Stress, Anxiety and Aggression

Question 1

What physiological reactions characterise stress?

Answer 1

Physiological reaction:
* caused by perception of aversive or threatening situations
* resulting in physical, emotional or psychological strain
* helping to prepare for fight-or-flight situations
* can be episodic or continuous
* adaptive but harmful

Question 2

Describe the Sympathetic-Adrenal-Medullary (SAM) system

Answer 2

Sympathetic-Adrenal-Medullary (SAM) system:
* threats require enhanced activity, so must mobilise energy resources
* to do this, the hypothalamus and sympathetic nervous system stimulate adrenal medulla to release epinephrine (to increase blood glucose) and norepinephrine (to increase blood pressure)

Question 3

Describe the Hypothalamic-Pituitary-Adrenal (HPA) axis

Answer 3

Hypothalamic-Pituitary-Adrenal (HPA) axis:
* paraventricular nucleus of the hypothalamus (PVN) releases corticotrophin releasing hormone (CRH), which stimulates anterior pituitary gland to release adrenocorticotropic hormone (ACTH)
* ACTH enters general circulation and stimulates adrenal cortex to secrete glucocorticoids, which increase glucose and decrease pain sensitivity

Question 4

Describe the effects of stress on the brain

Answer 4

Effects of stress on the brain:
* can be neurotoxic
* chronic exposure to glucocorticoids destroys hippocampal neurons as decreased glucose entry, and glutamate reuptake causes excessive Ca2+ influx and overexcitation of the postsynaptic neuron

Question 5

rats exposed to cats, monkey ranks

What are 2 pieces of evidence for stress-induced neurotoxicity?

Answer 5

Evidence for stress-induced neurotoxicity:
* Diamond et al. (1999) - rats exposed to cat smell/presence experienced an increase in blood glucocorticoids, an impaired primed-burst potentiation in the hippocampus and were impaired in the spatial task
* Uno et al. (1989) - bottom-rank monkeys exposed to continuous stress by upper-rank monkeys were found to have enlarged adrenal glands (due to excessive norepinephrine production) and hippocampal degradation

Question 6

What is PTSD?

Answer 6

WHAT IS PTSD?
Long-lasting psychological symptoms experienced after a traumatic event; such as flashbacks, hypervigilance, irritability, heightened reactions to sudden noises and detachment from social activities. Often triggered by cues related to the traumatic event.

Question 7

What are the brain changes associated with PTSD?

Answer 7

BRAIN CHANGES:
* reduced hippocampal size in combat veterans and police officers with PTSD and smaller hippocampus in MZ twins with PTSD; because hippocampus plays a role in distinguishing contexts; inability to do this in those with PTSD (threat generalisation)
* altered activity of amygdala and medial PFC
PFC involved in impulse control and emotional expression, inhibits amygdala; PTSD associated with reduced mPFC and greater amygdala activation to fearful faces (vs happy faces, compared to controls); indicates excessice emotional response + impaired inhibitory control

Question 8

Describe the treatments for PTSD

Answer 8

TREATMENTS:
antidepressants (SSRIs) have been associated with increased hippocampal volume (Bossini et al., 2007)
psychotherapy has been associated with decreased amygdala activity and increased PFC/hippocampus activity (Thomas et al., 2014):
* cue-exposure therapy - Role of cue-stress learnt associations, as cue alone can produce a conditioned fear response; can reduce/extinguish this response through exposure therapy. Involves repeated cue presentation over weeks in safe therapeutic context, reduces fear response to cue. Effective (Powers et al., 2010)

Question 9

Anxiety Disorders

Answer 9

WHAT IS ANXIETY?
Apprehensiveness, uneasiness or nervousness over an impending or anticipated ill; becomes a disorder when more intense, inappropriate or irrational

TYPES OF ANXIETY DISORDERS
* panic disorder - episodic attacks of acute anxiety; hyperventilation, irregular heartbeat, dizziness, fainting, fear of dying; role of cultural factors (USA higher than Asian, African, Latin American countries according to APA)
* agoraphobia - intense fear/anxiety about leaving home, being in public areas or crowds etc.; coping through avoidance due to disproportionate fear of e.g. panic attack
* GAD - excessive, uncontrollable worrying from wide range of situations, diffulty controlling symptoms; sweating, trembling, difficulty concentrating; women > men; cultural component (European descent > Asian, African, Latino)
* SAD - persistent, excessive fear of being exposed to scrutiny/judgement of others; sweating, blushing; men = women; cultural component (European descent > Asian, African, Latino)

Question 10

What are the brain changes associated with anxiety disorders?

