Genetic and Environmental Sources of Covariation Between Generalized Anxiety Disorder and Neuroticism
Abstract
OBJECTIVE: The authors examined the sources of covariation between generalized anxiety disorder and the personality trait of neuroticism. Because women have higher levels of neuroticism and twice the risk of lifetime generalized anxiety disorder of men, gender-specific effects were also explored. METHOD: Lifetime generalized anxiety disorder and neuroticism were assessed in more than 8,000 twins from male-male, female-female, and opposite-sex pairs through structured diagnostic interviews. Sex-limited Cholesky structural equation models were used to decompose the correlations between generalized anxiety disorder and neuroticism into genetic and environmental components, including sex-specific factors. RESULTS: Genetic correlations between generalized anxiety disorder and neuroticism were high and differed (nonsignificantly) between men and women (1.00 and 0.58, respectively). When nonsignificant gender differences were removed from the models, correlations between generalized anxiety disorder and neuroticism were estimated at 0.80 (95% confidence interval=0.52-1.00). The individual-specific environmental correlation between generalized anxiety disorder and neuroticism was estimated at 0.20 for both genders. CONCLUSIONS: There is substantial overlap between the genetic factors that influence individual variation in neuroticism and those that increase liability for generalized anxiety disorder, irrespective of gender. The life experiences that increase vulnerability to generalized anxiety disorder, however, have only modest overlap with those that contribute to an individual's level of neuroticism.
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Individuals with neuroticism tend to be more prone to developing anxiety.
“Individuals with neuroticism tend to be more prone to developing anxiety [30,31,32].”
From The Effect of Anxiety and Nutritional Habits on the Body Distortion of Athletes. (2025) · cites this paper as [31]
Cites
Akaike, H. (1987) · Psychometrika · doi:10.1007/bf02294359 · Cited by 5,264 · see citing works
Lesch, K.-P., Bengel, D., Heils, A., Sabol, S. Z., Greenberg, B. D., Petri, S., Benjamin, J., Müller, C. R., Hamer, D. H., & Murphy, D. L. (1996) · Science · doi:10.1126/science.274.5292.1527 · Cited by 5,162 · see citing works
Akaike, H. (1987) · Springer Series in Statistics · doi:10.1007/978-1-4612-1694-0_29 · Cited by 4,027 · see citing works
Methodology for Genetic Studies of Twins and Families
Neale, M. C., & Cardon, L. R. (1992) · doi:10.1007/978-94-015-8018-2 · Cited by 4,005 · see citing works
Influence of extraversion and neuroticism on subjective well-being: Happy and unhappy people.
Costa, P. T., & McCrae, R. R. (1980) · Journal of Personality and Social Psychology · doi:10.1037//0022-3514.38.4.668 · Cited by 2,648 · see citing works
Personality and Individual Differences: A Natural Science Approach
Eysenck, H. J., & Eysenck, M. W. (1985) · Medical Entomology and Zoology · Cited by 1,848 · see citing works
A Review and Meta-Analysis of the Genetic Epidemiology of Anxiety Disorders
Hettema, J. M., Neale, M. C., & Kendler, K. S. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.10.1568 · Cited by 1,563 · see citing works
Genes and environment in personality development
Loehlin, J. C. (1992) · DigitalGeorgetown (Georgetown University Library) · Cited by 799 · see citing works
Major Depression and Generalized Anxiety Disorder: Same Genes, (Partly) Different Environments?
Kendler, K. S. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820090044008 · Cited by 773 · see citing works
Genes, culture, and personality : an empirical approach
Eaves, L. J., Eysenck, H. J., & Martin, N. G. (1989) · Cited by 637 · see citing works
A Population-Based Twin Study of Lifetime Major Depression in Men and Women
Kendler, K. S., & Prescott, C. A. (1999) · Archives of General Psychiatry · doi:10.1001/archpsyc.56.1.39 · Cited by 512 · see citing works
Self-citationA Population-Based Twin Study of Major Depression in Women
Kendler, K. S. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820040009001 · Cited by 451 · see citing works
Genetic covariation between neuroticism and the symptoms of anxiety and depression
Jardine, R., Martin, N. G., Henderson, A. S., & Rao, D. C. (1984) · Genetic Epidemiology · doi:10.1002/gepi.1370010202 · Cited by 351 · see citing works
The power of the classical twin study to resolve variation in threshold traits
Neale, M., Eaves, L., & Kendler, K. (1994) · Behavior Genetics · doi:10.1007/bf01067191 · Cited by 328 · see citing works
The empirical basis of generalized anxiety disorder
Brown, T. A., Barlow, D. H., & Liebowitz, M. R. (1994) · American Journal of Psychiatry · doi:10.1176/ajp.151.9.1272 · Cited by 311 · see citing works
Neuroticism, major depression and gender: a population-based twin study
Fanous, A. H., GARDNER, C. O., Prescott, C. A., Cancro, R., & Kendler, K. S. (2002) · Psychological Medicine · doi:10.1017/s003329170200541x · Cited by 308 · see citing works
