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Many people have depression

  • Churchill, Lincoln, Gallop, Goodes
  • Books
    • Lewis Wolpert
    • Antonio Damasio
    • Joseph Le Doux
  • Depression is a distortion of normal sadness

When people are severely depressed, it's completely different to normal emotions

  • Low point prevalence, high lifetime prevalence.
  • 20% suffer from a mental illness each year, 5% clinically depressed each year, 3% now; 30-40% have depression at some point in their life.
  • Major depression (affective disorders) are the greatest-burden mental disorder
  • Two peaks in onset: late teens and old age
    • Therefore middle age is the highest prevalence (picking up all the people who remit and recur)

Burden of disease

  • Burden of disease used to be calculated from age-standardised mortality ratio
  • Now we add YLL and YLD; this is DALY
  • In 1990 unipolar major depression was fourth; it's predicted to be 2nd in 2020 (after ischaemic heart disease; mainly because the tobacco companies are selling in the developing world)
    • In 1990, unipolar depression was the largest cause of disability in the world (and certainly in australia)
  • Depression:
    • More than two weeks of persistently sad or blue^ and loss of interest^ plus 3 or more of the following:
    • Loss of energy
    • Change in sleep
    • Change in eating, weight
    • Change in ability to concentrate^
    • Change in ability to think or move quickly
    • Feelings of worthlessness, guilt^
    • Thoughts of death^
  • NB: the 5^ symptoms are as good as the 9
  • Pathognomonic: "persistent depression" is the first.
  • State the most important one first.

How do we recognise depression

  • Sad or low mood
  • Loss of interest or pleasure
  • Signficant loss or gain of appetite or weight
  • Insomnia or excessive sleep
  • Physical and mental agitation or slowing
  • Fatigue or loss of energy
  • Feelings of worthless or excessive guilt
  • Impaired thinking or concentration; indecisiveness
  • Suicidal thoughts, thoughts of death

Even if they say they're anxious/worried, you can notice that they're in fact depressed

(One or two of the first two, and 5 in total to make a diagnosis) - this is an artificial threshold that correlates well to need for treatment, disability, and likely response to treatment.

Major depressive disorder

(Dimensional=continuous; categorical=discrete)

  • Dimensional disorder; MDD >4/9 symptoms
  • Remits and recurs, on average 8 episodes of 6 months each; cumulative duration 4 years
  • People with severe MDD followed for 12 years
    • Well 6 years
    • Sub-threshold 4 years - ?Need for Rx; Should be planning not to be below-par
      • Treat even in remission because it corrodes the quality of life
    • MDD 2 years - Certainly need Rx
  • Occurs across all ages; 2/3 are female
    • This is closer to 50:50 in scandinavia where women are treated equally
  • Treated with antidepressants (Prozac or Cipramil) or Cognitive Behaviour Therapy
  • "There is no full satisfactory treatment for major depression" -
  • Medicines don't work well in mild and moderate depression (NNT=16)
    • Show a medium effect in severe depression (NNT=11)
    • Substantially better in severe depression (NNT=4)


  • This is the checklist to give to patients
  • Patients fill it in more accurately than doctors

iCBT (internet CBT) for depression

  • NNT=2, getting people below the threshold for diagnosis

Triggering factors

  • Stressful life events (usually some experience of loss; or feeling emotionally trapped in a situiation; or a sense of humiliation or shame)
    • Separation from a loved one
    • Threat of separation, etc

For most people, you're making up a triggering factor after the fact (not external cause, but internal cause)

Predisposing factors

  • Genes alone can sometimes cause depression

Adverse childhood environment

  • The impact of the environment is important
  • You don't get depressed because the event; it is that this event makes you vulnerable.

What causes mental disorders?

  • Family history of depression sensitizes people to stressors
  1. No familiality; no stressors prior to 18: risk 2.5%
  2. No familility, stressors present: risk 2.5%
  3. Familiality, no stressors: risk: 5.0%
  4. Familiality; stressors: risk: 7.5%

What are emotions? (Damasio)

  • A continuum
    • A state of emotion --> non-conscious (biology)
    • A state of feeling --> non-conscious “feeling”
    • A state of feeling made conscious --> conscious experience
  • Primary (universal) emotions:
    • Happiness, sadness, fear, anger, surprise, disgust (experienced automatically)
      • We don't know why sadness is ever a good thing (doesn't really help your performance)
  • Secondary emotions:
    • Embarrassment, jealousy, guilt, pride
  • Background emotions:
    • Wellbeing vs. malaise
    • Calm vs. tension

