04. Stress, anxiety, and aggression Flashcards
What is stress?
- Change that causes physical, emotional, or psychological strain.
What is the Sympathetic-Adrenal-Medullary (SAM) system?
The stress (sympathetic) response
Hypothalamus stimulates the adrenal medulla to release adrenaline/epinephrine (↑blood glucose) and noradrenaline/norepinephrine (↑ blood pressure)
Adrenaline is also secreted in the brain
What type of molecules are adrenaline and noradrenaline?
Catecholamines
What is the HPA (Hypothalamic-Pituitary-Adrenal) axis?
- The paraventricular nucleus of the hypothalamus (PVN) releases corticotropin-releasing hormone (CRH)
- CRH stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH)
- ACTH enters general circulation and stimulates the adrenal cortex to secrete glucocorticoids (e.g. cortisol) → increases glucose & decreases pain sensitivity
CRH is also secreted in the brain
What effect does stress have on the brain?
Stress is toxic
Too much glucocorticoids damages the hippocampus (learning & memory centre)
Evidence that stress is toxic
(Diamond et al., 1999)
- rats exposed to the smell and presence of cats
- increased levels of blood glucocorticoids
- impaired primed-burst potentiation in hippocampus
- impaired performance in spatial awareness tasks
What is Post-traumatic stress disorder (PTSD)
- a conditioned response to fear-related stimuli
- responses: flashbacks, hypervigilance, irritability, reactions to sudden noises
PTSD and Pavlov
- Neutral stimulus (helicopter) paired with a salient stimulus/experience (stress from war=US)
- over time, the conditioned stimulus (helicopter) evokes a conditioned fear response
PTSD and brain changes
- Reduced size of hippocampus in PTSD (Bremner et al. 1995; Gurvits et al., 1996; Lindauer et al., 2005)
Are there risk factors for PTSD?
- possibly a smaller hippocampus!
- monozygotic twin study from Vietnam war
- Smaller hippocampus -> less ability to distinguish threats -> PTSD
(Gilbertson et al. 2002)
How do the amygdala and prefrontal cortex (PFC) behave in PTSD?
- PFC is involved in impulse control so normally inhibits the amygdala (Rauch et al. 2006)
- PTSD linked to ↑amygdala and ↓PFC responses to fearful faces (Shin et al. 2005)
- opposite for happy face
How do we treat PTSD?
- Psychotherapy
- ↓amygdala activity, ↑PFC & ↑hippocampus activity (Thomaes et al., 2014)
- Antidepressants (SSRIs)
- Exposure therapy (undoing Pavlovian conditioning - extinction training)
Exposure therapy procedure
- in extinction training, the cue is repeatedly presented without the association, causing extinction of the association
- highly effective (Powers et al., 2010)
What is anxiety?
- normal (unlike stress)
- only concerning when abnormally high
What are anxiety disorders
- intense fear, inappropriate for situation
- likely due to stress
- more common in women
What are panic disorders
- episodic panic attacks
- symptoms: hyperventilation, irregular heart-beat, dizziness, faintness, fear of death & lack of control
- cultural influence: USA rates higher than Asia, Africa and Latin America
Brain changes and anxiety/panic disorders
PETs and fMRIs show:
- increased amygdala activity during panic attack (Pfleiderer et al., 2007)
- increased amygdala activity when presented with negative faces (anger, fear, disgust) (Phan et al., 2005)
- GAD adolescents have increased amygdala and decreased PFC activity (Monk et al., 2008)
- activity correlates with symptoms
Treatments for anxiety
- GABAergic drugs: benzodiazepines (BDZ). Unfortunately they can be abused, and cause withdrawal & sedation
- Flumazenil has the opposite effect - it disinhibits GABAA & causes panic attacks (∴ treatment for BDZ/alcohol overdose)
Evidence for GABAergic drugs
- animals taking them spend more time in anxiety-inducing situations (elevated & exposed areas on the “elevated plus maze” (EPM))
- reduced amygdala activity looking at negative faces (Paulus et al., 2005)
Why do GABAergic drugs work?
- they increase inhibition by binding to inhibitory GABAA receptors
What are the other treatments for anxiety disorders?
- Increasing neurosteroid synthesis (allopregnanolone) -> during panic attacks synthesis is decreased, so increasing synthesis reduces panic (Nothdufter et al., 2011)
- fluvoxamine, an SSRI reduces panic attacks (Asnis et al., 2001)
- D-cycloserine (DCS) reduces panic attacks (Ressler et al., 2004) and facilitates extinction of conditioned fear in animals (Walker et al. 2002)
SSRIs and DCS work alongside therapy, by facilitating learning!
What is Aggression?
Natural urge to enable survival
Behaviours: threat, defense, submission
Where is aggression controlled?
- Brain stem
- Stimulation of periaqueductal grey (PAG) area causes aggressive attack and predation in cats (Gregg and Siegel 2001)
- Medial Hypothalamus→Dorsal PAG: defensive rage
- Lateral Hypothamaus→Ventral PAG: Predatory attack
What reduces aggression? (neurotransmitter)
- Serotonin
- It inhibits both aggression and risk taking
- Either destruction of serotonergic axons (Vergnes et al., 1988) or reducing serotonin synthesis increases aggression (Mosienko et al. 2012)
- Monkeys low in serotonin show greater risk-taking and more fights (Howell et al., 2017)
- Therefore SSRIs (fluoxetine) can reduce aggression
