Biological Etiology of Major Depressive Disorder

Biochemdical
1. Neurotransmitter
  1. serotonin hypothesis
    1. Lacasse and Leo (2005)
      1. lack of evidence that any depressed person has low levels of serotonin
        no baseline balanced level of serotonin to measure against
        Cannot compare the level of serotonin before and after having depression
      2. common analogy for what is wrong with using the e ectiveness of a treatment as support for a causal explanation
        headaches are successfully treated by aspirin, but we do not have any theory suggesting that headaches are caused by a lack of aspirin
    2. Sarek, 2006
      1. tianeptine, a drug commonly used in Europe and South America to treat depression
        opposite action to fluoxetine
        prevention of neuronal damage due to stress
    3. significant in the pharmaceutical industry
      1. medical treatment
2. Hormone
  1. cortisol
    1. reactivity to stress
      1. Burke et al., 2005
        meta- analysis of studies connecting cortisol with depression
        difference in reactivity to stress between depressed and non-depressed people
        non- depressed people
        cortisol levels rise and fall rapidly
        depressed people
        more blunt reaction and remain under stress for longer
      2. Hormone--> reactivity to stress--> depression
      3. Depression--> change in hormone--> more reactive to stress
    2. history of many negative life events
      1. Cutuli et al., 2010
        homeless children
        age: 4-7
        significant correlation between high levels of cortisol and a history of many negative life events
        Negative life event--> Hormone~> Depression
  2. Correlation does not indicate causation
    1. Change in hormone --> depression
    2. Depression --> change in hormone
  3. Provide medical treatment
    1. easy to measure
    2. synthetic
    3. can be directly injected into bloodstream
Genetics
1. Evolution
  1. Hagen et al. (2004)
    1. signal need
    2. elicit help from others in the social group
  2. Logical
    1. e.g. the point that most suicides by depressed individuals are preceded by the threat of suicide, which therefore signals a need for help and attention
  3. impossible to test experimentally
  4. genetic basis of this evolved behaviour
2. Genes
  1. Twin Study
    1. Kendler et al., 2006
      1. Swedish
      2. over 42 000 participants
        Large Sample Size
      3. telephone interviews
        Self-reporting bias
        Participants may not have the insight to symptoms
      4. diagnose depression on the basis of (a) the presence of most of the DSM-IV symptoms or (b) having had a prescription for antidepressants
      5. concordance rates among monozygotic twins of 44% for female and 31% for male, compared with 16% and 11% for female and male dizygotic twins respectively
      6. indicate a strong genetic component
        Not purely genetic (if yes,monozygotic concordance rates would be much higher)
  2. Gene Mapping
    1. Caps et al. (2003)
      1. Relationship between 5-HTT gene and depression after stressful events
        Both genes and environmental factors are under investigation
        Difficult to conclude the gene is a major contribution to depression
        Unclear how environmental factors influence genes
        Compared participants with normal 5-HTT genes and a mutation with shorter alleles
        Large proportion of population carries the mutation of 5-HTT gene
        43%
        Participant with shorter alleles: more likely to become depressed after stressful event
        Vulnerability to depression after stress events
      2. 847 Caucasian New Zealanders
        large sample size
      3. Self-report on depression
        Cross checking with friends
  3. Ethics
    1. Having the genes does not equal having the disorder
  4. Confusing
    1. Levinson (2005)
      1. short allele on 5-HTT acts in a similar way of drugs improve the symptoms of depression (e.g. Prozac); it hinders reuptake of serotonin
  5. Predict who is vulnerable to depression
    1. Provide special treatment to prevent having the disorder
  6. Levinson (2005)
    1. the gene is more likely to make individuals more sensitive to stressful life events
  7. Diathesis–stress model
    1. explain behavior as a predispositional vulnerability together with stress from life experiences
      1. Lazarus (1993)
        if the combination of the predisposition and the stress exceeds a threshold, the person will develop a disorder

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Biological Etiology of Major Depressive Disorder

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	Created by S K about 8 years ago