Lecture 15: PTSD Flashcards
What is PTSD?
– Post-traumatic Stress Disorder (PTSD) is a mental health disorder that can develop following traumatic experiences.
– People with PTSD experience recurring memories and/or dreams related to a traumatic event for months to years. PTSD in thought to be a disturbance of memories
– Characterized as a stress response that won’t turn off.
Physiological arousal as if the event/danger is imminent, which fuels the belief of these recurring memories.
– Interpersonal trauma (e.g. sexual assault) is more likely to result in PTSD, compared with other forms of trauma (e.g. car accident, natural disaster);
– Most people who experience traumatic events will not develop PTSD.
What are the signs and symptoms of PTSD?
Onset of symptoms can occur up to a year after the event. Symptoms can include:
– Increased anxiety;
– Intrusive memories (related to event);
– Dreams or flashbacks of event;
– Irritability/impulse control issues;
– Social isolation;
– Emotional numbness.
Patients with PTSD will attempt to avoid any trauma-related cues, tends to change how a person thinks, feels and behaves.
What are the flashback symptoms of PTSD?
- Flashbacks are intrusive memories that are accompanied by high levels of arousal.
- Can involve a variety of sensory and/or behavioral systems (e.g. sense of smell, hiding); depends on the traumatic event
- Typically triggered automatically (not conscious, by autonomic nervous system) by situations that reflect aspects of the traumatic event > environmental cues.
- When input (e.g. noise) matches representations in the emotional memory network (e.g. noise of an ambulance), mutual activation spreads;
- Activation of verbal, behavioral and physiological responses lead to a re-experiencing of intrusive memories;
- Strong emotional component (e.g. fear, anxiety).`
How can you diagnose PTSD?
– Diagnosis of PTSD requires exposure to traumatic or stressful event (e.g. death, threatened or actual injury, sexual violence, etc.), along with a subset of other criteria.
– Traumatic event is persistently re-experienced in memories, nightmares, flashbacks, emotional distress, etc.
– Avoidance of trauma-related stimuli after the trauma;
– Negative thoughts or feelings that began or worsened after the trauma; ex. mild depression becoming worsened to major dep.
– Trauma-related arousal and reactivity;
These symptoms must last longer than 1 month, create functional impairments and are not due to medication, substance use or other illness.
What causes PTSD?
- We don’t really understand the pathophysiology of PTSD.
- Patients with PTSD show several neuroendocrine and brain abnormalities, all of which seem to play at least some role in stress, learning & memory:
1. Neuroendocrine disruptions;
2. Hippocampus;
3. Amygdala;
4. Prefrontal cortex.
- Patients with PTSD show several neuroendocrine and brain abnormalities, all of which seem to play at least some role in stress, learning & memory:
What are the neuroendocrine disruptions in PTSD?
- The sympathetic division of the ANS involves the release of epinephrine from the adrenal medulla; fight tor flight
- Epinephrine enhances memory formation in a dose-dependent way
- Chronic stress and/or traumatic events increase activation of sympathetic division;
- This system (stress-response) remains sensitized following traumatic events; always on edge, higher arousal levels
- Patients with PTSD typically show higher levels of circulating epinephrin, CRH and other stress-related catecholamines.
How is the hippocampus implicated in PTSD?
– Chronic stress and/or extremely traumatic events leads to extremely high levels of circulating glucocorticoids.
– High-levels of glucocorticoids damages neurons in the hippocampus
> Part of the negative feedback loop;
> Hippocampus has high density of GR’s which is sensitive to stress;
> Chronic stimulation of GR’s results in atrophy of hippocampal cells.
– positive correlation between hippocampal abnormality and severity of PTSD
> Reduced glucocorticoid-receptor density in the hippocampus;
> Reduced hippocampal volume (in some cases, not all);
> Hippocampus less able to depress the stress response.
How is the amygdala implicated in PTSD?
– The amygdala is an almond-shaped structure located deep in the temporal lobe (limbic structure).
– Plays a role for processing emotions and consolidating emotional memories (e.g. fear).
– Epinephrine directly and indirectly activates b-adrenergic receptors in the amygdala.
