The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
The co-morbidity of anxiety and depression in the perspective of genetic epidemiology. A review of twin and family studies
Open accessAbstract
BACKGROUND: Co-morbidity within anxiety disorders, and between anxiety disorders and depression, is common. According to the theory of Gray and McNaughton, this co-morbidity is caused by recursive interconnections linking the brain regions involved in fear, anxiety and panic and by heritable personality traits such as neuroticism. In other words, co-morbidity can be explained by one disorder being an epiphenomenon of the other and by a partly shared genetic etiology. The aim of this paper is to evaluate the theory of Gray and McNaughton using the results of genetic epidemiological studies. METHOD: Twenty-three twin studies and 12 family studies on co-morbidity are reviewed. To compare the outcomes systematically, genetic and environmental correlations between disorders are calculated for the twin studies and the results from the family studies are summarized according to the method of Klein and Riso. RESULTS: Twin studies show that co-morbidity within anxiety disorders and between anxiety disorders and depression is explained by a shared genetic vulnerability for both disorders. Some family studies support this conclusion, but others suggest that co-morbidity is due to one disorder being an epiphenomenon of the other. CONCLUSIONS: Discrepancies between the twin and family studies seem partly due to differences in used methodology. The theory of Gray and McNaughton that neuroticism is a shared risk factor for anxiety and depression is supported. Further research should reveal the role of recursive interconnections linking brain regions. A model is proposed to simultaneously investigate the influence of neuroticism and recursive interconnections on co-morbidity.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The text we found for this paper looks like another document, so the self-check wasn’t run.
Citations
Cites
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,845
Gray, J. A. (1982) · Behavioral and Brain Sciences · doi:10.1017/s0140525x00013066 · Cited by 4,477
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
Genetic Epidemiology of Major Depression: Review and Meta-Analysis
Sullivan, P. F., Neale, M. C., & Kendler, K. S. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.10.1552 · Cited by 3,431
The Structure of Common Mental Disorders
Krueger, R. F. (1999) · Archives of General Psychiatry · doi:10.1001/archpsyc.56.10.921 · Cited by 1,881
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
Best Estimate of Lifetime Psychiatric Diagnosis
Leckman, J. F. (1982) · Archives of General Psychiatry · doi:10.1001/archpsyc.1982.04290080001001 · Cited by 1,418
Classical twin studies and beyond
Boomsma, D., Busjahn, A., & Peltonen, L. (2002) · Nature Reviews Genetics · doi:10.1038/nrg932 · Cited by 1,105 · cited 2×
“A model is proposed to simultaneously investigate the influence of neuroticism and recursive interconnections on co-morbidity.”
BackgroundMethodSelf-citationKendler, K. S., Hettema, J. M., Butera, F., Gardner, C. O., & Prescott, C. A. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.8.789 · Cited by 966
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
Cited by
Sorted by citations
Items 301–317 of 317
(2010) · Biological Psychiatry · doi:10.1002/9780470689394.refs
van Dyck, R., van Balkom, A. J. L. M., van den Heuvel, O. A., & Middeldorp, C. M. (2014) · Wiley eBooks · doi:10.1002/9781118775349.ch67
Self-citationChildhood development of psychiatric disorders and related traits
Brikell, I., Lichtenstein, P., & Larsson, H. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821514-2.00006-4
Psychiatrie de l'enfant et de l'adolescent
Pop, D.-M., Leckwyck, M. V., & Beutler, H. (2014) · De Boeck Supérieur eBooks · doi:10.3917/dbu.holze.2014.01.0209
Comorbid and Secondary Depression in Child and Adolescent Anxiety
Garvey, R. W., Hiner, M. K., Kelly, C. A., & Andover, M. S. (2022) · Springer eBooks · doi:10.1007/978-3-031-14080-8_11
Hu, L., Ding, X., & Tang, M. (2023) · Journal of Psychiatry and Psychiatric Disorders · doi:10.26502/jppd.2572-519x0194
Lopez, M. L. G., & Pita, P. M. R. (2022) · Universidad Peruana de Ciencias Aplicadas (UPC) · doi:10.19083/tesis/667128
Nomograms based on clinical factors to predict abnormal metabolism of psychotropic drugs
Zhou, S., Hu, X., Zhou, P., Si, J., & Jiang, Y. (2025) · Biomedical Reports · doi:10.3892/br.2025.1961
Sawyers, C. K., Benstock, S. E., Verhulst, B., Straub, L. K., & Hettema, J. M. (2025) · medRxiv · doi:10.1101/2025.08.26.25334447
A Data-Driven Decomposition of Anxiety
Buchmann, A., Hase, A., Ritter, C. J., Müller, S. T., Haynes, M., Huber, S., Ghisleni, C., Tuura, R., & Hasler, G. (2025) · Psychopathology · doi:10.1159/000548258
Schismogenesis in anxiety spectrum disorders: a biopsychosocial perspective
García-Toro, M., & Gómez-Juanes, R. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1667066
Chen, X.-Y., Wang, Y., Chen, L., Liu, Y., Wang, X., Huang, L.-P., Wang, M.-T., & Li, M.-Q. (2026) · Brain Science Advances · doi:10.26599/bsa.2026.905014
Öztürk, G., & Şahin, D. (2026) · Türk Psikoloji Dergisi · doi:10.31828/turkpsikoloji.1719363
Li, S. R., Zheng, R., Liu, H., Zhang, L., Xu, S., & Chen, J. (2026) · Children and Youth Services Review · doi:10.1016/j.childyouth.2026.109147
Florentin, S., Bick, A. S., Azoulay, M., Klein, A., Klein, A., Ben‐Naim, S., Hemo, N. E., Yakirevich-Amir, N., Monk, C., Levin, N., et al. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15155766
Sleep and Psychopathology: Quantitative and Molecular Genetic Research on Comorbidity
Barclay, N. L., & Gregory, A. M. (2014) · Springer eBooks · doi:10.1007/978-1-4614-9509-3_5
McCrea, R. L. (2013) · UCL Discovery (University College London)
Metadata
- Authors
- MIDDELDORP, C. M., CATH, D. C., VAN DYCK, R., & BOOMSMA, D. I.
- Affiliations
- Vrije Universiteit Amsterdam (NL)
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2005-01-05
- Volume
- 35
- Issue
- 5
- Pages
- 611-624
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W2139775379
- Cited by
- 316
- References
- 64
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 13 · 2023: 15 · 2022: 14 · 2021: 19 · 2020: 14 · 2019: 14 · 2018: 12 · 2017: 12 · 2016: 19 · 2015: 22 · 2014: 20 · 2013: 16 · 2012: 14
- FWCI
- 19.95
- Type
- journal article
- Language
- en
- Open access
- green
- research.vu.nl
- Licence
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- ZonMw
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Keywords
- anxiety disorders, depression, comorbidities, neuroticism, heritability, twin studies, family studies, genetic epidemiology
- MeSH terms
- Anxiety, Depression, Family, Humans, Twins, Comorbidity, Twin Studies as Topic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review