Intergenerational influences of paternal combat-related trauma on offspring behavioral and brain function

Post-traumatic stress (PTS) is a debilitating mental health condition that is highly prevalent in Veteran populations owing to their increased exposure to combat-related trauma. PTS is associated with numerous comorbid conditions including major depressive disorder, anxiety, and chronic pain. Although the causal mechanisms are currently unknown, paternal trauma has been linked to an increased risk for pathology in their offspring. Therefore, using a preclinical model of combat trauma, we examined the relationship between paternal PTS and offspring socio-emotional functioning, pain perception, and gene expression changes pertinent to HPA-axis functioning, reward processing, and epigenetic regulation. Paternally experienced trauma produced persistent changes in sire anxiety, anhedonia, and sociability, as well as elevated levels of corticosterone and changes to gene expression. In addition, the paternal experiences prior to conception changed offspring behaviour and gene expression but did not modify the offspring's stress response in adolescence. Offspring born to fathers who experienced trauma exhibited changes to nociceptive sensitivity, social and anxiety-like behaviour, as well as changes in expression of <i>5HT1A</i>, <i>5HT2A, Comt, Dnmt3a, Drd2, FKBP5, NR3C1, Maoa</i>, and <i>Mecp2</i> in the adrenal gland, hippocampus, hypothalamus, prefrontal cortex, and thalamus. These results suggest that trauma in fathers may alter expression of genes that contribute to an increased risk for the development of mental health conditions, such as PTS and chronic pain, in their offspring. This model of paternally induced intergenerational transmission could be used to explore the efficacy of future therapeutic strategies to ameliorate some risk imparted upon offspring by Veteran fathers living with PTS.