@article{Navrady2017,
title = {Intelligence and neuroticism in relation to depression and psychological distress: Evidence from two large population cohorts.},
author = {LB Navrady,SJ Ritchie,SW Chan,DM Kerr,MJ Adams,EH Hawkins,D Porteous,IJ Deary,CR Gale, GD Batty, AM McIntosh.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28365468},
year = {2017},
date = {2017-01-17},
journal = {European Psychiatry},
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.},
keywords = {4844, depression, Intelligence, neuroticism},
pubstate = {published},
tppubtype = {article}
}

@online{Batty2016,
title = {Psychological distress, neuroticism, and cause-specific mortality: early prospective evidence from UK Biobank},
author = {G David Batty, Andrew M McIntosh, Tom C Russ, Ian J Deary, Catharine R Gale},
url = {http://jech.bmj.com/content/early/2016/08/12/jech-2016-207267.abstract},
year = {2016},
date = {2016-08-12},
abstract = {Background It is well established that psychological distress (depression and anxiety) is related to an increased risk of mortality. The personality trait of neuroticism, reflecting a relatively stable tendency towards negative emotions, has also been associated with elevated rates of death in some studies. Accordingly, we tested the possibility that it is the neuroticism trait itself, rather than the distress state, that is generating an increased risk of mortality.

Methods We used data from the UK Biobank study, a UK-wide prospective cohort study (2006–2010) in which distress was ascertained using the Patient Health Questionnaire and neuroticism using the Eysenck Personality Questionnaire-Revised Short Form.

Results A mean of 6.2 years of follow-up of 308 721 study members gave rise to 4334 deaths. Higher neuroticism was weakly associated with total mortality (age-adjusted and sex-adjusted HR per SD increase; 95% CI 1.05; 1.02 to 1.09), and moderately strongly correlated with distress symptoms (r=0.55, p<0.0001). Distress symptoms were positively related to risk of total mortality (age-adjusted and sex-adjusted HR per SD increase in distress; 95% CI 1.23; 1.20 to 1.26). This gradient was, in fact, slightly strengthened after adding neuroticism to the multivariable model (1.30; 1.26 to 1.34) but markedly attenuated after taking into account other covariates which included health behaviours and somatic disease (1.16; 1.12 to 1.20). Similar results were apparent when cardiovascular disease, cancer and external cause of death were the end points of interest.

Conclusions While there was good a priori reasons to anticipate the neuroticism would at least partially explain the relation between distress symptoms and cause-specific mortality, we found no such evidence in the present study.
},
keywords = {10279, mortality, neuroticism},
pubstate = {published},
tppubtype = {online}
}

@article{OkbayA2016b,
title = {Corrigendum: Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses},
author = {Okbay, A., Cesarini, D., et al
},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27089181},
year = {2016},
date = {2016-07-28},
journal = {Nature Genetics},
abstract = {Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.},
keywords = {depressive, genetics, GWAS, neuroticism, well-being},
pubstate = {published},
tppubtype = {article}
}

@article{Gale2016,
title = {Pleiotropy between neuroticism and physical and mental health: findings from 108 038 men and women in UK Biobank},
author = {C R Gale, S P Hagenaars, G Davies, W D Hill, D C M Liewald, B Cullen, B W Penninx, International Consortium for Blood Pressure GWAS, CHARGE Consortium Aging and Longevity Group, D I Boomsma, J Pell, A M McIntosh, D J Smith, I J Deary and S E Harris},
url = {http://www.nature.com/tp/journal/v6/n4/full/tp201656a.html},
year = {2016},
date = {2016-04-26},
journal = {Translational Psychiatry},
abstract = {People with higher levels of neuroticism have an increased risk of several types of mental disorder. Higher neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between neuroticism and 17 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between neuroticism scores in 108 038 people in the UK Biobank and health-related measures from 14 large genome-wide association studies (GWASs). Summary information for the 17 GWASs was used to create polygenic risk scores for the health-related measures in the UK Biobank participants. Associations between the health-related polygenic scores and neuroticism were examined using regression, adjusting for age, sex, genotyping batch, genotyping array, assessment centre and population stratification. Genetic correlations were identified between neuroticism and anorexia nervosa (rg=0.17), major depressive disorder (rg=0.66) and schizophrenia (rg=0.21). Polygenic risk for several health-related measures were associated with neuroticism, in a positive direction in the case of bipolar disorder, borderline personality, major depressive disorder, negative affect, neuroticism (Genetics of Personality Consortium), schizophrenia, coronary artery disease, and smoking (β between 0.009–0.043), and in a negative direction in the case of body mass index (β=−0.0095). A high level of pleiotropy exists between neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia.},
keywords = {6553, depression, neuroticism},
pubstate = {published},
tppubtype = {article}
}

