Caspi et al. (2003)

Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene.

Background information: Diathesis-stress theories of depression predict that individuals’ responses to stressful events depend on their genetic makeup and the nature of the environmental stress. Behavioural genetics research supports this prediction, documenting that the risk of depression after a stressful event is elevated among people who are at high genetic risk and diminished among those at low genetic risk. But it is not known if specific genes lower the risk of depression as a response to environmental stress or if it is others that raise the risk. Most research in this area has investigated the serotonin-transporter gene 5HTT. The serotonin transporter gene has received specific attention because it is related to the re-uptake of serotonin in the brain synapses. It was suspected that adaptations in this gene in what is known as the 5HTTPR (polymorphic region) affected the incidence of depression in an individual.

Aim: To investigate whether a functional change in the 5HTT gene is linked to a higher or lower risk of depression in an individual.

Method: The researchers used an opportunity sample from a cohort of participants who were part of another longitudinal study. There were 847 participants of 26 years old and they were split into three groups, depending on the length of the alleles on their 5HTT transporter gene.

• Group 1 - two short alleles
• Group 2 - one short and one long allele
• Group 3 - two long alleles

1. Stressful life events occurring after the 21^st birthday and before the 26^th birthday were assessed using a life-history calendar.

2. Past-year depression was assessed using the Diagnostic Interview Schedule.

3. A correlation was tested for between stressful life events and depression, between the length of the alleles and depression and an interaction between perceived stress and the length of the alleles.

4. A further test was done to see if life events could predict an increase in depression over time among individuals with one or two short alleles.

Results: As the graph below shows, the participants with two short alleles in the 5HTTPR gene reported more depression symptoms in response to stressful life events than either of the other two groups. Those participants with two long alleles reported fewer depression symptoms. Moreover, childhood maltreatment was predictive of depression in adulthood only in adults with either one or two short alleles.

Conclusion: While there is no direct relation between short alleles on the 5HTT gene and depression, there is a relationship between these and incidences of stress and subsequent depression. The long alleles seem to protect against suffering depression as a result of stress. The effects of the gene adaptation are dependent on environmental exposure to stress.

Evaluation:

Strengths: This was a very large cohort of males and females and the age was controlled in order to isolate the variable of number of stressful life events between the ages of 21 and 26. It was a natural experiment, with the naturally occurring IV being the length of the alleles. If the results are replicated this would suggest high reliability.

Limitations: Gene action is highly complex, and actions of other genes could not be controlled. While the stressful life events were standardised as employment, financial, housing, health and relationship, whether or not a participant experienced a certain event as stressful is highly personal. Moreover, the symptoms of depression were self-reported, although one colleague was contacted for each participant in order to verify the symptoms; self-reporting can be unreliable.

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