We have tested the diathesis-stress theory on an independent sample of individuals. Our study reinforces the evidence of additional risk in the aetiology of depression due to GxE effects.
However, larger sample sizes are required to robustly validate these findings. Introduction Stressful life events SLE have been consistently recognized as a determinant of depressive symptoms, with many studies reporting significant associations between SLE and major depressive disorder MDD 1 — 7. However, some individuals facing severe stress never present symptoms of depression Such vulnerability can be conceived as a set of biological factors that predispose to illness.
Several diathesis-stress models have been successfully applied across many psychopathologies 11 — The diathesis-stress model proposes that a latent diathesis may be activated by stress before psychopathological symptoms manifest. Some levels of diathesis to illness are present in everybody, with a threshold over which symptoms will appear. Exceeding such a threshold depends on the interaction between diathesis and the degree of adversity faced in SLE, which increases the liability to depression beyond the combined additive effects of the diathesis and stress alone Genetic risk factors can, therefore, be conceived as a genetic diathesis.
Thus, this genetically driven effect produced by the diathesis-stress interaction can be seen as a gene-by-environment interaction GxE. Therefore, interactions in depression are also expected to be highly polygenic. In recent years, with the increasing success of genome-wide association studies, GxE studies in depression have shifted towards hypothesis-free genome-wide and polygenic approaches that capture liability to depression using genetic data 17 — 23 , Recent advances in genomics and the massive effort from national institutions to collect genetic, clinical and environmental data on large population-based samples now provide an opportunity to empirically test the diathesis-stress model for depression.
The construction of polygenic risk scores PRS offers a novel paradigm to quantify genetic diathesis into a single genetic measure, allowing us to study GxE effects with more predictive power than any single variant 25 — PRS are genetic indicators of the aggregated number of risk alleles carried by an individual weighted by their allelic effect estimated from genome-wide association studies. This polygenic approach to assessing the diathesis-stress model for depression has been tested using either childhood trauma 17 , 19 , 24 or adult SLE 18 , 23 , 24 as measures of environmental adversity.
In this study, Colodro-Conde et al. Colodro-Conde et al. These schemas are thought to remain dormant until an individual experiences a stressful life event that is reminiscent of the original stressor, at which point the schemas become activated. Schemas are thus postulated to play an etiologic role in predisposing an individual to experience clinically-significant depression when the individual experiences stressful events that match, and thus activate, the negative schemas.
In particular, there now exists a large literature documenting the association of depression with dysfunctional attitudes and cognitive biases, but these findings are more consistent in demonstrating a connection between depression and concurrent cognitive dysfunction than in supporting the prediction that cognitive dysfunction precedes depression and that such cognitive biases are activated by stress.
The diathesis-stress predictions outlined in cognitive theory have not received more consistent support in part because multi-factorial research, comprising different levels of analysis, has rarely done justice to the many considerations unique to each level.
This concern applies to the manner in which both life stress and cognitive vulnerability have been traditionally assessed: often via self-report measures in which the target construct and the disorder under study are blended. Total Automatic Recall We have attempted to address the need for better assessment by using investigator-based measures of life stress and computer-based measures of cognitive vulnerability.
We assess life stress using the Life Events and Difficulties Schedule, which employs a semi-structured interview and a team of trained raters who make objective ratings of the reported events in terms of normative standards.
We have chosen to measure cognitive vulnerability via methods borrowed from experimental cognitive psychology, including the Emotion Stroop task, the Emotion Face Dot-Probe task, and incidental free-recall and cued-recall memory tests.
These tasks have permitted us to assess cognitive processes that are automatic, rather than strategic or controlled. Analyze This Our preliminary analyses have revealed that severe stressful life events occurring prior to depression onset are uniquely associated with elevated dysfunctional attitudes at onset, and that dysfunctional attitudes activated in this way abate with remission. We are currently analyzing the information processing data and expect parallel results.
Conclusions A diathesis-stress conceptualization coupled with application of a threshold-based diagnostic definition may explain several of the apparent complexities of major depression epidemiology. Our study reinforces the evidence of additional risk in the aetiology of depression due to GxE effects. Film buffs will recognize that the subheadings in this article are movie titles.
However, larger sample sizes are required to robustly validate these findings.
Several publications from our group have made use of these data 9 , 23 , 28 , 32 — The diathesis-stress model views psychological problems to be the result of stress affecting an individual who has a pre-existing vulnerability for developing a specific kind of problem. This resulted in assignment of values for diathesis and stress that were always positive and that had an approximately bell-shaped distribution when the standard deviation was small and was right skewed when the standard deviation was large [ 32 ].
Overall, due the low missingness rate imputation should have little influence on the results. These observations should encourage an empirical exploration of whether diathesis-stress interactions provide a more parsimonious framework for understanding depression than current approaches. Representation of these characteristics, either conceptually in clinical practice or mathematically in a simulation model, involves consideration of complex time-dependent patterns of incidence and recovery and a multiplicity of MD-related health states. One of the most prominent diathesis-stress theories was developed by APS Fellow Aaron Beck, who proposed that depression onset may be attributed largely to negative cognitions and corresponding patterns of information processing. In order to estimate the variance in depression explained by the genetic vulnerability, the stressors and their interactions, we fitted linear mixed models controlling for relatedness for the whole sample as well as stratified by sex. The quality of our measurement should match the comprehensiveness of our theory, because anything less impedes progress toward better understanding precisely how depression develops and is maintained.