Answer 10

BRAIN CHANGES
Pet/fMRI scans have shown:
* increased amygdala activity during panic attack and in response to presentations of faces of anger/disgust/fear in SAD
* increased amygdala and decreased ventrolateral PFC activation in adolescents with GAD
* lack of suppression of amygdala activation via vmPFC (which plays a role in fear inhibition)

Question 11

Describe the treatments for anxiety disorders

Answer 11

TREATMENTS
* GABAergic drugs - benzodiazapines bind to inhibitory GABAA receptor as an agonist (increases Cl- flux and hyperppolarisation)
~ decrease anxiety in animals (spend less time on ‘open arm’ in the elevated plus maze (EPM)
~ BDZ reduces amygdala activity when looking at emotional faces (Paulus et al., 2005)
~ Flumazenil (antagonist) disinhibits action at GABAA, produces panic response, used to treat BDZ overdose and acute alcohol intoxication
~ BDZ have abuse potential, withdrawal symptoms and sedation effects (excessive use causes respiratory depression); better compounds needed
* neurosteroids - increase activity of GABAA
~ neurosteroid synthesis suppressed during anxiety attack, resulting in suppression of GABAA receptor function
~ XBD173 enhances NS synthesis and reduces panic, without causing sedation/withdrawal symptoms
* SSRIs
~ fluvoxamine reduces panic attacks
~ D-cycloserine reduces panic attacks (indirect agonist of NMDA receptor)

Question 12

Aggression

Answer 12

WHAT IS AGGRESSION?
May involve behaviours related to threat, defense and submission; related to species survival, e.g. gaining access to mates, protecting offspring.

Question 13

What are the brain circuits associated with aggression?

Answer 13

BRAIN CIRCUITS
Programmed by the brainstem; Gregg and Siegel (2001) found electrical stimulation of periacqueductal grey (PAG) elicited aggressive attack/predation in cats
* medial hypothalamus-dorsal PAG = defensice rage
* lateral hypothalamus-ventral PAG = predatory attack

Question 14

What do animal studies show about aggression and serotonin?

Answer 14

AGGRESSION AND SEROTONIN
Animal studies:
* increasing serotonin transmission decreases aggression
* decreasing serotonin transmission by destroying axons or reducing serotonin synthesis increases aggression
* low levels of serotonin metabolite in CSF of monkeys linked to higher levels of aggression - e.g. picking fights with larger monkeys, more risk-taking

Question 15

What do human studies show about aggression and serotonin?

Answer 15

AGGRESSION AND SEROTONIN
Human studies:
* mixed evidence for inhibitory role of serotonergic neurons in aggression
* low level of serotonin metabolite in CSF linked to aggression and antisocial behaviour
* SSRI (fluoxetine) reduces aggression in some cases

Question 16

Aggression as a reward; animal studies

Answer 16

What constitues a reward?
Objects, actions or experiences that attain a positive motivational property (increases the probability of the eliciting behaviour reoccurring)

Aggression as a reward
Some individuals show appetitive aggression motivated by intrinsic reward, which may be an adaptation to violent environments.
Animal studies:
* Conditioned Place Preference (CPP) - one chamber paired with a reward, the other chamber is not; after several pairings, the reward-paired chamber acquires motivational significance (acts as conditioned stimulus) as the animal spends more time there in the absence of stimuli/develops a preference
When studying aggression, use male rodents which are territorial and attack intruders. One side/chamber paired with intruder, other one not. Resident spends more time on paired side even when intruder not present (thus attacking intruder is a rewarding experience)
* Operant Task - once trained, animals continue pressing the level (reward-seeking behaviour). Animals learn to press lever for intruder (aggression self-administration) and once trained will continue pressing level in the intruder’s absence (aggression-seeking).

Question 17

Aggression as a reward; brain circuitry

Answer 17

Nucleus accumbens (NAcc) and ventral tegmentum area (VTA) play key role in reward and motivated behaviour; activated by rewarding experiences and measured by activity-sensitive Fos proteins or optogenetics.

Fos proteins
Strong activity (influx of calcium ions into the presynaptic terminal) activates immediate early genes (e.g. c-Fos) which are rapidly transcribed and translated into proteins (e.g. Fos). Fos protein can be used as a neuronal activity marker, and can be detected in post-mortem examinations of brain tissue in a cryostat, using immunohistochemistry.

Optogenetics
Aggression SA/seeking activates the NAcc; but this is correlational evidence. To establish causation, use optogenetics to selectively activate/inhibit target neurons (e.g. NAcc).
* virus containing light-sensitive channels (opsins) injected into animal brain
* opsins expressed in target neurons
* insert fibre-optic cable and shine blue vs green light to selectively activate (blue) or inhibit (green) target neurons
* measure behaviour of interest to establish causation

Using optogenetic stimulation, Yu et al. (2014) found that activation of the VTA increases aggressive behaviour (tail rattling) in rats.