The diagnostic validity of anxiety disorders and their relationship to depressive illness
Breier, A. F., Charney, D. S., & Heninger, G. R. (1985) · American Journal of Psychiatry · doi:10.1176/ajp.142.7.787 · Cited by 243 · see citing works
Lake, R. I. E., Eaves, L. J., MAES, H. H. M., Heath, A. C., & Martin, N. G. (2000) · Behavior Genetics · doi:10.1023/a:1001918408984 · Cited by 223 · see citing works
Toward a definition of generalized anxiety disorder as an anxious temperament type
Akiskal, H. S. (1998) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1998.tb05969.x · Cited by 201 · see citing works
Fullerton, J. M., Cubin, M., Tiwari, H. K., Wang, C., Bomhra, A., Davidson, S. I., Miller, S., Fairburn, C. G., Goodwin, G. M., Neale, M. C., et al. (2003) · The American Journal of Human Genetics · doi:10.1086/374178 · Cited by 179 · see citing works
Sex differences and non-additivity in the effects of genes on personality
Eaves, L. J., Heath, A. C., Neale, M. C., Hewitt, J. K., & Martin, N. G. (1998) · Twin Research · doi:10.1375/twin.1.3.131 · Cited by 143 · see citing works
A Population-Based Twin Study of Generalized Anxiety Disorder in Men and Women
Hettema, J. M., Prescott, C. A., & Kendler, K. S. (2001) · The Journal of Nervous and Mental Disease · doi:10.1097/00005053-200107000-00001 · Cited by 135 · see citing works
Foley, D. L., Neale, M. C., & Kendler, K. S. (1998) · Psychological Medicine · doi:10.1017/s0033291798006977 · Cited by 71 · see citing works
Kirk, K. M., Birley, A. J., Statham, D. J., Haddon, B., Lake, R. I. E., Andrews, J. G., & Martin, N. G. (2000) · Twin Research · doi:10.1375/twin.3.4.299 · Cited by 65 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Brown, T. A., & Barlow, D. H. (2009) · Psychological Assessment · doi:10.1037/a0016608 · Cited by 639 · see citing works
“Extensive evidence indicates these constructs are strongly heritable (e.g., Fanous, Gardner, Prescott, Cancro, & Kendler, 2002; Fulker, 1981; Hettema, Prescott, & Kendler, 2004; Tellegen et al., 1988; Viken, Rose, Kaprio, & Koskenvuo, 1994) and stable over time (Costa & McCrae, 1988; Kasch,…”
A Population-Based Twin Study of the Relationship Between Neuroticism and Internalizing Disorders
Hettema, J. M., Neale, M. C., Myers, J., Prescott, C. A., & Kendler, K. S. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.5.857 · Cited by 633 · see citing works
“Consistent with this, our prior bivariate analysis of neuroticism and generalized anxiety disorder produced findings that did not strongly depend on the stringency of the definition used (7).”
BackgroundResultThe error-related negativity (ERN) and psychopathology: Toward an endophenotype
Olvet, D. M., & Hajcak, G. (2008) · Clinical Psychology Review · doi:10.1016/j.cpr.2008.07.003 · Cited by 574 · see citing works
Beesdo, K., Pine, D. S., Lieb, R., & Wittchen, H.-U. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.177 · Cited by 494 · see citing works
Munafò, M. R., Yalcin, B., Willis-Owen, S. A., & Flint, J. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.04.006 · Cited by 441 · see citing works
A major role for common genetic variation in anxiety disorders
Purves, K. L., Coleman, J. R. I., Meier, S. M., Rayner, C., Davis, K. A. S., Cheesman, R., Bækvad‐Hansen, M., Børglum, A. D., Cho, S. W., Deckert, J., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0559-1 · Cited by 412 · see citing works
The Serotonin-1A Receptor in Anxiety Disorders
Akimova, E., Lanzenberger, R. R., & Kasper, S. F. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.03.012 · Cited by 360 · see citing works
Jylhä, P., & Isometsä, E. (2006) · Depression and Anxiety · doi:10.1002/da.20167 · Cited by 355 · see citing works
“, 1983; Xie and Wu, 2003], the dimension of neuroticism alone in twins [Hettema et al., 2004; Martin et al., 1988] and in the general population [Henderson et al.”
BackgroundResultInfluentialKendler, K. S., Gardner, C. O., Gatz, M., & Pedersen, N. L. (2006) · Psychological Medicine · doi:10.1017/s0033291706009135 · Cited by 325 · see citing works
“Of particular interest is the personality trait of N, which has been shown to be a strong risk factor for both MD (e.g. Hirschfeld et al. 1989; Boyce et al. 1991; Kendler et al. 1993) and GAD (Hettema et al. 2004).”
BackgroundWilamowska, Z. A., Thompson-Hollands, J., Fairholme, C. P., Ellard, K. K., Farchione, T. J., & Barlow, D. H. (2010) · Depression and Anxiety · doi:10.1002/da.20735 · Cited by 314 · see citing works
Brown, T. A. (2007) · Journal of Abnormal Psychology · doi:10.1037/0021-843x.116.2.313 · Cited by 306 · see citing works
Tyrer, P., & Baldwin, D. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69865-6 · Cited by 404 · see citing works
Mennin, D. S., McLaughlin, K. A., & Flanagan, T. J. (2009) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2009.04.006 · Cited by 293 · see citing works
What is the genetic relationship between anxiety and depression?
