Financial difficulties but not other types of recent negative life events show strong interactions with 5-HTTLPR genotype in the development of depressive symptoms.
paper
Cited
Public
- Authors
- Gonda, X; Eszlari, N; Kovacs, D; Anderson, I M; Deakin, J F W; Juhasz, G; Bagdy, G
- Year
- 2016
- Journal
- Translational psychiatry
- PMID
- 27138797
- DOI
- 10.1038/tp.2016.57
- PMCID
- PMC5070066
Several studies indicate that 5-HTTLPR mediates the effect of childhood adversity in the development of depression, while results are contradictory for recent negative life events. For childhood adversity the interaction with genotype is strongest for sexual abuse, but not for other types of childhood maltreatment; however, possible interactions with specific recent life events have not been investigated separately. The aim of our study was to investigate the effect of four distinct types of recent life events in the development of depressive symptoms in a large community sample. Interaction between different types of recent life events measured by the List of Threatening Experiences and the 5-HTTLPR genotype on current depression measured by the depression subscale and additional items of the Brief Symptom Inventory was investigated in 2588 subjects in Manchester and Budapest. Only a nominal interaction was found between life events overall and 5-HTTLPR on depression, which failed to survive correction for multiple testing. However, subcategorising life events into four categories showed a robust interaction between financial difficulties and the 5-HTTLPR genotype, and a weaker interaction in the case of illness/injury. No interaction effect for the other two life event categories was present. We investigated a general non-representative sample in a cross-sectional approach. Depressive symptoms and life event evaluations were self-reported. The 5-HTTLPR polymorphism showed a differential interaction pattern with different types of recent life events, with the strongest interaction effects of financial difficulties on depressive symptoms. This specificity of interaction with only particular types of life events may help to explain previous contradictory findings.
Linear regression analysis indicated a significant interaction effect between the 5-HTTLPR genotype and specific types of recent life events on current depression scores in the total population and subpopulations. Recent life events are categorised as 0 (no recent life events reported), 1 (1 life event reported) and 2 or more life events reported in the last year. s.e.m. is displayed. Linear regression indicated a significant interaction between the 5-HTTLPR genotype and recent life events related to illness and injury (RLE-illness) on current depression scores in the combined (Budapest+Manchester) sample according to the additive (P=0.016, FDR q=0.038) and dominant (P=0.009, FDR q=0.035) models (a); a significant interaction effect between the 5-HTTLPR genotype and recent life events related to financial difficulties in the last year (RLE-financial) on current depression scores in the combined (Budapest+Manchester) sample according to additive (P=0.017, FDR q=0.038) and recessive models (P=0.002, FDR q=0.016) (b); a significant interaction effect between the 5-HTTLPR genotype and recent life events related to financial difficulties in the last year (RLE-financial) on current depression scores in the Budapest sample according to additive (P=0.007, FDR q=0.035) and recessive models (P=0.001, FDR q=0.012) (c); and a significant interaction effect between the 5-HTTLPR genotype and recent life events related to financial difficulties in the last year (RLE-financial) in the Manchester sample on current depression scores according to the recessive model (P=0.00997, FDR q=0.035) (d). The increasing number of s alleles increases current depression score with the increasing number of recent life events related to illness and injury (a) or financial difficulties according to the additive model (b, c), and current depression score increases with the increasing number of recent life events related to financial difficulties in those carrying the ss genotype according to the recessive model (d). FDR, false discovery rate.
