title: Animal models to improve our understanding and treatment of suicidal behavior.
abstract: Worldwide, suicide is a leading cause of death. Although a sizable proportion of deaths by suicide may be preventable, it is well documented that despite major governmental and international investments in research, education and clinical practice suicide rates have not diminished and are even increasing among several at-risk populations. Although nonhuman animals do not engage in suicidal behavior amenable to translational studies, we argue that animal model systems are necessary to investigate candidate endophenotypes of suicidal behavior and the neurobiology underlying these endophenotypes. Animal models are similarly a critical resource to help delineate treatment targets and pharmacological means to improve our ability to manage the risk of suicide. In particular, certain pathophysiological pathways to suicidal behavior, including stress and hypothalamic-pituitary-adrenal axis dysfunction, neurotransmitter system abnormalities, endocrine and neuroimmune changes, aggression, impulsivity and decision-making deficits, as well as the role of critical interactions between genetic and epigenetic factors, development and environmental risk factors can be modeled in laboratory animals. We broadly describe human biological findings, as well as protective effects of medications such as lithium, clozapine, and ketamine associated with modifying risk of engaging in suicidal behavior that are readily translatable to animal models. Endophenotypes of suicidal behavior, studied in animal models, are further useful for moving observed associations with harmful environmental factors (for example, childhood adversity, mechanical trauma aeroallergens, pathogens, inflammation triggers) from association to causation, and developing preventative strategies. Further study in animals will contribute to a more informed, comprehensive, accelerated and ultimately impactful suicide research portfolio.
authors.affiliation: Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Gould
authors.affiliation: Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Georgiou
authors.affiliation: Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.|Rocky Mountain Mental Illness Research Education and Clinical Center, Denver, CO, USA.|Military and Veteran Microbiome Consortium for Research and Education, U.S. Department of Veterans Affairs, Washington, DC, USA.|Department of Physical Medicine and Rehabilitation, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Brenner
authors.affiliation: Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA.
authors.forename: L
authors.initials: L
authors.lastname: Brundin
authors.affiliation: Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Psychology, Notre Dame of Maryland University, Baltimore, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Can
authors.affiliation: Department of Emergency Psychiatry and Post Acute Care, CHU Montpellier, Montpellier, France.|Université Montpellier, Inserm U1061, Montpellier, France.
authors.forename: P
authors.initials: P
authors.lastname: Courtet
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO, USA.|Department of Psychology, University of Colorado, Boulder, Boulder, CO, USA.|Department of Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
authors.forename: Z R
authors.initials: ZR
authors.lastname: Donaldson
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Dwivedi
authors.affiliation: Department of Emergency Psychiatry and Post Acute Care, CHU Montpellier, Montpellier, France.|Université Montpellier, Inserm U1061, Montpellier, France.
authors.forename: S
authors.initials: S
authors.lastname: Guillaume
authors.affiliation: Department of Psychology, University of Minnesota, Minneapolis, MN, USA.|Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: I I
authors.initials: II
authors.lastname: Gottesman
authors.affiliation: Department of Psychiatry, University of Utah, Salt Lake City, UT, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kanekar
authors.affiliation: Rocky Mountain Mental Illness Research Education and Clinical Center, Denver, CO, USA.|Military and Veteran Microbiome Consortium for Research and Education, U.S. Department of Veterans Affairs, Washington, DC, USA.|Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.|Department of Physical Medicine and Rehabilitation and Center for Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Lowry
authors.affiliation: Rocky Mountain Mental Illness Research Education and Clinical Center, Denver, CO, USA.|Department of Psychiatry, University of Utah, Salt Lake City, UT, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Renshaw
authors.affiliation: Department of Psychiatry, University of Halle-Wittenberg, Halle, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Rujescu
authors.affiliation: Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA, USA.
authors.forename: E G
authors.initials: EG
authors.lastname: Smith
authors.affiliation: Department of Psychiatry, McGill University, Montreal, QC, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Turecki
authors.affiliation: Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Zanos
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Zarate
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: P A
authors.initials: PA
authors.lastname: Zunszain
authors.affiliation: Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.|Rocky Mountain Mental Illness Research Education and Clinical Center, Denver, CO, USA.|Military and Veteran Microbiome Consortium for Research and Education, U.S. Department of Veterans Affairs, Washington, DC, USA.|VISN 5 Mental Illness Research Education and Clinical Center, Baltimore MD, USA.
authors.forename: T T
authors.initials: TT
authors.lastname: Postolache
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D012307:Risk Factors; D059020:Suicidal Ideation; D013405:Suicide / Q000523:psychology*; D013406:Suicide, Attempted / Q000517:prevention & control* / Q000523:psychology*; D000092864:Suicide Prevention