Skip to main content Accessibility help
×
Home
Hostname: page-component-684899dbb8-489z4 Total loading time: 0.565 Render date: 2022-05-24T13:21:44.030Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "useNewApi": true }

Familial coaggregation of major psychiatric disorders in first-degree relatives of individuals with autism spectrum disorder: a nationwide population-based study

Published online by Cambridge University Press:  11 September 2020

Hohui E. Wang
Affiliation:
Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA
Chih-Ming Cheng
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan
Ya-Mei Bai
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan
Ju-Wei Hsu
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan
Kai-Lin Huang
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan
Tung-Ping Su
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan Department of Psychiatry, General Cheng Hsin Hospital, Taipei, Taiwan
Shih-Jen Tsai
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan
Cheng-Ta Li
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan
Tzeng-Ji Chen
Affiliation:
Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan
Bennett L. Leventhal*
Affiliation:
Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA
Mu-Hong Chen*
Affiliation:
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan
*
Authors for correspondence: Mu-Hong Chen, E-mail: kremer7119@gmail.com; Bennett L. Leventhal, E-mail: Bennett.Leventhal@ucsf.edu
Authors for correspondence: Mu-Hong Chen, E-mail: kremer7119@gmail.com; Bennett L. Leventhal, E-mail: Bennett.Leventhal@ucsf.edu

Abstract

Background

Family coaggregation of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia have been presented in previous studies. The shared genetic and environmental factors among psychiatric disorders remain elusive.

Methods

This nationwide population-based study examined familial coaggregation of major psychiatric disorders in first-degree relatives (FDRs) of individuals with ASD. Taiwan's National Health Insurance Research Database was used to identify 26 667 individuals with ASD and 67 998 FDRs of individuals with ASD. The cohort was matched in 1:4 ratio to 271 992 controls. The relative risks (RRs) and 95% confidence intervals (CI) of ADHD, ASD, BD, MDD and schizophrenia were assessed among FDRs of individuals with ASD and ASD with intellectual disability (ASD-ID).

Results

FDRs of individuals with ASD have higher RRs of major psychiatric disorders compared with controls: ASD 17.46 (CI 15.50–19.67), ADHD 3.94 (CI 3.72–4.17), schizophrenia 3.05 (CI 2.74–3.40), BD 2.22 (CI 1.98–2.48) and MDD 1.88 (CI 1.76–2.00). Higher RRs of schizophrenia (4.47, CI 3.95–5.06) and ASD (18.54, CI 16.18–21.23) were observed in FDRs of individuals with both ASD-ID, compared with ASD only.

Conclusions

The risk for major psychiatric disorders was consistently elevated across all types of FDRs of individuals with ASD. FDRs of individuals with ASD-ID are at further higher risk for ASD and schizophrenia. Our results provide leads for future investigation of shared etiologic pathways of ASD, ID and major psychiatric disorders and highlight the importance of mental health care delivered to at-risk families for early diagnoses and interventions.

Type
Original Articles
Copyright
Copyright © The Author(s), 2020. 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.)

