Diathesis-stress theories of depression predict that an individual's reaction to stressful events depends on their genetic make-up.  If an individual has a specific genetic predisposition toward a disorder (genotype), then interaction with stressors in the environment may cause these genes to be expressed. The aim of this study was to determine whether there is evidence for a gene-environment interaction (G x E) for a mutation of the serotonin transporter gene - 5-HTT. The serotonin transporter is involved in the reuptake of serotonin in brain synapses.

Caspi and his team looked at a sample of 847 New Zealand 26-year-olds. All were members of a cohort that had been assessed for mental health on an every-other-year basis until they were 21. They were divided into three groups based on their 5-HTT alleles: Group 1 had two short alleles; Group 2 had one short and one long allele; Group 3 had two long alleles. The mutation of the 5-HTT gene has the shorter alleles. Roughly 43% of people have the shorter alleles.

The participants were asked to fill in a "Stressful life events" questionnaire which asked them about the frequency of 14 different events - including financial, employment, health, and relationship stressors - between the ages of 21 and 26.  They were also assessed for depression.

People who had inherited one or more short versions of the allele demonstrated more symptoms of depression and suicidal ideation in response to stressful life events. The effect was strongest for those with three or more stressful life events. Simply inheriting the gene was not enough to lead to depression, but the genes' interaction with stressful life events increased one's likelihood of developing depression.

In a later study by Wilhelm et al (2006), the researchers looked at DNA samples from 127 people who are part of a longitudinal prospective study looking at mental health. The sample had been monitored for over 25 years.  At five-year intervals, scientists recorded any major life events and signs of depression. They found that 80 percent of those with two short 5-HTT genes became depressed after three or more negative life events in a year, whereas those with two long genes appeared resilient - only 30 percent developed the illness in similar situations.  They also found that childhood maltreatment predicted adult depression only among individuals carrying a short allele and not among those carrying the longer allele.

However, much more research is needed before a clear relationship between a gene and a depression can be established.

• The study is correlational, so no cause and effect relationship can be determined.
• The study makes the assumption that serotonin causes depression.
• Information about life-events was self-reported.  It may be the salience of the negative life events which plays a role in depression - that is, those that recalled them more easily may have a tendency towards depression.  Those who are more resilient, may not recall negative life events as easily.
• The theory acknowledges the interaction between both biological and environmental factors in depression.  This is a more holistic approach, not reductionist.
• Later studies have not been able to show similar results. Risch et al (2009) carried out a meta-analysis of attempted replications and found that the results were not able to be replicated. It appears that the study has low reliability.
• There were some participants who did not carry the gene mutation who became depressed; therefore, we cannot say that gene expression alone can cause depression.