Post Traumatic Stress Disorder

Question 1

When was PTSD originally defined in DSM-III?

Answer 1

1980

Question 2

What was PTSD originally known as?

Answer 2

“Soldier’s Heart”, “Shell Shock”, “Battle Fatigue”, “Delayed Stress”

Question 3

What is a key problem surrounding PTSD?

Answer 3

There are many people who experience traumatic events who do not go on to develop PTSD (why do some people respond to trauma in ways that other’s don’t)

Question 4

It’s normal to experience upsetting/confusing thoughts after a traumatic event… but in most people these improve naturally over a few weeks. However, symptoms/criteria for PTSD include:

Answer 4

▪ A stressor event (the ‘trauma’)
▪ Intrusion symptoms
▪ Alterations in arousal/reactivity
▪ Negative alterations in cognition/mood
▪ Avoidance behaviours

Question 5

what is ‘complex’ PTSD?

Answer 5

trauma episode is related to multiple events over an extended period of time (i.e. abuse), rather than a single traumatic event/short series of events

Question 6

What is the criteria for PTSD?

Answer 6

▪ Stressor
▪ Alteration in arousal and reactivity
▪ Intrusion Symptoms
▪ Negative alterations in cognition/mood
▪ Avoidance

Question 7

What criteria must symptoms hit before it can be diagnosed as PTSD?

Answer 7

Symptoms last for more than a month. Symptoms create distress or functional impairment (e.g. social, occupational). Symptoms are not due to medication, substance use or other illness

Question 8

What are stressors?

Answer 8

Person exposed to: death, threatened death, actual or threatened serious injury, or actual or threatened sexual violence, via…

▪ Direct exposure (happens to them)
▪ Witnessing the trauma (seeing somebody experience the event)
▪ Learning relative/close friend was exposed to a trauma
▪ Indirect exposure to aversive details of trauma (e.g., first responders, medics) – remember everyone’s meaning of trauma is different

Question 9

what are alterations in arousal and reactivity?

Answer 9

Trauma-related arousal and reactivity began or worsened after trauma:

▪ Irritability or aggression
▪ Risky or destructive behaviour
▪ Hypervigilance
▪ Heightened startle reaction
▪ Difficulty concentrating
▪ Difficulty sleeping

Question 10

What are intrusion symptoms?

Answer 10

Traumatic event persistently re-experienced via…

▪ Unwanted upsetting memories
▪ Nightmares
▪ Flashbacks
▪ Emotional distress after exposure to reminders
▪ Physical reactivity after exposure to reminders

Question 11

What is negative alterations in cognition

Answer 11

Negative thoughts/feelings began or worsened after trauma:

▪ Inability to recall key features of the trauma (issues with recall in trauma)
▪ Overly negative thoughts/assumptions about oneself/the world
▪ Exaggerated blame of self or others for causing the trauma
▪ Negative affect
▪ Decreased interest in activities
▪ Feeling isolated
▪ Difficulty experiencing positive affect

Question 12

What is avoidance?

Answer 12

Avoidance of trauma-related stimuli after the trauma, in the following way(s):
▪ Trauma-related thoughts or feelings
▪ Trauma-related external reminders

This means they’re avoiding specific traumas in terms of locations but also thoughts and feelings

Question 13

Complex neurobiology of PTSD:

Answer 13

Prefrontal cortex (Dorsolateral PFC and Orbitofrontal Cortex (/Ventromedial PFC))

Cingulate cortex (Anterior cingulate cortex)

Limbic regions (Thalamus (not specifically PTSD but characterises anxiety disorder more generally), Amygdala (not specifically PTSD but characterises anxiety disorder more generally) and Hippocampus)

Neuroendocrine system (the HPA)

Question 14

Amygdala:

Answer 14

▪ Part of the limbic system
▪ Involved in emotion processing (of all kinds)
▪ Component of the reward, motivation and learning networks
▪ Stimulates the HPA

Question 15

The link between the amygdala and PTSD:

Answer 15

▪ PTSD Veterans, Combat Veterans and controls scanned with PET (metabolic measure of blood flow and energy use within the brain)
▪ Played white noise and combat sounds
▪ PTSD veterans showed a greater physiological responses: stress and skin response to combat noise than white noise
▪ PTSD veterans showed a greater response to combat noise in left amygdala
▪ Combat sound more distressing to PTSD sample than non-combat control and regular control
▪ Combat controls show heightened amygdala responses, but only slightly when combat sounds are played
▪ Whereas, those with PTSD showed a much greater response in the left amgdala when combat sounds were played compared to white noise

Question 16

why can’t you use fMRI scanners with soldiers?