References

Akutagava-Martins, G. C., Rohde, L. A., & Hutz, M. H. (2016). Genetics of attention-deficit/hyperactivity disorder: An update. Expert Review of Neurotherapeutics, 16(2), 145156. doi: 10.1586/14737175.2016.1130626.CrossRefGoogle ScholarPubMed
American Psychiatric Association. (2013). Neurodevelopmental Disorders. In Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596.dsm01.Google Scholar
Ayano, G., Maravilla, J. C., & Alati, R. (2019). Risk of autistic spectrum disorder in offspring with parental mood disorders: A systematic review and meta-analysis. Journal of Affective Disorders, 248, 185197. doi: 10.1016/j.jad.2019.01.038.CrossRefGoogle ScholarPubMed
Bai, D., Yip, B. H. K., Windham, G. C., Sourander, A., Francis, R., Yoffe, R., … Sandin, S. (2019). Association of genetic and environmental factors with autism in a 5-country cohort. JAMA Psychiatry, 76(10), 10351043. doi: 10.1001/jamapsychiatry.2019.1411.CrossRefGoogle Scholar
Baio, J., Wiggins, L., Christensen, D. L., Maenner, M. J., Daniels, J., Warren, Z., … Dowling, N. F. (2018). Prevalence of autism Spectrum disorder Among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2014. MMWR Surveillance Summaries, 67(6), 123. doi: 10.15585/mmwr.ss6706a1CrossRefGoogle ScholarPubMed
Chen, S. H., Chen, Y. C., Chen, T. J., & Ma, H. (2014). Epidemiology of burns in Taiwan: A nationwide report including inpatients and outpatients. Burns: Journal of the International Society for Burn Injuries, 40(7), 13971405. doi: 10.1016/j.burns.2014.01.014.CrossRefGoogle ScholarPubMed
Chen, M. H., Hsu, J. W., Huang, K. L., Su, T. P., Li, C. T., Lin, W. C., … Bai, Y. M. (2019). Risk and coaggregation of major psychiatric disorders among first-degree relatives of patients with bipolar disorder: A nationwide population-based study. Psychological Medicine, 49(14), 23972404. doi: 10.1017/S003329171800332X.CrossRefGoogle ScholarPubMed
Chen, M. H., Pan, T. L., Huang, K. L., Hsu, J. W., Bai, Y. M., Su, T. P., … Chen, T. J. (2019). Coaggregation of Major psychiatric disorders in first-degree relatives of individuals with attention-deficit/hyperactivity disorder: A nationwide population-based study. Journal of Clinical Psychiatry, 80(3), 18m12371. doi: 10.4088/JCP.18m12371.Google ScholarPubMed
Cheng, C. M., Chang, W. H., Chen, M. H., Tsai, C. F., Su, T. P., Li, C. T., … Bai, Y. M. (2018). Co-aggregation of major psychiatric disorders in individuals with first-degree relatives with schizophrenia: A nationwide population-based study. Molecular Psychiatry, 23(8), 17561763. doi: 10.1038/mp.2017.217dmCrossRefGoogle ScholarPubMed
Cohrs, A. C., & Leslie, D. L. (2017). Depression in parents of children diagnosed with autism Spectrum disorder: A claims-based analysis. Journal of Autism and Developmental Disorders, 47(5), 14161422. doi: 10.1007/s10803-017-3063-y.CrossRefGoogle ScholarPubMed
Cook, E. H. Jr., & Scherer, S. W. (2008). Copy-number variations associated with neuropsychiatric conditions. Nature, 455(7215), 919923. doi:10.1038/nature07458.CrossRefGoogle ScholarPubMed
Cross-Disorder Group of the Psychiatric Genomics, C. (2013). Identification of risk loci with shared effects on five major psychiatric disorders: A genome-wide analysis. Lancet (London, England), 381(9875), 13711379. doi: 10.1016/S0140-6736(12)62129-1CrossRefGoogle Scholar
Cukier, H. N., Dueker, N. D., Slifer, S. H., Lee, J. M., Whitehead, P. L., Lalanne, E., … Pericak-Vance, M. A. (2014). Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders. Molecular Autism, 5(1), 1. doi: 10.1186/2040-2392-5-1.CrossRefGoogle ScholarPubMed
Daniels, J. L., Forssen, U., Hultman, C. M., Cnattingius, S., Savitz, D. A., Feychting, M., & Sparen, P. (2008). Parental psychiatric disorders associated with autism spectrum disorders in the offspring. Pediatrics, 121(5), e1357e1362. doi:10.1542/peds.2007-2296 .CrossRefGoogle ScholarPubMed