> Helps consolidate emotional memories;
> Responsible for fear acquisition.
Following a traumatic event:
- The “fast” stress response releases epinephrine from the adrenal medulla;
- Epinephrine stimulates the the Vagus Nerve (cranial nerve IX). This nerve carries information from your gut to your brain where it synapses with the nucleus of the solitary tract (NTS).
- NTS then releases epinephrine onto the amygdala (b-adrenergic receptors) > memory storage
Per epi > VN > NTS > Amygdala
How is the amygdala involved in fear acquisition (research study)?
- Following the training trial, animals associated the dark component with a foot shock.
- Upon testing them at a future date, animals will spend almost all of their time in the light compartment
- Unless, of course, we give them b-blockers during the training trial! Epinephrine binds to b-adrenergic receptors in the amygdala so you get a fear response, and it activates the hippocampus. B-blockers are b-adrenergic receptor antagonists (block the receptor so that epinephrine does not bind to it) so the animal will not remember which side they were shocked on and spend equal amounts of time in both compartments during testing
How is the prefrontal cortex implicated in PTSD?
– The prefrontal cortex (PFC) is critical for controlling activity of the amygdala.
> PFC allows inhibition of inappropriate cognitive and emotional responses to stimuli;
> Facilitates planning and executive function;
> Involved in modulation of the emotional valence assigned to specific memories, through inhibition of amygdala; allows us to think that that memory wasn’t as emotional
– PFC has inhibitory control of amygdala activation (PFC turns on GABA interneurons which release GABA onto the amygdala which turns amygdala off)
– Epinephrine, especially at high levels, can impair the PFC function.
– PTSD patients typically show a hyporesponsiveness in the PFC, which normally provides inhibitory control over the amygdala.
– PFC is thicker in people who showed rapid extinction of a conditioned emotional response;
– Reduced PFC volume in adults who sustained emotional maltreatment as children.
What is reconsolidation and how can b-blockers be used as a treatment for PTSD?
– Administering b-blockers (e.g. propranolol) shortly after a traumatic event can reduce physiological responses (e.g. heart rate) to later recollection of said event
– Reconsolidation is a process wherein previously-consolidated memories (i.e. long-term storage) can be changed/modified through reactivation of thememory trace. Once a memory is recalled, it enters a phase where it is malleable, and requires an active process to stabilize memory once recall is complete. Some treatments involve asking patients to describe, in painful detail, the trauma they experienced. So by recalling memories from long-term storage to working memory, and then administering the b-blockers simultaneously, you are getting rid of the emotional component of the memory thus changing the memory when you store the memory into long-term (dampening the emotional component of the memory). On subsequent trials, physiological response to describing trauma was less pronounced
What is memory extinction?
Memory Extinction: when a conditioned stimulus no longer predicts the unconditioned stimulus, the conditioned response gradually stops (over time).
– Repeat the conditioned stimulus (e.g. sound) in absence of foot shock;
– Over time, mice and rats will begin to show less and less freezing behaviors in response to cues;
– Suggests that the memory is becoming extinct.
– This has been shown to be effective in animals models if delivered the day after the traumatic experience, but not 30 days later.
– Prefrontal cortex also plays a role in memory extinction.
Inhibitory control over amygdala;
What is virtual reality exposure therapy?
– Virtual Reality (VR) is now being used for the prevention and treatment of PTSD.
– Controlled virtual immersion environment;
– Combines realistic stress scenes, sounds, odors, movements, etc.
– Allows people to relive traumatic events in absence of real harm; administer b-blockers
This technology is now being used prior to stress exposure to soldiers, police, firefighters and other first responders > prevention.
How can cannabis help with PTSD?
- We know people who consume cannabis are at higher risk for experiencing PTSD later in life;
- We know that people with PTSD self-medicate with cannabis > helps with impulse control issues, sleep, relieves nightmares, etc
- Cannabis, particularly CBD, can facilitate memory extinction;
- Cannabis, particularly CBD, interferes with memory reconsolidation;
- In humans, cannabis has been shown to alter aspects of aversive memories and improves PTSD symptoms -less emotional, less flashbacks, etc
