The Open University since 2006
Alternatively you can skip the navigation by pressing 'Enter'.
Full Steam Ahead: Episode oneSaturday, 23rd July 2016 16:30 - BBC TwoThe first episode of Full Steam Ahead looks at the way Britain changed in the 19th century due to the railways Read more: Full Steam Ahead: Episode one
Thinking Allowed July 2016: Food bank Britain, Food poverty in EuropeMonday, 25th July 2016 00:15 - BBC Radio 4
Exodus: Our Journey To Europe: EPISODE 1Wednesday, 27th July 2016 02:45 - BBC Two
Exodus: Our Journey To Europe: EPISODE 2Thursday, 28th July 2016 00:45 - BBC Two (except Scotland and Northern Ireland)
Full Steam Ahead: Episode oneAvailable until Monday, 22nd August 2016 17:30The first episode of Full Steam Ahead looks at the way Britain changed in the 19th century due to the railways Read more: Full Steam Ahead: Episode one
Thinking Allowed July 2016: Food bank Britain, Food poverty in EuropeAvailable for over a year
Exodus: Our Journey To Europe: EPISODE 3Available until Friday, 19th August 2016 01:15
Exodus: Our Journey To Europe: EPISODE 2Available until Friday, 19th August 2016 00:15
OpenLearn Live: 22nd July 2016A biochemist with a fearsome reputation; how drones are helping ferrets and keeping your workers... Read more: OpenLearn Live: 22nd July 2016
Full Steam AheadIt’s Full Steam Ahead for historians Ruth Goodman, Alex Langlands and Peter Ginn as they bring... Read more: Full Steam Ahead
Employment relations and employee engagementThis free course, Employment relations and employee engagement, looks at raising levels of... Try: Employment relations and employee engagement now
Introduction to bookkeeping and accountingLearn about the essential numerical skills required for accounting and bookkeeping. This free... Try: Introduction to bookkeeping and accounting now
In this free course, Understanding depression and anxiety, we consider some risk and causal factors for some depression and anxiety disorders – that is, the possible aetiology of such disorders. A multitude of genetic, neurobiological, psychological and social factors are likely to be relevant.
After studying this course, you should be able to:
- describe how stressful life events may be linked to emotional disorders such as depression and anxiety
- describe the main features of the physiological stress response
- evaluate the role of genetic and environmental factors in emotional disorders
- describe the different kinds of biological abnormalities that have been linked to emotional disorders.
- Learning outcomes
- 1 Understanding the role of stress
- 2 Stress and the brain
- 3 The life cycle model of stress
- 4 Insights from antidepressants
- 4.1 The monoamine hypothesis of mood disorders
- 4.2 Evidence for the monoamine hypothesis
- Current section: 4.3 Tryptophan depletion experiments
- 4.4 The neurotrophic hypothesis of mood disorders
- 4.5 Depression and levels of BDNF
- 4.6 Stress, depression and neurogenesis in the hippocampus
- 4.7 Antidepressants, BDNF levels and neurogenesis in the hippocampus
- 5 The network hypothesis of mood disorders
- 6 Genes and environment: bringing it all together
- Keep on learning
Study this free course
Enrol to access the full course, get recognition for the skills you learn, track your progress and on completion gain a statement of participation to demonstrate your learning to others. Make your learning visible!
4.3 Tryptophan depletion experiments
While the monoamine hypothesis still underlies the treatment of depression, researchers now consider that, in its original form at least, it is too simplistic to explain the complex aetiology of depression.
The hypothesis postulates that low levels of monoamines cause depression, and as we have seen in Section 4.2, there appears to be some evidence for this. However investigations into the link between monoamine levels and depression were typically carried out on people who were depressed at the time.
Why might this be a problem when studying, for instance, serotonin levels in depressed people?
Because cause cannot be distinguished from effect. Low serotonin levels in depressed people could be a cause of depression, but they could also be a result of depression. Or some unknown, third factor could underlie both depression and low serotonin levels.
Researchers have since tried to clarify the relationship between low monoamine levels and depression experimentally, by depleting the levels of monoamines in the brains of participants.
Serotonin is manufactured in the body from a chemical commonly found in the diet; the amino acid tryptophan. Tryptophan is found in protein-rich foods, including meat, eggs, cheese and soybeans.
By feeding participants a special, otherwise well-balanced, diet free of tryptophan it is possible to reduce serotonin levels in their brains. The levels of the other monoamines, noradrenalin and dopamine, can also be depleted using similar techniques. Amino acids are the building blocks of proteins. Proteins are molecules that contribute to the structure and functioning of all our cells, including our neurons.
