Mental health phenotyping in UK Biobank

Davis, Katrina; Hotopf, Matthew

doi:10.1002/pnp.522

Cited by 22 publications

(45 citation statements)

References 24 publications

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“…Nonetheless, the MDD and trauma-related phenotypes were defined in UK Biobank participants, who show a “volunteer selection bias” (Fry et al ., 2017) which refers to the tendency of research participants to be more health-conscious and have a higher level of social capital than non-participants (Manolio et al ., 2012). Furthermore, individuals who completed the follow-up Mental Health Questionnaire, compared with UK Biobank participants overall and the general population, are more likely to have a university degree, come from a higher socioeconomic background and report fewer disabilities and fewer chronic health problems (Davis et al ., 2019). Therefore, although the UK Biobank offers the opportunity to amalgamate genetic and phenotypic in a large, homogenous, single-population cohort, its demographic features mean the MDD and trauma phenotypes may not be representative of the experiences of wider populations.…”

Section: Discussionmentioning

confidence: 99%

Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder

Mundy

Hübel

Levey

et al. 2020

Preprint

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Background: Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences following psychological trauma exposure. The disorders have high genetic overlap. We investigated whether the genetics of PTSD were associated with reported trauma in individuals with MDD. Since trauma is associated with recurrent MDD, we also investigated whether the genetics of PTSD are associated with episode recurrence. Methods: Genetic correlations were estimated between PTSD and MDD in the presence and MDD in the absence of reported exposure to psychological trauma, and recurrent and single-episode MDD, based on genetic data from UK Biobank Mental Health Questionnaire respondents (N=157,358). Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and Million Veteran Program. Polygenic risk scores were generated to investigate whether individuals with MDD who have higher genetic risk for PTSD were more likely to report psychological trauma than those with lower genetic risk. Results: Individuals with MDD with a higher genetic risk for PTSD were significantly more likely to report exposure to psychological trauma than those with lower risk [OR=1.06 (1.03-1.09) Empricial p<0.001]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in the absence of reported psychological trauma [rg differences = ~0.2, p<0.008]. Participants who had experienced recurrent depressive episodes reported significantly higher trauma rates than participants who had experienced a single episode [chisquare>167, p<0.001]. Conclusions: Genetic risk for PTSD in individuals with MDD may influence the way in which traumatic life events are perceived, responded to and reported.

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Section: Discussionmentioning

confidence: 99%

Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder

Mundy

Hübel

Levey

et al. 2020

Preprint

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“…For further details see in Table 1, Supplementary Table 1 and Supplementary Data 1. Categories included: (1) Mental health (N discovery = 7970 and N replication = 3880), including self-reported symptoms of major psychiatric conditions 46 . In this category, three definitions for depression were included: broad depression, which was a self-declared definition of whether the participant had seen a psychiatrist for nerves, anxiety, tension or depression 6,25 , probable depression which was derived from an abbreviated set of self-declared symptoms of major depression and hospital admission history 47 , and CIDI depression, a measure assessing full diagnostic criteria for depression based on questions from a shortened version of the structured CIDI 46 This included four tests conducted at the assessment centres, four tests conducted online and a general measure 46 derived based on the tests conducted at the assessment centres that have larger sample sizes (see more details in Supplementary Methods).…”

Section: Methodsmentioning

confidence: 99%

“…Neuroimaging phenotypes. Neuroimaging data consisted of: (1) intracranial and subcortical volumes (N discovery = 10,631 and N replication = 5553), containing eight major structures 46 ; (2) T2 flair imaging for the whole brain (N discovery = 9829 and N replication = 5472) and in subcortical regions (N discovery = 9702 and N replication = 5187), which assess plausible white matter hyperintensity, (3) white matter microstructure, indexed by FA, MD, neurite density (ICVF), isotropic volume fraction and orientation dispersion index (N discovery = 9377 and N replication = 5239) for measures of white matter microstructure, in which we included three measures of association, projection and thalamic radiation subsets, and 15 major individual white matter tracts 26 ; (4) pair-wise resting-state functional (rsfMRI) connectivity (N discovery = 9745 and N replication = 5241) of 21 nodes over the whole brain 28 ; and finally (5) the amplitude of low-frequency rsfMRI signal fluctuation of the 21 nodes (N discovery = 9745 and N replication = 5241). All four types of neuroimaging data consisted of the imaging-derived phenotypes provided by UK Biobank.…”

Section: Methodsmentioning

confidence: 99%

A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

et al. 2020

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Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, p FDR < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, p FDR : 0.049 to 1.28 × 10 −14) and we find a significant and positive interaction between depression-PRS and adverse environmental exposures on mental health outcomes. This study reveals replicable associations between depression-PRS and white matter microstructure. Our results indicate that white matter microstructure differences may be a causal consequence of liability to depression.

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“…There were two diagnostic definitions related to lifetime experience of MDD. The first definition was based on the questions from Composite International Diagnostic Interview (CIDI‐SF, Kessler, Andrews, Mroczek, Ustun, & Wittchen, 1998), which was administered as part of the UK Biobank online mental health questionnaire at a subsequent time after the imaging assessment (Davis et al, 2019; UK Biobank, 2017). Briefly, participants were classed as having had lifetime experience of MDD (past MDD, pMDD‐UKB‐CIDI) if they reported experiencing one or more depressive episodes in their life according to the DSM criteria (American Psychiatric Association, 2000).…”

Section: Methodsmentioning

confidence: 99%

Automated classification of depression from structural brain measures across two independent community‐based cohorts

Stolicyn

Harris

Shen

et al. 2020

Human Brain Mapping

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Major depressive disorder (MDD) has been the subject of many neuroimaging case–control classification studies. Although some studies report accuracies ≥80%, most have investigated relatively small samples of clinically‐ascertained, currently symptomatic cases, and did not attempt replication in larger samples. We here first aimed to replicate previously reported classification accuracies in a small, well‐phenotyped community‐based group of current MDD cases with clinical interview‐based diagnoses (from STratifying Resilience and Depression Longitudinally cohort, ‘STRADL’). We performed a set of exploratory predictive classification analyses with measures related to brain morphometry and white matter integrity. We applied three classifier types—SVM, penalised logistic regression or decision tree—either with or without optimisation, and with or without feature selection. We then determined whether similar accuracies could be replicated in a larger independent population‐based sample with self‐reported current depression (UK Biobank cohort). Additional analyses extended to lifetime MDD diagnoses—remitted MDD in STRADL, and lifetime‐experienced MDD in UK Biobank. The highest cross‐validation accuracy (75%) was achieved in the initial current MDD sample with a decision tree classifier and cortical surface area features. The most frequently selected decision tree split variables included surface areas of bilateral caudal anterior cingulate, left lingual gyrus, left superior frontal, right precentral and paracentral regions. High accuracy was not achieved in the larger samples with self‐reported current depression (53.73%), with remitted MDD (57.48%), or with lifetime‐experienced MDD (52.68–60.29%). Our results indicate that high predictive classification accuracies may not immediately translate to larger samples with broader criteria for depression, and may not be robust across different classification approaches.

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Mental health phenotyping in UK Biobank

Cited by 22 publications

References 24 publications

Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder

Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder

A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

Automated classification of depression from structural brain measures across two independent community‐based cohorts

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