Lasting Consequences of Traumatic Events on Behavioral and Skeletal Parameters in a Mouse Model for Post-Traumatic Stress Disorder (PTSD)

BACKGROUND: Post-traumatic stress disorder (PTSD) is an anxiety disorder that not only affects mental health, but may also affect bone health. However, there have been no studies to examine the direct relationship between PTSD and bone. METHODOLOGY/PRINCIPAL FINDINGS: We employed electric shocks in mice to simulate traumatic events that cause PTSD. We also injected the anxiogenic drug FG-7142 prior to electric shocks. Electric shocks created lasting conditioned fear memory in all mice. In young mice, electric shocks elicited not only behavioral response but also skeletal response, and injection of FG-7142 appeared to increase both types of response. For example in behavioral response within the first week, mice shocked alone froze an average of 6.2 sec in 10 sec tests, and mice injected with FG-7142 froze 7.6 sec, both significantly different (P<0.05) from control mice, which only froze 1.3 sec. In skeletal response at week 2, shocks alone reduced 6% bone mineral content (BMC) in total body (P = 0.06), while shocks with FG-7142 injection reduced not only 11% BMC (P<0.05) but also 6% bone mineral density (BMD) (P<0.05). In addition, FG-7142 injection also caused significant reductions of BMC in specific bones such as femur, lumbar vertebra, and tibia at week 3. Strong negative correlations (R(2) = −0.56, P<0.05) and regression (y = 0.2527−0.0037 * x, P<0.01) between freezing behavior and total body BMC in young mice indicated that increased contextual PTSD-like behavior was associated with reduced bone mass acquisition. CONCLUSIONS/SIGNIFICANCE: This is the first study to document evidence that traumatic events induce lasting consequences on both behavior and skeletal growth, and electric shocks coupled with injection of anxiogenic FG-7142 in young mice can be used as a model to study the effect of PTSD-like symptoms on bone development.