Task 5 - Genes, Stress and Emotionality Flashcards
Resilience
“bouncing back from difficult experiences”
- adaptive stress responses, stress recovery, coping self-efficacy, strong cognitive re-appraisal, good emotion regulation
- has a heritable component as indicated by genetic correlation between emotion-oriented coping and resilience
Serotonergic system and Gene x Environment interaction
- polymorphism 5-HHTLPR influences the ability to encode transporter proteins
short allele: reduced expression of serotonin transporters -> lower resilience, people with this polymorphism are more likely to develop a disorder after stress (gene X environment interaction)
long allele: increase number of serotonin transporters
APA axis
- stress response system, genetic variants in this systems are likely to influence the response to stressors and therefore influence resilience
- CHRH1 associated with reduced risk of depression after exposure to life stress
- high number of FKBP5 lead to decreased negative feedback regulation in the HPA axis
Synaptic plasticity and resilience
- neurotrophin BDNF associated with regulation of synaptic plasticity -> alterations might contribute to psychiatric disorders (PTSD; MDD; AD)
Genome-wide association studies (and resilience)
- take genome from a looot of people and look at SNPs variations within the sample. By this, disorders can be linked to genetic variations
- GWAS and resilience: 16% heritability based on SNPs
Interaction of stress and genetic factors in development of depression - Explain the link of genes to depression and why there are only a few robust studies.
- depression has heritability of 37-40%
- GWAS have identified candidate genes (e.g. 5-HTTLPR)
Problems with the Gene x Environment interaction
- methodological issues (interview vs. self-reports, direction of causality)
- how to define and detect life events in subjects?
Gene x Environment interaction and 5-HTTLPR in depression: meta analysis (BLEYS)
Explain why there is a need for this meta analysis.
- the study investigates where the contradictory findings concering the role of 5_HTTLPR in interaction with stress on depression
Mixed findings might be a result from:
- differences in categorical or dimensional diagnostics in the studies
- interview vs. self report
- timing of stress might be important (early sensitization effects)
Gene x Environment interaction and 5-HTTLPR in depression: meta analysis (BLEYS)
Explain the method.
- Meta analysis to investigate effect sizes and publication bias
- stratified meta analysis (wtf is this) to investigate potential moderation of methodological factors on heterogenitiy in studies
- meta-regression to investigate influence on methodological approaches on overall effect size
Gene x Environment interaction and 5-HTTLPR in depression: meta analysis (BLEYS)
Explain the results.
- meta analysis
- no publication bias
- !significant effect of 5-HHTLPR in interaction with stress on depression! - stratified (wtf) meta analysis
- heterogenity of effect sizes were not caused by methodological approach differences - Meta-regression
- combined set of predictors explained 42% of heterogenity
- hint that categorical and interview assessment might be beneficial
Bottom line: the study confirms the assumed 5-HTTLPR interaction with stress on depression
Interaction between 5-HHTLRP, impact of stressful life events and trait neurotocism on depressive symptoms (MARKUS)
Explain, the variants of 5-HTTLRP, the cognitive vulnerability-transactional model of depression and what comes with trait neuroticism (and if 5HHTLPR has an influence on neuroticism).
5-HHTLPR variants
- biallelic approach: short and long allele
- triallelic approach: s allele, and two long alleles (La and Lg) -> might influence the interaction
people high on neurotocism:
-are more vulnerable to experience stress
-have low expectations of self-efficacy
-have less adaptive coping strategies
are most vulnerable to develop MDD
-5-HTTLPR has no direct influence on trait neuroticism, BUT might act as a moderator fro the interaction between 5-HHTLPR and life events on depression.
Interaction between 5-HHTLRP, impact of stressful life events and trait neurotocism on depressive symptoms (MARKUS)
Explain the hypothesis and methods.
Hypothesis: s-allele genotypes are more susceptible to life events in terms of depression when they are high on neuroticism (3-way interaction)
Measurements:
- genotype
- depressive symptoms
- neurotocism
- negative life events (self-report)
Interaction between 5-HHTLRP, impact of stressful life events and trait neurotocism on depressive symptoms (MARKUS)
Explain the main results (especially the 3-way interaction) and the overall conclusion.
- Effects of 5-HHTLPR, life events, and neuroticism on depression scores
- Main effects for neuroticism and impact of life events independently on depression scores
- NO main effect of 5-HTTLPR on depression (contradicts Bleys paper - Does it??)
- 3-WAY INTERACTION: only the short allele carriers displayed vulnerability to depression exclusively when reporting exposure to high-impact life events and show high neuroticism.
- similar results for the biallelic and triallelic approach - Effects of 5-HTTLPR and neuroticism on impact of life events:
- main effect of neuroticism: s and ll carrieres with high neuroticism experienced comparable variability in impact of life events
- no effect of genotype and no interaction btween genotype and neuroticim - Effects of 5-HTTLPR on neuroticism
- no effect found for 5-HTTLPR on neuroticism
Conclusion
- cognitive vulnerabilities (neuroticism) may mediate the 5-HTTLPR genotype x life event interaction on depression
- 5-HTTLPR is NOT directly linked to depression
Does psychological resilience buffer against the link between 5-HHTLPR polymorphism and depresssion following stress? (SHARPLEY)
Explain what they did in their study. Focus on the aspects of resilience. What are the hypotheses?
The study investigates the associations between:
- 5-HHTLPR ad depression
- 5-HHTLPR and resilience
- resilience and depression
Hypotheses:
- PCa patients who carry the s allele will have higher depression scores than carriers of the long allele
- PCa patients with higher resilience will have lower depression scores than patients with low resilience.
Does psychological resilience buffer against the link between 5-HHTLPR polymorphism and depresssion following stress? (SHARPLEY)
Explain their sample and measurements.
sample: older men who received the diagnosis of prostate cancer
measures: -depression PHQ9 -resilience with CDRISC: -> scale level -> factor level personal competence trust in one's instinct positive acceptance of change control spiritual influences -> item level
Does psychological resilience buffer against the link between 5-HHTLPR polymorphism and depresssion following stress? (SHARPLEY)
Explain the main findings and the overall conclusion.
- No association between 5-HHTLPR and elevated depression after stressor -> reject hypo 1
- negative association between resilience and depression after stressor
- only 1 factor made a significant contribution to the effect (personal competence)
- only 1 item was significantly related to 5-HHTLRP: only ll carriers (ll or ls??) showed inverse correlation between resilience and depression
Conclusion
- specific aspects of resilience have a protective function against depression following a stressor
- ss allele might negate the protective function of resilience against depression OR resilience might nullify the effect of ss allele on depression
