary Clinics of North America Small Animal Practice · doi:10.1016/j.cvsm.2020.03.001 · Cited by 32
Central and Peripheral Inflammation: A Common Factor Causing Addictive and Neurological Disorders and Aging-Related Pathologies
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“In contrast, stress-resilient mice do not show these alterations one day after exposure to social defeat stress [114,122,123].”
Background
Behavioral Traits Associated With Resilience to the Effects of Repeated Social Defeat on Cocaine-Induced Conditioned Place Preference in Mice
Calpe-López, C., García-Pardo, M. P., Martínez-Caballero, M. Á., Santos-Ortíz, A., & Aguilar, M. A. (2020) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00278 · Cited by 27
“There are recent reviews about the causes of resilience that highlight the importance of neuroplasticity in several brain networks, changes at the blood-brain barrier, genetic factors, and the role of the immune system, the metabolism and the gut microbiota (Cathomas et al., 2019; Feder et al., 2019; Holz et al., 2019…”
Background
Resilience and its association with post-traumatic stress disorder, anxiety, and depression symptoms in the aftermath of trauma: A cross-sectional study from Nepal
Dhungana, S., Koirala, R., Ojha, S. P., & Thapa, S. B. (2022) · SSM - Mental Health · doi:10.1016/j.ssmmh.2022.100135 · Cited by 33
Ketamine as a prophylactic resilience-enhancing agent
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Psychosocial Resilience to Inflammation-Associated Depression: A Prospective Study of Breast-Cancer Survivors
Manigault, A. W., Kuhlman, K. R., Irwin, M. R., Cole, S. W., Ganz, P. A., Crespi, C. M., & Bower, J. E. (2022) · Psychological Science · doi:10.1177/09567976221079633 · Cited by 29
Role of the gut–brain axis via the subdiaphragmatic vagus nerve in stress resilience of 3,4-methylenedioxymethamphetamine in mice exposed to chronic restrain stress
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“…– brain axis including the gut microbiota may contribute to resilience versus susceptibility in rodents after repeated stress (Bailey et al., 2011; Cathomas et al., 2019; Szyszkowicz et al., 2017; Wang et al., 2020; Wang et al., 2021a, 2021b; Wei et al., 2022a; Wei et al., 2022b; Yang et al.,…”
Stress resilience is established during development and is regulated by complement factors
Swaminathan, A., Gliksberg, M., Anbalagan, S., Wigoda, N., & Levkowitz, G. (2023) · Cell Reports · doi:10.1016/j.celrep.2022.111973 · Cited by 26
Worst Pain Severity Profiles of Oncology Patients Are Associated With Significant Stress and Multiple Co-Occurring Symptoms
Shin, J., Harris, C., Oppegaard, K. R., Kober, K. M., Paul, S. M., Cooper, B. A., Hammer, M. J., Conley, Y. P., Levine, J. D., & Miaskowski, C. A. (2021) · Journal of Pain · doi:10.1016/j.jpain.2021.07.001 · Cited by 28
Why do we hunger for touch? The impact of daily gentle touch stimulation on maternal‐infant physiological and behavioral regulation and resilience
Puyvelde, M. V., Staring, L., Schaffers, J., Rivas-Smits, C., Groenendijk, L., Smeyers, L., Collette, L., Schoofs, A., den Bossche, N. V., & McGlone, F. P. (2021) · Infant Mental Health Journal · doi:10.1002/imhj.21949 · Cited by 25
From psychosomatic medicine, brain–computer interface to brain–apparatus communication
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Repeated use of 3,4-methylenedioxymethamphetamine is associated with the resilience in mice after chronic social defeat stress: A role of gut–microbiota–brain axis
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Differences in gut microbiota associated with stress resilience and susceptibility to single prolonged stress in female rodents
Tanelian, A., Nankova, B. B., Cheriyan, A., Arens, C., Hu, F., & Sabban, E. L. (2023) · Neurobiology of Stress · doi:10.1016/j.ynstr.2023.100533 · Cited by 25
Association between childhood trauma and Internet gaming disorder: a moderated mediation analysis with depression as a mediator and psychological resilience as a moderator
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“The possible explanation of this result is that students with higher psychological resilience demonstrated enhanced emotional regulation skills and a reduced likelihood of experiencing heightened negative emotional arousal [42].”