Hettema, J. M. (2008) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.30171 · Cited by 207 · see citing works
Genetics of generalized anxiety disorder and related traits
Gottschalk, M. G., & Domschke, K. (2017) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2017.19.2/kdomschke · Cited by 194 · see citing works
Goldberg, D. P., Krueger, R. F., Andrews, G., & Hobbs, M. J. (2009) · Psychological Medicine · doi:10.1017/s0033291709990298 · Cited by 184 · see citing works
“Kendler et al. 2003). The Kendler group report that the internalizing genetic risk factor is composed of discrete but intercorrelated factors : one for anxious-misery with major depressive disorder (MDD) and GAD, and the other a fear risk factor with phobic disorders. Panic loaded moderately on the first genetic risk…”
MethodResultHettema, J. M., An, S., Neale, M. C., Bukszár, J., van den Oord, E. J. C. G., Kendler, K. S., & Chen, X. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001845 · Cited by 175 · see citing works
Strober, M., Freeman, R., Lampert, C., & Diamond, J. (2007) · International Journal of Eating Disorders · doi:10.1002/eat.20429 · Cited by 149 · see citing works
Influence of RGS2 on Anxiety-Related Temperament, Personality, and Brain Function
Smoller, J. W., Paulus, M. P., Fagerness, J. A., Purcell, S., Yamaki, L. H., Hirshfeld‐Becker, D. R., Biederman, J., Rosenbaum, J. F., Gelernter, J. E., & Stein, M. B. (2008) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2007.48 · Cited by 148 · see citing works
“Prior studies suggest that introversion is more specifically related to BI and social anxiety,(44,50,54,55) whereas neuroticism appears to be a nonspecific risk factor for depression and anxiety disorders (especially generalized anxiety disorder).(56,57) Although neuroticism mainly captures negative emotionality and w…”
Backgroundvan den Oord, E. J. C. G., Kuo, P., Hartmann, A. M., Webb, B. T., Möller, H., Hettema, J. M., Giegling, I., Bukszár, J., & Rujescu, D. (2008) · Archives of General Psychiatry · doi:10.1001/archpsyc.65.9.1062 · Cited by 131 · see citing works
Selective mutism and social anxiety disorder: All in the family?
CHAVIRA, D. A., SHIPON-BLUM, E., HITCHCOCK, C., COHAN, S., & STEIN, M. B. (2007) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/chi.0b013e318149366a · Cited by 127 · see citing works
“In both clinical and general population studies, neuroticism has been identified as a risk factor for anxiety (Hettema et al., 2004; Jylha and Isometsa, 2006).”
BackgroundPregabalin for the treatment of generalized anxiety disorder: an update
Baldwin, D. S., Ajel, Nowak, Rafiq, & Masdrakis, V. G. (2013) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s36453 · Cited by 125 · see citing works
“GAD shares a common heritability with major depression(16) and with the personality trait of “neuroticism”.(17,18) The 5-hydroxtryptamine (5-HT; serotonin) transporter gene-linked polymorphic region short/short genotype is more frequent in patients with GAD,(19) and variations in two sub-types of the glutamic acid dec…”
The nosologic relationship between generalized anxiety disorder and major depression
Hettema, J. M. (2008) · Depression and Anxiety · doi:10.1002/da.20491 · Cited by 119 · see citing works
Personality and anxiety disorders
Brandes, M., & Bienvenu, O. J. (2006) · Current Psychiatry Reports · doi:10.1007/s11920-006-0061-8 · Cited by 118 · see citing works
Symptom-level modelling unravels the shared genetic architecture of anxiety and depression
Thorp, J. G., Campos, A. I., Grotzinger, A. D., Gerring, Z. F., An, J., Ong, J., Wang, W., Shringarpure, S., Byrne, E. M., MacGregor, S., et al. (2021) · Nature Human Behaviour · doi:10.1038/s41562-021-01094-9 · Cited by 108 · see citing works
Brown, T. A., & Rosellini, A. J. (2011) · Journal of Abnormal Psychology · doi:10.1037/a0023035 · Cited by 108 · see citing works
Carpenter, W. T., Bustillo, J. R., Thaker, G. K., van Os, J., Krueger, R. F., & Green, M. J. (2009) · Psychological Medicine · doi:10.1017/s0033291709990286 · Cited by 99 · see citing works
Secondary depression in severe anxiety disorders: a population-based cohort study in Denmark
Meier, S. M., Petersen, L., Mattheisen, M., Mors, O., Mortensen, P. B., & Laursen, T. M. (2015) · The Lancet Psychiatry · doi:10.1016/s2215-0366(15)00092-9 · Cited by 98 · see citing works
A longitudinal etiologic model for symptoms of anxiety and depression in women
Kendler, K., & Gardner, C. (2011) · Psychological Medicine · doi:10.1017/s0033291711000225 · Cited by 95 · see citing works
“Consistent with prior studies (Kendler et al. 1993, 2006 ; Hettema et al. 2004), these risk factors were substantially correlated.”
ResultInteractions between child and parent temperament and child behavior problems
Rettew, D. C., Stanger, C., McKee, L. G., Doyle, A., & Hudziak, J. J. (2006) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2005.12.008 · Cited by 91 · see citing works
“Similarly, the interactions do not contradict the importance of the genetic influence of these temperamental traits [43] or their shared genes with certain psychiatric disorders [44].”
