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  1. Article ; Online: Genetic risk of major depressive disorder: the moderating and mediating effects of neuroticism and psychological resilience on clinical and self-reported depression.

    Navrady, L B / Adams, M J / Chan, S W Y / Ritchie, S J / McIntosh, A M

    Psychological medicine

    2017  Volume 48, Issue 11, Page(s) 1890–1899

    Abstract: Background: Polygenic risk scores (PRS) for depression correlate with depression status and chronicity, and provide causal anchors to identify depressive mechanisms. Neuroticism is phenotypically and genetically positively associated with depression, ... ...

    Abstract Background: Polygenic risk scores (PRS) for depression correlate with depression status and chronicity, and provide causal anchors to identify depressive mechanisms. Neuroticism is phenotypically and genetically positively associated with depression, whereas psychological resilience demonstrates negative phenotypic associations. Whether increased neuroticism and reduced resilience are downstream mediators of genetic risk for depression, and whether they contribute independently to risk remains unknown.
    Methods: Moderating and mediating relationships between depression PRS, neuroticism, resilience and both clinical and self-reported depression were examined in a large, population-based cohort, Generation Scotland: Scottish Family Health Study (N = 4166), using linear regression and structural equation modelling. Neuroticism and resilience were measured by the Eysenck Personality Scale Short Form Revised and the Brief Resilience Scale, respectively.
    Results: PRS for depression was associated with increased likelihood of self-reported and clinical depression. No interaction was found between PRS and neuroticism, or between PRS and resilience. Neuroticism was associated with increased likelihood of self-reported and clinical depression, whereas resilience was associated with reduced risk. Structural equation modelling suggested the association between PRS and self-reported and clinical depression was mediated by neuroticism (43-57%), while resilience mediated the association in the opposite direction (37-40%). For both self-reported and clinical diagnoses, the genetic risk for depression was independently mediated by neuroticism and resilience.
    Conclusions: Findings suggest polygenic risk for depression increases vulnerability for self-reported and clinical depression through independent effects on increased neuroticism and reduced psychological resilience. In addition, two partially independent mechanisms - neuroticism and resilience - may form part of the pathway of vulnerability to depression.
    MeSH term(s) Adult ; Depressive Disorder, Major/epidemiology ; Depressive Disorder, Major/genetics ; Depressive Disorder, Major/physiopathology ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Multifactorial Inheritance/genetics ; Neuroticism ; Resilience, Psychological ; Risk ; Scotland/epidemiology ; Self Report
    Language English
    Publishing date 2017-11-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 217420-0
    ISSN 1469-8978 ; 0033-2917
    ISSN (online) 1469-8978
    ISSN 0033-2917
    DOI 10.1017/S0033291717003415
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The role of neuroticism in self-harm and suicidal ideation: results from two UK population-based cohorts.

    Hafferty, Jonathan D / Navrady, L B / Adams, M J / Howard, D M / Campbell, A I / Whalley, H C / Lawrie, S M / Nicodemus, K K / Porteous, D J / Deary, I J / McIntosh, A M

    Social psychiatry and psychiatric epidemiology

    2019  Volume 54, Issue 12, Page(s) 1505–1518

    Abstract: Background: Self-harm is common, debilitating and associated with completed suicide and increased all-cause mortality, but there is uncertainty about its causal risk factors, limiting risk assessment and effective management. Neuroticism is a stable ... ...

    Abstract Background: Self-harm is common, debilitating and associated with completed suicide and increased all-cause mortality, but there is uncertainty about its causal risk factors, limiting risk assessment and effective management. Neuroticism is a stable personality trait associated with self-harm and suicidal ideation, and correlated with coping styles, but its value as an independent predictor of these outcomes is disputed.
    Methods: Prior history of hospital-treated self-harm was obtained by record-linkage to administrative health data in Generation Scotland:Scottish Family Health Study (N = 15,798; self-harm cases = 339) and by a self-report variable in UK Biobank (N = 35,227; self-harm cases = 772). Neuroticism in both cohorts was measured using the Eysenck Personality Questionnaire-Short Form. Associations of neuroticism with self-harm were tested using multivariable regression following adjustment for age, sex, cognitive ability, educational attainment, socioeconomic deprivation, and relationship status. A subset of GS:SFHS was followed-up with suicidal ideation elicited by self-report (n = 3342, suicidal ideation cases = 158) and coping styles measured by the Coping Inventory for Stressful Situations. The relationship of neuroticism to suicidal ideation, and the role of coping style, was then investigated using multivariable logistic regression.
    Results: Neuroticism was positively associated with hospital-associated self-harm in GS:SFHS (per EPQ-SF unit odds ratio 1.2 95% credible interval 1.1-1.2, p
    Conclusions: Neuroticism is an independent predictor of hospital-treated self-harm risk. Neuroticism and emotion-orientated coping styles are also predictive of suicidal ideation.
    MeSH term(s) Adaptation, Psychological ; Adolescent ; Adult ; Emotions ; Female ; Humans ; Male ; Middle Aged ; Neuroticism ; Odds Ratio ; Regression Analysis ; Risk Factors ; Scotland ; Self Report ; Self-Injurious Behavior/psychology ; Stress, Psychological/psychology ; Suicidal Ideation ; United Kingdom ; Young Adult
    Language English
    Publishing date 2019-05-23
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 623071-4
    ISSN 1433-9285 ; 0037-7813 ; 0933-7954
    ISSN (online) 1433-9285
    ISSN 0037-7813 ; 0933-7954
    DOI 10.1007/s00127-019-01725-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Genetic and environmental contributions to psychological resilience and coping.

