Caspi et al. (2003)

Biological etiology — 5-HTT gene & MDD

diathesis-stress model as it applies to depression

he idea that an individual's reaction to stressful events depends on their genetic makeup. If someone has a genetic predisposition (genotype), interaction with environmental stressors may cause those genes to be expressed, leading to a disorder.

5-HTT gene and why is it relevant to depression

The serotonin transporter gene — it is involved in the reuptake of serotonin in brain synapses. A mutation produces shorter alleles, which are linked to increased vulnerability to depression.

aim

To determine whether there is evidence for a gene-environment interaction for a mutation of the 5-HTT serotonin transporter gene in predicting MDD

participants

847 New Zealanders aged 26, all part of a cohort assessed for mental health every other year until age 21

participants group divisions

By their 5-HTT alleles — Group 1: two short alleles; Group 2: one short, one long allele; Group 3: two long alleles. Roughly 43% of people naturally carry shorter alleles

key findings

People with one or more short alleles showed 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

key conclusion about gene expression

Simply inheriting the short allele was not enough to cause depression — it was the interaction between the gene and stressful life events that increased the likelihood of developing MDD

Wilhelm et al. (2006) follow-up study

In a 25-year longitudinal study of 127 people, 80% of those with two short 5-HTT alleles became depressed after three or more negative life events in a year, vs. only 30% of those with two long alleles. Childhood maltreatment also only predicted adult depression in those carrying a short allele

type of study

Correlational — no cause-and-effect relationship can be established between the gene mutation and depression

assumptions

assumes that serotonin causes depression, but this has not been conclusively proven and the relationship between serotonin and MDD is more complex than the study implies

self-report method

Participants self-reported stressful life events, so recall may be biased — those predisposed to depression may recall negative events more easily (salience bias), while more resilient individuals may underreport them

why is it a holistic study

Because it acknowledges the interaction between both biological (gene mutation) and environmental (stressful life events) factors in depression, rather than reducing the cause to one factor alone

Risch et al. (2009) findings

A meta-analysis of attempted replications found the original results could not be replicated — suggesting the study has low reliability

participants without the gene mutation

Some participants who did not carry the short allele still developed depression, meaning gene expression alone cannot be said to cause MDD — other factors must also be involved