10. Anxiety and Depression

• neurological basis of mood is poorly understood and is worked out through drug therapies
• anxiety disorder = inappropriate or excessive anticipatory manifestation of the fear response to a stressor

  • defensive behaviours
  • autonomic reflexes
  • corticosteroid decretions
  • negative emotions

  interferes with normal life
• types of anxiety disorder: general anxiety disorder, phobia anxiety, panic disorder
• in response to a stressor, the hypothalamus releases CRF, which acts on the anterior pituitary to release ACTH. this acts on the adrenal gland to release cortisol
• cortisol normally has a negative feedback mechanism on the hypothalamus, decreasing the release of CRH and then ACTH

  • this can become dysregulated in individuals with anxiety disorders
  • individuals with anxiety disorders can also have chronic activation of the HPA axis
• benzodiazepines are anti-anxiety medications that act on the GABA A receptor - bind to allosteric site and increase GABA affinity leading to increased Cl- influx and hyperpolarisation

  • cause sedation and can cause overdoses with alcohol
  • long term use can lead to tolerance and dependence
• buspirone is a 5-HT1A partial agonist. these are slower to act that benzodiazepines but have better side effects, and are non-addictive
• beta adrenoceptor antagonists are used to reduce the somatic symptoms of anxiety such as tremors and sweating

  • used for situational phobias
• antidepressant drugs like SSRIs can be used to treat anxiety
• major depression disorder can be reactive or endogenous (rarer)
• the monoamine theory of depression states that depression is due to hypoactivity at monoaminergic synapses in the brain

  • antidepressants increase monoamines in the brain rapidly
  • however antidepressants take multiple weeks to work?
  • amphetamine and cocaine also increase monoamines but do not act as antidepressants
• antidepressants: MAOIs, TCAs and SSRIs
• monoamine oxidase inhibitors increase the amount of monoamine in the presynaptic terminal

  • takes 4 weeks to work, but has an immediate effect of euphoria
  • cheese reaction - MAO normally metabolises tyramine in the diet (cheese, wine) and inhibiting this leads to high tyramine levels, causing vasoconstriction and hypertensive crisis
• TCAs and SSRIs inhibit reuptake of monoamines at the synapse

  • TCAs are sedative and anti-muscarinic, overdose is possible
  • SSRIs have lower side effects than MAOIs and TCAs
• the network hypothesis theory of depression suggests that hyperactivity of the neuroendocrine stress response may lead to depression, as not all individuals have a loss of cortisol negative feedback

  • hippocampus loses neuroplasticity

  suggests antidepressants may increase monoamines which leads to increased plasticity, restoring the network