A gedanken experiment to find a neuroanatomical model for post-traumatic stress disorder

Post-traumatic stress disorder is a persistent stress syndrome in which abnormal brain physiology persists long after cessation of the acute psychological event that causes it. Normal physiological homeostasis depends on equilibria. The basic unit of equilibrium is the negative feedback loop (NFL) and the simplest way to disrupt homeostasis would be to break an NFL. The resulting model requires two nuclei in the brain reciprocally-connected in an NFL, one of which, in response to the perception of overwhelming threats or demands, generates rapid pacemaker firing which leads to excitotoxic cell death in the other. The injured nucleus must also be able to undergo neurogenesis, which would explain clinical recovery. The relevant site of neurogenesis is the hippocampus, which is reciprocally connected with the dorsal raphe nucleus (DRN), a serotonergic pacemaker nucleus which has been shown to light up on PET scan (i.e. undergo burst firing) in response to stress. The model postulates that the DRN delivers an excitotoxic blow to the hippocampus. Then, via a second pathway, it promotes neurogenesis. The model incorporates potential sites of action for several psychoactive drugs, including anti-depressants and lithium, which promote neurogenesis; and valproate and atypical anti-psychotics, which block excitotoxicity. The theory has the advantage of being formulated in terms of how the brain actually works, i.e. through the interaction between pacemakers and processed sensory input from the outside world. It also directs pharmacological thinking to the role played by pacemakers and pacemaker currents.