caspi et al

BIOLOGICAL FACTORS & GENE–ENVIRONMENT INTERACTION IN DEPRESSION

KEY TERMS

• Serotonin: A neurotransmitter involved in mood regulation; low levels are often linked to symptoms of depression.

• Gene Mutation: A permanent change in the DNA sequence of a gene, potentially affecting its function.

• MDD (Major Depressive Disorder): A serious mental disorder characterized by persistent sadness, loss of interest, and other emotional and physical symptoms.

• Gene-Environment Interaction: The idea that certain genetic predispositions may be expressed only when triggered by specific environmental factors.

THEORY: Diathesis-Stress Model

• Suggests that individuals have a biological vulnerability (diathesis) to mental disorders, which is only triggered when combined with environmental stress.

• Applied to depression: not everyone with a genetic predisposition develops depression—life stressors often activate the condition.

• The 5-HTT gene, involved in serotonin reuptake, has two alleles: short (s) and long (l). The short allele is associated with reduced serotonin transporter efficiency and possibly greater emotional sensitivity to stress.

AIM

• To investigate whether a gene–environment interaction exists for the 5-HTT serotonin transporter gene mutation in the development of major depressive disorder (MDD).

METHOD (Caspi et al., 2003)

• Participants: 847 New Zealanders (age 26), from a longitudinal Dunedin cohort.

• Genetic Grouping:
  

  • Group 1: Two short alleles (s/s)

  • Group 2: One short, one long allele (s/l)

  • Group 3: Two long alleles (l/l)

• Procedure:
  

  • Participants completed a stressful life events questionnaire, reporting 14 types of stressors (e.g., financial, relationship, health) between ages 21–26.

  • Depression symptoms and suicidal thoughts were assessed using a standardized clinical interview.

Variables

• Independent Variables (IVs):
  

  1. Genotype: Type of 5-HTT allele (s/s, s/l, l/l)

  2. Environmental stress: Number of reported stressful life events

• Dependent Variable (DV):
  

  1. Level of depressive symptoms and diagnosis of MDD, including suicidal ideation

FINDINGS

• Participants with one or two short alleles experienced significantly more depressive symptoms after stressful events.

• Highest depression levels occurred in those with two short alleles and multiple life stressors.

• No major increase in depression was found in individuals with two long alleles, even under stress.

• Simply inheriting the short allele did not cause depression—stress was a necessary trigger.

APPLICATIONS

• Demonstrates the importance of gene–environment interaction in depression.

• Suggests more personalised interventions (e.g., stress management programs) for individuals with known genetic vulnerabilities.

• Encourages a holistic view of mental health—integrating biology with environmental and psychological factors.

EVALUATION

Strengths

• Holistic approach: Integrates genetic and environmental factors—supports diathesis-stress model.

• Large sample size (847): Increases generalizability and statistical power.

• Longitudinal design: Tracks participants over time, helping to establish temporal relationships.

Limitations

• Correlational: No causal relationship can be confirmed between the gene, stress, and depression.

• Self-report bias: Stressful life events were self-reported—subject to memory distortion or social desirability.

• Low reliability: Meta-analyses (e.g., Risch et al., 2009) failed to replicate findings, casting doubt on the robustness.

• Not fully explanatory: Some people with the short allele did not develop depression; others without the mutation did, suggesting additional factors are involved.

ETHICAL CONSIDERATIONS

• Informed consent: Participants were informed about genetic testing and mental health research.

• Confidentiality: Sensitive genetic and psychological data were securely protected.

• Psychological harm: Discussion of stress and depression may cause distress—mental health support should be provided.

• Genetic determinism risk: Results may contribute to stigma or fatalistic thinking (e.g., “I’m genetically doomed”).

UNANSWERED QUESTIONS / CRITICAL THINKING

• Is serotonin dysregulation a cause or symptom of depression?

• What protective factors (e.g., social support, coping skills) reduce depression risk even in genetically vulnerable individuals?

• How do other genes interact with 5-HTT, and can future research better explain inconsistencies?

CONCLUSION

• Caspi et al. (2003) provides strong evidence for the gene–environment interaction in depression and supports the diathesis-stress model.

• The study advanced biological psychology by highlighting how genetic predispositions require environmental triggers.

• However, replication issues, correlational design, and ethical concerns suggest that conclusions should be interpreted cautiously.

• Overall, depression is best understood through a biopsychosocial approach, rather than solely genetic or environmental explanations.