Post-Traumatic Stress Disorder

Plasticity of the Amygdala

May account for learning, and contributes to fear memory. Fibers from the thalamus and cortex induces long-term potentiation in the lateral amygdala. NMDA receptors are critical for synaptic transmission and plasticity.

Post Traumatic Stress Disorder

*Features*: life-threatening trauma, re experiences with physical reactions, avoiding reminders and emotional attachment, being on guard (hyperarousal). *Associated symptoms*: depression, substance abuse, social discord, self destructive behavior, and suicide.

Anxiety Disorders

*Panic disorder*: recurrent panic attacks. *Social phobia*: fear of uncomfortable social interactions. *Specific phobias*: fear of heights, closed spaces, etc. *Generalized anxiety disorder*: excessive worrying. *Post-traumatic stress disorder*: trauma. All share anxiety and fear as core symptoms. Learned and innate fear.

Risk and Resiliency

*Risk factors*: type and severity of trauma, gender, age, education, previous psychiatric problems, and family history, childhood or prior abuse in military. Those individuals with a history of one trauma are at an increased risk for additional trauma in both military and civilian populations. *Resiliency*: treatment, social support, higher education have cognitive reserve protection.

PTSD in the Military

33% of Vietnam veterans, 20% of those coming from Iraq and Afghanistan. Typically presents 3-9 months after returning from tour. *Combat stressors*: dead bodies, being shot at, being attacked, rocket or mortar, knowing a KIA.

PTSD Chronicity

82% have chronic symptoms (>3 months). 14% of living World War 2 and Korean veterans still meet PTSD criteria 50 years later.

Preventing PTSD

Acute post-trauma administration of *beta-adrenergic receptor antagonists* may prevent PTSD. Decreases hyperarousal with repeated exposure. Not yet incorporated into practice.

Reconsolidation

After memory retrieval, protein synthesis in the amygdala is required to maintain the memory. Reactivated memories are labile and require protein synthesis again. The time between reactivation and reconsolidation provides an *opportunity for destabilization* of the memory if protein synthesis can be blocked (*Anisomycin*).

Amygdala

Central to theories of learned fear. Receives inputs from many brain regions (sensory, hippocampus, prefrontal cortex). Send output to multiple brain regions that produce manifestations of fear (freezing, blood pressure, stress hormones, startle reflex).

Fear Conditioning

Conditioned fear causes cardiovascular changes (BP) which are sensitive to amygdala and hypothalamic lesions. Lesion to the *hippocampus* causes loss of context conditioning (trapped in box), but cue conditioning (bell ring) remains. Lesion to the *amygdala* results in loss of both contact & cue fear conditioning.

Pavlovian Fear Conditioning

Correlates with memory of a fearful event and hyperarousal. Demonstrated that a sound correlated with a painful shock led to fear, eventually conditioning for the sound alone caused fear.

Extinction of Conditioned Fear

If the memory exist in the cortex alone it generates a new inhibitory memory called *extinction*. Impaired extinction may contribute to PTSD (coupled w/ stress or chronic ETOH intake). NMDA receptors facilitate extinction of conditioned fear. *NMDAR agonist d-cycloserine* accelerates the extinction of fear.

Protein Synthesis

Long-lasting plasticity requires protein synthesis. In the amygdala it is required for consolidation of fear memories. If protein synthesis in the amygdala is damaged long-term memory of trauma is gone.

Extinction of Memory

More difficult to eliminate than conditioned fear. Extending the time between extinction and testing causes a spontaneous recovery of the memory. *Renewal*: extinction of memory is context dependent, changing the context renews the originally conditioned fear response.

NMDA Inhibition

NMDA antagonists to NMDA receptor inhibits the acquisition of fear conditioning, if given prophylactically can prevent memory of trauma.

Treatment

Psychological treatment: cognitive behavioral therapy, exposure therapy desensitization. No specific pharmacological treatments. Psych meds are used to target various symptoms: mood and anxiety (antidepressants), hyperarousal (anti-convulsants, adrenergic blockers, benzodiazepines).