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Biol Psychiatry. 2019 Sep 15;86(6):483-491. doi: 10.1016/j.biopsych.2019.06.030. Epub 2019 Jul 29.

Multidimensional Predictors of Susceptibility and Resilience to Social Defeat Stress.

Author information

1
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, the Rockefeller University, New York, New York. Electronic address: cnasca@rockefeller.edu.
2
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Psychiatry and Neuroscience, CERVO Brain Research Center, Faculty of Medicine, Université Laval, Quebec City, Canada.
3
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
4
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, the Rockefeller University, New York, New York; Biostatistics, Center for Clinical and Translational Science, the Rockefeller University, New York, New York.
5
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, the Rockefeller University, New York, New York.
6
Sackler Program for Epigenetics and Psychobiology, Douglas Research Centre, McGill University, Montreal, Canada.
7
Department of Oncological Sciences, Tisch Cancer Institute and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
8
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, the Rockefeller University, New York, New York; Center for Neuroscience in Women's Health, Stanford University, Palo Alto, California.
9
Sackler Program for Epigenetics and Psychobiology, Douglas Research Centre, McGill University, Montreal, Canada; Department of Psychiatry, McGill University, Montreal, Canada; Singapore Institute for Clinical Sciences, Singapore.

Abstract

BACKGROUND:

Previous studies identified several separate risk factors for stress-induced disorders. However, an integrative model of susceptibility versus resilience to stress including measures from brain-body domains is likely to yield a range of multiple phenotypic information to promote successful adaptation to stress.

METHODS:

We used computational and molecular approaches to test whether 1) integrative brain-body behavioral, immunological, and structural domains characterized and predicted susceptibility or resilience to social defeat stress (SDS) in mice and 2) administration of acetyl-L-carnitine promoted resilience at the SDS paradigm.

RESULTS:

Our findings identified multidimensional brain-body predictors of susceptibility versus resilience to SDS. The copresence of anxiety, decreased hippocampal volume, and elevated systemic interleukin-6 characterized a susceptible phenotype that developed behavioral and neurobiological deficits after exposure to SDS. The susceptible phenotype showed social withdrawal and impaired transcriptomic-wide changes in the ventral dentate gyrus after SDS. At the individual level, a computational approach predicted whether a given animal developed SDS-induced social withdrawal, or remained resilient, based on the integrative in vivo measures of anxiety and immune system function. Finally, we provide initial evidence that administration of acetyl-L-carnitine promoted behavioral resilience at the SDS paradigm.

CONCLUSIONS:

The current findings of multidimensional brain-body predictors of susceptibility versus resilience to stress provide a starting point for in vivo models of mechanisms predisposing apparently healthy individuals to develop the neurobiological and behavioral deficits resulting from stress exposure. This framework can lead to novel therapeutic strategies to promote resilience in susceptible phenotypes.

KEYWORDS:

Acetylcarnitine; Biomarkers; Epigenetic; Individual differences; Phenotype; Risk factors

PMID:
31466563
PMCID:
PMC6730655
[Available on 2020-09-15]
DOI:
10.1016/j.biopsych.2019.06.030

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