Hostname: page-component-78c5997874-t5tsf Total loading time: 0 Render date: 2024-11-10T07:19:01.149Z Has data issue: false hasContentIssue false

Genetic contributions to anxiety disorders: where we are and where we are heading

Published online by Cambridge University Press:  09 February 2021

Helga Ask*
Affiliation:
Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway
Rosa Cheesman
Affiliation:
PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
Eshim S. Jami
Affiliation:
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands Department of Clinical, Educational and Health Psychology, Division of Psychology and Language Sciences, University College London, London, UK
Daniel F. Levey
Affiliation:
Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, Connecticut
Kirstin L. Purves
Affiliation:
Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
Heike Weber
Affiliation:
Department of Psychology, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
*
Author for correspondence: Helga Ask, E-mail: helga.ask@fhi.no

Abstract

Anxiety disorders are among the most common psychiatric disorders worldwide. They often onset early in life, with symptoms and consequences that can persist for decades. This makes anxiety disorders some of the most debilitating and costly disorders of our time. Although much is known about the synaptic and circuit mechanisms of fear and anxiety, research on the underlying genetics has lagged behind that of other psychiatric disorders. However, alongside the formation of the Psychiatric Genomic Consortium Anxiety workgroup, progress is rapidly advancing, offering opportunities for future research.

Here we review current knowledge about the genetics of anxiety across the lifespan from genetically informative designs (i.e. twin studies and molecular genetics). We include studies of specific anxiety disorders (e.g. panic disorder, generalised anxiety disorder) as well as those using dimensional measures of trait anxiety. We particularly address findings from large-scale genome-wide association studies and show how such discoveries may provide opportunities for translation into improved or new therapeutics for affected individuals. Finally, we describe how discoveries in anxiety genetics open the door to numerous new research possibilities, such as the investigation of specific gene–environment interactions and the disentangling of causal associations with related traits and disorders.

We discuss how the field of anxiety genetics is expected to move forward. In addition to the obvious need for larger sample sizes in genome-wide studies, we highlight the need for studies among young people, focusing on specific underlying dimensional traits or components of anxiety.

Type
Invited Review
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

All authors contributed equally to this work.

References

American Psychiatric Association. (2013a). Diagnostic and statistical manual of mental disorders (5th ed.). American Psychiatric Association. https://doi.org/10.1176/appi.books.9780890425596Google Scholar
Andero, R., Choi, D. C., & Ressler, K. J. (2014). BDNF-TrkB receptor regulation of distributed adult neural plasticity, memory formation, and psychiatric disorders. Progress in Molecular Biology and Translational Science, 122, 169192. https://doi.org/10.1016/B978-0-12-420170-5.00006-4CrossRefGoogle ScholarPubMed
Askew, C., & Field, A. P. (2008). The vicarious learning pathway to fear 40 years on. Clinical Psychology Review, 28(7), 12491265. https://doi.org/10.1016/j.cpr.2008.05.003CrossRefGoogle Scholar
Balamotis, M. A., Tamberg, N., Woo, Y. J., Li, J., Davy, B., Kohwi-Shigematsu, T., & Kohwi, Y. (2012). Satb1 ablation alters temporal expression of immediate early genes and reduces dendritic spine density during postnatal brain development. Molecular and Cellular Biology, 32(2), 333347. https://doi.org/10.1128/MCB.05917-11CrossRefGoogle ScholarPubMed
Bandelow, B., Michaelis, S., & Wedekind, D. (2017). Treatment of anxiety disorders. Dialogues in Clinical Neuroscience, 19(2), 93107.Google ScholarPubMed
Bandyopadhyay, B., Chanda, V., & Wang, Y. (2017). Finding the sources of missing heritability within rare variants through simulation. Bioinformatics and Biology Insights, 11, 1177932217735096. https://doi.org/10.1177/1177932217735096CrossRefGoogle ScholarPubMed
Beesdo, K., Knappe, S., & Pine, D. S. (2009). Anxiety and anxiety disorders in children and adolescents: Developmental issues and implications for DSM-V. The Psychiatric Clinics of North America, 32(3), 483524. https://doi.org/10.1016/j.psc.2009.06.002CrossRefGoogle ScholarPubMed
Belsky, J. (2016). The differential susceptibility hypothesis. JAMA Pediatrics, 170(4), 321. https://doi.org/10.1001/jamapediatrics.2015.4263CrossRefGoogle ScholarPubMed
Benke, K. S., Nivard, M. G., Velders, F. P., Walters, R. K., Pappa, I., Scheet, P. A., … Early Genetics and Lifecourse Epidemiology Consortium. (2014). A genome-wide association meta-analysis of preschool internalizing problems. Journal of the American Academy of Child and Adolescent Psychiatry, 53(6), 667676. e7. https://doi.org/10.1016/j.jaac.2013.12.028CrossRefGoogle ScholarPubMed
Bourrat, P., Lu, Q., & Jablonka, E. (2017). Why the missing heritability might not be in the DNA. Bioessays: News and Reviews in Molecular, Cellular and Developmental Biology, 39(7), 1700067. https://doi.org/10.1002/bies.201700067.CrossRefGoogle Scholar
Breen, G., Li, Q., Roth, B. L., O'Donnell, P., Didriksen, M., Dolmetsch, R., … Edenberg, H. J. (2016). Translating genome-wide association findings into new therapeutics for psychiatry. Nature Neuroscience, 19(11), 13921396. https://doi.org/10.1038/nn.4411CrossRefGoogle ScholarPubMed
Bulik-Sullivan, B., Loh, P.-R., Finucane, H. K., Ripke, S., Yang, J., Schizophrenia Working Group of the Psychiatric Genomics Consortium, Patterson, N., … Neale, B. M. (2015). LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nature Genetics, 47(3), 291295. h https://doi.org/10.1038/ng.3211.CrossRefGoogle ScholarPubMed