BackgroundMennin, D. S., Heimberg, R. G., Fresco, D. M., & Ritter, M. R. (2008) · Depression and Anxiety · doi:10.1002/da.20493 · Cited by 91 · see citing works
“Indeed, studies indicate that neuroticism is highly genetically related to both GAD [Hettema et al., 2004] and MDD [Fanous et al.”
BackgroundMolecular genetics of anxiety in mice and men
Hovatta, I., & Barlow, C. (2008) · Annals of Medicine · doi:10.1080/07853890701747096 · Cited by 90 · see citing works
“The personality trait neuroticism, as defined by the Eysenck Personality Questionnaire (EPQ) (7), has been shown to have considerable overlap with anxiety disorders, both with anxiety symptoms (8,9) and clinical disorders (10,11).”
Methodvan der Heiden, C., Melchior, K., Muris, P., Bouwmeester, S., Bos, A., & van der Molen, H. (2010) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2009.12.005 · Cited by 93 · see citing works
Animal models of gene–environment interactions in schizophrenia
Ayhan, Y., Sawa, A., Ross, C. A., & Pletnikov, M. V. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.04.010 · Cited by 87 · see citing works
“There have been numerous studies suggestive of interactions between environmental and genetic factors in schizophrenia [19,22,51,59].”
BackgroundGenome-wide meta-analyses of stratified depression in Generation Scotland and UK Biobank
Hall, L. S., Adams, M. J., Arnau‐Soler, A., Clarke, T., Howard, D. M., Zeng, Y., Davies, G., Hagenaars, S. P., Fernandez-Pujals, A. M., Gibson, J., et al. (2018) · Translational Psychiatry · doi:10.1038/s41398-017-0034-1 · Cited by 84 · see citing works
Personality, Preoperative Anxiety, and Postoperative Outcomes: A Review
Ji, W., Sang, C., Zhang, X., Zhu, K., & Bo, L. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph191912162 · Cited by 95 · see citing works
“[46] found that the genes that influence neuroticism also influence the risk of generalized anxiety disorder.”
BackgroundBrown, T. A., & Naragon‐Gainey, K. (2012) · Behavior Therapy · doi:10.1016/j.beth.2012.11.002 · Cited by 86 · see citing works
Hansell, N. K., Wright, M. J., Medland, S. E., Davenport, T. A., Wray, N. R., Martin, N. G., & Hickie, I. B. (2011) · Psychological Medicine · doi:10.1017/s0033291711002431 · Cited by 87 · see citing works
A Genome-Wide Association Study of Neuroticism in a Population-Based Sample
Calboli, F. C. F., Tozzi, F., Galwey, N. W., Antoniades, A., Mooser, V., Preisig, M., Vollenweider, P., Waterworth, D. M., Waeber, G., Johnson, M. R., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011504 · Cited by 85 · see citing works
Significant correlation in linkage signals from genome-wide scans of schizophrenia and schizotypy
Fanous, A. H., Neale, M. C., Gardner, C. O., Webb, B. T., Straub, R. E., O’Neill, F. A., Walsh, D., Riley, B. P., & Kendler, K. S. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001996 · Cited by 85 · see citing works
Rettew, D. C., Vink, J. M., Willemsen, G. A. H. M., Doyle, A., Hudziak, J. J., & Boomsma, D. I. (2006) · Twin Research and Human Genetics · doi:10.1375/183242706776403028 · Cited by 82 · see citing works
Surtees, P. G., Wainwright, N. W. J., Willis‐Owen, S. A. G., Sandhu, M. S., Luben, R., Day, N., & Jonathan Flint, C. (2006) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2006.01.004 · Cited by 82 · see citing works
Gupta, P., Galimberti, M., Liu, Y., Beck, S., Wingo, A. P., Wingo, T. S., Adhikari, K., Kranzler, H. R., Program, V. M. V., Stein, M. B., et al. (2024) · Nature Human Behaviour · doi:10.1038/s41562-024-01951-3 · Cited by 100 · see citing works
“A list of lead independent SNPs found in the AFR sample for each trait is provided in Supplementary Tables 1–5.”
Structure of internalising symptoms in early adulthood
Fergusson, D. M., Horwood, L. J., & Boden, J. M. (2006) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.106.022384 · Cited by 78 · see citing works
“…methods for classifying internalising disorders and for understanding the aetiological processes that underlie these disorders (Kendler et al, 1992; Brown et al, 1998; Kovacs & Devlin, 1998; Krueger et al, 1998; Krueger, 1999; Hudson et al, 2003; Lilienfeld, 2003; Hettema et al, 2004; Clark, 2005).”
BackgroundMethodMikolajewski, A. J., Allan, N. P., Hart, S. A., Lonigan, C. J., & Taylor, J. E. (2012) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-012-9681-0 · Cited by 76 · see citing works
“Although there is limited research examining young samples, several studies have examined the common genetic and environmental influences of neuroticism (a personality construct similar to negative affect) and internalizing disorders in adults (Hettema et al. 2004, 2006; Jardine et al. 1984).”
