Treatment of trauma with lithium to forestall the development of posttraumatic stress disorder by pharmacological induction of a mild transient amnesia

Abstract

Posttraumatic stress disorder (PTSD) is a severe anxiety disorder that develops after exposure to trauma. Symptoms include persistent reexperiencing, persistent avoidance, persistent numbing, and persistent hyperarousal. Subsequent to trauma exposure, the onset of symptoms of an acute stress reaction can typically develop over varying amounts of time from days to months. Current pharmacotherapies for PTSD are available after symptoms manifest, and primarily consist of selective serotonin reuptake inhibitor (SSRI) antidepressants. There are currently no FDA approved pharmacological interventions available for the treatment of acutely traumatized individuals to forestall the development of PTSD after trauma and prior to the onset of symptoms.A prominent model of PTSD developed by Roger Pitman attributes the pathogenesis of PTSD to over-consolidated traumatic memories that are mediated by endogenous stress hormones released with trauma and after trauma.The molecular processes of memory consolidation in neurons are mediated by intracellular signaling pathways. One secondary messenger signaling pathway with a putative role in long-term potentiation (LTP) is the inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) secondary messenger system.Lithium, a treatment for bipolar disorder, and a pharmacotherapy that is associated with inducing transient impairments in cognition, memory, and learning, is an inhibitor of inositol monophosphatase (IMP), an enzyme in the IP3 and DAG secondary messenger pathway.I am advancing the hypothesis that the administration of lithium for a brief interval to traumatized individuals at risk for PTSD within the time period after trauma and prior to the onset of symptoms could potentially forestall the development of PTSD by disrupting LTP. I am proposing that this treatment will reduce the incidence of PTSD and reduce the severity of symptoms in those who eventually develop PTSD.