6.1 Stress and PTSD

What is stress?

An adaption mechanism of an organism to adapt to its environment. It is a disturbance of the system (imbalance), which is essential for survival.

What is the active condition of the autonomic nervous system called?

Sympathetic

What is the idle condition of the autonomic nervous system called?

Parasympathetic

What are the 3 levels of stress response?

1. Brain stem (locus coeruleus): reflexes

2. Hypothalamus & pituitary gland: hormones

3. Amygdala & prefrontal cortex: cognition

What is meant by the SAM-axis and what is its role?

Sympatho-adrenomedullary; initiates sympathetic activities such as adrenaline release by adrenal glands.

What is the role of the locus coeruleus?

Attention, memory, cognitive control, emotion, stress, sleep-wake cycli, posture (balance), and arousal.

Why does the level of the hypothalamus and pituitary gland go slower?

Because hormones move slower than neurotransmitters; it reaches your entire brain in 20 minutes.

Describe the elements/steps of the HPA-axis and their roles.

1. Hypothalamus: produces corticotropin-releasing-hormone (CRH)

2. CRH stimulates the pituitary gland (hypofyse)

3. Pituitary gland: produces adrenocorticotrophic hormone (ACTH)

4. ACTH stimulates: adrenal gland (bijnier)

5. Adrenal glands: produce cortisol

What is the role of cortisol?

Essential for cell growth, anti-inflammation, glucose metabolism, mobilisation if energy resources and stress regulation.

What happens during a hyper cortisol?

• Increased glucose concentration;

• Binge eating;

• Decrease of bone and muscle density;

• Depression.

What happens during a hypo cortisol?

• Less movement and activity;

• Disturbed temperature regulation;

• Autoimmune diseases (diabetes).

What type of feedback does the hippocampus give as an effect of increased cortisol levels in terms of stress regulation?

Negative feedback

What happend when there are toxic levels of cortisol detected in rats?

In rats, cortisol decreases neurogenesis and increases oligodendrogenesis.

What are the 5 roles of the prefrontal cortex?

• Processing new sensory information and memory;

• Inhibition of noradregeneric processes;

• Inhibition of detrimental (harmful) behaviour of inadequate coping;

• Monitoring performance and results

• Meta level: new strategies and adaptation

What are the the 6 roles of the amygdala?

• Fear conditioning;

• Threat appraisal;

• Emotional memory in co-op with hippocampus;

• Processing affective information;

• Interpretation of emotions in co-op with (prefrontal) cortex;

• The emotional brain by Joseph Le Doux.

How was the condition PTSD previously named previously?

Shell shock

What is psychological trauma?

Damage to the mind caused by exposure to an event that is accompanied with an overwhelming amount of stress, that direct adjustment is not possible. It results in a disturbance in the stress response-system, which is prolonged (or even persistent).

What are examples of psychological trauma?

• Victim of robbery;

• Rape;

• Participating in acts of war / violence;

• Witnessing horrific events.

What are the DSM-5 criteria of PTSD

A. Stressor (extreme traumatic experience);

B. Intrusion (reliving; flashbacks, nightmares);

C. Avoidance (emotional numbing; trigger avoidance);

D. Negative alternations in cognitions and mood;

E. Alternations in arousal and reactivity (highly irritable; anger outburst, startle response).

What are possible co-morbidites of PTSD?

• Alcohol/drugs (ab)use;

• Depression;

• Impulsive/aggressive behaviour.

What are occupational/professional groups with a high risk at PTSD?

• Hospital doctors;

• Ambulance personnel;

• Caretakers of handicapped people;

• Police officers;

• Defensity personnel;

• Firemen.

What are the three levels of PTSD (neurobiology)?

1. Increased sympathic activity;

2. Stress-hormone dysregulation;

3. Imbalanced ‘cognitive’ stress response system.

Which 2 things cause low cortisol levels in stress-hormone dysregulation?

• Adrenal gland insufficiency;

• HPA underactivity.

What causes low cortisol levels in PTSD patients?

Increased negative feedback sensitivity; even the tiniest amount of cortisol inhibit the production of new cortisol.

What happens during increased negative feedback sensitivity in PTSD patients?

GR (hyper)sensitivity in pituitary gland.

What do studies in PTSD patients using synthetic steroids (dexamethasone) suggest?

Cortisol sensitivity may be a fundamental state → early feedback to stop release of cortisol.

How can a disbalance in the ‘cognitive’ stress response system be recognised?

It is reflected by aberrations in brain structures (involved in memory and emotion processing and monitoring.

In which brain structures can aberrations occur in PTSD patients?

• Amygdala: processes memory and emotional reactions → is overly responsive in PTSD patients

• Medial PFC (anterior cingulate cortex): involved in rational decision-making → appears smaller in PTSD patients

• Hippocampus: has roles in long-term memory formation → appears smaller in PTSD patients

With what does the increased amygdala response correlati?

Symptom severity

What are two studies performed on the amygdala response in PTSD patients?

1. Faces (Shin 2005, William 2006): happy vs. fearful, fearful vs. neutral

2. Words (Protopopescu 2005): trauma-related vs. unrelated

What is normally the role of the prefrontal cortex?

It inhibits certain behaviours.

What happens when the activity of the prefrontal cortex is decreased?

Appraisal problems

What happens to the prefrontal cortex when there are high symptoms?

The prefrontal cortex is more inactive.

What are 2 theories regarding the amygdala and the prefrontal cortex?

• The amygdala is not working, which leads to the overactivity of the prefrontal cortex.

• The prefrontal cortex is not working, which leads to the overactivity of the amygdala.

What happens to the hippocampus in PTSD patients?

The activity is either increased or decreased, but it differs per patient.

What are possible explanations for the differences in findings for the hippocampus?

• Task and analyses related;

• Anterior;

• Posterior.

What are the roles of the anterior part of the hippocampus?

• Stress response;

• Emotion related memory (mediated by the amygdala).

What is the role of the superior part of the hippocampus?

Spatial functions

What is mainly correlated with symptom severity?

Smaller hippocampus volumes

With which 2 brain structures is the white matter connected?

vmPFC and hippocampus

What happens when the amygdala hyperresponsive to threat signals (bottom-up)?

Excessive stress response

What happens when there is less top-down amygdala-control?

• Diminished inhibition of amygdala;

• Prevents extinction.

What are 3 additional findings related to aberrant functions (learning & memory)?

• Smaller hippocampus (risk factor)

• Integrity of connections with hippocampus

  -> memory related problems (extinction)

• Less activity PFC->limited working memory

  -> impaired cognitive functions (inhibition)

What are 7 symptoms of PTSD?

• Flashbacks;

• Nightmares;

• Sleeping problems;

• Avoidance;

• Hyperalertness;

• Irritability;

• Outbursts of anger impulsivity.

What happens to the locus coeruleus in PTSD?

Increased LC responsivity

What is the result of increased NA levels?

Sleep problems & hyperalert all day.