A General Population Twin Study of the CBCL/6-18 DSM-Oriented Scales
Spatola, C. A. M., Fagnani, C., Pesenti‐Gritti, P., Ogliari, A. L., Stazi, M., & Battaglia, M. (2007) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/chi.0b013e3180335b12 · Cited by 74 · see citing works
Risk factors predict post-traumatic stress disorder differently in men and women
Christiansen, D. M., & Elklit, A. (2008) · Annals of General Psychiatry · doi:10.1186/1744-859x-7-24 · Cited by 74 · see citing works
Cortisol and ACTH responses to the Dex/CRH Test: Influence of temperament
Tyrka, A. R., Wier, L. M., Price, L. H., Rikhye, K., Ross, N. S., Anderson, G. M., Wilkinson, C. W., & Carpenter, L. L. (2008) · Hormones and Behavior · doi:10.1016/j.yhbeh.2007.12.004 · Cited by 71 · see citing works
“…et al., 2006b; Rosenbaum et al., 1988), they share genetic risk factors with mood and anxiety disorders (Fanous et al., 2002; Hettema et al., 2006; Hettema et al., 2004; Kendler et al., 1993a; Nash et al., 2004; Sen et al., 2004; Smoller et al., 2003; Smoller et al., 2005), and they are…”
BackgroundThe heritability of perceived stress
Federenko, I. S., Schlotz, W., Kirschbaum, C., Bartels, M., Hellhammer, D. H., & Wüst, S. (2006) · Psychological Medicine · doi:10.1017/s0033291705006616 · Cited by 70 · see citing works
“In support of this argument, a high covariance attributable to additive genetic factors was observed in a study of the sources of covariance between neuroticism and generalized anxiety disorder, which is characterized by excessive chronic worry in multiple areas of life (Hettema et al. 2004).”
BackgroundAging faster: worry and rumination in late life are associated with greater brain age
Karim, H., Ly, M., Yu, G. Z., Krafty, R., Tudorascu, D., Aizenstein, H., & Andreescu, C. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.01.009 · Cited by 66 · see citing works
“Anxiety and its disorders encompass multiple clinical constructs such as worry, rumination, and somatization (Zebb and Beck, 1998) and are highly comorbid with both depression and neuroticism (Clark et al., 1994; Hettema et al., 2004, 2006).”
Genetic contributions to anxiety disorders: where we are and where we are heading
Ask, H., Cheesman, R., Jami, E. S., Levey, D. F., Purves, K. L., & Weber, H. (2021) · Psychological Medicine · doi:10.1017/s0033291720005486 · Cited by 72 · see citing works
Baker, E. K., & Richdale, A. L. (2017) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-017-3042-3 · Cited by 68 · see citing works
Olvet, D. M., & Hajcak, G. (2011) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsr007 · Cited by 65 · see citing works
“Both neuroticism (Kendler et al., 1993; Hettema et al., 2004; Ormel et al., 2004) and an increased ERN (Gehring et al.”
BackgroundRosellini, A. J., & Brown, T. A. (2019) · Psychological Assessment · doi:10.1037/pas0000649 · Cited by 64 · see citing works
Emotional Intelligence, Health, and Stress
Matthews, G., Zeidner, M., & Roberts, R. D. (2017) · Wiley eBooks · doi:10.1002/9781118993811.ch18 · Cited by 63 · see citing works
Bifactor Models of Religious and Spiritual Struggles: Distinct from Religiousness and Distress
Stauner, N., Exline, J. J., Grubbs, J. B., Pargäment, K. I., Bradley, D., & Uzdavines, A. (2016) · Religions · doi:10.3390/rel7060068 · Cited by 66 · see citing works
“This construct shares heritable influences with anxiety [71].”
BackgroundThe Developmental Psychopathology of Worry
Kertz, S. J., & Woodruff‐Borden, J. (2011) · Clinical Child and Family Psychology Review · doi:10.1007/s10567-011-0086-3 · Cited by 60 · see citing works
Nes, R. B., Røysamb, E., Reichborn‐Kjennerud, T., Harris, J. R., & Tambs, K. (2007) · Twin Research and Human Genetics · doi:10.1375/twin.10.3.450 · Cited by 61 · see citing works
“…a considerable overlap between genetic factors for N and genetic factors associated with internalizing disorders (Hettema et al., 2006) such as MD (Fanous et al., 2002 ) and GAD (Hettema et al., 2004), as well as between N and subthreshold symptoms of anxiety and depression (Jardine et al., 1984).”
BackgroundInfluentialGeneralized Anxiety Disorder: Revisited
Showraki, M., Showraki, T., & Brown, K. (2020) · Psychiatric Quarterly · doi:10.1007/s11126-020-09747-0 · Cited by 58 · see citing works
Mackintosh, M., Gatz, M., Wetherell, J. L., & Pedersen, N. L. (2006) · Twin Research and Human Genetics · doi:10.1375/183242706776402902 · Cited by 53 · see citing works
Jylhä, P. J., Melartin, T. K., & Isometsä, E. T. (2008) · Journal of Affective Disorders · doi:10.1016/j.jad.2008.06.011 · Cited by 55 · see citing works
“, 1991) studies, and for anxiety disorders in prospective epidemiological studies (Hettema et al., 2004; Kendler et al., 2007; Moffitt et al., 2007).”