    Navrady, Lauren B / Zeng, Yanni / Clarke, Toni-Kim / Adams, Mark J / Howard, David M / Deary, Ian J / McIntosh, Andrew M

    Wellcome open research

    2018  Volume 3, Page(s) 12

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2018-02-15
    Publishing country England
    Document type Journal Article
    ISSN 2398-502X
    ISSN 2398-502X
    DOI 10.12688/wellcomeopenres.13854.1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Intelligence and neuroticism in relation to depression and psychological distress: Evidence from two large population cohorts.

    Navrady, L B / Ritchie, S J / Chan, S W Y / Kerr, D M / Adams, M J / Hawkins, E H / Porteous, D / Deary, I J / Gale, C R / Batty, G D / McIntosh, A M

    European psychiatry : the journal of the Association of European Psychiatrists

    2017  Volume 43, Page(s) 58–65

    Abstract: Background: Neuroticism is a risk factor for selected mental and physical illnesses and is inversely associated with intelligence. Intelligence appears to interact with neuroticism and mitigate its detrimental effects on physical health and mortality. ... ...

    Abstract Background: Neuroticism is a risk factor for selected mental and physical illnesses and is inversely associated with intelligence. Intelligence appears to interact with neuroticism and mitigate its detrimental effects on physical health and mortality. However, the inter-relationships of neuroticism and intelligence for major depressive disorder (MDD) and psychological distress has not been well examined.
    Methods: Associations and interactions between neuroticism and general intelligence (g) on MDD, self-reported depression, and psychological distress were examined in two population-based cohorts: Generation Scotland: Scottish Family Health Study (GS:SFHS, n=19,200) and UK Biobank (n=90,529). The Eysenck Personality Scale Short Form-Revised measured neuroticism and g was extracted from multiple cognitive ability tests in each cohort. Family structure was adjusted for in GS:SFHS.
    Results: Neuroticism was strongly associated with increased risk for depression and higher psychological distress in both samples. Although intelligence conferred no consistent independent effects on depression, it did increase the risk for depression across samples once neuroticism was adjusted for. Results suggest that higher intelligence may ameliorate the association between neuroticism and self-reported depression although no significant interaction was found for clinical MDD. Intelligence was inversely associated with psychological distress across cohorts. A small interaction was found across samples such that lower psychological distress associates with higher intelligence and lower neuroticism, although effect sizes were small.
    Conclusions: From two large cohort studies, our findings suggest intelligence acts a protective factor in mitigating the effects of neuroticism on psychological distress. Intelligence does not confer protection against diagnosis of depression in those high in neuroticism.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Depressive Disorder, Major/psychology ; Female ; Health Surveys ; Humans ; Intelligence/physiology ; Male ; Middle Aged ; Neuroticism/physiology ; Personality ; Psychiatric Status Rating Scales ; Risk Factors ; Stress, Psychological/psychology ; Young Adult
    Language English
    Publishing date 2017-01-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 1074337-6
    ISSN 1778-3585 ; 0767-399X ; 0924-9338
    ISSN (online) 1778-3585
    ISSN 0767-399X ; 0924-9338
    DOI 10.1016/j.eurpsy.2016.12.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Cohort Profile: Stratifying Resilience and Depression Longitudinally (STRADL): a questionnaire follow-up of Generation Scotland: Scottish Family Health Study (GS:SFHS).

