LC1 - Psychobiology of stress , emotions and affective disorders

Question 1

stress

Answer 1

• The disruption of homeostasis through physical or psychological stimuli
• A discrepancy between the demands of a situation and the resources of the person’s biological, psychological or social systems
• Loss of control on its environment
  o uncertainty, not able to predict or influence its relevant environment
• Maintain homeostasis regarding the internal and external environment
• Response:
  o Internal environment  physiological response
  o External environment  behavioral response

Question 2

acute vs chronic

Answer 2

• Acute: state of the organism after a transient decrease in the predictability of and/or influence of relevant environmental factors
• Chronic: state of the organism after a tonic decrease in the predictability of and/or influence on relevant environmental factors

Question 3

phases of stress response

Answer 3

1. Alarm phase – adrenaline + cortisol –> acute stress (fear/anxiety)
2. Adaptation/resistance phase – e.g. adrenal hypertrophy, etc. –> chronic stress (anxiety disorders and depression)
3. Exhaustion phase – e.g. ulcers, infection, psychiatric disorders etc. –> chronic stress (anxiety disorders and depression)

Question 4

acute physiological effects

Answer 4

cardiovascualr tone increase, immune activation, metabolism, CBF, memory, loss of appetitie, loss of sexual behaviour, vasoconstrciotn

Question 5

drivers of stress

Answer 5

• Autonomic Nervous System (ANS), i.e., sympathetic system ([m]sec range)
  o e.g. activation adrenals (medulla) ~ adrenaline
  o Fight-flight: Cannon
• Endocrine System (> seconds, days, weeks, months)
  o Hypothalamus-Pituitary-Adrenal cortex (HPA-axis) ~ cortisol/corticosterone

Question 6

ANS

Answer 6

• A novel stressful stimulus, once perceived, is relayed from the sensory cortex of the brain through the hypothalamus to the locus coeruleus (LC) in the brain stem
• Increased rate of noradrenergic (NA) activity in the LC makes the subject to become alert and attentive to the environment
• LC/NA (NE) system
• If a stimulus is perceived as a threat, a more intense and prolonged discharge of the LC activates the sympathetic division of the ANS
• This activation is associated with specific physiological actions in the system, both directly and indirectly through the release of adrenaline and to a lesser extent noradrenaline from the medulla of the adrenal glands

Question 7

HPA

Answer 7

image LC1
- Positive and negative feedback loop
o Negative feedback might occur at all levels (to varying extend)

• Desensitisation occurs at hippocampus level –> repsnds less to stessors
  o In chronic stress –> excitotoxicity and cell death

Question 8

cortisol acute effects

Answer 8

• Control of stress responsiveness (HPA-axis)
  o MR: control sensitivity of stress response system (set threshold)
  o GR: restrain stress-induced responses (negative feedback)
• Mobilization of energy (GR)
• Suppression of immunity (anti-inflammatory: GR)
• Behavioral inhibition/attention (medial prefrontal cortex: GR)
• Motivation (orbitofrontal cortex, n. accumbens: GR)
• Information Processing (hippocampus)
• Information processing is necessary for behavioral response towards stressor
• (also causes pre-term delivery and leads to ripening of lungs)

Question 9

GRs

Answer 9

• Mineralocorticoid receptor (MR)
  o High affinity for cortisol/corticosterone
  o In limbic system (hippocampus)
• Glucocorticoid receptor (GR)
  o Lower affinity for cortisol/corticosterone
  o Ubiquitous (hippocampus, amydala, prefrontal cortex)

Question 10

memory emotion interface

Answer 10

• Emotional memory is stored extremely well in order to be able to respond adequately towards a similar future stressor or threat
  1. Amygdala
• Part of the limbic system (emotion circuit)
• Connects to lateral (sympathetic activation) and medial hypothalamus (fear) and locus coeruleus (arousal)  fight or flight
• Connects to paraventricular nucleus of hypothalamus (HPA-axis)  endocrine response
• Amygdala mediates emotional memory
• Basal Lateral Amygdala (BLA) ~ major input (though also output)
  o Lateral hypothalamus Preganglions in brain stem and spinal chord ~ sympathetic activation
  o Locus Coeruleus ~ arousal
  o Medial hypothalamus Gray areas ~ fear behavior (fight-flight)
  o Paraventricular Nucleus (PVN) of Hypothalamus ~ endocrine response (HPA-axis)
• Central Amygdala (CeA) ~ major
• Amygdala stimulation:
  o plasma noradrenaline, CRF, ACTH and cortisol increase
  o fear/anxiety and aggression increase
• Amygdala lesion:
  o plasma noradrenaline, CRF, ACTH and cortisol decrease
  o fear/anxiety and aggression decrease
  o memory deficits
• Amygdala mediates Emotional Memory!!

2. Hippocampus
   * Part of limbic system
   * Stress-related projections:
    Hypothalamic paraventricular nucleus (HPA-axis)
   * Hippocampus inhibits the HPA-axis
3. HPA-axis
   * Spatial-learning  learning a position in space (mouse water-maze experiment)
    Blocking the MR and GR receptors or removing the stress hormones impairs the spatial learning
    MR – acquisition
    GR - consolidation

Question 11

MDD - causes

Answer 11

o HPA-axis hyperactivity (corticosteroid hypothesis)
o Neurotransmitter systems (monoamine hypothesis)
o Decrease in neurogenesis/neuroplasticity (neurogenesis/neurotrophin hypothesis)
o Immune disbalance (cytokine hypothesis)
o Combinations of different pathophysiologies