DeLong, R., & Nohria, C. (1994). Psychiatric family history and neurological disease in autistic spectrum disorders. Developmental Medicine & Child Neurology, 36(5), 441448.Google ScholarPubMed
Doherty, J. L., & Owen, M. J. (2014). Genomic insights into the overlap between psychiatric disorders: Implications for research and clinical practice. Genome Medicine, 6(4), 29. doi: 10.1186/gm546.CrossRefGoogle ScholarPubMed
Eriksson, M. A., Westerlund, J., Anderlid, B. M., Gillberg, C., & Fernell, E. (2012). First-degree relatives of young children with autism spectrum disorders: Some gender aspects. Research in Developmental Disabilities, 33(5), 16421648. doi: 10.1016/j.ridd.2012.03.025.CrossRefGoogle ScholarPubMed
Executive Yuan, Taiwan (2013). The republic of China yearbook. Taiwan, Republic of China: Executive Yuan.Google Scholar
Fan, M., Liu, B., Jiang, T., Jiang, X., Zhao, H., & Zhang, J. (2010). Meta-analysis of the association between the monoamine oxidase-A gene and mood disorders. Psychiatric Genetics, 20(1), 17. doi: 10.1097/YPG.0b013e3283351112.CrossRefGoogle ScholarPubMed
Folstein, S., & Rutter, M. (1977). Infantile autism: A genetic study of 21 twin pairs. Journal of Child Psychology and Psychiatry, 18(4), 297321.CrossRefGoogle ScholarPubMed
Ghirardi, L., Brikell, I., Kuja-Halkola, R., Freitag, C. M., Franke, B., Asherson, P., … Larsson, H. (2018). The familial co-aggregation of ASD and ADHD: A register-based cohort study. Molecular Psychiatry, 23(2), 257262. doi: 10.1038/mp.2017.17.CrossRefGoogle ScholarPubMed
Hisle-Gorman, E., Susi, A., Stokes, T., Gorman, G., Erdie-Lalena, C., & Nylund, C. M. (2018). Prenatal, perinatal, and neonatal risk factors of autism spectrum disorder. Pediatric Research, 84(2), 190198. doi: 10.1038/pr.2018.23.CrossRefGoogle ScholarPubMed
Jacquemont, S., Coe, B. P., Hersch, M., Duyzend, M. H., Krumm, N., Bergmann, S., … Eichler, E. E. (2014). A higher mutational burden in females supports a “female protective model” in neurodevelopmental disorders. American Journal of Human Genetics, 94(3), 415425. doi: 10.1016/j.ajhg.2014.02.001.CrossRefGoogle Scholar
Janecka, M., Kodesh, A., Levine, S. Z., Lusskin, S. I., Viktorin, A., Rahman, R., … Reichenberg, A. (2018). Association of autism Spectrum disorder with prenatal exposure to medication affecting neurotransmitter systems. JAMA Psychiatry, 75(12), 12171224. doi: 10.1001/jamapsychiatry.2018.2728.CrossRefGoogle ScholarPubMed
Jokiranta-Olkoniemi, E., Cheslack-Postava, K., Sucksdorff, D., Suominen, A., Gyllenberg, D., Chudal, R., … Sourander, A. (2016). Risk of psychiatric and neurodevelopmental disorders Among siblings of probands with autism Spectrum disorders. JAMA Psychiatry, 73(6), 622629. doi: 10.1001/jamapsychiatry.2016.0495.CrossRefGoogle ScholarPubMed
Kuo, C. F., Grainge, M. J., Valdes, A. M., See, L. C., Luo, S. F., Yu, K. H., … Doherty, M. (2015). Familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families. JAMA Internal Medicine, 175(9), 15181526. doi: 10.1001/jamainternmed.2015.3528.CrossRefGoogle ScholarPubMed
Lee, S. H., Ripke, S., Neale, B. M., Faraone, S. V., Purcell, S. M., Perlis, R. H., & Wray, N. R. (2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics, 45(9), 984994. doi:10.1038/ng.2711.Google ScholarPubMed
Liu, C. Y., H, Y., Chuang, Y. L., Chen, Y. J., Weng, W. S., & Liu, J. S. (2006). Incorporating development stratification of Taiwan townships into sampling design of large scale health interview survey. Journal of Health Management, 4, 122.Google Scholar
