Symptoms of major depression: Their stability, familiality, and prediction by genetic, temperamental, and childhood environmental risk factors

Kendler, Kenneth S.; Aggen, Steven H.

doi:10.1002/da.22591

Cited by 8 publications

(6 citation statements)

References 27 publications

(41 reference statements)

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“…not a function of the depressive state). Kendler & Aggen (2017) further demonstrated that, within individuals, symptom presentation is only modestly heritable ( r ~0.3) across depressive episodes. These scenarios are not mutually exclusive: indeed, given the complexity of psychopathology, the current results may be due to a combination of ethnicity-specific genetic factors, ascertainment strategy, and the impact of sociocultural/environmental factors on fine-scale clinical heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

“…Yet, another potential explanation for the overall absence of associations with MDD clinical features is that clinical presentation is pathoplastic (Keller et al 2007; Kendler & Aggen, 2017) – that is, subject to environmental factors and individual variation in risk that is not a function of core physiological processes/genetic liability. Keller et al (2007) reported that MDD symptom endorsement varied in conjunction with exposure to diverse stressful life events, which suggests that genetic factors are not markedly influential on heterogeneity in symptom profiles, assuming environmental risk factors are independent (i.e.…”

Section: Discussionmentioning

confidence: 99%

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Polygenic risk for severe psychopathology among Europeans is associated with major depressive disorder in Han Chinese women

et al. 2017

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Background Previous studies have demonstrated that several major psychiatric disorders are influenced by shared genetic factors. This shared liability may influence clinical features of a given disorder (e.g. severity, age at onset). However, findings have largely been limited to European samples; little is known about the consistency of shared genetic liability across ethnicities. Method The relationship between polygenic risk for several major psychiatric diagnoses and major depressive disorder (MDD) was examined in a sample of unrelated Han Chinese women. Polygenic risk scores (PRSs) were generated using European discovery samples and tested in the China, Oxford, and VCU Experimental Research on Genetic Epidemiology [CONVERGE (maximum N = 10 502)], a sample ascertained for recurrent MDD. Genetic correlations between discovery phenotypes and MDD were also assessed. In addition, within-case characteristics were examined. Results European-based polygenic risk for several major psychiatric disorder phenotypes was significantly associated with the MDD case status in CONVERGE. Risk for clinically significant indicators (neuroticism and subjective well-being) was also associated with case–control status. The variance accounted for by PRS for both psychopathology and for well-being was similar to estimates reported for within-ethnicity comparisons in European samples. However, European-based PRS were largely unassociated with CONVERGE family history, clinical characteristics, or comorbidity. Conclusions The shared genetic liability across severe forms of psychopathology is largely consistent across European and Han Chinese ethnicities, with little attenuation of genetic signal relative to within-ethnicity analyses. The overall absence of associations between PRS for other disorders and within-MDD variation suggests that clinical characteristics of MDD may arise due to contributions from ethnicity-specific factors and/or pathoplasticity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Polygenic risk for severe psychopathology among Europeans is associated with major depressive disorder in Han Chinese women

et al. 2017

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“…The systems exhibit both multifinality (i.e., the same set of causal agents can lead to different mental health outcomes) and equifinality (i.e., diverse causes can produce the same disorder) [4,5]. The systems are heterogeneous, with individuals differing not only in the specific constellation of symptoms experienced, but also in the etiological factors that precede and predict illness onset [6,7]. Further, systems within individuals are dynamic: they rise and fall and evolve over time.…”

Section: Introductionmentioning

confidence: 99%

Systems all the way down: embracing complexity in mental health research

Fried

Robinaugh

2020

BMC Med

112

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In this editorial for the collection on complexity in mental health research, we introduce and summarize the inaugural contributions to this collection: a series of theoretical, methodological, and empirical papers that aim to chart a path forward for investigating mental health in all its complexity. A central theme emerges from these contributions: if we are to make genuine progress in explaining, predicting, and treating mental illness, we must study the systems from which psychopathology emerges. As the articles in this collection make clear, the systems that give rise to psychopathology encompass a host of components across biological, psychological, and social levels of analysis, intertwined in a web of complex interactions. The task of advancing our understanding of these systems will be a challenging one. Yet, this challenge presents a unique opportunity. From physics to ecology, there is a rapidly evolving body of interdisciplinary research dedicated to investigating complex systems. This work provides clear guidance for psychiatric research, opportunities for collaboration, and a set of tools and concepts from which we can draw in our efforts to understand mental health, helping us move toward our ultimate aim of improving the prevention and treatment of psychopathology.

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“…Keller et al (2007) found that chronic stress was associated with some but not all symptoms, such as fatigue and hypersomnia. Likewise, genetic disposition to specific symptoms is uncertain, as Kendler and Aggen (2017) detected only modest concordance of individual MDD symptoms among monozygotic twins, while there were separate environmental factors for different symptoms. Another study found that chronic stress, prior history of depression, higher number of stressful life events, childhood stress, and sex predicted worsening of only certain MDD symptoms (Fried et al, 2014).…”

Section: Differential Validity Of Individual Depressive Symptomsmentioning

confidence: 99%

Test-retest & familial concordance of MDD symptoms

Kaiser

Funkhouser

Mittal

et al. 2020

Psychiatry Research

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Psychopathology research has increasingly sought to study the etiology and treatment of individual symptoms, rather than categorical diagnoses. However, it is unclear whether commonly used measures have adequate psychometric properties for assessing individual symptoms. This study examined the test-retest reliability and familial concordance (an indicator of validity) of the symptoms of Major Depressive Disorder (MDD), a disorder consisting of nine core symptoms, most of which are aggregated (e.g., symptom 7 of the DSM criteria for MDD is worthlessness or guilt). Lifetime MDD symptoms were measured in 504 young adults (237 sibling pairs) using the Structured Clinical Interview for DSM-5 (SCID). Fifty-one people completed a second SCID within three weeks of their first SCID. Results indicated that aggregated and unaggregated symptoms demonstrated moderate to substantial test-retest reliability and generally significant, but slight to fair familial concordance (with the highest familial concordance being for markedly diminished interest or pleasure and its unaggregated components -decreased interest and decreased pleasure). Given the increasing focus on the differential validity of individual MDD symptoms, the present study suggests that interview-based assessments of depression can assess most individual symptoms with adequate levels of reliability and validity.

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Symptoms of major depression: Their stability, familiality, and prediction by genetic, temperamental, and childhood environmental risk factors

Cited by 8 publications

References 27 publications

Polygenic risk for severe psychopathology among Europeans is associated with major depressive disorder in Han Chinese women

Polygenic risk for severe psychopathology among Europeans is associated with major depressive disorder in Han Chinese women

Systems all the way down: embracing complexity in mental health research

Test-retest & familial concordance of MDD symptoms

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