Burgess, S., Bowden, J., Fall, T., Ingelsson, E., & Thompson, S. G. (2017). Sensitivity analyses for robust causal inference from mendelian randomization analyses with multiple genetic variants. Epidemiology (Cambridge, Mass.), 28(1), 3042. https://doi.org/10.1097/EDE.0000000000000559CrossRefGoogle ScholarPubMed
Cai, N., Kendler, K., & Flint, J. (2018). Minimal phenotyping yields GWAS hits of low specificity for major depression. BioRxiv. https://doi.org/10.1101/440735Google Scholar
Celano, C. M., Daunis, D. J., Lokko, H. N., Campbell, K. A., & Huffman, J. C. (2016). Anxiety disorders and cardiovascular disease. Current Psychiatry Reports, 18(11), 101. https://doi.org/10.1007/s11920-016-0739-5CrossRefGoogle ScholarPubMed
Cheesman, R., Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Purves, K. L., Pingault, J.-B., Breen, G., Rijsdij, K. F., Plomin, R., & Eley, T. C. (2018). Extracting stability increases the SNP heritability of emotional problems in young people. Translational Psychiatry, 8(1), 223. https://doi.org/10.1038/s41398-018-0269-5CrossRefGoogle ScholarPubMed
Cheesman, R., Rayner, C., & Eley, T. (2019). The genetic basis of child and adolescent anxiety. In Compton, SN, Villabø, MA, & Kristensen (Eds), Pediatric anxiety disorders (pp. 1746). London: Elsevier. https://doi.org/10.1016/B978-0-12-813004-9.00003-7.CrossRefGoogle Scholar
Choi, K. W., Chen, C.-Y., Stein, M. B., Klimentidis, Y. C., Wang, M.-J., Koenen, K. C., Smoller, J. W., & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. (2019). Assessment of bidirectional relationships between physical activity and depression Among adults: A 2-sample mendelian randomization study. JAMA Psychiatry, 76(4), 399408. https://doi.org/10.1001/jamapsychiatry.2018.4175CrossRefGoogle ScholarPubMed
Coleman, J. R. I., Lester, K. J., Keers, R., Roberts, S., Curtis, C., Arendt, K., … Eley, T. C. (2016). Genome-wide association study of response to cognitive-behavioural therapy in children with anxiety disorders. The British Journal of Psychiatry, 209(3), 236243. https://doi.org/10.1192/bjp.bp.115.168229CrossRefGoogle ScholarPubMed
Coleman, J. R. I., Peyrot, W. J., Purves, K. L., Davis, K. A. S., Rayner, C., Choi, S. W., … Breen, G. (2020). Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK biobank. Molecular Psychiatry, 25(7), 14301446. https://doi.org/10.1038/s41380-019-0546-6CrossRefGoogle ScholarPubMed
Correia, C. T., Coutinho, A. M., Sequeira, A. F., Sousa, I. G., Lourenço Venda, L., Almeida, J. P., … Vicente, A. M. (2010). Increased BDNF levels and NTRK2 gene association suggest a disruption of BDNF/TrkB signaling in autism. Genes, Brain, and Behavior, 9(7), 841848. https://doi.org/10.1111/j.1601-183X.2010.00627.xCrossRefGoogle ScholarPubMed
Costello, E. J., Mustillo, S., Erkanli, A., Keeler, G., & Angold, A. (2003). Prevalence and development of psychiatric disorders in childhood and adolescence. Archives of General Psychiatry, 60(8), 837844. https://doi.org/10.1001/archpsyc.60.8.837CrossRefGoogle ScholarPubMed
Craske, M. G. (2003). Why more women than men?. In Craske, MG (Ed.), Origins of phobias and anxiety disorders (pp. 175203). Oxford: Elsevier. https://doi.org/10.1016/B978-008044032-3/50008-3.CrossRefGoogle Scholar
Craske, M. G., Rauch, S. L., Ursano, R., Prenoveau, J., Pine, D. S., & Zinbarg, R. E. (2009). What is an anxiety disorder? Depression and Anxiety, 26(12), 10661085. https://doi.org/10.1002/da.20633CrossRefGoogle ScholarPubMed
Craske, M. G., Stein, M. B., Eley, T. C., Milad, M. R., Holmes, A., Rapee, R. M., & Wittchen, H.-U. (2017). Anxiety disorders. Nature Reviews. Disease Primers, 3, 17024. https://doi.org/10.1038/nrdp.2017.24CrossRefGoogle ScholarPubMed
Crocq, M.-A. (2015). A history of anxiety: From Hippocrates to DSM. Dialogues in Clinical Neuroscience, 17(3), 319325.Google ScholarPubMed
Davies, N. M., Howe, L. J., Brumpton, B., Havdahl, A., Evans, D. M., & Davey Smith, G. (2019). Within family mendelian randomization studies. Human Molecular Genetics, 28(R2), R170R179. https://doi.org/10.1093/hmg/ddz204CrossRefGoogle ScholarPubMed
Davies, M. N., Verdi, S., Burri, A., Trzaskowski, M., Lee, M., Hettema, J. M., … Spector, T. D. (2015). Generalised anxiety disorder – A twin study of genetic architecture, genome-wide association and differential gene expression. Plos One, 10(8), e0134865. https://doi.org/10.1371/journal.pone.0134865CrossRefGoogle ScholarPubMed
Deckert, J., & Erhardt, A. (2019). Predicting treatment outcome for anxiety disorders with or without comorbid depression using clinical, imaging and (epi)genetic data. Current Opinion in Psychiatry, 32(1), 16. https://doi.org/10.1097/YCO.0000000000000468CrossRefGoogle ScholarPubMed
Deckert, J., Weber, H., Villmann, C., Lonsdorf, T. B., Richter, J., Andreatta, M., … Reif, A. (2017). GLRB Allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: A potential neurogenetic pathway to panic disorder. Molecular Psychiatry, 22(10), 14311439. https://doi.org/10.1038/mp.2017.2CrossRefGoogle ScholarPubMed
de Lijster, J. M., Dierckx, B., Utens, E. M. W. J., Verhulst, F. C., Zieldorff, C., Dieleman, G. C., & Legerstee, J. S. (2017). The age of onset of anxiety disorders. Canadian Journal of Psychiatry, 62(4), 237246. https://doi.org/10.1177/0706743716640757CrossRefGoogle Scholar
Demange, , et al. (2020). Parental influences on offspring education: indirect genetic effects of non-cognitive skills. Biorxiv. https://doi.org/10.1101/2020.09.15.296236CrossRefGoogle Scholar
Dick, D. M., Barr, P. B., Cho, S. B., Cooke, M. E., Kuo, S. I.-C., Lewis, T. J., … Su, J. (2018). Post-GWAS in psychiatric genetics: A developmental perspective on the “other” next steps. Genes, Brain, and Behavior, 17(3), e12447. https://doi.org/10.1111/gbb.12447CrossRefGoogle ScholarPubMed