Answer 16

magnets are dangerous when soldiers potentially still have metal in them etc. from previous wombs so instead PET scans are preferred in this circumstance

Question 17

Cingulate Cortex

Answer 17

▪ ACC = Anterior cingulate cortex
▪ Involved in attention, reward, decision making and emotion
▪ Part of frontal-striatal network
▪ Also part of the “salience network” (sometimes called ventral attention network) à involved in alerting attention to threats/unexpected stimuli/changes to our environment

Question 18

Heterogeneity in PTSD treatment responses related to ventral attention network (Etkin et al., 2019)

Answer 18

▪ Resting-state fMRI study of PTSD patients and controls
▪ Reports rsfMRI connectivity of brain networks and cognitive testing
▪ Results show PTSD patients with poor verbal memory and weak connectivity in ventral attention network (pink) had poorer treatment response
▪ Shows neural and cognitive factors that impair treatment
▪ Found PTSD patients with poorer connectivity in VAN had poorer response and poor verbal memory - potentially a biomarker for poor treatment response

Question 19

Atypical ACC responses in PTSD

Answer 19

▪ 8 War veterans with PTSD vs. 8 War veterans without PTSD
▪ Subjects counted the number of combat words, negative words and neutral words
▪ Results showed a diminished (reduced) response to negative words in rostral anterior cingulate cortex (ACC)
▪ ACC mediates / controls response to negative stimuli in healthy brain

Question 20

Thalamus

Answer 20

▪ Important for joining up our sensory information and sending it out to the brain
▪ The brain’s relay station for sensory information
▪ Many substructures, important visual areas include the pulvinar and the lateral geniculate nucleus (LGN)
▪ Thalamus responds to bottom-up (environmentally given) and top-down (governed by our higher order goals) input
▪ The hypothalamus forms a key part of the HPA axis

Question 21

Dorsolateral Prefrontal Cortex (DLPFC)

Answer 21

▪ Part of fronto-parietal attention network Implicated in studies of cognitive control
▪ Greater BOLD activity when controlling cognitive response
▪ Part of Frontal-Striatal Network
*underactive/hypoactive in depression

Question 22

Orbitofrontal Cortex (OFC)

Answer 22

▪ Also called ventromedial prefrontal cortex)
▪ OFC involved in decision making and future planning
▪ Also task switching and evaluation
▪ On the pathway between DLPFC and the amygdala

Question 23

Meta-analysis of PTSD

Answer 23

▪ Compared fMRI studies of PTSD, Social Anxiety, Phobias and Fear
▪ Patients with any of the three disorders showed greater activity than matched comparison subjects in the amygdala and insula (part of the cingulate) PTSD specifically showed hypoactivity in ventromedial prefrontal (also called OFC), thalamus and cingulat

Question 24

Hippocampus

Answer 24

▪ Part of the limbic system
▪ Memory processing (of all kinds)
▪ Attenuates the HPA-axis (helps control it)

Question 25

Hippocampus and PTSD

Answer 25

▪ Meta-analysis of 1868 patients (794 PTSD patients) looking at hippocampal volume
▪ Smaller hippocampus = increased chance of PTSD
▪ Arguably the most replicated structural abnormality found in PTSD is a lower volume of the hippocampus

Question 26

40 Monozygotic twin pairs had their hippocampus volume examined (one twin having gone to war (combat veteran), the other hadn’t) to see whether change in hippocampus volume was a cause of result of trauma

Answer 26

▪ Looked to see if non-combat twin hippocampal size predicts the PTSD symptoms of their combat exposed twins (trying to suggest whether hippocampal volume acts as a risk factor prior to combat/trauma experience/PTSD)
▪ Results showed hippocampal volume predicted severity of PTSD in the combat exposed twin and the non-combat exposed twin
▪ Smaller hippocampus increases likelihood of mental illness
▪ A risk factor for PTSD, not a result of trauma

Question 27

The neurotrophic hypothesis of depression and could the involvement of the hippocampus be due to depression rather than PTSD?