Backgroundde Bruin, G. O., Rassin, E., & Muris, P. (2006) · Journal of Psychopathology and Behavioral Assessment · doi:10.1007/s10862-006-9029-6 · Cited by 54 · see citing works
“As such, it is not surprising that neuroticism is thought to be closely related to worry and GAD (Brown, Chorpita, & Barlow, 1998; Hettema, Prescott, & Kendler, 2004; Keogh, French, & Reidy, 1998; Steptoe & Kearsley, 1990).”
BackgroundNeuroticism and stress: the role of displacement behavior
Mohiyeddini, C., Bauer, S., & Semple, S. (2015) · Anxiety Stress & Coping · doi:10.1080/10615806.2014.1000878 · Cited by 53 · see citing works
Ahmadzadeh, Y. I., Schoeler, T., Han, M., Pingault, J., Creswell, C., & McAdams, T. A. (2021) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2020.12.037 · Cited by 53 · see citing works
Emotional Consequences of Finasteride: Fool’s Gold
Ganzer, C. A., & Jacobs, A. R. (2016) · American Journal of Men s Health · doi:10.1177/1557988316631624 · Cited by 51 · see citing works
Xia, J., He, Q., Li, Y., Xie, D., Zhu, S., Chen, J., Shen, Y., Zhang, N., Wei, Y., Chen, C., et al. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.06.053 · Cited by 50 · see citing works
“, 2002) which also contributes to the correlation between MDD and anxiety disorders (Hettema et al., 2004; Hettema et al., 2006; Jardine et al., 1984; Kendler et al., 2007).”
BackgroundIdentifying interactions between genes and early environment in the mouse
Carola, V., Frazzetto, G., & Gross, C. T. (2005) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2005.00152.x · Cited by 50 · see citing works
“…et al. 1999; Chapman et al. 2004; Kendler et al. 2000), and studies taking into account interactions between environmental and genetic factors have been more successful in predicting disease susceptibility (Caspi et al. 2002; Caspi et al. 2003; Gross & Hen 2004; Hettema et al. 2004; Kendler 2001).”
BackgroundChristiansen, D., & Elklit, A. (2012) · Post Traumatic Stress Disorders in a Global Context · doi:10.5772/28363 · Cited by 56 · see citing works
“disorders, including depression and anxiety disorders (Hettema et al., 2004; Kendler et al., 2004).”
BackgroundElklit, A., & Blum, A. (2010) · British Journal of Clinical Psychology · doi:10.1348/014466510x527676 · Cited by 48 · see citing works
Spinhoven, P., de Rooij, M., Heiser, W. J., Smit, J. H., & Penninx, B. W. J. H. (2009) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2009.05.002 · Cited by 47 · see citing works
“Because Neuroticism may be heritable [36–38] and may account for the onset, overlap and course of depression and anxiety [22], the possibility of a common genetic liability between Neuroticism and comorbid internalized disorders seems a promising avenue for further research [39,40].”
BackgroundHink, L. K., Rhee, S. H., Corley, R. P., Cosgrove, V. E., Hewitt, J. K., Schulz‐Heik, R. J., Lahey, B. B., & Waldman, I. D. (2013) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-013-9730-3 · Cited by 46 · see citing works
“…studies have demonstrated common genetic influences between neuroticism and psychiatric disorders (Carey and DiLalla 1994; Fanous et al. 2002; Hettema et al. 2004; Hettema et al. 2006; Jardine et al. 1984; Kendler et al. 2007; Mackinnon et al. 1990; Singh and Waldman 2010) and between…”
BackgroundSoskin, D. P., Carl, J. R., Alpert, J. E., & D, M. F. M. (2012) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2012.00318.x · Cited by 44 · see citing works
“Twin studies have found a high degree of overlap between the genetic factors thought to underlie high NA, measured as neuroticism, and anxiety and depressive disorders [25,26].”
BackgroundLeyfer, O. T., Gallo, K. P., Cooper‐Vince, C. E., & Pincus, D. B. (2013) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2013.01.010 · Cited by 45 · see citing works
Lundell, I. W., Poromaa, I. S., Ekselius, L., Georgsson, S., Frans, Ö., Helström, L., Högberg, U., & Svanberg, A. S. (2017) · BMC Women s Health · doi:10.1186/s12905-017-0417-8 · Cited by 41 · see citing works
“The findings is in accordance with previous studies indicating that high scores of Neuroticism is associated with PTSD [13, 16, 23] especially in women [22, 38].”
ResultRettew, D. C., Doyle, A., Kwan, M., Stanger, C., & Hudziak, J. J. (2006) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2006.02.002 · Cited by 41 · see citing works
“A large twin study conducted in Australia (Jardine, Martin, & Henderson, 1984) reported the genetic correlation between neuroticism and anxiety to be approximately .8. Hettema, Prescott, and Kendler (2004) recently found evidence that not only is there a high degree of correlation between neuroticism and generalized a…”
BackgroundNeurobiology of Generalized Anxiety Disorder
Stein, M. B. (2009) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.s.7002.03 · Cited by 41 · see citing works
The many faces of anxiety-neurobiological correlates of anxiety phenotypes
Andreescu, C., Mennin, D. S., Tudorascu, D., Sheu, L. K., Walker, S. E., Banihashemi, L., & Aizenstein, H. J. (2015) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2015.08.013 · Cited by 40 · see citing works
“Additionally, personality traits such as neuroticism are highly comorbid with anxiety disorders (Clark et al., 1994; Hettema et al., 2004, 2006).”