Domschke, K., & Deckert, J. (2012). Genetics of anxiety disorders - status quo and quo vadis. Current Pharmaceutical Design, 18(35), 56915698. https://doi.org/10.2174/138161212803530781CrossRefGoogle Scholar
Duncan, L. E., Ostacher, M., & Ballon, J. (2019). How genome-wide association studies (GWAS) made traditional candidate gene studies obsolete. Neuropsychopharmacology, 44(9), 15181523. https://doi.org/10.1038/s41386-019-0389-5CrossRefGoogle ScholarPubMed
Dunn, E. C., Sofer, T., Gallo, L. C., Gogarten, S. M., Kerr, K. F., Chen, C.-Y., … Smoller, J. W. (2017). Genome-wide association study of generalized anxiety symptoms in the hispanic community health study/study of latinos. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 174(2), 132143. https://doi.org/10.1002/ajmg.b.32448CrossRefGoogle ScholarPubMed
Eaves, L., Silberg, J., & Erkanli, A. (2003). Resolving multiple epigenetic pathways to adolescent depression. Journal of Child Psychology and Psychiatry, 44(7), 10061014. https://doi.org/10.1111/1469-7610.00185CrossRefGoogle ScholarPubMed
Eley, T. C. (2014). The future of therapygenetics: Where will studies predicting psychological treatment response from genomic markers lead? Depression and Anxiety, 31(8), 617620. https://doi.org/10.1002/da.22292CrossRefGoogle ScholarPubMed
Erhardt, A., Akula, N., Schumacher, J., Czamara, D., Karbalai, N., Müller-Myhsok, B., … Binder, E. B. (2012). Replication and meta-analysis of TMEM132D gene variants in panic disorder. Translational Psychiatry, 2, e156. https://doi.org/10.1038/tp.2012.85CrossRefGoogle ScholarPubMed
Erhardt, A., Czibere, L., Roeske, D., Lucae, S., Unschuld, P. G., Ripke, S., … Binder, E. B. (2011). TMEM132D, A new candidate for anxiety phenotypes: Evidence from human and mouse studies. Molecular Psychiatry, 16(6), 647663. https://doi.org/10.1038/mp.2010.41CrossRefGoogle ScholarPubMed
Erskine, H. E., Moffitt, T. E., Copeland, W. E., Costello, E. J., Ferrari, A. J., Patton, G., … Scott, J. G. (2015). A heavy burden on young minds: The global burden of mental and substance use disorders in children and youth. Psychological Medicine, 45(7), 15511563. https://doi.org/10.1017/S0033291714002888CrossRefGoogle Scholar
Field, A. P., Argyris, N. G., & Knowles, K. A. (2001). Who's afraid of the big bad wolf: A prospective paradigm to test Rachman's indirect pathways in children. Behaviour Research and Therapy, 39(11), 12591276. https://doi.org/10.1016/S0005-7967(00)00080-2CrossRefGoogle ScholarPubMed
Forstner, A. J., Awasthi, S., Wolf, C., Maron, E., Erhardt, A., Czamara, D., … Schumacher, J. (2019). Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression. Molecular Psychiatry. https://doi.org/10.1038/s41380-019-0590-2Google ScholarPubMed
Franić, S., Middeldorp, C. M., Dolan, C. V., Ligthart, L., & Boomsma, D. I. (2010). Childhood and adolescent anxiety and depression: Beyond heritability. Journal of the American Academy of Child and Adolescent Psychiatry, 49(8), 820829. https://doi.org/10.1016/j.jaac.2010.05.013CrossRefGoogle ScholarPubMed
Fraser, A., Macdonald-Wallis, C., Tilling, K., Boyd, A., Golding, J., Davey Smith, G., … Lawlor, D. A. (2013). Cohort profile: The Avon Longitudinal Study of parents and children: ALSPAC mothers cohort. International Journal of Epidemiology, 42(1), 97110. https://doi.org/10.1093/ije/dys066CrossRefGoogle ScholarPubMed
Freud, S. (1959). Inhibitions, symptoms and anxiety. In Strachey, J. (Ed.), The standard edition of the complete psychological works of Sigmund Freud (Vol. 20, pp. 87131). London: The Hogarth Press. (Original work published 1926).Google Scholar
Gandy, M., Sharpe, L., Perry, K. N., Miller, L., Thayer, Z., Boserio, J., & Mohamed, A. (2013). Rates of DSM-IV mood, anxiety disorders, and suicidality in Australian adult epilepsy outpatients: A comparison of well-controlled versus refractory epilepsy. Epilepsy & Behavior, 26(1), 2935. https://doi.org/10.1016/j.yebeh.2012.10.023CrossRefGoogle ScholarPubMed
GBD 2017 Disease and Injury Incidence and Prevalence Collaborators (2018). Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. The Lancet, 392(10159), 17891858. https://doi.org/10.1016/S0140-6736(18)32279-7CrossRefGoogle Scholar
Gregersen, N. O., Lescai, F., Liang, J., Li, Q., Als, T., Buttenschøn, H. N., … Demontis, D. (2016). Whole-exome sequencing implicates DGKH as a risk gene for panic disorder in the Faroese population. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 171(8), 10131022. https://doi.org/10.1002/ajmg.b.32464CrossRefGoogle ScholarPubMed
Hannigan, L. J., Askeland, R. B., Ask, H., Tesli, M., Corfield, E., Ayorech, Z., … Havdahl, A. (2020). Genetic liability for schizophrenia and childhood psychopathology in the general population. MedRxiv. https://doi.org/10.1101/2020.05.01.20086215Google Scholar
Hannigan, L. J., Walaker, N., Waszczuk, M. A., McAdams, T. A., & Eley, T. C. (2017). Aetiological influences on stability and change in emotional and behavioural problems across development: A systematic review. Psychopathology Review, 4(1), 52108. https://doi.org/10.5127/pr.038315CrossRefGoogle ScholarPubMed
Hernández Blázquez, M., & Cruzado, J. A. (2016). A longitudinal study on anxiety, depressive and adjustment disorder, suicide ideation and symptoms of emotional distress in patients with cancer undergoing radiotherapy. Journal of Psychosomatic Research, 87, 1421. https://doi.org/10.1016/j.jpsychores.2016.05.010CrossRefGoogle ScholarPubMed
Hettema, J. M., Neale, M. C., & Kendler, K. S. (2001). A review and meta-analysis of the genetic epidemiology of anxiety disorders. The American Journal of Psychiatry, 158(10), 15681578. https://doi.org/10.1176/appi.ajp.158.10.1568CrossRefGoogle ScholarPubMed
Hettema, J. M., Prescott, C. A., & Kendler, K. S. (2004). Genetic and environmental sources of covariation between generalized anxiety disorder and neuroticism. The American Journal of Psychiatry, 161(9), 15811587. https://doi.org/10.1176/appi.ajp.161.9.1581CrossRefGoogle ScholarPubMed