Answer 27

▪ Human post-mortem data shows decreased BDNF in hippocampus
▪ Impairs memory encoding
▪ Demonstrates neuroplasticity at a very specific anatomical level
Not clear if this is a cause or a result of depression (and some studies show the reverse

Question 28

Hypothalamic-pituitary-adrenal (HPA) axis

Answer 28

▪ HPA axis coordinates neuroendocrine stress response systems
▪ The HPA axis involves the brain (specifically the hypothalamus) … but also the adrenal glands near your kidneys!
▪ The hypothalamus and pituitary gland are located just above the brainstem. The adrenal glands are found on top of the kidneys.

Question 29

What happens upon stress exposure

Answer 29

1. Neurons in the hypothalamus (specifically the paraventricular nucleus, PVN) release corticotropin-releasing hormone (CRH)
2. Which stimulates the production and release of adrenocorticotropin (ACTH) from the anterior pituitary…
3. and ACTH in turn stimulates the release of glucocorticoids (including cortisol) from the adrenal gland.

Question 30

Glucocorticoids modulate metabolism, immune response and brain function and are basically involved in your fight or flight response, getting the body and brain ready to act

Several brain pathways modulate HPA axis activity including…

Answer 30

▪ The hippocampus and prefrontal cortex (PFC) inhibit the HPA
▪ The amygdala stimulates neurons in the hypothalamus

But the final outputs of the HPA axis also act on the brain (because of feedback loops which acts upon these brain regions)…
▪ Glucocorticoids exert negative feedback control of the HPA axis by downregulating hippocampal and PVN neurons (to tell your brain to stop doing that? I think?).
▪ Sustained glucocorticoid exposure has adverse effects on hippocampal neurons…

Question 31

The HPA axis (our flight or fight system) in PTSD

Several studies (examples earlier) suggest differences in regions like the hippocampus and amygdala, which help to regulate the HPA axis
Studies are not totally consistent however in the overall direction of effect on the HPA axis in PTSD…

Answer 31

▪ Some suggest cortisol is actually reduced in PTSD, possibly due to negative feedback effects
▪ Some studies suggest subtypes in PTSD differ with regards to their cortisol/HPA reactivity (e.g. childhood trauma)
▪ There are multiple ways to measure “cortisol levels”, and this might be the source of some of the confusion!
▪ However’s no consistency into whether you have an overreactive or underreactive HPA/cortical levels in PTSD

Question 32

What is clinical neuroscience still yet to figure out?

Answer 32

▪ brain regions/systems may be an effect of trauma
▪ Which are pre-dispositional risk factors for PTSD
▪ Which may be better explained by co-occurring factors (e.g. depression)

Question 33

Why should be not target the HPA-axis (aka. give cortisol-based treatments)

Answer 33

The problem is Is a dysregulated HPA axis the cause of PTSD? Or is it a risk-factor for PTSD? Or is it a consequence? Treating a risk factor/consequence might be no help once disorder has arisen!

Question 34

PTSD treatments using cortisol:

Answer 34

▪ Hydrocortisone is a steroid that work as a hormone replacement for cortisol
▪ There have been some studies on the possibility of using hydrocortisone for treating PTSD
▪ Systematic review (Kothgassner et al., 2021) of 8 studies suggest that hydrocortisone helps as a preventative after trauma against developing PTSD… but does very little if given after PTSD has been developed already
▪ Not currently a recommended drug treatment for PTSD

Question 35

What happens when SSRIs (antidepressants) are used to treat PTSD?

Answer 35

reduce PTSD symptoms – but it is a small-moderate effect, and not universal (but properly not treating the core neurobiological mechanisms but it’s providing some relaxation

Question 36

What is extinction?