BackgroundImaging Genomics Applied to Anxiety, Stress Response, and Resiliency
Xu, K., Monique Ernst, D., & Goldman, D. A. (2006) · Neuroinformatics · doi:10.1385/ni:4:1:51 · Cited by 37 · see citing works
“Anxiety is a heritable complex trait in humans (Stevenson et al., 1992; Eley, 1999; Eley et al., 2003; Hettema et al., 2004) and other species including nonhuman primates and rodents (Williamson et al.”
BackgroundTian, L., Jiang, S., & Huebner, E. S. (2018) · School Psychology · doi:10.1037/spq0000257 · Cited by 35 · see citing works
Mohammadkhani, P., Abasi, I., Pourshahbaz, A., Mohammadi, A., & Fatehi, M. (2016) · Iranian Journal of Psychiatry and Behavioral Sciences · doi:10.17795/ijpbs-5047 · Cited by 36 · see citing works
“While difficulties in emotion regulation and maladaptive emotion regulation strategies contribute to emotional disorders, personality traits such as neuroticism may also play a pivotal role in etiology and maintenance of emotional disorders (29, 30).”
BackgroundIs the Generalized Anxiety Disorder Symptom of Worry Just Another Form of Neuroticism?
Hale, W. W., Klimstra, T. A., & Meeus, W. (2010) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.09m05506blu · Cited by 33 · see citing works
Self-rated importance of religion predicts one-year outcome of patients with panic disorder
Bowen, R., Baetz, M., & D’Arcy, C. (2006) · Depression and Anxiety · doi:10.1002/da.20157 · Cited by 33 · see citing works
“Anxiety symptoms were the target of treatment, and worry and stress are more directly associated with anxiety and phobias than with depression [Hettema et al., 2004].”
The effects of personality traits on quality of life
Bal, M. D., & Şahin, N. H. (2011) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0b013e31821e2494 · Cited by 32 · see citing works
“Studies have shown that women who have neurotic personality traits are much more vulnerable to both depression(6,7,16) and anxiety.(17,18) In similar studies, it was determined that there is a strong relationship between depression and neuroticism(8,15,19) and a moderate relationship(15) between depression and introve…”
BackgroundAragam, N., Wang, K.-S., Anderson, J. L., & Liu, X. (2012) · Journal of Molecular Neuroscience · doi:10.1007/s12031-012-9931-1 · Cited by 32 · see citing works
“Neuroticism also has genetic covariance with depression and anxiety (Jardine et al. 1984; Kendler et al. 1992, 1993; Fanous et al. 2002; Hettema et al. 2004; Hueazo-Diaz et al. 2005; Hettema et al. 2006b).”
BackgroundFamily Matters: Happiness in Nuclear Families and Twins
Nes, R. B., Czajkowski, N., & Tambs, K. (2010) · Behavior Genetics · doi:10.1007/s10519-010-9365-x · Cited by 41 · see citing works
“2002) and generalised anxiety disorder (Hettema et al. 2004) as well as for neuroticism and subthreshold symptoms of anxiety and depression (Jardine et al.”
BackgroundAnxiety symptoms in obsessive-compulsive disorder and generalized anxiety disorder
Citkowska-Kisielewska, A., Rutkowski, K., Sobański, J. A., Dembińska, E., & Mielimąka, M. (2019) · Psychiatria Polska · doi:10.12740/pp/105378 · Cited by 30 · see citing works
“…different anxiety disorders is believed to be a clinical sign of common etiopathogenetic factors, including a common genetic and neurobiological background, expressed in such features as the domination of negative affect, ‛neuroticism’, avoidance of threats, or ‛intolerance of uncertainty’ [8–11].”
Hidalgo, R. B., & Sheehan, D. V. (2012) · Handbook of clinical neurology · doi:10.1016/b978-0-444-52002-9.00019-x · Cited by 28 · see citing works
Scheuringer, A., Lundin, C., Derntl, B., Pletzer, B. A., & Poromaa, I. S. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.104544 · Cited by 28 · see citing works
Common mental health disorders.
Bessant, M., & Ekers, D. (2011) · PubMed · Cited by 28 · see citing works
New Approaches to the Genetic Analysis of Neuroticism and Anxiety
Fullerton, J. M. (2005) · Behavior Genetics · doi:10.1007/s10519-005-9000-4 · Cited by 27 · see citing works
“Neuroticism manifests at one extreme as anxiety, depression, moodiness, low self-esteem, and diffidence (Cloninger, 1994; Digman, 1990; Dreary and Matthews, 1993; Loehlin and Nichols, 1976; Zuckerman et al., 1988), and genetic susceptibility to neuroticism is shared with two other common psychiatric disorders, major d…”
BackgroundChavira, D. A., Stein, M. B., Golinelli, D., Sherbourne, C. D., Craske, M. G., Sullivan, G., Bystritsky, A., & Roy‐Byrne, P. (2009) · The Journal of Nervous and Mental Disease · doi:10.1097/nmd.0b013e3181b97d4d · Cited by 26 · see citing works
“In both clinical and general population studies alike, neuroticism has been identified as a risk factor for Axis I and Axis II disorders (Hettema et al., 2004; Jylha and Isometsa, 2006; Miller and Pilkonis, 2006).”