Hettema, J. M., Prescott, C. A., Myers, J. M., Neale, M. C., & Kendler, K. S. (2005). The structure of genetic and environmental risk factors for anxiety disorders in men and women. Archives of General Psychiatry, 62(2), 182189. https://doi.org/10.1001/archpsyc.62.2.182CrossRefGoogle ScholarPubMed
Hettema, J. M., Verhulst, B., Chatzinakos, C., Bacanu, S.-A., Chen, C.-Y., Ursano, R. J., … Stein, M. B. (2020). Genome-wide association study of shared liability to anxiety disorders in Army STARRS. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 183(4), 197207. https://doi.org/10.1002/ajmg.b.32776CrossRefGoogle ScholarPubMed
Hirschfeld, R. M. A. (2001). The comorbidity of major depression and anxiety disorders: Recognition and management in primary care. Primary Care Companion to the Journal of Clinical Psychiatry, 3(6), 244254. https://doi.org/10.4088/pcc.v03n0609CrossRefGoogle ScholarPubMed
Howard, D. M., Adams, M. J., Clarke, T.-K., Hafferty, J. D., Gibson, J., Shirali, M., … McIntosh, A. M. (2019). Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nature Neuroscience, 22(3), 343352. https://doi.org/10.1038/s41593-018-0326-7CrossRefGoogle ScholarPubMed
Jami, E. S., Hammerschlag, A. R., Ip, H. F., Allegrini, A. G., Benyamin, B., Border, R., … Middeldorp, C. M. (2020). Genome-wide association meta-analysis of childhood and adolescent internalising symptoms. MedRxiv, 2020.09.11.20175026.Google Scholar
Jones, H. J., Martin, D., Lewis, S. J., Davey Smith, G., O'Donovan, M. C, Owen, M. J., … Zammit, S. (2020). A Mendelian randomization study of the causal association between anxiety phenotypes and schizophrenia. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 183(6), 360369. http://dx.doi.org/10.1002/ajmg.b.v183.6.CrossRefGoogle Scholar
Kaabi, B., Gelernter, J., Woods, S. W., Goddard, A., Page, G. P., & Elston, R. C. (2006). Genome scan for loci predisposing to anxiety disorders using a novel multivariate approach: Strong evidence for a chromosome 4 risk locus. American Journal of Human Genetics, 78(4), 543553. https://doi.org/10.1086/501072CrossRefGoogle ScholarPubMed
Kawamura, Y., Otowa, T., Koike, A., Sugaya, N., Yoshida, E., Yasuda, S., … Sasaki, T. (2011). A genome-wide CNV association study on panic disorder in a Japanese population. Journal of Human Genetics, 56(12), 852856. https://doi.org/10.1038/jhg.2011.117CrossRefGoogle Scholar
Keers, R., Coleman, J. R. I., Lester, K. J., Roberts, S., Breen, G., Thastum, M., … Eley, T. C. (2016). A genome-wide test of the differential susceptibility hypothesis reveals a genetic predictor of differential response to psychological treatments for child anxiety disorders. Psychotherapy and Psychosomatics, 85(3), 146158. https://doi.org/10.1159/000444023CrossRefGoogle ScholarPubMed
Kendler, K. S., Eaves, L. J., Loken, E. K., Pedersen, N. L., Middeldorp, C. M., Reynolds, C., … Gardner, C. O. (2011). The impact of environmental experiences on symptoms of anxiety and depression across the life span. Psychological Science, 22(10), 13431352. https://doi.org/10.1177/0956797611417255CrossRefGoogle ScholarPubMed
Kendler, K. S., Gardner, C. O., Gatz, M., & Pedersen, N. L. (2007). The sources of co-morbidity between major depression and generalized anxiety disorder in a Swedish national twin sample. Psychological Medicine, 37(3), 453462. https://doi.org/10.1017/S0033291706009135CrossRefGoogle Scholar
Kendler, K. S., Jacobson, K. C., Myers, J., & Prescott, C. A. (2002). Sex differences in genetic and environmental risk factors for irrational fears and phobias. Psychological Medicine, 32(2), 209217. https://doi.org/10.1017/s003329170100513xCrossRefGoogle ScholarPubMed
Kessler, R. C., Aguilar-Gaxiola, S., Alonso, J., Chatterji, S., Lee, S., Ormel, J., … Wang, P. S. (2009). The global burden of mental disorders: An update from the WHO World Mental Health (WMH) surveys. Epidemiologia e Psichiatria Sociale, 18(1), 2333. https://doi.org/10.1017/S1121189X00001421CrossRefGoogle ScholarPubMed
Kessler, R. C., Avenevoli, S., Costello, E. J., Georgiades, K., Green, J. G., Gruber, M. J., … Merikangas, K. R. (2012a). Prevalence, persistence, and sociodemographic correlates of DSM-IV disorders in the National Comorbidity Survey Replication Adolescent Supplement. Archives of General Psychiatry, 69(4), 372380. https://doi.org/10.1001/archgenpsychiatry.2011.160Google Scholar
Kessler, R. C., Chiu, W. T., Demler, O., Merikangas, K. R., & Walters, E. E. (2005). Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry, 62(6), 617627. https://doi.org/10.1001/archpsyc.62.6.617CrossRefGoogle ScholarPubMed
Kessler, R. C., Petukhova, M., Sampson, N. A., Zaslavsky, A. M., & Wittchen, H.-U. (2012b). Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. International Journal of Methods in Psychiatric Research, 21(3), 169184. https://doi.org/10.1002/mpr.1359CrossRefGoogle Scholar
Krueger, R. F. (1999). The structure of common mental disorders. Archives of General Psychiatry, 56(10), 921926. https://doi.org/10.1001/archpsyc.56.10.921CrossRefGoogle ScholarPubMed
Kuhnt, S., Brähler, E., Faller, H., Härter, M., Keller, M., Schulz, H., … Mehnert, A. (2016). Twelve-Month and lifetime prevalence of mental disorders in cancer patients. Psychotherapy and Psychosomatics, 85(5), 289296. https://doi.org/10.1159/000446991CrossRefGoogle ScholarPubMed
Kupfer, D. J. (2015). Anxiety and DSM-5. Dialogues in Clinical Neuroscience, 17(3), 245246.Google ScholarPubMed
Lamb, D. J., Middeldorp, C. M., van Beijsterveldt, C. E. M., Bartels, M., van der Aa, N., Polderman, T. J. C., & Boomsma, D. I. (2010). Heritability of anxious-depressive and withdrawn behavior: Age-related changes during adolescence. Journal of the American Academy of Child and Adolescent Psychiatry, 49(3), 248255. https://doi.org/10.1016/j.jaac.2009.11.014Google ScholarPubMed
