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Séminaire - Carmen SandiNeurobiological mechanisms linking early life stress with adult pathological aggression

Abstract :

A major risk factor for violence perpetration is childhood exposure to violence, but the neurobiological mechanisms of these long-term effects remain uncertain. Using an animal model devoid of human cultural factors, we find that exposing peripubertal male rats to fear-inducing experiences produced pathological aggression both towards other male conspecifics and towards their female partners during adulthood. Importantly, their offspring also shows increased aggression towards females even without postnatal father-offspring interaction. In searching for key neurobiological mechanisms translating stress effects into increased aggression, we find alterations in amygdala-medial orbitofrontal circuit activity, the testosterone/corticosterone ratio, and the serotonergic system. We also find evidence for a programing role of glucocorticoids and for a link between altered polysialylation of the neural cell adhesion molecule during development and pathological aggression. These findings will be discussed within a broader context reflecting on the societal implications of stress.

Selected publications

Marquez C., Poirier G., Cordero M.I., Larsen M.H, Groner A., Marquis J., Magistretti P., Trono D. and Sandi C. (2013) Peripuberty stress leads to abnormal aggression, altered amygdala and orbitofrontal reactivity and increased prefrontal MAOA gene expression. Translational Psychiatry 3: e216. doi: 10.1038/tp.2012.144.

Cordero M.I., Poirier G.L., Márquez C., Veenit V., Fontana X., Salehi B., Ansermet F. and Sandi C. (2012) Evidence for biological roots in the transgenerational transmission of intimate partner violence. Translational Psychiatry 2:e106. doi: 10.1038/tp.2012.32.

Conboy L. and Sandi C (2010) Stress at learning facilitates memory formation by regulating AMPA receptor trafficking through a glucocorticoid action. Neuropsychopharmacology 35: 674-685.

Luksys G., Gerstner W., and Sandi C. (2009) Stress, genotype and norepinephrine in prediction of mouse behavior using reinforcement learning. Nature Neuroscience 12: 1180-1186.

Sandi C. and Richter-Levin G. (2009) From high anxiety trait to depression: A neurocognitive hypothesis, Trends in Neuroscience 32: 312-320.

Katia Touyarot (katia.touyarot @ enscbp.fr)