Shared biology of emotion

  • Emotions are complicated collections of chemical and neural responses
    • Have a regulatory role that creates circumstances that are advantageous to an organism and assists it in the maintenance of life
    • Can be helpful – ie: the Yerkes Dodson curve
  • Learning and culture alter the expression of emotion and give it new meanings
    • The biology, however, is due to innate brain devices and is evolutionarily the same
  • Biology:
    • Neural devices are limited to specific areas of the brain
      • Don’t often involve conscious awareness
    • Emotions are stereotyped automatically (predictable, replicated)
      • Individual variation is changed by culture and learning
    • Sadness/depression are mainly in humans/primates. "This thing has a life of its own". It has a genetic risk, and is predisposed by childhood adversity or adverse life events, but clinical depression can arise from a person without an unremarkably bad life.
  • Analogy:
    • Emotions use the body as their theatre to alter,eg:
      • Internal milieu
      • Visceral vestibular systems
      • Musculoskeletal systems
    • Manifest as an interplay between different body systems

Conscious and subconscious

  • Subconscious:
    • Basic life regulation
    • Emotions-->body systems (preconscious level)
    • Feelings
  • Conscious
    • Feelings
    • Behaviours/responses to emotions

Areas of the brain

  • Amygdala, ventromedial prefrontal, brainstem, hypothalamus, basal forebrain
  • Limbic system – primitive brain
    • Comprises a large part of the brain in animals (reflexes, instincts)
    • As higher cortical function has evolved, limbic system has decreased in relative size
  • Papez circuit:
    • 2 steps, 1st is before conscious awareness
      • Part 1: emotional stimuli --> thalamus --> hypothalamus --> bodily responses (eg. cortisol with stress)
        • Thus response occurs in the body before aware, eg. snake, HR increases, muscles tense before visual sends message to register there is a snake
      • Part 2: thalamus --> sensory cortex --> cingulate cortex (integrates feelings etc), input from hypothalamus, hippocampus --> feelings


  • Adults, 3.2% experienced depression in the last month, 6.3% in the last year (1/17)
    • Not just sadness, this is clinical depression where there is interference with people’s lives and functionality
  • 20% chance of experiencing depression throughout life
  • Symptoms:
    • Emotional
      • Depressed mood
      • Reduced interest/pleasure
      • Despair
    • Physical
      • Changes in weight/appetite
      • Agitation/retardation
      • Sleep problems
      • Difficulties concentrating, thinking clearly
      • Reduced energy levels
    • Cognitive
      • Feelings of worthlessness
      • Suicidal thoughts
      • Indecisiveness
  • Global burden of disease:
    • Economic loss (mainly due to loss of function)
    • Depression ranks highest, > 10% of total disability
      • Other mental health problems also in the top 10
      • Depression hits people in their formative years and recurs, thus induces high economic loss/disability
    • If project disease burden (ie. premature death and disability)
      • 2020, depression goes from 4th to 2nd highest worldwide

Brain systems – sadness/depression

  • Only higher species experience
    • Anxiety and fear, other less complex animals can experience
    • Maybe sadness/depression is associated with our sense of consciousness?
  • How is it natural/adaptive?
    • Advanced species are social beings, we relate and have relationships
      • Part of being human
    • Thus,itmaybeanadaptationtohelpuscopewithlossofrelationsandallowforsocialhealing
      • Other sadness is an elaboration of this as we became able to think more abstractly: conceptual loss
  • Sadness is normal
    • Depression is the same process gone awry, a distortion of normal sadness
  • Genetic associations:
    • Process:
      • Initial factors:
  • Genetics
  • Social support
  • Childhood experiences
  • Cognitive thinking styles, personality – genetics?
    • Progression:
      • Anxiety, sub-clinical depression
      • Self-esteem
      • Later:
        • Life events, chronic difficulties
          • Social support
      • Leading to depression

Stressful life events

  • Loss events ie. relationship loss, death, unemployment, ill health
  • Sense of entrapment --> loss of control
  • Humiliation/stress

Genes and the environment

  • Genetics: thought to explain 30-40% of the cause of depression/anxiety
    • Strong association between genetic risk and likelihood of stressful life events leading to depression
      • Ie. family history closely showed risk in presence of a stressful life event
  • Environmental factors also important
    • Ie. if we don’t experience stressful life events, won’t get depressed


  • Serotonin reuptake transporter takes up serotonin and removes from synapse
    • Polymorphisms:
      • Short/short, long/short, long/long
  • Long/long is normal
  • short/short doesn’t do well with stress
    • associated with amygdala neural activity
  • s/s with increased life events has increased rates of depression vs l/l