Lecrubier, Y. (2007). Widespread underrecognition and undertreatment of anxiety and mood disorders: Results from 3 European studies. The Journal of Clinical Psychiatry, 68(Suppl 2), 3641.Google ScholarPubMed
Lee, W. E., Wadsworth, M. E. J., & Hotopf, M. (2006). The protective role of trait anxiety: A longitudinal cohort study. Psychological Medicine, 36(3), 345351. https://doi.org/10.1017/S0033291705006847CrossRefGoogle ScholarPubMed
Lesko, L. J., & Woodcock, J. (2004). Translation of pharmacogenomics and pharmacogenetics: A regulatory perspective. Nature Reviews. Drug Discovery, 3(9), 763769. https://doi.org/10.1038/nrd1499CrossRefGoogle ScholarPubMed
Lester, K. J., & Eley, T. C. (2013). Therapygenetics: Using genetic markers to predict response to psychological treatment for mood and anxiety disorders. Biology of Mood & Anxiety Disorders, 3(1), 4. https://doi.org/10.1186/2045-5380-3-4CrossRefGoogle ScholarPubMed
Levey, D. F., Gelernter, J., Polimanti, R., Zhou, H., Cheng, Z., Aslan, M., … Stein, M. B. (2020). Reproducible genetic risk loci for anxiety: Results from ~200000 participants in the million veteran program. The American Journal of Psychiatry, 177(3), 223232. https://doi.org/10.1176/appi.ajp.2019.19030256CrossRefGoogle ScholarPubMed
Lewis, A. (1970). The ambiguous word “anxiety”. International Journal of Psychiatry, 9, 6279.Google ScholarPubMed
Loerinc, A. G., Meuret, A. E., Twohig, M. P., Rosenfield, D., Bluett, E. J., & Craske, M. G. (2015). Response rates for CBT for anxiety disorders: Need for standardized criteria. Clinical Psychology Review, 42, 7282. https://doi.org/10.1016/j.cpr.2015.08.004CrossRefGoogle ScholarPubMed
Magnus, P., Birke, C., Vejrup, K., Haugan, A., Alsaker, E., Daltveit, A. K., … Stoltenberg, C. (2016). Cohort profile update: The Norwegian mother and child cohort study (moba). International Journal of Epidemiology, 45(2), 382388. https://doi.org/10.1093/ije/dyw029CrossRefGoogle Scholar
Maron, E., Lan, C.-C., & Nutt, D. (2018). Imaging and genetic approaches to inform biomarkers for anxiety disorders, obsessive-compulsive disorders, and PSTD. Current Topics in Behavioral Neurosciences, 40, 219292. https://doi.org/10.1007/7854_2018_49CrossRefGoogle ScholarPubMed
McAdams, T. A., Gregory, A. M., & Eley, T. C. (2013). Genes of experience: Explaining the heritability of putative environmental variables through their association with behavioural and emotional traits. Behavior Genetics, 43(4), 314328. https://doi.org/10.1007/s10519-013-9591-0CrossRefGoogle ScholarPubMed
McGrath, L. M., Weill, S., Robinson, E. B., Macrae, R., & Smoller, J. W. (2012). Bringing a developmental perspective to anxiety genetics. Development and Psychopathology, 24(4), 11791193. https://doi.org/10.1017/S0954579412000636CrossRefGoogle ScholarPubMed
McLean, C. P., Asnaani, A., Litz, B. T., & Hofmann, S. G. (2011). Gender differences in anxiety disorders: Prevalence, course of illness, comorbidity and burden of illness. Journal of Psychiatric Research, 45(8), 10271035. https://doi.org/10.1016/j.jpsychires.2011.03.006CrossRefGoogle ScholarPubMed
Meier, S. M., & Deckert, J. (2019). Genetics of anxiety disorders. Current Psychiatry Reports, 21(3), 16, 1-8. https://doi.org/10.1007/s11920-019-1002-7CrossRefGoogle ScholarPubMed
Meier, S. M., Mattheisen, M., Mors, O., Mortensen, P. B., Laursen, T. M., & Penninx, B. W. (2016). Increased mortality among people with anxiety disorders: Total population study. The British Journal of Psychiatry, 209(3), 216221. https://doi.org/10.1192/bjp.bp.115.171975CrossRefGoogle ScholarPubMed
Meier, S. M., Trontti, K., Purves, K. L., Als, T. D., Grove, J., Laine, M., … Mors, O. (2019). Genetic variants associated with anxiety and stress-related disorders: A genome-wide association study and mouse-model study. JAMA Psychiatry. https://doi.org/10.1001/jamapsychiatry.2019.1119CrossRefGoogle ScholarPubMed
Miloyan, B., Bulley, A., Bandeen-Roche, K., Eaton, W. W., & Gonçalves-Bradley, D. C. (2016). Anxiety disorders and all-cause mortality: Systematic review and meta-analysis. Social Psychiatry and Psychiatric Epidemiology, 51(11), 14671475. https://doi.org/10.1007/s00127-016-1284-6CrossRefGoogle ScholarPubMed
Montalvo-Ortiz, J. L., Gelernter, J., Hudziak, J., & Kaufman, J. (2016). RDoc and translational perspectives on the genetics of trauma-related psychiatric disorders. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 171B(1), 8191. https://doi.org/10.1002/ajmg.b.32395CrossRefGoogle ScholarPubMed
Morimoto, Y., Ono, S., Kurotaki, N., Imamura, A., & Ozawa, H. (2020). Genetic and epigenetic analyses of panic disorder in the post-GWAS era. Journal of Neural Transmission, 127, 1517-1526. https://doi.org/10.1007/s00702-020-02205-yCrossRefGoogle ScholarPubMed
Morimoto, Y., Shimada-Sugimoto, M., Otowa, T., Yoshida, S., Kinoshita, A., Mishima, H., … Ono, S. (2018). Whole-exome sequencing and gene-based rare variant association tests suggest that PLA2G4E might be a risk gene for panic disorder. Translational Psychiatry, 8(1), 41. https://doi.org/10.1038/s41398-017-0088-0CrossRefGoogle ScholarPubMed
Morneau-Vaillancourt, G., Coleman, J. R. I., Purves, K. L., Cheesman, R., Rayner, C., Breen, G., & Eley, T. C. (2020). The genetic and environmental hierarchical structure of anxiety and depression in the UK biobank. Depression and Anxiety, 37(6), 512520. https://doi.org/10.1002/da.22991CrossRefGoogle ScholarPubMed
Morris, T. T., Davies, N. M., Hemani, G., & Smith, G. D. (2020). Population phenomena inflate genetic associations of complex social traits. Science Advances, 6(16), eaay0328. https://doi.org/10.1126/sciadv.aay0328CrossRefGoogle ScholarPubMed
Nagel, M., Jansen, P. R., Stringer, S., Watanabe, K., de Leeuw, C. A., Bryois, J., … Posthuma, D. (2018a). Meta-analysis of genome-wide association studies for neuroticism in 449484 individuals identify novel genetic loci and pathways. Nature Genetics, 50(7), 920927. https://doi.org/10.1038/s41588-018-0151-7CrossRefGoogle Scholar
