Indicators of mental disorders in UK Biobank—A comparison of approaches

Davis, Katrina; Cullen, Breda; Adams, Mark; Brăilean, Anamaria; Breen, Gerome; Coleman, Jonathan R. I.; Dregan, Alexandru; Gaspar, Héléna; Hübel, Christopher; Lee, William; McIntosh, Andrew M.; Nolan, John; Pearsall, R. Scott; Hotopf, Matthew

doi:10.1002/mpr.1796

Cited by 84 publications

(99 citation statements)

References 55 publications

(94 reference statements)

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“…The reported prevalence of PLEs in this imaging sample (4.75%) is similar to that in the whole UK Biobank sample (5%) [62], and with previous population studies [63,64]. We did not find any significant association between PRSSZ and total number of PLEs in the entire UKBiobank sample (N = 308,693), consistent with previous studies investigating this relationship in adolescence [65,66].…”

Section: Psychotic-like Experiencessupporting

confidence: 91%

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Psychotic-like experiences, polygenic risk scores for schizophrenia and structural properties of the salience, default mode and central-executive networks in healthy participants from UK Biobank

Alloza

Cábez

Bastin

et al. 2019

Preprint

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AbstractSchizophrenia is a highly heritable disorder with considerable phenotypic heterogeneity. Hallmark psychotic symptoms can be considered as existing on a continuum from non-clinical to clinical populations. Assessing genetic risk and psychotic-like experiences (PLEs) in non-clinical populations and their associated neurobiological underpinnings can offer valuable insights into symptom-associated brain mechanisms without the potential confounds of the effects of schizophrenia and its treatment. We leveraged a large population-based cohort (UKBiobank) including information on PLEs, polygenic risk scores for schizophrenia (PRSSZ) and multi-modal brain imaging in combination with network neuroscience. Morphometric (cortical thickness, volume) and water diffusion (fractional anisotropy) properties of the regions and pathways belonging to the salience, default-mode and central-executive networks were computed. We hypothesized that these anatomical concomitants of functional dysconnectivity would be negatively associated with PRSSZ and PLEs. PRSSZ was significantly associated with a latent measure of cortical thickness across the salience network (r = −0.069, p = 0.010) and PLEs showed a number of significant associations with properties of the salience and default mode networks (involving the insular cortex, supramarginal gyrus and pars orbitalis, pFDR < 0.050); with the cortical thickness of the insula largely mediating the relationship between PRSSZ and auditory hallucinations. These results are consistent with the hypothesis that higher genetic liability for schizophrenia is related to subtle disruptions in brain structure and predisposes to PLEs even among healthy participants. In addition, our study suggests that networks engaged during auditory hallucinations show structural associations with PLEs in the general population.

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Section: Psychotic-like Experiencessupporting

confidence: 91%

“…However, due to the still modest frequencies of PLEs in this sample, results should be interpreted cautiously. A previous study has indicated a potential "healthy volunteer" selection bias in this sample [86], in particular, people with lower socio-economic status, chronic illness, and smokers were under-represented [62].…”

Section: Limitationsmentioning

confidence: 87%

Psychotic-like experiences, polygenic risk scores for schizophrenia and structural properties of the salience, default mode and central-executive networks in healthy participants from UK Biobank

Alloza

Cábez

Bastin

et al. 2019

Preprint

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“…Participants were asked to enter their own birth-weight through verbal interview with 277,000 participants completed (UK Biobank field ID: 20022). In order to obtain a comprehensive and accurate control group of depressed and nondepressed patients, Patient Health Questionnaire (PHQ-9) and another strict criterion based on composite international diagnostic interview short-form (CIDI-SF) [18,19] were selected as the measurement of brain structure. The total intracranial volume was defined as the sum of total gray matter, white matter, and cerebrospinal fluid.…”

Section: Uk Biobank Phenotypes Of Birth Weight Depression and Brainmentioning

confidence: 99%

Evaluating the effect of birth weight on brain volumes and depression: An observational and genetic study using UK Biobank cohort

Chu

et al. 2020

Eur. Psychiatr.

