Caspi et al (2003)

Serotonin

• A neurotransmitter Involved in regulating mood, often implicated by depression

  Gene mutation

• A permanent alteration in the DNA sequence that makes up a gene

  MDD

• Major depressive disorder, is a complex condition with biological, psychological and social factors

  CONTEXT

• The study investigates the gene-environment interaction by examining the role of serotonin transporter gene mutation in the development of depression under stressful circumstances.

  THEORY

• The diathesis stress model posits that individuals with a genetic predisposition for depression are more likely to develop the disorder when exposed to significant stress. The 5-HTT gene affects serotonin reuptake and is hypothesised to interact with stressors to influence depression.

  AIM

• To investigate weather a gene environment interaction exists fr the 5-HTT serotonin transporter gene mutation in the development of major depressive disorder

  METHOD

• Participants 847 new zelanders, aged 26 from a longitudinal cohort study.

• Participants were divided into 3 groups based on their 5-HTT alleles

  Group 1 ; 2 short alleles

  Group 2 ; 1 short and 1 long alleles

  Group 3 ;2 long alleles

• Participants completed a stressful life events questionnaire, reporting on 14 life stressors (eg. Financial, health, relationship issues) between ages 21 and 26

• Depression symptoms and suicidal ideation were assessed

  FINDINGS

• Those with one or more short alleles experienced more depressive symptoms in response to stress

• The highest levels of depression were found in participants with short alleles who experienced more stressful life events

• Simply inheriting the gene did not result in depression ; stress was a crucial factor in triggering gene expression

  APPLICATIONS

• Highlights the interaction of genetics and environment in depression, promoting a holistic approach to mental health research

• Offers insights for personalised medicine suggesting that individuals with certain genetic profiles might benefit from targeted interventions, such as stress management programs

  EVALUATION

  Strengths

• Holistic approach, combines genetic predisposition with environmental influences, moving beyond reductionist explanations of depression

• Large sample size, the inclusion of 847 participants enhances the generalizability of the findings

• Provides evidence supporting diathesis stress model of depression

  Limitations

• Correlational study, cannot establish causation between the 5-HTT gene, stress and depression

• Self report bias, participants reports of stressful life events may be inaccurate or influenced by recall bias

• Low reliability, follow up studies, such as risch et al (2009),failed to replicate findings, raising questions about robustness of results

• Gene expression in other contexts, the study cannot explain why individuals without gene mutation also experience depression

  ETHICAL CONSIDERATION

• Informed consent, participants were informed about the study’s purpose and genetic testing implications

• Confidentiality, genetic and mental health data were securely protected

• Psychological harm, discussing stressors and depression symptoms could distress participants : researchers needed to ensure access to mental health support

• Genetic determinism, finings may lead to stigmatisation or fatalistic attitudes among individuals identified as genetically vulnerable to depression

  UNANSWERED QUESTIONS

• Is serotonin dysregulation a cause of consequence of depression?

  CONCLUSION

• This study underscores the complex interplay between genetic predisposition (5-HTT) and environmental stress in influencing depression

• While it has expanded understanding of gene-environment interactions, methodological and ethical concerns warrant cautious interpretation of the findings