Nagel, M., Watanabe, K., Stringer, S., Posthuma, D., & van der Sluis, S. (2018b). Item-level analyses reveal genetic heterogeneity in neuroticism. Nature Communications, 9(1), 905. https://doi.org/10.1038/s41467-018-03242-8CrossRefGoogle Scholar
Neale, M. C., & Cardon, L. R. (1992). Methodology for genetic studies of twins and families. Springer Netherlands. https://doi.org/10.1007/978-94-015-8018-2CrossRefGoogle Scholar
Nepon, J., Belik, S.-L., Bolton, J., & Sareen, J. (2010). The relationship between anxiety disorders and suicide attempts: Findings from the national epidemiologic survey on alcohol and related conditions. Depression and Anxiety, 27(9), 791798. https://doi.org/10.1002/da.20674CrossRefGoogle ScholarPubMed
Nivard, M. G., Dolan, C. V., Kendler, K. S., Kan, K. J., Willemsen, G., van Beijsterveldt, C. E. M., … Boomsma, D. I. (2015a). Stability in symptoms of anxiety and depression as a function of genotype and environment: A longitudinal twin study from ages 3 to 63 years. Psychological Medicine, 45(5), 10391049. https://doi.org/10.1017/S003329171400213XCrossRefGoogle Scholar
Nivard, M. G., Middeldorp, C. M., Dolan, C. V., & Boomsma, D. I. (2015b). Genetic and environmental stability of neuroticism from adolescence to adulthood. Twin Research and Human Genetics, 18(6), 746754. https://doi.org/10.1017/thg.2015.80CrossRefGoogle Scholar
Okbay, A., Baselmans, B. M. L., De Neve, J.-E., Turley, P., Nivard, M. G., Fontana, M. A., … Cesarini, D. (2016). Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nature Genetics, 48(6), 624633. https://doi.org/10.1038/ng.3552CrossRefGoogle ScholarPubMed
Ollendick, T. H., & King, N. J. (1991). Origins of childhood fears: An evaluation of Rachman's theory of fear acquisition. Behaviour Research and Therapy, 29(2), 117123. https://doi.org/10.1016/0005-7967(91)90039-6CrossRefGoogle ScholarPubMed
Ormel, J., Jeronimus, B. F., Kotov, R., Riese, H., Bos, E. H., Hankin, B., … Oldehinkel, A. J. (2013). Neuroticism and common mental disorders: Meaning and utility of a complex relationship. Clinical Psychology Review, 33(5), 686697. https://doi.org/10.1016/j.cpr.2013.04.003CrossRefGoogle ScholarPubMed
Otowa, T., Hek, K., Lee, M., Byrne, E. M., Mirza, S. S., Nivard, M. G., … … Hettema, J. M. (2016). Meta-analysis of genome-wide association studies of anxiety disorders. Molecular Psychiatry, 21(10), 1485. https://doi.org/10.1038/mp.2016.11CrossRefGoogle ScholarPubMed
Otowa, T., Kawamura, Y., Nishida, N., Sugaya, N., Koike, A., Yoshida, E., … Sasaki, T. (2012). Meta-analysis of genome-wide association studies for panic disorder in the Japanese population. Translational Psychiatry, 2, e186. https://doi.org/10.1038/tp.2012.89CrossRefGoogle ScholarPubMed
Otowa, T., Maher, B. S., Aggen, S. H., McClay, J. L., van den Oord, E. J., & Hettema, J. M. (2014). Genome-wide and gene-based association studies of anxiety disorders in European and African American samples. Plos One, 9(11), e112559. https://doi.org/10.1371/journal.pone.0112559CrossRefGoogle ScholarPubMed
Otowa, T., Tanii, H., Sugaya, N., Yoshida, E., Inoue, K., Yasuda, S., … Sasaki, T. (2010). Replication of a genome-wide association study of panic disorder in a Japanese population. Journal of Human Genetics, 55(2), 9196. https://doi.org/10.1038/jhg.2009.127CrossRefGoogle Scholar
Otowa, T., Yoshida, E., Sugaya, N., Yasuda, S., Nishimura, Y., Inoue, K., … Okazaki, Y. (2009). Genome-wide association study of panic disorder in the Japanese population. Journal of Human Genetics, 54(2), 122126. https://doi.org/10.1038/jhg.2008.17CrossRefGoogle ScholarPubMed
Pasquini, M., Biondi, M., Costantini, A., Cairoli, F., Ferrarese, G., Picardi, A., & Sternberg, C. (2006). Detection and treatment of depressive and anxiety disorders among cancer patients: Feasibility and preliminary findings from a liaison service in an oncology division. Depression and Anxiety, 23(7), 441448. https://doi.org/10.1002/da.20198CrossRefGoogle Scholar
Plomin, R. (2014). Genotype-environment correlation in the era of DNA. Behavior Genetics, 44(6), 629638. https://doi.org/10.1007/s10519-014-9673-7CrossRefGoogle ScholarPubMed
Plomin, R., DeFries, J. C., & Loehlin, J. C. (1977). Genotype-environment interaction and correlation in the analysis of human behavior. Psychological Bulletin, 84(2), 309322. https://doi.org/10.1037/0033-2909.84.2.309CrossRefGoogle ScholarPubMed
Plomin, R., Haworth, C. M. A., & Davis, O. S. P. (2009). Common disorders are quantitative traits. Nature Reviews. Genetics, 10(12), 872878. https://doi.org/10.1038/nrg2670CrossRefGoogle ScholarPubMed
Polderman, T. J. C., Benyamin, B., de Leeuw, C. A., Sullivan, P. F., van Bochoven, A., Visscher, P. M., & Posthuma, D. (2015). Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nature Genetics, 47(7), 702709. https://doi.org/10.1038/ng.3285CrossRefGoogle ScholarPubMed
Purves, K. L., Coleman, J. R. I., Meier, S. M., Rayner, C., Davis, K. A. S., Cheesman, R., … Eley, T. C. (2019). A major role for common genetic variation in anxiety disorders. Molecular Psychiatry, 25, 3292-3303. https://doi.org/10.1038/s41380-019-0559-1Google Scholar
Rachman, S. (1977). The conditioning theory of fear acquisition: A critical examination. Behaviour Research and Therapy, 15(5), 375387. https://doi.org/10.1016/0005-7967(77)90041-9CrossRefGoogle ScholarPubMed
Rachman, S. (1990). The determinants and treatment of simple phobias. Advances in Behaviour Research and Therapy, 12(1), 130. https://doi.org/10.1016/0146-6402(90)90005-BCrossRefGoogle Scholar
Rachman, S. (1991). Neo-conditioning and the classical theory of fear acquisition. Clinical Psychology Review, 11(2), 155173. https://doi.org/10.1016/0272-7358(91)90093-ACrossRefGoogle Scholar