@article{Okbay2016,
title = {Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.},
author = {Okbay A, Baselmans BM, De Neve JE, Turley P, Nivard MG, Fontana MA, Meddens SF, Linnér RK, Rietveld CA, Derringer J, Gratten J, Lee JJ, Liu JZ, de Vlaming R, Ahluwalia TS, Buchwald J, Cavadino A, Frazier-Wood AC, Furlotte NA, Garfield V, Geisel MH, Gonzalez JR, Haitjema S, Karlsson R, van der Laan SW, Ladwig KH, Lahti J, van der Lee SJ, Lind PA, Liu T, Matteson L, Mihailov E, Miller MB, Minica CC, Nolte IM, Mook-Kanamori D, van der Most PJ, Oldmeadow C, Qian Y, Raitakari O, Rawal R, Realo A, Rueedi R, Schmidt B, Smith AV, Stergiakouli E, Tanaka T, Taylor K, Wedenoja J, Wellmann J, Westra HJ, Willems SM, Zhao W; LifeLines Cohort Study, Amin N, Bakshi A, Boyle PA, Cherney S, Cox SR, Davies G, Davis OS, Ding J, Direk N, Eibich P, Emeny RT, Fatemifar G, Faul JD, Ferrucci L, Forstner A, Gieger C, Gupta R, Harris TB, Harris JM, Holliday EG, Hottenga JJ, De Jager PL, Kaakinen MA, Kajantie E, Karhunen V, Kolcic I, Kumari M, Launer LJ, Franke L, Li-Gao R, Koini M, Loukola A, Marques-Vidal P, Montgomery GW, Mosing MA, Paternoster L, Pattie A, Petrovic KE, Pulkki-Råback L, Quaye L, Räikkönen K, Rudan I, Scott RJ, Smith JA, Sutin AR, Trzaskowski M, Vinkhuyzen AE, Yu L, Zabaneh D, Attia JR, Bennett DA, Berger K, Bertram L, Boomsma DI, Snieder H, Chang SC, Cucca F, Deary IJ, van Duijn CM, Eriksson JG, Bültmann U, de Geus EJ, Groenen PJ, Gudnason V, Hansen T, Hartman CA, Haworth CM, Hayward C, Heath AC, Hinds DA, Hyppönen E, Iacono WG, Järvelin MR, Jöckel KH, Kaprio J, Kardia SL, Keltikangas-Järvinen L, Kraft P, Kubzansky LD, Lehtimäki T, Magnusson PK, Martin NG, McGue M, Metspalu A, Mills M, de Mutsert R, Oldehinkel AJ, Pasterkamp G, Pedersen NL, Plomin R, Polasek O, Power C, Rich SS, Rosendaal FR, den Ruijter HM, Schlessinger D, Schmidt H, Svento R, Schmidt R, Alizadeh BZ, Sørensen TI, Spector TD, Steptoe A, Terracciano A, Thurik AR, Timpson NJ, Tiemeier H, Uitterlinden AG, Vollenweider P, Wagner GG, Weir DR, Yang J, Conley DC, Smith GD, Hofman A, Johannesson M, Laibson DI, Medland SE, Meyer MN, Pickrell JK, Esko T, Krueger RF, Beauchamp JP, Koellinger PD, Benjamin DJ, Bartels M, Cesarini D },
url = {http://www.ncbi.nlm.nih.gov/pubmed/?term=Genetic+variants+associated+with+subjective+well-being%2C+depressive+symptoms%2C+and+neuroticism+identified+through+genome-wide+analyses},
year = {2016},
date = {2016-04-18},
journal = {Nature Genetics},
abstract = {Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.},
keywords = {11425, depression, genetics, neuroticism},
pubstate = {published},
tppubtype = {article}
}

