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TASK 5: Genes, stress and emotionality (Guffin (STUDY - Caspi et al.: (s…

- - - - explanations: heterogeneity, existence of multiple tiny genetic effects that require even larger samples + failure to take into account gene interplay with environmental factors, variety of environment assessment tools used, nature of the evaluated stressor itself, underrepresentation of low- and middle-income countries
  - - - homozygotes for the 5-HTTLPR s allele were more vulnerable to depression at high stressful live events exposure, but showed reduced rates of depression at low stressful events exposure, appearing to benefit from a better environment
- - - - less active causing lower 5-HTT binding + mRNA expression
      - may promote 5-HT dysfunction found in depression
    - - third functional allele has been described
        
        resulting from an A to G substitution in the L allele (LA and LG)
        
        a) LA allele -> higher 5-HTT expression than the LG and the S allele
        b) LG and the S allele have a comparable low 5-HTT expression
      -  failure to differentiate between these alleles may be a reason for the discrepancy in previous research
  - - - Data were analyzed and reported for:
        
        a) Biallelic: LS classification (without controlling for Lg and La differences)
        
        b) Triallelic (La, Lg, S): L’S’ classification
    - - only the low-allele expressing (S) 5-HTTLPR carriers showed vulnerability to depression exclusively when reporting exposure to high-impact events and showed high neuroticism
      - main effects of neuroticism and impact of life events  both factors associated independently with higher depression scores
      - no main effect of the 5-HTTLPR genotype on depressive symptomatology  no differences in depression scores between S (S’) and L (L’) allele carriers
      - results of the current study were generally similar for a biallelic and a triallelic approach
    - - carrying an S allele conferred a vulnerability to nonclinical depressive symptomatology only in individuals with high trait neuroticism who reported exposure to high-impact events
      - depression is unlikely to be directly linked to the mutual interaction of one gene and one environmental factor  importance of cognitive moderating factors  5-HTTLPR by life events interaction on depressive symptoms may be conditional on a cognitive vulnerability (neuroticism) to attribute events as highly threatening
      - S allele does not contribute directly toward high trait neuroticism
      - 5-HTTLPR genotype and trait neuroticism mediate the depressogenic effect of life events
- - - - tested whether the relationship between childhood maltreatment and a subsequent depressive episode diagnosis was moderated by 5-HTTLPR genotype
        
        biallelic + triallelic approach
    - - replicated important findings of the original study in a sample of young adults from a middle-income country: association between childhood maltreatment and depression was related to the number of S alleles carried, with progressively higher risk for individuals with more copies of the short variant
      - S allele conferred an increased risk for depression at age 18/19 only for those individuals who suffered maltreatment before age 15
    - - genetic variant in the 5-HTTLPR moderates the link between childhood maltreatment and youth depression
      - association between child maltreatment and youth depression was strongest among SS homozygotes, followed by SL heterozygotes, and LL homozygotes
      - importance of the assessment of temporal order in G3E studies  early exposure to maltreatment significantly increases the risk for depression regardless of 5-HTTLPR genotype
- - - - a) test for differences in the ability to suppress physiological responses (indicated by EDA) to aversive visual stimuli in a laboratory situation dependent on the presence or absence of the 5-HTTLPR S-allele
      - b) test whether habitual coping strategies have any predictive value for successful coping in an acute stress situation when a person is encouraged to suppress unwanted feelings
    - - coping questionnaire, gene samples
      - emotion regulation experiment: within-subject design  viewed emotional pictures + instructed:
      - a) suppress their emotions
      - b) or watch affective stimuli without suppression
      - skin conductance responses (SCR) were recorded
    - - S-allele carriers showed increased SCRs when watching aversive stimuli in the uninstructed condition
      - when receiving an emotion regulation instruction, they were able to down-regulate their arousal resulting in comparable SCRs as observed in LL-carriers
      - Phasic skin conductance in the four experimental conditions divided by genotype
        
         S-allele: larger reactivity to negative stimuli in the non-regulation condition as compared to neutral stimuli
        
         difference disappears in the regulation condition
        
         Carriers of the S-allele show higher skin conductance in general
      - CONCLUSION:
        
        first study showing an impact of 5-HTTLPR on physiological emotion regulation
        
        S-allele carriers have the same emotional arousal as L-allele carriers, when they get a supportive instruction to suppress unwanted feelings
        
        L′L′-carriers do not seem to need such an advice
        
        Carriers of at least one S′-allele showed an increased SCR to aversive pictures that was significantly lowered when they were instructed to suppress their emotions and arousal
        
        homozygote L′-allele carriers did not downregulate their physiological arousal in the emotion regulation condition but showed a lowered SCR in both conditions
        
        SUMMARY
        
         5-HTTLPR influences the extent to that people psychophysiologically experience emotional stimuli
        
         especially people with a 5-HTTLPR L′L′ genotype seem to be better in unconscious coping
        
         when helping people to use a particular strategy in an emotionally stressful situation, the risk of developing a psychopathology might be decreased
        
         carriers of the L′-allele tend to be physiologically rather less reactive in emotionally stressful situations and do not need any advices to successfully downregulate their arousal
        
         S′-allele carriers do profit from a helpful instruction to keep their physiological arousal down