    Navrady, L B / Wolters, M K / MacIntyre, D J / Clarke, T-K / Campbell, A I / Murray, A D / Evans, K L / Seckl, J / Haley, C / Milburn, K / Wardlaw, J M / Porteous, D J / Deary, I J / McIntosh, A M

    International journal of epidemiology

    2017  Volume 47, Issue 1, Page(s) 13–14g

    MeSH term(s) Adaptation, Psychological ; Aged ; Cohort Studies ; Cross-Sectional Studies ; Depressive Disorder, Major/epidemiology ; Depressive Disorder, Major/psychology ; Family Health ; Female ; Health Status ; Humans ; Male ; Mental Health ; Middle Aged ; Resilience, Psychological ; Scotland/epidemiology ; Socioeconomic Factors ; Substance-Related Disorders/epidemiology ; Substance-Related Disorders/psychology ; Surveys and Questionnaires
    Language English
    Publishing date 2017-10-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 187909-1
    ISSN 1464-3685 ; 0300-5771
    ISSN (online) 1464-3685
    ISSN 0300-5771
    DOI 10.1093/ije/dyx115
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Self-reported medication use validated through record linkage to national prescribing data.

    Hafferty, Jonathan D / Campbell, Archie I / Navrady, Lauren B / Adams, Mark J / MacIntyre, Donald / Lawrie, Stephen M / Nicodemus, Kristin / Porteous, David J / McIntosh, Andrew M

    Journal of clinical epidemiology

    2017  Volume 94, Page(s) 132–142

    Abstract: Objectives: Researchers need to be confident about the reliability of epidemiologic studies that quantify medication use through self-report. Some evidence suggests that psychiatric medications are systemically under-reported. Modern record linkage ... ...

    Abstract Objectives: Researchers need to be confident about the reliability of epidemiologic studies that quantify medication use through self-report. Some evidence suggests that psychiatric medications are systemically under-reported. Modern record linkage enables validation of self-report with national prescribing data as gold standard. Here, we investigated the validity of medication self-report for multiple medication types.
    Study design and setting: Participants in the Generation Scotland population-based cohort (N = 10,244) recruited 2009-2011 self-reported regular usage of several commonly prescribed medication classes. This was matched against Scottish NHS prescriptions data using 3- and 6-month fixed time windows. Potential predictors of discordant self-report, including general intelligence and psychological distress, were studied via multivariable logistic regression.
    Results: Antidepressants self-report showed very good agreement (κ = 0.85, [95% confidence interval (CI) 0.84-0.87]), comparable to antihypertensives (κ = 0.90 [CI 0.89-0.91]). Self-report of mood stabilizers showed moderate-poor agreement (κ = 0.42 [CI 0.33-0.50]). Relevant past medical history was the strongest predictor of self-report sensitivity, whereas general intelligence was not predictive.
    Conclusion: In this large population-based study, we found self-report validity varied among medication classes, with no simple relationship between psychiatric medication and under-reporting. History of indicated illness predicted more accurate self-report, for both psychiatric and nonpsychiatric medications. Although other patient-level factors influenced self-report for some medications, none predicted greater accuracy across all medications studied.
    MeSH term(s) Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Antidepressive Agents/classification ; Antidepressive Agents/therapeutic use ; Cohort Studies ; Databases, Factual ; Drug Prescriptions ; Female ; Humans ; Logistic Models ; Male ; Mental Disorders/drug therapy ; Middle Aged ; Prescription Drugs/classification ; Prescription Drugs/therapeutic use ; Reproducibility of Results ; Scotland/epidemiology ; Self Report ; Treatment Outcome ; Young Adult
    Chemical Substances Antidepressive Agents ; Prescription Drugs
    Language English
    Publishing date 2017-10-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639306-8
    ISSN 1878-5921 ; 0895-4356
    ISSN (online) 1878-5921
    ISSN 0895-4356
    DOI 10.1016/j.jclinepi.2017.10.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Genome-wide association study of antidepressant treatment resistance in a population-based cohort using health service prescription data and meta-analysis with GENDEP.

    Wigmore, Eleanor M / Hafferty, Jonathan D / Hall, Lynsey S / Howard, David M / Clarke, Toni-Kim / Fabbri, Chiara / Lewis, Cathryn M / Uher, Rudolf / Navrady, Lauren B / Adams, Mark J / Zeng, Yanni / Campbell, Archie / Gibson, Jude / Thomson, Pippa A / Hayward, Caroline / Smith, Blair H / Hocking, Lynne J / Padmanabhan, Sandosh / Deary, Ian J /
    Porteous, David J / Mors, Ole / Mattheisen, Manuel / Nicodemus, Kristin K / McIntosh, Andrew M

    The pharmacogenomics journal

    2019  Volume 20, Issue 2, Page(s) 329–341

    Abstract: ... of (a) antidepressant treatment resistance and (b) stages of antidepressant resistance by inferring antidepressant ...