Rayner, C., Coleman, J. R. I., Purves, K. L., Cheesman, R., Hübel, C., Gaspar, H., … Eley, T. C. (2019a). Genetic influences on treatment-seeking for common mental health problems in the UK biobank. Behaviour Research and Therapy, 121, 103413. https://doi.org/10.1016/j.brat.2019.103413CrossRefGoogle Scholar
Rayner, C., Coleman, J. R. I., Purves, K. L., Hodsoll, J., Goldsmith, K., Alpers, G. W., … … Eley, T. C. (2019b). A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders. Translational Psychiatry, 9(1), 150. https://doi.org/10.1038/s41398-019-0481-yCrossRefGoogle Scholar
Ressler, K. J. (2020). Translating across circuits and genetics toward progress in fear- and anxiety-related disorders. The American Journal of Psychiatry, 177(3), 214222. https://doi.org/10.1176/appi.ajp.2020.20010055CrossRefGoogle ScholarPubMed
Rice, F., Harold, G. T., & Thapar, A. (2002). Assessing the effects of age, sex and shared environment on the genetic aetiology of depression in childhood and adolescence. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 43(8), 10391051. https://doi.org/10.1111/1469-7610.00231CrossRefGoogle ScholarPubMed
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Ripke, S., Walters, J. T., & O'Donovan, M. C. (2020). Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia. MedRxiv. https://doi.org/10.1101/2020.09.12.20192922Google Scholar
Roberts, S., Wong, C. C. Y., Breen, G., Coleman, J. R. I., De Jong, S., Jöhren, P., … Eley, T. C. (2017). Genome-wide expression and response to exposure-based psychological therapy for anxiety disorders. Translational Psychiatry, 7(8), e1219. https://doi.org/10.1038/tp.2017.177CrossRefGoogle ScholarPubMed
Rosenbaum, J. (2019). New directions in anxiety disorder treatment. General Psychiatry, 32(6), e100166. https://doi.org/10.1136/gpsych-2019-100166CrossRefGoogle ScholarPubMed
Roy, M. A., Neale, M. C., Pedersen, N. L., Mathé, A. A., & Kendler, K. S. (1995). A twin study of generalized anxiety disorder and major depression. Psychological Medicine, 25(5), 10371049. https://doi.org/10.1017/s0033291700037533CrossRefGoogle ScholarPubMed
Savage, J. E., Sawyers, C., Roberson-Nay, R., & Hettema, J. M. (2017). The genetics of anxiety-related negative valence system traits. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 174(2), 156177. https://doi.org/10.1002/ajmg.b.32459CrossRefGoogle ScholarPubMed
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511(7510), 421427. https://doi.org/10.1038/nature13595CrossRefGoogle Scholar
Schumacher, J., Kristensen, A. S., Wendland, J. R., Nöthen, M. M., Mors, O., & McMahon, F. J. (2011). The genetics of panic disorder. Journal of Medical Genetics, 48(6), 361368. https://doi.org/10.1136/jmg.2010.086876CrossRefGoogle ScholarPubMed
Shimada-Sugimoto, M., Otowa, T., & Hettema, J. M. (2015). Genetics of anxiety disorders: Genetic epidemiological and molecular studies in humans. Psychiatry and Clinical Neurosciences, 69(7), 388401. https://doi.org/10.1111/pcn.12291CrossRefGoogle ScholarPubMed
Silberg, J., Rutter, M., Neale, M., & Eaves, L. (2001). Genetic moderation of environmental risk for depression and anxiety in adolescent girls. The British Journal of Psychiatry, 179, 116121. https://doi.org/10.1192/bjp.179.2.116CrossRefGoogle ScholarPubMed
Smith, D. J., Escott-Price, V., Davies, G., Bailey, M. E. S., Colodro-Conde, L., Ward, J., … … O'Donovan, M. C. (2016). Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci. Molecular Psychiatry, 21(6), 749757. https://doi.org/10.1038/mp.2016.49CrossRefGoogle ScholarPubMed
Smoller, J. W. (2016). The genetics of stress-related disorders: PTSD, depression, and anxiety disorders. Neuropsychopharmacology, 41(1), 297319. https://doi.org/10.1038/npp.2015.266CrossRefGoogle ScholarPubMed
Smoller, J. W. (2020). Anxiety genetics goes genomic. The American Journal of Psychiatry, 177(3), 190194. https://doi.org/10.1176/appi.ajp.2020.20010038CrossRefGoogle ScholarPubMed
Smoller, J. W., Andreassen, O. A., Edenberg, H. J., Faraone, S. V., Glatt, S. J., & Kendler, K. S. (2019). Psychiatric genetics and the structure of psychopathology. Molecular Psychiatry, 24(3), 409420. https://doi.org/10.1038/s41380-017-0010-4CrossRefGoogle ScholarPubMed
So, H.-C., Chau, C. K.-L., Chiu, W.-T., Ho, K.-S., Lo, C.-P., Yim, S. H.-Y., & Sham, P.-C. (2017). Analysis of genome-wide association data highlights candidates for drug repositioning in psychiatry. Nature Neuroscience, 20(10), 13421349. https://doi.org/10.1038/nn.4618CrossRefGoogle Scholar
So, H.-C., Chau, C. K.-L., Lau, A., Wong, S.-Y., & Zhao, K. (2019). Translating GWAS findings into therapies for depression and anxiety disorders: Gene-set analyses reveal enrichment of psychiatric drug classes and implications for drug repositioning. Psychological Medicine, 49(16), 26922708. https://doi.org/10.1017/S0033291718003641CrossRefGoogle ScholarPubMed
Spielberger, C. D. (1985). Anxiety, cognition and affect: A state-trait perspective. In Tuma, A. H., & Maser, J. D. (Eds.), Anxiety and the anxiety disorders (pp. 171182). New Jersey: Lawrence Erlbaum Associates, Inc.Google Scholar
Stein, M. B., Chen, C.-Y., Jain, S., Jensen, K. P., He, F., Heeringa, S. G., … Army STARRS Collaborators. (2017). Genetic risk variants for social anxiety. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 174(2), 120131. https://doi.org/10.1002/ajmg.b.32520CrossRefGoogle ScholarPubMed
Strawn, J. R., & Levine, A. (2020). Treatment response biomarkers in anxiety disorders: From neuroimaging to neuronally-derived extracellular vesicles and beyond. Biomarkers in Neuropsychiatry, 3, 100024.CrossRefGoogle ScholarPubMed
Sullivan, P. F., Kendler, K. S., & Neale, M. C. (2003). Schizophrenia as a complex trait: Evidence from a meta-analysis of twin studies. Archives of General Psychiatry, 60(12), 11871192. https://doi.org/10.1001/archpsyc.60.12.1187CrossRefGoogle ScholarPubMed
