W10 L24: Mental Health 

A brief history of “mental health science”

Mental health/illness recognised as problems with body/brain function near the turn of the 19th century

  • Psychoanalysis (pioneered by S Freud) relies on the verbal analysis of trauma & dreams

    • Much of mental life in happens in the subconscious
    • Early life experiences determine adult behaviour Behaviourism is a branch of psychology defined by the work of BF Skinner

  • Behaviourism is a branch of psychology defined by the work of BF Skinner

    • Emphasises the adaptation of behaviour = everything is learned behaviour
    • Mental illness maybe ‘unlearned’
    • Psychotherapy focusses on reversing negative behavioural patterns
Modern mental health science
  • Modern MHS is focussed on identifying multilevel interactions between genes, neuronal circuits and behaviour

 

Developing novel treatments
  • Molecular medicine aims to develop treatment based on genes linked to psychiatric disorders
  • Approach is difficult→ Psychiatric disorder definitions are still based on interviews w/ a clinician (no biomarker, e.g. a blood test for depression)
  • Many loci have been identified through genome wide association studies, many w/ small effect sizes:
    • a complex network of genes influences complex neuronal networks to cause complex behavioural changes

 

Induced pluripotent stem cells
  • An alternative path to new treatments for psychiatric disorders

 

Anxiety Disorders

Types of anxiety disorders

 

Neural mechanisms of anxiety – the stress response
  • The stress response is triggered by the HPA (gone over in previous lectures)

 

Amygdala and the hippocampus modulate the stress response
  • Amygdala stimulates HPA as during fear response
  • Hippocampus inhibits HPA through cell that express glucocorticoid receptors (sensitive to cortisol)
    • too much stress - HPA should be reduced (impaired in anxiety disorders)

 

 

Treatments for anxiety

Psychotherapy:

  • Gradual increase in anxiety inducing stimulus
    • Slowly alter (desensitise) underlying brain pathways

 

Pharmacotherapy (use of psychoactive medications):

Anxiolytic drugs:

  • Anxiety can be attributed to overactive (excitatory) neural pathways
  • Activate inhibitory signalling in the brain using drugs that enhance the effect of GABA on receptors

➢ Increased inhibition

 

Recent evidence suggests that pharmacotherapy & psychotherapy work better when delivered together.

Depression
Symptoms of major depression

Major depression is a mood disorder.

  • 5-13 % of the general population will experience an episode of depression in their lifetime
  • Symptoms include:
    • Loss of appetite (or increased appetite)
    • Insomnia (or hypersomnia)
    • Fatigue
    • Feelings of worthlessness and guilt
    • A diminished ability to concentrate
    • Recurrent thoughts of death

 

Theories of depression: monoamine theory
  • Reserpine (against high blood pressure) caused depression in 20 % of cases
  • Reserpine depletes monoamines (serotonin, dopamine, noradrenaline)
  • Early antidepressant imipramine inhibits serotonin reuptake = increased serotonin
    • Reduced serotonin signalling is major cause of depression

 

 

Theories of depression: Diathesis-Stress

 

Treatments for mood disorders: Antidepressants
  • Most current antidepressants block re-uptake of serotonin at the synaptic cleft:
    • increased serotonin

Problems:

  • antidepressants only work in about 2/3 of all patients
  • Take 6 weeks to show clinical effects

 

Ketamine
  • Approved as novel antidepressant treatment in 2019
  • 1st new class of antidepressant for 30 years
  • Blocks NMDA receptors on inhibitory interneurons
  • Activates other signalling pathways for protein translation and synaptogenesis

 

Modern concepts of depression

Today:

  • Depression & other psychiatric disorders are complex multifactorial diseases
  • Genetic disposition, development, early-life experiences & late-life experiences contribute to risk
  • Ability to manage stressful situations in late-life might be crucial for fending off conversion to psychiatric disorder (building resilience)

 

COVID-19 and mental health
  • Data from US health system (69 million records)
  • Covid-19 infection increases the risk of being diagnosed w/ additional psychiatric disorders such as depression of anxiety compared to influenza

 

Mental health is a continuum

 

Summary:

  • Mental health science links genetic, molecular & brain mechanisms to pathological changes in behaviour
  • Developing novel treatments will rely on molecular medicine approaches, e.g. induced pluripotent stem cells
  • Anxiety disorders are characterised by constant & excessive anxiety and worry
  • Anxiety can due to activation of the HPA
  • Amygdala enhances/hippocampus reduces HPA activation
  • Psychotherapy & pharmacotherapy are used to treat anxiety
  • Major depression occurs in up in 5-10% of the general population
  • Antidepressants include SSRI and more recently Ketamine
  • MD is a complex disorder caused by a genetic, developmental & environmental factors