BackgroundMinoretti, P., Politi, P., Martinelli, V., Emanuele, E., Bertona, M., Falcone, C., & Geroldi, D. (2006) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2006.01.001 · Cited by 26 · see citing works
“Neuroticism is also known to possess good psychometric properties of item and construct validity, stability, and cross-cultural validation [21].”
BackgroundIs it Generalized Anxiety Disorder or Poverty? An Examination of Poor Mothers and Their Children
Baer, J. C., Kim, M., & Wilkenfeld, B. F. (2012) · Child and Adolescent Social Work Journal · doi:10.1007/s10560-012-0263-3 · Cited by 26 · see citing works
A longitudinal examination of psychosocial impairment across the anxiety disorders
Naragon‐Gainey, K., Gallagher, M. W., & Brown, T. A. (2013) · Psychological Medicine · doi:10.1017/s0033291713001967 · Cited by 26 · see citing works
“…that GAD may be the ‘basic emotional disorder’ (e.g. Brown et al. 1998) because it is largely isomorphic with neuroticism, a trait that is closely associated with co-morbidity among the mood and anxiety disorders (e.g. Hettema et al. 2004; Watson et al. 2005; Weinstock & Whisman, 2006).”
BackgroundNeuroimaging and Human Genetics
Winterer, G., Hariri, A. R., Goldman, D. A., & Weinberger, D. R. (2005) · International review of neurobiology · doi:10.1016/s0074-7742(05)67010-9 · Cited by 26 · see citing works
Bailey, J. S., Grabowski-Boase, L., Steffy, B. M., Wiltshire, T., Churchill, G. A., & Tarantino, L. M. (2008) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2008.00415.x · Cited by 25 · see citing works
“A clear genetic basis for neuroticism, the personality dimension most highly correlated with anxiety-related disorders, exists as well, and the genetic factors associated with both exhibit substantial overlap (Hettema et al. 2004; Jardine et al. 1984; Kendler et al. 1993).”
BackgroundStress-Induced and Fear Circuitry Disorders: Refining the Research Agenda for DSM-V
Charney, D. S., Sirovatka, P. J., & Regier, D. A. (2008) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9780890427750 · Cited by 25 · see citing works
Franz, C. E., York, T. P., Eaves, L. J., Prom‐Wormley, E. C., Jacobson, K. C., Lyons, M. J., Grant, M. D., Xian, H., Panizzon, M. S., Jimenez, E., et al. (2011) · Behavior Genetics · doi:10.1007/s10519-010-9428-z · Cited by 24 · see citing works
“The heritability estimates of the personality trait of neuroticism/ negative emotionality (variously defined) range from 30 to 60% and may be higher in men than in women (Eaves et al. 1998; Hettema et al. 2004; Jang et al. 1996; Kendler et al. 2006a, b).”
BackgroundSpinhoven, P., Elzinga, B. M., Karin Roelofs, A., Hovens, J. G. F. M., van Oppen, P., Zitman, F. G., & Penninx, B. W. J. H. (2011) · The Journal of Nervous and Mental Disease · doi:10.1097/nmd.0b013e318229d21f · Cited by 24 · see citing works
“, 1994) may both be heritable (e.g., Fanous et al., 2002; Hettema et al., 2004; Viken et al., 1994) and account not only for the onset and course of depression but also for its recurrence.”
BackgroundA translational approach to the genetics of anxiety disorders
McGregor, N. W., Dimatelis, J. J., van Zyl, P. J., Hemmings, S. M. J., Kinnear, C. J., Russell, V. A., Stein, D. J., & Löchner, C. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.12.030 · Cited by 24 · see citing works
- Authors
- Hettema, J. M., Prescott, C. A., & Kendler, K. S.
- Affiliations
- Virginia Commonwealth University (US)
- Venue
- American Journal of Psychiatry
- Published
- 2004-09-01
- Volume
- 161
- Issue
- 9
- Pages
- 1581-1587
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2079459508
- Cited by
- 224
- References
- 24
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 5 · 2021: 13 · 2020: 6 · 2019: 12 · 2018: 6 · 2017: 9 · 2016: 4 · 2015: 8 · 2014: 4 · 2013: 8 · 2012: 11
- FWCI
- 16.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA009095, AA-09095)
- National Institute of Mental Health (K08MH066277, R01MH040828, MH 40828, MH/AA/DA-49492)
- National Institute on Drug Abuse (DA11287, R01DA011287)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Personality Traits and Psychology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- generalized anxiety disorder, neuroticism, personality traits, genetic correlation, environmental correlation, sex differences, twin studies, heritability
- MeSH terms
- Adult, Anxiety Disorders, Diseases in Twins, Female, Humans, Male, Middle Aged, Models, Genetic, Neurotic Disorders, Personality, Personality Inventory, Phenotype, Psychiatric Status Rating Scales, Risk Factors, Sex Factors, Social Environment, Twins, Dizygotic, Twins, Monozygotic, Genetic Variation, Genetic Predisposition to Disease
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