Answer 36

▪ a fear response can be inhibited (very behavioural idea)
▪ Essential process in which a learned fear response can be learned to no longer be a learned fear response
▪ Heavily studied in animal literature (e.g. Pavlov)
▪ Offers a behavioral and neural explanation of why CBT works
▪ Extinction is a form of learning, it is not “unlearning”
▪ Extinction = learning new skills

Question 37

Pavlovian Fear Conditioning + Extinction

Answer 37

▪ Pairing of the conditioned stimulus (CS) and unconditioned stimulus (US) leads to the conditioned response (CR)
▪ Extinction is the reduction of the CR by repeated presentation of the CS in the absence of the US
▪ Not unlearned but relearned the stimulus is no longer predicted as something bad happening, extinction has happened to the conditioned respons

Question 38

How does extinction work in the brain?

Answer 38

▪ Greater vmPFC (also called OFC) activity equals greater extinction learning (implicated in extinction learning)
▪ dACC (dorsal ACC) activity is negatively correlated with extinction
▪ vmPFC signals amygdala to reduce and control fear response
▪ High connectivity between vmPFC and dACC leads to stronger extinction
** connected via signals to the amygdala
▪ How well connected vmPFC is to the Anterior Cingulate
^ overlap with those implicated in PTSD

Question 39

What does EMDR stand for?

Answer 39

Eye movement desentization and reprogramming

Question 40

What does EMDR do?

Answer 40

same affect as REM sleep, allowing us to properly consolidate episodic memory

Question 41

EMDR

Answer 41

▪ Developed initially by Francine Shapiro in the late 1980s (Shapiro, 1989a,b)
▪ The patient follows with their eyes rapidly moving stimulus (often clinician’s fingers) while holding different aspects of traumatic event in mind (talking about traumatic stress)
▪ Systematic reviews of RCTs suggest that it is effective (even more so than some other trauma therapies) (Wilson et al., 2018)
▪ Recommended by NICE as a treatment for PTSD
▪ But…we don’t really know how this works!
▪ Theory: processing that EMDR sets off are related to memory and PTSD is framed as this rouge memory processing issue - not consolidating and integrating that memory as you typically do

Question 42

Neurobiological Hypotheses

Answer 42

▪ One theory is that EMDR is related to memory processes
▪ PTSD could be considered a consequence of failed memory processing - arises when brain fails to consolidate and integrate an episodic memory, leads to continued maintenance of the memory and the feelings associated with it
▪ REM (Rapid Eye Movement) sleep argued to be important for memory consolidation
▪ EDMR → induces a physiological state similar to that in REM sleep - by doing this over and over again, you create this consolidation process that would happen normally

▪ Various brain regions involved in REM sleep - some of which have also been implicated in PTSD
▪ fMRI studies which examined brain activity before and after EMDR found changes in the activity of the amygdala, thalamus, caudate nucleus (bit of limbic system), and the OFC and dlPFC (Rousseau et al., 2019)
▪ In PTSD patients, EMDR therapy elicited significant functional decreases in deep gray matter (including the amygdala, thalamus, and caudate nucleus) and cortical activities (including notably the precuneus, and the ventromedial and dorsolateral prefrontal cortex - arguably hitting regions associated with PTSD - it creates this context for proper memory consolidation),

Question 43

When fMRI studies which examined brain activity before and after EMDR found:

Answer 43

changes in the activity of the amygdala, thalamus, caudate nucleus (bit of limbic system), and the OFC and dlPFC (Rousseau et al., 2019)

Question 44

PTSD patients, EMDR therapy elicited significant functional decreases

Answer 44

in deep gray matter (including the amygdala, thalamus, and caudate nucleus) and cortical activities (including notably the precuneus, and the ventromedial and dorsolateral prefrontal cortex - arguably hitting regions associated with PTSD - it creates this context for proper memory consolidation),

Question 45

Why is EDMR so powerful?

Answer 45

The rapid back-and-forth movement of the eyes (tapping) stimulates the brain’s information processing system, allowing it to process and integrate traumatic memories.