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Background. Birth weight influences not only brain development, but also mental health outcomes, including depression, but the underlying mechanism is unclear. Methods. The phenotypic data of 12,872–91,009 participants (59.18–63.38% women) from UK Biobank were included to test the associations between the birth weight, depression, and brain volumes through the linear and logistic regression models. As birth weight is highly heritable, the polygenic risk scores (PRSs) of birth weight were calculated from the UK Biobank cohort (154,539 participants, 56.90% women) to estimate the effect of birth weight-related genetic variation on the development of depression and brain volumes. Finally, the mediation analyses of step approach and mediation analysis were used to estimate the role of brain volumes in the association between birth weight and depression. All analyses were conducted sex stratified to assess sex-specific role in the associations. Result. We observed associations between birth weight and depression (odds ratio [OR] = 0.968, 95% confidence interval [CI] = 0.957–0.979, p = 2.29 × 10−6). Positive associations were observed between birth weight and brain volumes, such as gray matter (B = 0.131, p = 3.51 × 10−74) and white matter (B = 0.129, p = 1.67 × 10−74). Depression was also associated with brain volume, such as left thalamus (OR = 0.891, 95% CI = 0.850–0.933, p = 4.46 × 10−5) and right thalamus (OR = 0.884, 95% CI = 0.841–0.928, p = 2.67 × 10−5). Additionally, significant mediation effects of brain volume were found for the associations between birth weight and depression through steps approach and mediation analysis, such as gray matter (B = –0.220, p = 0.020) and right thalamus (B = –0.207, p = 0.014). Conclusions. Our results showed the associations among birth weight, depression, and brain volumes, and the mediation effect of brain volumes also provide evidence for the sex-specific of associations.

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“…Anxiety and depression were de ned according to the previous study [29], which was based on the general anxciety disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) [30,31]. Fluid intelligence score was described as a simple unweighted sum of the number of correct answers given to the 13 uid intelligence questions.…”

Section: Uk Biobank Samples and Mental Phenotypesmentioning

confidence: 99%

Evaluating the genetic effects of sex hormone on the development of mental traits: a polygenic score analysis and genome-wide genetic interaction analysis in the UK Biobank cohort

Liang¹,

Cheng²,

Ye³

et al. 2020

Preprint

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Objective: To evaluate the genetic effects of sex hormone on the development of mental traits.Methods: The SNPs significantly associated with sex hormone traits were driven from a two-stage genome-wide association study (GWAS). Four sex hormone were selected in this study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic risk scores (PRS) of sex hormone traits were calculated from individual-level genotype data of the UK Biobank cohort. We then used logistic and linear regression models to assess the associations between individual PRS of sex hormone traits and the frequency of alcohol consumption, anxiety, intelligence and so on. Finally, genome-wide genetic interaction study (GWGIS) was performed to detect novel candidate genes interacting with the sex hormone on the development of fluid intelligence and the frequency of smoking and alcohol consumption by PLINK2.0.Results: We observed positive associations between SHBG and the frequency of alcohol consumption (b=0.01, p=3.84×10–11) in males and females. In addition, estradiol was positively associated with the frequency of alcohol consumption (b=0.01, p=1,96×10–8), fluid intelligence (b=0.01, p=1.90×10–2) and the frequency of smoking (b=0.01, p=1.77×10–2) in males. Moreover, SHBG was associated with the frequency of alcohol consumption (b=0.01, p=2.60×10–3), fluid intelligence (b=0.01, p=4.25×10–2) and anxiety (b=-0.01, p=3.79×10–2) in females. Finally, GWGIS identified one significant loci, Tenascin R (TNR) (rs34633780, p=3.45×10–8) interacting with total testosterone for fluid intelligence.Conclusion: Our study results support the genetic effects of sex hormone on the development of intelligence and the frequency of alcohol consumption.

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Indicators of mental disorders in UK Biobank—A comparison of approaches

Cited by 84 publications

References 55 publications

Psychotic-like experiences, polygenic risk scores for schizophrenia and structural properties of the salience, default mode and central-executive networks in healthy participants from UK Biobank

Psychotic-like experiences, polygenic risk scores for schizophrenia and structural properties of the salience, default mode and central-executive networks in healthy participants from UK Biobank

Evaluating the effect of birth weight on brain volumes and depression: An observational and genetic study using UK Biobank cohort

Evaluating the genetic effects of sex hormone on the development of mental traits: a polygenic score analysis and genome-wide genetic interaction analysis in the UK Biobank cohort

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