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| 20 | Discussion | In our study we detected a robust significant interaction effect between the 5-HTTLPR genotype and… |
| 21 | Discussion | events, namely those associated with financial difficulties, and less robustly illness/injury, in… |
| 22 | Discussion — Selective effects of recent life events related to financial difficulties in interaction with the 5-HTTLPR genotype in the development of depressive symptoms | Our studies indicate a robust and selective effect for financial-related life events in ss genotype… |
| 23 | Discussion — Selective effects of recent life events related to financial difficulties in interaction with the 5-HTTLPR genotype in the development of depressive symptoms | Our findings are not only novel but could also help to explain why contradictory results emerged in… |
| 24 | Discussion — Selective effects of recent life events related to financial difficulties in interaction with the 5-HTTLPR genotype in the development of depressive symptoms | that may have divergent consequences. Identifying which environments and effects are most prominent… |
| 25 | Discussion — Selective effects of recent life events related to financial difficulties in interaction with the 5-HTTLPR genotype in the development of depressive symptoms | Imaging studies support the well-known difference between early and recent life events in the… |
| 26 | Discussion — Selective effects of recent life events related to financial difficulties in interaction with the 5-HTTLPR genotype in the development of depressive symptoms | method, interacted with the 5-HTTLPR genotype on the structural connectivity between the hippocampus… |
| 27 | Discussion — Selective effects of recent life events related to financial difficulties in interaction with the 5-HTTLPR genotype in the development of depressive symptoms | Previous work has supported the importance of financial stress in the development of depression.… |
| 28 | Discussion — Selective effects of recent life events related to financial difficulties in interaction with the 5-HTTLPR genotype in the development of depressive symptoms | In studies investigating the contribution of genetic and environmental factors in the development of… |
| 29 | Discussion — Selective effects of recent life events related to financial difficulties in interaction with the 5-HTTLPR genotype in the development of depressive symptoms | However, genetic liability to major depression may also increase the risk of being exposed to… |
| 30 | Discussion — Selective effects of recent life events related to financial difficulties in interaction with the 5-HTTLPR genotype in the development of depressive symptoms | Financial problems and difficulties may encompass several effects related to economic and financial… |
| 31 | Discussion — Selective effects of recent life events related to financial difficulties in interaction with the 5-HTTLPR genotype in the development of depressive symptoms | not captured in social network- or illness-related life events, which may also account for their… |
| 32 | Discussion — Interaction of life events and 5-HTTLPR in the two genders | Analysing the two genders separately, we found that all significant associations disappeared in… |
| 33 | Discussion — Interaction of life events and 5-HTTLPR in the two genders | Previous research indicates that 5-HTTLPR variants exert their effect on a number of phenomena in a… |
| 34 | Discussion — Interaction of life events and 5-HTTLPR in the two genders | behaviour in women, and with aggression, conduct disorder and externalising behaviours in men.63… |
| 35 | Discussion — Interaction of life events and 5-HTTLPR in the two genders | Differences in the effect of 5-HTTLPR are plausible, given that the serotonergic function shows… |
| 36 | Discussion — Interaction of life events and 5-HTTLPR in the two genders | It is likely that the gender effect observable in case of 5-HTTLPR may be related to the effect of… |
| 37 | Discussion — Interaction of life events and 5-HTTLPR in the two genders | Therefore, our results contradict previous findings as they reflect an opposite pattern compared… |
| 38 | Discussion — No significant main effect for 5-HTTLPR or in interaction with total life events in the development of depressive symptoms | It is also noteworthy that in our study we found no significant main effect for the 5-HTTLPR… |
| 39 | Discussion — No significant main effect for 5-HTTLPR or in interaction with total life events in the development of depressive symptoms | Furthermore, in accordance with several earlier studies and certain meta-analyses13, 14 our results… |
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. | 2018 | 28373689 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| A Double Hit of Social and Economic Stress in Mice Precipitates Changes in Decision-Making Strategies. | Durand-de Cuttoli R et al. | — | 2024 | → |
| The relationship between patterns of negative life experiences and clinical presentation in a psychiatric sample. | Young Choi J | — | 2024 | → |
| Comparative Proteomic Characterization of Ventral Hippocampus in Susceptible and Resilient Rats Subjected to Chronic Unpredictable Stress. | Zhang Y et al. | — | 2021 | → |
| Inflamed Mind: Multiple Genetic Variants of <i>IL6</i> Influence Suicide Risk Phenotypes in Interaction With Early and Recent Adversities in a Linkage Disequilibrium-Based Clumping Analysis. | Bokor J et al. | — | 2021 | → |
| Treatment-Resistant Depression Revisited: A Glimmer of Hope. | Halaris A et al. | — | 2021 | → |
| "Out, out, brief candle! Life's but a walking shadow": <i>5-HTTLPR</i> Is Associated With Current Suicidal Ideation but Not With Previous Suicide Attempts and Interacts With Recent Relationship Problems. | Bokor J et al. | — | 2020 | → |
| 5-HTTLPR-brain-derived neurotrophic factor (BDNF) gene interactions and early adverse life events effect on impulsivity in suicide attempters. | Jiménez-Treviño L et al. | — | 2019 | → |
| Effects of Different Stressors Are Modulated by Different Neurobiological Systems: The Role of GABA-A Versus CB1 Receptor Gene Variants in Anxiety and Depression. | Gonda X et al. | — | 2019 | → |
| Examining the effect of 5-HTTLPR on depressive symptoms in postmenopausal women 1 year after initial breast cancer treatment. | Wang JS et al. | — | 2019 | → |
| Financial Stress Interacts With <i>CLOCK</i> Gene to Affect Migraine. | Baksa D et al. | — | 2019 | → |
| Genetic variants in major depressive disorder: From pathophysiology to therapy. | Gonda X et al. | — | 2019 | → |
| No Support for Historical Candidate Gene or Candidate Gene-by-Interaction Hypotheses for Major Depression Across Multiple Large Samples. | Border R et al. | — | 2019 | → |
| The UKB envirome of depression: from interactions to synergistic effects. | Hullam G et al. | — | 2019 | → |
| Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. | Culverhouse RC et al. | — | 2018 | → |