    Abstract Antidepressants demonstrate modest response rates in the treatment of major depressive disorder (MDD). Despite previous genome-wide association studies (GWAS) of antidepressant treatment response, the underlying genetic factors are unknown. Using prescription data in a population and family-based cohort (Generation Scotland: Scottish Family Health Study; GS:SFHS), we sought to define a measure of (a) antidepressant treatment resistance and (b) stages of antidepressant resistance by inferring antidepressant switching as non-response to treatment. GWAS were conducted separately for antidepressant treatment resistance in GS:SFHS and the Genome-based Therapeutic Drugs for Depression (GENDEP) study and then meta-analysed (meta-analysis n = 4213, cases = 358). For stages of antidepressant resistance, a GWAS on GS:SFHS only was performed (n = 3452). Additionally, we conducted gene-set enrichment, polygenic risk scoring (PRS) and genetic correlation analysis. We did not identify any significant loci, genes or gene sets associated with antidepressant treatment resistance or stages of resistance. Significant positive genetic correlations of antidepressant treatment resistance and stages of resistance with neuroticism, psychological distress, schizotypy and mood disorder traits were identified. These findings suggest that larger sample sizes are needed to identify the genetic architecture of antidepressant treatment response, and that population-based observational studies may provide a tractable approach to achieving the necessary statistical power.
    MeSH term(s) Adult ; Antidepressive Agents/therapeutic use ; Cohort Studies ; Data Analysis ; Depressive Disorder, Treatment-Resistant/drug therapy ; Depressive Disorder, Treatment-Resistant/epidemiology ; Depressive Disorder, Treatment-Resistant/genetics ; Drug Prescriptions ; Female ; Genetic Predisposition to Disease/epidemiology ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study/methods ; Health Services ; Humans ; Male ; Middle Aged ; Population Surveillance ; Scotland/epidemiology
    Chemical Substances Antidepressive Agents
    Language English
    Publishing date 2019-01-31
    Publishing country United States
    Document type Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
    ZDB-ID 2106831-8
    ISSN 1473-1150 ; 1470-269X
    ISSN (online) 1473-1150
    ISSN 1470-269X
    DOI 10.1038/s41397-019-0067-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Genetic and environmental contributions to psychological resilience and coping [version 1; referees

    Lauren B Navrady / Yanni Zeng / Toni-Kim Clarke / Mark J Adams / David M Howard / Ian J Deary / Andrew M McIntosh

    Wellcome Open Research, Vol

    2 approved]

    2018  Volume 3

    Abstract: Background: Twin studies indicate that genetic and environmental factors contribute to both psychological resilience and coping style, but estimates of their relative molecular and shared environmental contributions are limited. The degree of overlap in ... ...

    Abstract Background: Twin studies indicate that genetic and environmental factors contribute to both psychological resilience and coping style, but estimates of their relative molecular and shared environmental contributions are limited. The degree of overlap in the genetic architectures of these traits is also unclear. Methods: Using data from a large population- and family-based cohort Generation Scotland (N = 8,734), we estimated the genetic and shared environmental variance components for resilience, task-, emotion-, and avoidance-oriented coping style in a linear mixed model (LMM). Bivariate LMM analyses were used to estimate the genetic correlations between these traits. Resilience and coping style were measured using the Brief Resilience Scale and Coping Inventory for Stressful Situations, respectively. Results: The greatest proportion of the phenotypic variance in resilience remained unexplained, although significant contributions from common genetic variants and family-shared environment were found. Both task- and avoidance-oriented coping had significant contributions from common genetic variants, sibling- and couple-shared environments, variance in emotion-oriented coping was attributable to common genetic variants, family- and couple-shared environments. The estimated correlation between resilience and emotion-oriented coping was high for both common-variant-associated genetic effects (rG = -0.79, se = 0.19), and for the additional genetic effects from the pedigree (rK = -0.94, se = 0.30). Genetic correlations between resilience and task- and avoidance-oriented coping did not meet statistical significance. Conclusions: Both genetics and shared environmental effects were major contributing factors to coping style, whilst the variance in resilience remains largely unexplained. Strong genetic overlap between resilience and emotion-oriented coping suggests a relationship whereby genetic factors that increase negative emotionality also lead to decreased resilience. We suggest that genome-wide family-based studies ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 333
    Language English
    Publishing date 2018-02-01T00:00:00Z
    Publisher Wellcome
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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