Background
Neuroendocrine Response to Psychosocial Stressors, Inflammation Mediators and Brain-periphery Pathways of Adaptation
Palego, L., Giannaccini, G., & Betti, L. (2020) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/1871524920999201214231243 · Cited by 25
Neuroinflammatory and behavioral susceptibility profile of mice exposed to social stress towards cocaine effects
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Resilience and Vulnerability to Stress-Induced Anhedonia: Unveiling Brain Gene Expression and Mitochondrial Dynamics in a Mouse Chronic Stress Depression Model
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Li, Y., Fan, Y., Sun, Y., Alolga, R. N., Xiao, P., & Ma, G. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.777987 · Cited by 21
Neurophysiological dynamics for psychological resilience: A view from the temporal axis
Watanabe, N., & Takeda, M. (2021) · Neuroscience Research · doi:10.1016/j.neures.2021.11.004 · Cited by 24
Resilience to social defeat stress in adolescent male mice
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“Studies suggest that a correct reaction of the body is crucial for an adaptive response to the environment and to avoid stress-related deficits (Cathomas et al., 2019; Dutcher and Creswell, 2018).”
Dopamine error signal to actively cope with lack of expected reward
Ishino, S., Kamada, T., Sarpong, G. A., Kitano, J., Tsukasa, R., Mukohira, H., Sun, F., Li, Y., Kobayashi, K., Naoki, H., et al. (2023) · Science Advances · doi:10.1126/sciadv.ade5420 · Cited by 25
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“However, mechanisms of brain–immune interactions suggest that peripheral immune gene expression bidirectionally affects brain transcription and may contribute to neuropsychopathology [83, 90, 91].”
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The Neurobiology of Resilience: Complexity and Hope
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Distinct Circuits From the Central Lateral Amygdala to the Ventral Part of the Bed Nucleus of Stria Terminalis Regulate Different Fear Memory
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Inflammation in Posttraumatic Stress Disorder: Dysregulation or Recalibration?
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Brain–spleen connection aids antibody production
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Central and peripheral stress-induced epigenetic mechanisms of resilience
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“Pups exposed to severe stressors have increased probability of being stress susceptible and develop depression-like behaviors in the future, however, if the stressor is less severe, than pups will develop a resilient phenotype later in life [3].”
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“between the peripheral immune system and the brain relevant to the etio-pathology of both schizophrenia and MDD (Cathomas et al., 2019; Müller and Schwarz, 2010).”
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Harnessing the Neurobiology of Resilience to Protect the Mental Well-Being of Healthcare Workers During the COVID-19 Pandemic
Rajkumar, R. P. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.621853 · Cited by 19
Selenomethionine alleviated fluoride-induced toxicity in zebrafish (Danio rerio) embryos by restoring oxidative balance and rebuilding inflammation homeostasis
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Authors: Cathomas, F., Murrough, J. W., Nestler, E. J., Han, M.-H., & Russo, S. J.
Affiliations: Icahn School of Medicine at Mount Sinai (US)
Corresponding author: Russo, Scott J.
ORCID: Cathomas, Flurin
Murrough, James W.
Nestler, Eric J.
Han, Ming-Hu
Russo, Scott J.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2019-09
Volume: 86
Issue: 6
Pages: 410-420
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2019.04.011
PMC: PMC6717018
OpenAlex: W2936176560
Cited by: 296
References: 151
Citations by year: 2026: 22 · 2025: 55 · 2024: 55 · 2023: 36 · 2022: 45 · 2021: 40 · 2020: 38 · 2019: 5
FWCI: 5.09
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
National Center for Complementary and Integrative Health (P50 AT008661-01)
Janssen Pharmaceuticals
National Institute of Mental Health (P50 MH096890, R01 MH090264, R01 MH104559, R56 MH115409)
Sunovion
Novartis
Sage Therapeutics
Avanir Pharmaceuticals
Allergan Foundation
Janssen Research and Development
Topics: Social Sciences › Psychology › Clinical Psychology › Resilience and Mental Health
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: resilience, stress resilience, stress-related neuropsychiatric disorders, major depressive disorder, post-traumatic stress disorder, individual differences in stress response, brain circuits, immune system, gut microbiota, blood-brain barrier, neuroimmune interactions
MeSH terms: Gastrointestinal Microbiome, Adaptation, Psychological, Blood-Brain Barrier, Brain, Major Depressive Disorder, Humans, Immune System, Synaptic Transmission, Neurobiology, Psychophysiology, Stress Disorders, Post-Traumatic, Resilience, Psychological

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Neurobiology of Resilience: Interface Between Mind and Body

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