PTSD

Question 1

What is PTSD?

Answer 1

Posttraumatic 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  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.

Question 2

physiological arousal

Answer 2

PTSD is characterized by physiological arousal stemming from recurring memories and dreams related to traumatic evens.
PTSD patients feel as if they are reliving their trauma;
The physiological response enhances their belief that the danger is imminent;

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.
Children (< 10) appear to be less likely to show any distress in the form of PTSD;

Question 3

Signs & Symptoms

Answer 3

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.

Question 4

Flashbacks

Answer 4

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).

Typically triggered automatically 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 reexperiencing of intrusive memories;
Strong emotional component (e.g. fear, anxiety).

Question 5

Diagnosis

Answer 5

PTSD is a DSM-V Mental Disorder.

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;
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.

Question 6

What Causes PTSD?

Answer 6

We don’t really understand the pathophysiology of PTSD.
Human life is a complex myriad of experiences that complicates simple extrapolations from a single stressful event.
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.

Question 7

Neuroendocrine Disruptions

Answer 7

Recall: the rapid response to a stressor is part of the autonomic nervous system.
The sympathetic division of the ANS involves the release of
epinephrine from the adrenal medulla;
- Drives the sympathetic division of the ANS;
- Fight or Flight response.
Epinephrine strengthens the formation of emotional memories via activation of the amygdala (stay tuned).
- Epinephrine enhances memory formation in a dose-dependent way.
Patients with PTSD typically show higher levels of circulating epinephrine and other stress-related catecholamines.
- Chronic stress and/or traumatic events increase activation of sympathetic division;
- This system remains sensitized following traumatic events.

Question 8

Hippocampus

Answer 8

Glucocorticoid Receptors & HPA Axis
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 à sensitive to stress;
- Chronic stimulation of GR’s results in atrophy of hippocampal cells.

Question 9

hippocampal abnormalities

Answer 9

PTSD patients show hippocampal abnormalities correlated to the amount of trauma experienced
- Reduced glucocorticoid-receptor density in the hippocampus;
- Reduced hippocampal volume (in some cases, not all);
- Hippocampus less able to depress the stress response.
Patients with PTSD show elevated levels of circulating epinephrine, CRH and other stress-related catecholamines.

Question 10

Amygdala

Answer 10

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.

Question 11

Ever had a gut feeling?

Answer 11

Following a traumatic event:

• The “fast” stress response releases epinephrine from the adrenal medulla;
• Circulating epinephrine stimulates the Vagus Nerve (Cranial Nerve X);
• Vagus Nerve directly activates the nucleus of the solitary tract (NTS);
• NTS activates the the amygdala àmemory storage.

Question 12

Amygdala & Fear Acquisition

Answer 12

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 (to avoid being shocked, wouldn’t you?)
Unless, of course, we give them b- blockers during the training trial!
If peripheral epinephrine is blocked (b- blockers), the animal will not remember which side they were shocked on and spend equal amounts of time in both compartments during testing.

Question 13

facilitate the consolidation of memories.

Answer 13

Therefore, it appears that one function of peripheral epinephrine’s actions on the brain is to facilitate the consolidation of memories.
Specifically, emotional memories.

Question 14

Prefrontal Cortex

Answer 14

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.
PFC has inhibitory control of amygdala activation.
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.

Question 15

Beta-Blockers

Answer 15

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.
b-blockers appear to counter the effect of epinephrine secreted in response to the fearful experience.
- Normally epinephrine binds to b-adrenergic receptors;
- b-blockersareb-adrenergicreceptorantagonists(blockactivityofthis
receptor).

Question 16

Beta-Blockers treatments

Answer 16

Some treatments involve asking patients to describe, in painful detail, the trauma they experienced.
- Recalling traumatic memory brings memory from long-term storage to working/short-term memory;
- Simultaneously given propranolol (b-blocker);
- On subsequent trials, physiological response to describing trauma was
less pronounced;
- Seems to dampen the emotional weight of that memory, but not the declarative memory itself.

Question 17

Erasing Bad Memories

Answer 17

Can memories already consolidated be altered?
Reconsolidation is a process wherein previously- consolidated memories (i.e. long-term storage) can be changed/modified through reactivation of the memory trace.
- Requires memory to be recalled and actively reconsolidated.
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.
Can reconsolidation be used to reduce the symptoms of PTSD?

Question 18

Erasing Bad Memories

Answer 18

Memory Extinction – when a conditioned stimulus no longer predicts the unconditioned stimulus, the conditioned response gradually stops (over time).
In animals, we can extinct a fear-acquisition memory.
- 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.

Question 19

Can this be used as treatment for PTSD Erasing Bad Memories?

Answer 19

Can this be used as treatment for PTSD?
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;
- 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.

Question 20

Virtual Reality

Answer 20

Virtual Reality (VR) is now being used for the prevention and treatment of PTSD.
Virtual Reality Exposure Therapy
- Controlled virtual immersion environment;
- Combines realistic stress scenes, sounds, odors, movements, etc.
- Allows people to relive traumatic events in absence of real harm;
This technology is now being used prior to stress exposure to soldiers, police, firefighters and other first responders (arrow) prevention.

Question 21

Cannabis & PTSD

Answer 21

The intersection between cannabis and PTSD is interesting, but complicated:

• 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 (arrow) helps with impulse control issues, sleep, relieves nightmares, etc.
• We know that cannabis, in some cases, can be used as a treatment for PTSD (same reasons as above).

Question 22

Is there evidence to support this form of treatment for Cannabis & PTSD?

Answer 22

Is there evidence to support this form of treatment?

• 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.