The Circuitry of Fear: Understanding the Neurobiology of PTSD
LAS VEGAS—A better understanding of the neurobiology of posttraumatic stress disorder (PTSD) can help explain how current treatments work and how future therapies will change the way clinicians treat PTSD, said Kerry J. Ressler, MD, PhD, of Emory University in Atlanta, in a presentation at the 26th Annual U.S. Psychiatric and Mental Health Congress .
Although fear is a natural human response, approximately 5% to 10% of the general population and 15% to 25% of veterans experience PTSD after exposure to death, actual or threatened serious injury, or actual or threatened sexual violence.
“We can think of PTSD scientifically as a pathological fear reaction,” said Dr. Ressler.
The Neurobiological Underpinnings of PTSD
Clinicians now know that PTSD has neurobiological origins. Research has centered on determining why some survivors of trauma recover, while others show symptoms of PTSD.
Studies indicate that elevated heart rate in the presence of low cortisol is predictive of who will later develop PTSD. Patients with PTSD may also experience biological sensitization, in which chronic corticotropin-releasing factor (CRF) hypersecretion leads to blunted adrenocorticotropic (ACTH) response to CRF, resulting in low cortisol.
“The idea is that lower cortisol, chronically, due to dysregulated stress feedback, prevents the stress axis from regulating itself,” said Dr. Ressler. He added, “The brain’s stress response pathway stays in this hyperaroused state.”
PTSD could result from over-learning of trauma memory and a failure of extinction, the process that creates new, competing inhibitory memories that dissociate from the traumatic memory.
“Extinction is not an erasure of memory; rather, it’s a new creation of a new inhibitory memory saying that in this place, I’m safe,” said Dr. Ressler.
As a result of failure of extinction, patients with PTSD constantly re-experience fear in stressful situations or in response to an unconditioned stimulus.
Patients’ experiences are evident in the brain, specifically the amygdala, the prefrontal cortex, and the hippocampus. Hyperarousal and avoidance in PTSD are related to increased activation of the amygdala, and MRI scans of patients with PTSD show that the disorder is associated with lower hippocampal volume. This finding was replicated in four independent studies in combat veterans and abuse survivors, with 69% of individuals correctly classified based on MRI.
The hippocampus plays a role in spatial acting, explained Dr. Ressler. “Animal studies now suggest that the hippocampus is involved in and required for inhibiting the amygdala in learning that this place is now safe.”
Exposure therapy takes advantage of this mechanism by repeatedly walking the patient through the trauma memory so that the emotional brain learns that a place is safe. The amygdala makes that connection and the hippocampus maps the space, but a smaller, less functional hippocampus disrupts this process. “[The hippocampus] might not be able to modulate the amygdala in learning to inhibit fear,” said Dr. Ressler.
Patients with PTSD may benefit from psychosocial treatments such as exposure therapy, which teaches patients to relax and cope with stress while undergoing progressive exposure to the traumatic memories. Psychodynamic treatments, cognitive behavioral therapy (CBT), anxiety management, eye movement desensitization and reprocessing (EMDR), and group therapy are also used for PTSD, but the strongest evidence supports exposure techniques.
“One of the main arguments in the field is which is better, cognitive therapy or exposure therapy,” said Dr. Ressler. He added, “There doesn’t seem to be a lot of data for cognitive and exposure therapy specifically combined.”
Pharmacological treatments also may help patients with PTSD. The selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine improve outcomes, said Dr. Ressler. He noted that these medications may take longer than expected to reach a full treatment effect. If patients are improving after a few weeks, they might continue to improve eight to 10 weeks after beginning treatment.
Continuing research suggests that future treatments may involve drugs that target the specific causes of the disorder.
For example, in trauma situations new memories are not created immediately but actually take hours or days to consolidate. “If we understand the gene processes and neural processes and protein processes that are happening during that consolidation, we could have this period where we intervene to prevent the development of PTSD,” said Dr. Ressler.
Understanding the processes that occur duing that time might one day allow for the creation of intervention protocols similar to those used today for stroke. After experiencing trauma, patients at risk for PTSD might receive an intervention that prevents consolidation of traumatic memories during that critical window of time.
“We have a long way to go with PTSD,” said Dr. Ressler. “But I want to make a more optimistic point—we understand quite a lot about the circuitry of fear. In the next decade we’re going to have targeted, rationally designed therapeutics based on our biology.”