Sullivan, P. F., Neale, M. C., & Kendler, K. S. (2000). Genetic epidemiology of major depression: Review and meta-analysis. The American Journal of Psychiatry, 157(10), 15521562. https://doi.org/10.1176/appi.ajp.157.10.1552CrossRefGoogle ScholarPubMed
Tam, V., Patel, N., Turcotte, M., Bossé, Y., Paré, G., & Meyre, D. (2019). Benefits and limitations of genome-wide association studies. Nature Reviews. Genetics, 20(8), 467484. https://doi.org/10.1038/s41576-019-0127-1CrossRefGoogle ScholarPubMed
Tambs, K., Czajkowsky, N., Røysamb, E., Neale, M. C., Reichborn-Kjennerud, T., Aggen, S. H., … Kendler, K. S. (2009). Structure of genetic and environmental risk factors for dimensional representations of DSM-IV anxiety disorders. The British Journal of Psychiatry, 195(4), 301307. https://doi.org/10.1192/bjp.bp.108.059485CrossRefGoogle ScholarPubMed
Trzaskowski, M., Eley, T. C., Davis, O. S. P., Doherty, S. J., Hanscombe, K. B., Meaburn, E. L., … Plomin, R. (2013). First genome-wide association study on anxiety-related behaviours in childhood. Plos One, 8(4), e58676. https://doi.org/10.1371/journal.pone.0058676CrossRefGoogle ScholarPubMed
Viana, A. G., Beidel, D. C., & Rabian, B. (2009). Selective mutism: A review and integration of the last 15 years. Clinical Psychology Review, 29(1), 5767. https://doi.org/10.1016/j.cpr.2008.09.009CrossRefGoogle ScholarPubMed
Visscher, P. M., Wray, N. R., Zhang, Q., Sklar, P., McCarthy, M. I., Brown, M. A., & Yang, J. (2017). 10 Years of GWAS discovery: Biology, function, and translation. American Journal of Human Genetics, 101(1), 522. https://doi.org/10.1016/j.ajhg.2017.06.005CrossRefGoogle Scholar
Vukasović, T., & Bratko, D. (2015). Heritability of personality: A meta-analysis of behavior genetic studies. Psychological Bulletin, 141(4), 769785. https://doi.org/10.1037/bul0000017CrossRefGoogle ScholarPubMed
Walter, S., Glymour, M. M., Koenen, K., Liang, L., Tchetgen Tchetgen, E. J., Cornelis, M., … Kubzansky, L. D. (2013). Performance of polygenic scores for predicting phobic anxiety. Plos One, 8(11), e80326. https://doi.org/10.1371/journal.pone.0080326CrossRefGoogle ScholarPubMed
Waszczuk, M. A., Zavos, H. M. S., Gregory, A. M., & Eley, T. C. (2014). The phenotypic and genetic structure of depression and anxiety disorder symptoms in childhood, adolescence, and young adulthood. JAMA Psychiatry, 71(8), 905916. https://doi.org/10.1001/jamapsychiatry.2014.655CrossRefGoogle Scholar
Waszczuk, M. A., Zavos, H. M. S., Gregory, A. M., & Eley, T. C. (2016). The stability and change of etiological influences on depression, anxiety symptoms and their co-occurrence across adolescence and young adulthood. Psychological Medicine, 46(1), 161175. https://doi.org/10.1017/S0033291715001634CrossRefGoogle ScholarPubMed
Watson, D. (2005). Rethinking the mood and anxiety disorders: A quantitative hierarchical model for DSM-V. Journal of Abnormal Psychology, 114(4), 522536. https://doi.org/10.1037/0021-843X.114.4.522CrossRefGoogle ScholarPubMed
Weber, H., Richter, J., Straube, B., Lueken, U., Domschke, K., Schartner, C., … Reif, A. (2016). Allelic variation in CRHR1 predisposes to panic disorder: Evidence for biased fear processing. Molecular Psychiatry, 21(6), 813822. https://doi.org/10.1038/mp.2015.125CrossRefGoogle ScholarPubMed
Wigmore, E. M., Hafferty, J. D., Hall, L. S., Howard, D. M., Clarke, T.-K., Fabbri, C., … McIntosh, A. M. (2020). Genome-wide association study of antidepressant treatment resistance in a population-based cohort using health service prescription data and meta-analysis with GENDEP. The Pharmacogenomics Journal, 20(2), 329341. https://doi.org/10.1038/s41397-019-0067-3CrossRefGoogle Scholar
Wray, N. R., Lin, T., Austin, J., McGrath, J. J., Hickie, I. B., Murray, G. K., … Visscher, P. M. (2020). From basic science to clinical application of polygenic risk scores: A primer. JAMA Psychiatry, 78(1), 101-109. https://doi.org/10.1001/jamapsychiatry.2020.3049Google Scholar
Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., & Bybjerg-Grauholm, J. … et al. the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2018). Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nature Genetics, 50(5), 668681. https://doi.org/10.1038/s41588-018-0090-3CrossRefGoogle ScholarPubMed
Young, A. I., Benonisdottir, S., Przeworski, M., & Kong, A. (2019). Deconstructing the sources of genotype-phenotype associations in humans. Science (New York, N.Y.), 365(6460), 13961400. https://doi.org/10.1126/science.aax3710CrossRefGoogle ScholarPubMed
Zamani, M., Alizadeh-Tabari, S., & Zamani, V. (2019). Systematic review with meta-analysis: The prevalence of anxiety and depression in patients with irritable bowel syndrome. Alimentary Pharmacology & Therapeutics, 50(2), 132143. https://doi.org/10.1111/apt.15325CrossRefGoogle ScholarPubMed
Zavos, H. M. S., Rijsdijk, F. V., Gregory, A. M., & Eley, T. C. (2010). Genetic influences on the cognitive biases associated with anxiety and depression symptoms in adolescents. Journal of Affective Disorders, 124(1–2), 4553. https://doi.org/10.1016/j.jad.2009.10.030CrossRefGoogle ScholarPubMed
Zhang, H.-T., Huang, Y., Masood, A., Stolinski, L. R., Li, Y., Zhang, L., … O'Donnell, J. M. (2008). Anxiogenic-like behavioral phenotype of mice deficient in phosphodiesterase 4B (PDE4B). Neuropsychopharmacology, 33(7), 16111623. https://doi.org/10.1038/sj.npp.1301537CrossRefGoogle Scholar
Zhu, Z., Zheng, Z., Zhang, F., Wu, Y., Trzaskowski, M., Maier, R., … Yang, J. (2018). Causal associations between risk factors and common diseases inferred from GWAS summary data. Nature Communications, 9(1), 224. https://doi.org/10.1038/s41467-017-02317-2CrossRefGoogle ScholarPubMed
Ziegler, C., Grundner-Culemann, F., Schiele, M. A., Schlosser, P., Kollert, L., Mahr, M., … Domschke, K. (2019). The DNA methylome in panic disorder: A case-control and longitudinal psychotherapy-epigenetic study. Translational Psychiatry, 9(1), 314. https://doi.org/10.1038/s41398-019-0648-6CrossRefGoogle ScholarPubMed