The findings of a meta-analysis by Ruhé et al. (2007) on the results of studies of monoamine depletion are summarised in Table 1. (A meta-analysis is discussed in the related OpenLearn course.) The groups listed in Table 1 are:
- Group 1 – healthy participants who do not, and have never had, major depression (MD), and have no family history of MD
- Group 2 – Healthy participants who do not, and have never had, MD, but do have a family history of MD
- Group 3 – Patients in remission from MD who are not currently taking antidepressants
- Group 4 – Patients in remission from MD who are currently taking antidepressants.
Table 1 Reaction to monoamine depletion.
|Group 1||Group 2||Group 3||Group 4|
|Depletion of tryptophan/serotonin||No lowering of mood||Slightly lowered mood||Moderate decrease in mood||Induced relapse in those taking antidepressants that affect the serotonin system (such as SSRIs and SNRIs)|
|Depletion of noradrenalin/dopamine levels||No lowering of mood||Slightly lowered mood||No lowering of mood||(no studies were available in this category)|
Activity 8 Serotonin levels and mood
Do any of these results (Table 1) suggest that lowering serotonin levels causes a lowering of mood or results in depression?
Patients in remission from MD who were taking antidepressants such as SSRIs and SNRIs that affect the serotonin system (Group 4) were likely to have a relapse if tryptophan/serotonin was depleted. Patients in remission from MD, but who were not currently taking antidepressants (Group 3) were also likely to experience low mood if serotonin was depleted. Participants (Group 2) who had a family history of depression showed slightly lowered mood. Thus lowering serotonin levels can have an effect on mood, albeit to different extents.
However, healthy participants without a personal or family history of major depression (Group 1) showed no mood changes, so serotonin depletion did not lower mood in everyone.
Overall, therefore, the results in Table 1 do not suggest a direct or consistent link between monoamine levels and major depression.
Activity 9 Analysing tryptophan depletion
Booij et al. (2002), also analysed studies on tryptophan depletion, showed that (a) having had previous depressive episodes, (b) being female, (c) having had treatment with an SSRI, and (d) having a history of suicidal thoughts or attempts, were all strong predictors of whether tryptophan depletion (and hence serotonin depletion) would depress mood.
Consider Booij et al.’s suggestions above. Do any of them chime with any of the findings shown in Table 1?
Yes, (a) is consistent with the lowering of mood of patients in Group 3 and Group 4; (c) is consistent with the relapse of patients in Group 4.
One possibility is that a depressive episode changes the serotonin system in some way, making a person more vulnerable to the effects of future changes in serotonin levels. A related possibility is that a subgroup of those with depression have a vulnerability or diathesis, due to their genetic make-up, that affects the workings of the serotonin system, making them particularly susceptible to depression when serotonin levels are depleted.
Is there any information in Table 1 which might fit in with this?
Yes – the finding that people in Group 2, who have not experienced major depression themselves but have a family history of depression, experience some lowering of mood following serotonin depletion.
To conclude, tryptophan-depletion experiments suggest that serotonin depletion has some effects on mood, but that there is no simple relationship between levels of monoamines and depression.
The next section considers an even more significant problem with the monoamine hypothesis, one that has fuelled much research and has led to a more sophisticated chemical and molecular hypothesis for the aetiology of depression.
Copyright & revisions
Originally published: Monday, 14th September 2015
Last updated on: Monday, 14th September 2015
- Creative-Commons: The Open University is proud to release this free course under a Creative Commons licence. However, any third-party materials featured within it are used with permission and are not ours to give away. These materials are not subject to the Creative Commons licence. See terms and conditions. Full details can be found in the Acknowledgements and our FAQs section.
- This site has Copy Reuse Tracking enabled - see our FAQs for more information.
If you enjoyed this, why not follow a feed to find out when we have new things like it? Choose an RSS feed from the list below. (Don't know what to do with RSS feeds?)
Remember, you can also make your own, personal feed by combining tags from around OpenLearn.
- Latest OpenLearn pages
- Latest pages from OpenLearn - Health
- Latest pages from OpenLearn - Health Studies
- Latest pages tagged - SDK228_2
- Latest pages tagged - depression
- Latest pages tagged - anxiety
- Latest pages tagged - brain
- Latest pages tagged - emotional disorders
- Latest pages tagged - sadness
- Latest comments on this page
All our alternative formats are free for you to download, for more information about the different formats we offer please see our FAQs. The most frequently used are Word (for accessibility), PDF (for print) and ePub and Kindle to download to eReaders*.
- Word (2.2 MB)
- PDF (1.1 MB)
- ePub 3.0 (7.4 MB)
- ePub 2.0 (1.3 MB)
- Kindle (721 KB)
- RSS (349 KB)
- HTML (10.5 MB)
- SCORM (10.5 MB)
- OUXML Package (46 KB)
- OUXML File (150 KB)
- IMS Common cartridge
- Moodle backup (7.6 MB)
*Please note you will need an ePub and Mobi reader for these formats.