@article{Smith2016,
title = {Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci.},
author = {DJ Smith, V Escott-Price, G Davies, ME Bailey, L Colodro-Conde, J Ward, A Vedernikov, R Marioni, B Cullen, D Lyall, SP Hagenaars, DC Liewald,M Luciano,CR Gale, SJ Ritchie, C Hayward, B Nicholl, B Bulik-Sullivan,M Adams, B Couvy-Duchesne,N Graham,D Mackay,J Evans, BH Smith, DJ Porteous, SE Medland, NG Martin, P Holmans, AM McIntosh, JP Pell, IJ Deary, MC O'Donovan.},
year = {2016},
date = {2016-04-12},
journal = {Molecular Psychiatry - Nature},
abstract = {Neuroticism is a personality trait of fundamental importance for psychological well-being and public health. It is strongly associated with major depressive disorder (MDD) and several other psychiatric conditions. Although neuroticism is heritable, attempts to identify the alleles involved in previous studies have been limited by relatively small sample sizes. Here we report a combined meta-analysis of genome-wide association study (GWAS) of neuroticism that includes 91 370 participants from the UK Biobank cohort, 6659 participants from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and 8687 participants from a QIMR (Queensland Institute of Medical Research) Berghofer Medical Research Institute (QIMR) cohort. All participants were assessed using the same neuroticism instrument, the Eysenck Personality Questionnaire-Revised (EPQ-R-S) Short Form's Neuroticism scale. We found a single-nucleotide polymorphism-based heritability estimate for neuroticism of ∼15% (s.e.=0.7%). Meta-analysis identified nine novel loci associated with neuroticism. The strongest evidence for association was at a locus on chromosome 8 (P=1.5 × 10-15) spanning 4 Mb and containing at least 36 genes. Other associated loci included interesting candidate genes on chromosome 1 (GRIK3 (glutamate receptor ionotropic kainate 3)), chromosome 4 (KLHL2 (Kelch-like protein 2)), chromosome 17 (CRHR1 (corticotropin-releasing hormone receptor 1) and MAPT (microtubule-associated protein Tau)) and on chromosome 18 (CELF4 (CUGBP elav-like family member 4)). We found no evidence for genetic differences in the common allelic architecture of neuroticism by sex. By comparing our findings with those of the Psychiatric Genetics Consortia, we identified a strong genetic correlation between neuroticism and MDD and a less strong but significant genetic correlation with schizophrenia, although not with bipolar disorder. Polygenic risk scores derived from the primary UK Biobank sample captured ∼1% of the variance in neuroticism in the GS:SFHS and QIMR samples, although most of the genome-wide significant alleles identified within a UK Biobank-only GWAS of neuroticism were not independently replicated within these cohorts. The identification of nine novel neuroticism-associated loci will drive forward future work on the neurobiology of neuroticism and related phenotypes.Molecular Psychiatry advance online publication, 12 April 2016; doi:10.1038/mp.2016.49.},
keywords = {6553, genetics, neuroticism},
pubstate = {published},
tppubtype = {article}
}

@article{Lyall2016,
title = {Low birth weight and features of neuroticism and mood disorder in 83 545 participants of the UK Biobank cohort},
author = {Donald M. Lyall, Hazel M. Inskip, Daniel Mackay, Ian J. Deary, Andrew M. McIntosh, Matthew Hotopf, Tony Kendrick, Jill P. Pell, Daniel J. Smith},
url = {http://bjpo.rcpsych.org/content/2/1/38},
year = {2016},
date = {2016-01-27},
journal = {British Journal of Psychiatry Open},
abstract = {Background Low birth weight has been inconsistently associated with risk of developing affective disorders, including major depressive disorder (MDD). To date, studies investigating possible associations between birth weight and bipolar disorder (BD), or personality traits known to predispose to affective disorders such as neuroticism, have not been conducted in large cohorts.

Aims To assess whether very low birth weight (<1500 g) and low birth weight (1500–2490 g) were associated with higher neuroticism scores assessed in middle age, and lifetime history of either MDD or BD. We controlled for possible confounding factors.

Method Retrospective cohort study using baseline data on the 83 545 UK Biobank participants with detailed mental health and birth weight data. Main outcomes were prevalent MDD and BD, and neuroticism assessed using the Eysenck Personality Inventory Neuroticism scale - Revised (EPIN-R)

Results Referent to normal birth weight, very low/low birth weight were associated with higher neuroticism scores, increased MDD and BD. The associations between birth weight category and MDD were partially mediated by higher neuroticism.

Conclusions These findings suggest that intrauterine programming may play a role in lifetime vulnerability to affective disorders.},
keywords = {7155, birth weight, neuroticism},
pubstate = {published},
tppubtype = {article}
}