Malhotra, D., & Sebat, J. (2012). CNVs: Harbingers of a rare variant revolution in psychiatric genetics. Cell, 148(6), 12231241. doi: 10.1016/j.cell.2012.02.039.CrossRefGoogle ScholarPubMed
Mandy, W., & Lai, M. C. (2016). Annual research review: The role of the environment in the developmental psychopathology of autism spectrum condition. Journal of Child Psychology and Psychiatry, 57(3), 271292. doi: 10.1111/jcpp.12501.CrossRefGoogle ScholarPubMed
Matson, J. L., & Shoemaker, M. (2009). Intellectual disability and its relationship to autism spectrum disorders. Research in Developmental Disabilities, 30(6), 11071114. doi: 10.1016/j.ridd.2009.06.003.CrossRefGoogle ScholarPubMed
McCarthy, S. E., Gillis, J., Kramer, M., Lihm, J., Yoon, S., Berstein, Y., … Corvin, A. (2014). De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability. Molecular Psychiatry, 19(6), 652658. doi: 10.1038/mp.2014.29.CrossRefGoogle ScholarPubMed
National Statistical Bureau, Taiwan. (2019). Population and Housing. Retrieved from https://eng.stat.gov.tw/ct.asp?xItem=41871&ctNode=2265&mp=5.Google Scholar
Owen, M. J. (2012). Intellectual disability and major psychiatric disorders: A continuum of neurodevelopmental causality. British Journal of Psychiatry, 200(4), 268269. doi: 10.1192/bjp.bp.111.105551.CrossRefGoogle ScholarPubMed
Pickles, A., Starr, E., Kazak, S., Bolton, P., Papanikolaou, K., Bailey, A., … Rutter, M. (2000). Variable expression of the autism broader phenotype: Findings from extended pedigrees. Journal of Child Psychology and Psychiatry, 41(4), 491502.CrossRefGoogle ScholarPubMed
Piven, J., Chase, G. A., Landa, R., Wzorek, M., Gayle, J., Cloud, D., & Folstein, S. (1991). Psychiatric disorders in the parents of autistic individuals. Journal of the American Academy of Child and Adolescent Psychiatry, 30(3), 471478. doi: 10.1097/00004583-199105000-00019.CrossRefGoogle ScholarPubMed
Piven, J., Palmer, P., Jacobi, D., Childress, D., & Arndt, S. (1997). Broader autism phenotype: Evidence from a family history study of multiple-incidence autism families. American Journal of Psychiatry, 154(2), 185190. doi: 10.1176/ajp.154.2.185.Google ScholarPubMed
Rees, E., Han, J., Morgan, J., Carrera, N., Escott-Price, V., Pocklington, A. J., … Owen, M. J. (2020). De novo mutations identified by exome sequencing implicate rare missense variants in SLC6A1 in schizophrenia. Nature Neuroscience, 23(2), 179184. doi: 10.1038/s41593-019-0565-2.CrossRefGoogle Scholar
Risch, N., Hoffmann, T. J., Anderson, M., Croen, L. A., Grether, J. K., & Windham, G. C. (2014). Familial recurrence of autism spectrum disorder: Evaluating genetic and environmental contributions. American Journal of Psychiatry, 171(11), 12061213. doi: 10.1176/appi.ajp.2014.13101359.CrossRefGoogle ScholarPubMed
Robinson, E. B., Samocha, K. E., Kosmicki, J. A., McGrath, L., Neale, B. M., Perlis, R. H., & Daly, M. J. (2014). Autism spectrum disorder severity reflects the average contribution of de novo and familial influences. Proceedings of the National Academy of Sciences of the United States of America, 111(42), 1516115165. doi:10.1073/pnas.1409204111.CrossRefGoogle ScholarPubMed
Robinson, E. B., St Pourcain, B., Anttila, V., Kosmicki, J. A., Bulik-Sullivan, B., Grove, J., … Daly, M. J. (2016). Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population. Nature Genetics, 48(5), 552555. doi: 10.1038/ng.3529.CrossRefGoogle ScholarPubMed
Sandin, S., Lichtenstein, P., Kuja-Halkola, R., Hultman, C., Larsson, H., & Reichenberg, A. (2017). The heritability of autism Spectrum disorder. JAMA, 318(12), 11821184. doi: 10.1001/jama.2017.12141.CrossRefGoogle ScholarPubMed
Sandin, S., Lichtenstein, P., Kuja-Halkola, R., Larsson, H., Hultman, C. M., & Reichenberg, A. (2014). The familial risk of autism. JAMA, 311(17), 17701777. doi: 10.1001/jama.2014.4144.CrossRefGoogle ScholarPubMed
