TB4 Lecture 1; Depression

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  • Created on: 18-05-15 13:53

DSM V Criteria for Major Depressive Disorder (MPD)

The criteria for a diagnosis of MPD is at least 5 symptoms from the list, with at least one being 1) or 2).

  • 1) Depressed mood by either self report (sad, empty, hopeless) or observation (tearful)
  • 2) Diminished interest or pleasure at all in almost all (motivational) activities
    • 3) Significant weight loss or gain
    • 4) Insomnia or hypersomnia nearly every day
    • 5) Psychomotor agitation/retardation
    • 6) Feelings of worthlessness/inappropriate guilt
    • 7) Diminished thinking/concentration abilities
    • 8) Recurrent thoughts of death (not just dying) or recurrent suicidal ideation.
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Serotonin; emotional effects of depletion

Serotonin is thought to be heavily implicated in depression, but levels can be highly variant across individuals. Most of the important serotonin neurons are found in the Raphe and related nuclei.


  • Delgado et al (1999); Investigated the effects of a tryptophan free diet on previously depressed pps.
    • Tryptophan is the beginning amino acid for the serotonin molecule, which cannot be produced by the brain so it needs to be ingested. A tryptophan free diet would lower pps levels of serotonin.
    • They found that over 50% showed a signif. increase in depressive symptoms.
  • Booji et al (2002); Reviewed depression literature and the range of intervening factors on levels of serotonin depletion.
    • Found that serotonin levels do not affect everyone's emotions equally. Biological women are more susceptible to loss of tryptophan, as well as people with recurrent or previous episodes of depression.
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The genetics and the environment on serotonin

Caspi et al (2003)Uher & McGuffin (2010); Investigating the role of genes that influence the production of serotonin reuptake sites. The genes that were targeted were S-type and L-type.

  • Both found a strong relationship between the precise polymorphism of the gene for serotonin reuptake sites and depressive responses to early life stress.
    • The S (short) type gene was found to be the most predictive of these later negative responses to stress.
      • This indicates a strong genetic and environmental interaction which can affect the brain and its neurotransmitters.
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MPD Treatment; Antidepressants

The three main types of antidepressents focused on are;

  • Monoamine Oxidase Inhibitors
    • Work by blocking the ability of the enzyme monoamine oxidase to break down monoamines inside axon terminals.
    • Side effects included extremely high blood pressure if taken with a diet including cheese or red wine.
  • Tricyclic antidepressents
    • Inhibit the reuptake of monoamines.
    • Examples of these are Imipramine and amitryptaline.
    • Side effects include drowsiness, low blood pressure and weight gain
  • Selective serotonin reuptake inhibitors (SSRIs)
    • Found to be at least as effective as tricyclic anti-depressents but with far fewer side effects.
    • The most famous known SSRI is fluoxetine but other examples include sertraline and paroxetine.
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Antidepressant research

Yatham et al (1999); One of the first studies that investigated the widespread effect of SSRIs on brain serotonin function.

  • Found that the antidepressent treatment was successful.

Pratt et al (2011); Found that around 11% of US citizens take antidepressents, with AFAB individuals taking more than AMABs. Of any gender antidepressents are taken more than any other prescribed drug in the US.

Effectiveness research

Geddes et al (2003); Conducted a meta-analysis of 31 antidepressent clinical studies.

  • Results clearly showed that AD usage helped prevent relapse.
    • However, ADs are not a 'miracle drug', they also have their downsides such as a build-up of effect is needed (not instant), motivational factors may implicate course of treatment due to the long term nature of ADS
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Attributional styles and negative thinking

Attributional styles are used to explain how peoples susceptibility to MPD differs. If an event is perceived as uncontrollable, attribution is implicitly made of its causes (Abramsen, Seligman, Teasdale (1978).

There are 3 dimensions to attributional style;

  • 1) Internal v.s external.
  • 2) Global v.s specific.
  • 3) Stable v.s unstable.


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Research into attributional styles

  • It is thought that the most susceptible style for MPD is internalstableglobal. Thoughts are directed inwards at the self and are generalisable to all situations.
  • It is thought the least susceptible style to MPD is externalunstablespecific. Thoughts are situational and targeted outwards so the self is not implicated.

Metalsky et al (1982);

  • Tested students for attributional style and then asked them about their future exam grades.
    • It was found that the more internal or global students for negative outcomes had more severe depressive mood responses to a low midterm grade.
      • Negative attributional style may be an important predictor for susceptibility to depression during adverse life events.

Rygula et al (2012);

  • Tested mice under 3 conditions, first all associated a lever with a reward and lever with no electroshock. Second, they were either simply handled (control) or tickled, with joy as recorded high-frequency squeaks. The rats were then allowed to 'choose' which lever to press.
    • It was found that tickled rats tended to press the reward lever and controls the avoidance lever. (Reflects attribution styles...just)
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MPD Treatment; Interpersonal psychotherapy

The assumption behind this therapy is that depression occurs in an interpersonal context, so clarifying and negotiating this context is important. There are 4 main areas;

1) Grief reaction; If relevent, clients explore their feelings with the lost person, and acknowledge feelings of anger. The new attitudes towards the lost person 'fell the empty space' of MPD.

2) Interpersonal role dispute; If differing expectations between partners/parents of roles continues, resentment and MPD may result. Therapy aims to resolve these disputes.

3) Interpersonal role transition; Significant life events can be difficult to cope with. Therapy aims to develop social support systems and interpersonal psychological skills required for their new role and for boosting self esteem.

4) Interpersonal deficits; Depression may arise from lack of social skills and shyness. Therapy explores social skill/assertiveness training.

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Interpersonal psychotherapy research

Supporting research

Mufson et al (2004);

Compared IP therapy with 'regular treatment' (school counselling) control.

Found that IPT more effective compared at 8 weeks.

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MPD Treatment; CBT

CBT is based on the assumption that depression is caused by negative thinking (Aaron) (Beck) in these areas;

  • Maladaptive attitudes and negative schemas
    • Beginning in childhood, e.g believing that parental affection depends on success in school. Can lie 'dormant' until activation by adverse life events.
  • The cognitive triad
    • Once activated, negative schemas can cause 3 types of negative thinking; (the triad)
      • 1) Negative thoughts about oneself.
      • 2) Negative thoughts about the current situation.
      • 3) Negative thoughts about the future.

It is thought that errors in logic maintain the cognitive triad, including arbitrary inferences (negative conclusions from little/contradictory evidence), selective abstraction (innapropriate focus on negative aspects of things) and automatic thoughts (e.g I always mess things up).

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CBT Treatment research

CBT works in 4 phases.

  • 1) Increasing activities and mood
  • 2) Examining and invalidating negative thoughts; Patients taught to recognise and record negative thoughts, therapy then challenged their validity.
  • 3) Identifying distorted thinking and negative bias; Errors in logic identified and challenged.
  • 4) Altering primary attitudes; Fundamental maladaptive attitudes changed.

Hollon et al (2005); Found that CBT was the most effective in reducing relapse over the long term compared to ADs.

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ECT and it's evaluation

In the 1930s, ECT seemed to eliminate SZ like symptoms. However later controlled studies found it not effective at all for SZ.

However in depression, research suggests that ECT is generally effective for severe cases where other treatment is failing.

Persad (1990); 80-90% of depressive pps improved significantly after treatment of ECT even with no response to ADs.

Greenblatt (1977); Improvements are more rapid than other treatments, so may be good for suicidal ideation.

Sackheim (2000); Double-blind procedure, showed that ECT was effective even in medication  resistant inpatients, effectiveness was dose-dependent.

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Deep brain Stimulation and it's effects (DBS)

The white matter below Area 25, the junction located near the centr of the brain has shown in experimental treatments that when inhibited, lifted depressive symptoms.

Mayberg et al (2005); It is thought that the overactivity of this area, the subgenual cingulate cortex is associated with treatment resistent depression. Inhibition through chronic stimulation lifted depressive symptoms in 4/6 pps.

Clearly the fundamental causes of depression are unknown, with both physiological and psychological causes are only associated with depression.

The most effective path of treatment as it stands seems to be a combination of CBT and ADs.

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