Scherer, N., Verhey, I., & Kuper, H. (2019). Depression and anxiety in parents of children with intellectual and developmental disabilities: A systematic review and meta-analysis. PLoS One, 14(7), e0219888. doi: 10.1371/journal.pone.0219888.CrossRefGoogle ScholarPubMed
Schieve, L. A., Clayton, H. B., Durkin, M. S., Wingate, M. S., & Drews-Botsch, C. (2015). Comparison of perinatal risk factors associated with autism Spectrum disorder (ASD), intellectual disability (ID), and Co-occurring ASD and ID. Journal of Autism and Developmental Disorders, 45(8), 23612372. doi: 10.1007/s10803-015-2402-0.CrossRefGoogle Scholar
Singh, T., Walters, J. T. R., Johnstone, M., Curtis, D., Suvisaari, J., Torniainen, M., … Barrett, J. C. (2017). The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability. Nature Genetics, 49(8), 11671173. doi: 10.1038/ng.3903.CrossRefGoogle ScholarPubMed
Stessman, H. A., Xiong, B., Coe, B. P., Wang, T., Hoekzema, K., Fenckova, M., … Eichler, E. E. (2017). Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Nature Genetics, 49(4), 515526. doi: 10.1038/ng.3792.CrossRefGoogle ScholarPubMed
Sullivan, P. F., Magnusson, C., Reichenberg, A., Boman, M., Dalman, C., Davidson, M., … Lichtenstein, P. (2012). Family history of schizophrenia and bipolar disorder as risk factors for autism. Archives of General Psychiatry, 69(11), 10991103. doi: 10.1001/archgenpsychiatry.2012.730.CrossRefGoogle ScholarPubMed
Taylor, M. J., Charman, T., & Ronald, A. (2015). Where are the strongest associations between autistic traits and traits of ADHD? Evidence from a community-based twin study. European Child & Adolescent Psychiatry, 24(9), 11291138. doi: 10.1007/s00787-014-0666-0.CrossRefGoogle ScholarPubMed
Tick, B., Bolton, P., Happe, F., Rutter, M., & Rijsdijk, F. (2016). Heritability of autism spectrum disorders: A meta-analysis of twin studies. Journal of Child Psychology and Psychiatry, 57(5), 585595. doi: 10.1111/jcpp.12499.CrossRefGoogle ScholarPubMed
Yelland, L. N., Salter, A. B., & Ryan, P. (2011). Performance of the modified Poisson regression approach for estimating relative risks from clustered prospective data. American Journal of Epidemiology, 174(8), 984992. doi: 10.1093/aje/kwr183.CrossRefGoogle ScholarPubMed
Yip, B. H. K., Bai, D., Mahjani, B., Klei, L., Pawitan, Y., Hultman, C. M., … Sandin, S. (2018). Heritable variation, with little or No maternal effect, accounts for recurrence risk to autism Spectrum disorder in Sweden. Biological Psychiatry, 83(7), 589597. doi: 10.1016/j.biopsych.2017.09.007CrossRefGoogle ScholarPubMed
Zou, G. (2004). A modified Poisson regression approach to prospective studies with binary data. American Journal of Epidemiology, 159(7), 702706. doi: 10.1093/aje/kwh090.CrossRefGoogle ScholarPubMed
Supplementary material: PDF

Wang et al. supplementary material

Wang et al. supplementary material

Download Wang et al. supplementary material(PDF)
PDF 140 KB
2
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Familial coaggregation of major psychiatric disorders in first-degree relatives of individuals with autism spectrum disorder: a nationwide population-based study
Available formats
×

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

Familial coaggregation of major psychiatric disorders in first-degree relatives of individuals with autism spectrum disorder: a nationwide population-based study
Available formats
×

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

Familial coaggregation of major psychiatric disorders in first-degree relatives of individuals with autism spectrum disorder: a nationwide population-based study
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *