Parental psychiatric diagnoses as predictive factors for autism spectrum disorder in the child: confluence of genetics and environment

Autism spectrum disorder (autism) is a neurodevelopmental condition that affects over 28 million people globally.1Solmi M. Song M. Yon D.K. et al.Incidence, prevalence, and global burden of autism spectrum disorder from 1990 to 2019 across 204 countries.Mol Psychiatry. 2022; 27: 4172-4180Crossref Scopus (44) Google Scholar With age-adjusted prevalence estimates ranging from 429 cases per 100,000 in Denmark to 707 cases per 100,000 in Sweden,1Solmi M. Song M. Yon D.K. et al.Incidence, prevalence, and global burden of autism spectrum disorder from 1990 to 2019 across 204 countries.Mol Psychiatry. 2022; 27: 4172-4180Crossref Scopus (44) Google Scholar Nordic countries are among those with the highest prevalence of autism,1Solmi M. Song M. Yon D.K. et al.Incidence, prevalence, and global burden of autism spectrum disorder from 1990 to 2019 across 204 countries.Mol Psychiatry. 2022; 27: 4172-4180Crossref Scopus (44) Google Scholar though this could reflect the use of more comprehensive detection methods rather than an underlying increased autism susceptibility. Currently, the etiology of autism is understood as multifactorial and driven by genetic, epigenetic, and environmental (non-genetic) influences.2Saxena R. Babadi M. Namvarhaghighi H. Roullet F.I. Role of environmental factors and epigenetics in autism spectrum disorders.Prog Mol Biol Transl Sci. 2020; 173: 35-60Crossref PubMed Scopus (27) Google Scholar Parental mental health conditions are hypothesized to increase the likelihood of autism in the child, in part through shared genetic pathways. Mental health conditions, including autism, likely have polygenetic origins, meaning the accumulation of many common genetic variants may augment the chances of developing the condition.3Havdahl A. Niarchou M. Starnawska A. Uddin M. van der Merwe C. Warrier V. Genetic contributions to autism spectrum disorder.Psychol Med. 2021; 51: 2260-2273Crossref PubMed Scopus (59) Google Scholar,4Visscher P.M. Wray N.R. Zhang Q. et al.10 years of GWAS discovery: biology, function, and translation.Am J Hum Genet. 2017; 101: 5-22Summary Full Text Full Text PDF PubMed Scopus (1980) Google Scholar Autism may share underlying genetic contributions with other mental health conditions.3Havdahl A. Niarchou M. Starnawska A. Uddin M. van der Merwe C. Warrier V. Genetic contributions to autism spectrum disorder.Psychol Med. 2021; 51: 2260-2273Crossref PubMed Scopus (59) Google Scholar Two population-based studies found positive associations between maternal psychiatric conditions diagnosed before birth and child autism, with less consistent positive associations between paternal psychiatric conditions and child autism.5Chien Y. Wu C. Chang Y. Cheong M. Yao T. Tsai H. Associations between parental psychiatric disorders and autism spectrum disorder in the offspring.Autism Res. 2022; 15: 2409-2419Crossref PubMed Scopus (3) Google Scholar,6Jokiranta E. Brown A.S. Heinimaa M. Cheslack-Postava K. Suominen A. Sourander A. Parental psychiatric disorders and autism spectrum disorders.Psychiatry Res. 2013; 207: 203-211Crossref PubMed Scopus (89) Google Scholar The mechanisms by which parental mental health conditions could contribute to autism may include inherited genetic factors, environmental exposures, timing of exposures, and interactions between environmental exposures and genetics. In this issue of the Lancet Regional Health–Europe, Yin et al. contributed to this field by investigating the relationship between autism in the child and 16 parental psychiatric diagnoses.7Yin Weiyao Anna Pulakka Reichenberg A. et al.A comprehensive assessment of parental psychiatric disorders and risk of offspring autism: Swedish-Finnish register based study.Lancet Reg Health Eur. 2024; https://doi.org/10.1016/j.lanepe.2024.100902Summary Full Text Full Text PDF Google Scholar This population-based cohort study followed 1,488,920 children born in Sweden between 1997 and 2016 until autism diagnosis or the end of the study period in 2017. Child autism diagnoses and psychiatric diagnoses of their biological parents were based on ICD codes from Swedish National Registers. Parental diagnoses were made prior to the birth of the child.7Yin Weiyao Anna Pulakka Reichenberg A. et al.A comprehensive assessment of parental psychiatric disorders and risk of offspring autism: Swedish-Finnish register based study.Lancet Reg Health Eur. 2024; https://doi.org/10.1016/j.lanepe.2024.100902Summary Full Text Full Text PDF Google Scholar Overall, findings indicated that parental psychiatric diagnoses increase the likelihood of autism in the child.7Yin Weiyao Anna Pulakka Reichenberg A. et al.A comprehensive assessment of parental psychiatric disorders and risk of offspring autism: Swedish-Finnish register based study.Lancet Reg Health Eur. 2024; https://doi.org/10.1016/j.lanepe.2024.100902Summary Full Text Full Text PDF Google Scholar Yin et al. found that child autism diagnosis had the highest likelihood when psychiatric diagnoses occurred in both parents (aHR = 3.76, 95% CI = 3.48–4.07), followed by the mother only (aHR = 2.34, 95% CI = 2.24–2.43), and then the father only (aHR = 2.02, 95% CI = 1.92–2.12), compared to children whose parents had no psychiatric diagnosis. The likelihood of autism in the child increased as the number of parental psychiatric diagnoses increased. All psychiatric disorders were associated with increased likelihood of autism in the child compared to no parental diagnosis. Autism in both parents was associated with the highest likelihood of autism in the child (aHR = 10.29, 95% CI = 3.86–27.42), reflecting previous findings on familial occurrence of autism.3Havdahl A. Niarchou M. Starnawska A. Uddin M. van der Merwe C. Warrier V. Genetic contributions to autism spectrum disorder.Psychol Med. 2021; 51: 2260-2273Crossref PubMed Scopus (59) Google Scholar To demonstrate reliability, the main findings of the study were replicated using a Finish cohort.7Yin Weiyao Anna Pulakka Reichenberg A. et al.A comprehensive assessment of parental psychiatric disorders and risk of offspring autism: Swedish-Finnish register based study.Lancet Reg Health Eur. 2024; https://doi.org/10.1016/j.lanepe.2024.100902Summary Full Text Full Text PDF Google Scholar Additional questions remain that were beyond the scope of this study. The finding that all parental psychiatric diagnoses were associated with autism in the child suggests that there may be commonalities in mechanisms driving autism across different parental diagnoses. Psychiatric diagnoses likely do not represent discrete exposure liability categories and research that delves beyond diagnoses could reveal common etiologic threads across disorders that drive autism development.8Pacheco J. Garvey M.A. Sarampote C.S. Cohen E.D. Murphy E.R. Friedman-Hill S.R. Annual Research Review: the contributions of the RDoC research framework on understanding the neurodevelopmental origins, progression and treatment of mental illnesses.J Child Psychol Psychiatry. 2022; 63: 360-376Crossref Scopus (29) Google Scholar For example, stress is associated with mental health conditions as a result of psychiatric symptoms or social stigma.9Dubreucq J. Plasse J. Franck N. Self-stigma in serious mental illness: a systematic review of frequency, correlates, and consequences.Schizophr Bull. 2021; 47: 1261-1287Crossref PubMed Scopus (114) Google Scholar Maternal stress during pregnancy has been associated with an increased likelihood of child autism, potentially via dysregulation of the maternal immune system.2Saxena R. Babadi M. Namvarhaghighi H. Roullet F.I. Role of environmental factors and epigenetics in autism spectrum disorders.Prog Mol Biol Transl Sci. 2020; 173: 35-60Crossref PubMed Scopus (27) Google Scholar Future studies should consider measuring maternal stress during pregnancy, and analyzing it in conjunction with genetic and epigenetic markers of autism to understand the interplay between parental physiological states like stress and genetic load in autism development. Timing of related exposures should be investigated further. The nature of symptoms and treatments associated with a psychiatric diagnosis can vary throughout the life course.8Pacheco J. Garvey M.A. Sarampote C.S. Cohen E.D. Murphy E.R. Friedman-Hill S.R. Annual Research Review: the contributions of the RDoC research framework on understanding the neurodevelopmental origins, progression and treatment of mental illnesses.J Child Psychol Psychiatry. 2022; 63: 360-376Crossref Scopus (29) Google Scholar Most environmental exposures associated with autism occur during the prenatal and early postnatal period, when most neuronal growth and organization occurs.2Saxena R. Babadi M. Namvarhaghighi H. Roullet F.I. Role of environmental factors and epigenetics in autism spectrum disorders.Prog Mol Biol Transl Sci. 2020; 173: 35-60Crossref PubMed Scopus (27) Google Scholar Children whose mothers experienced acute psychiatric problems or used psychiatric medications during pregnancy could experience a higher burden of exposures during a sensitive developmental period compared to children whose mothers have a psychiatric diagnosis but did not have symptoms or use medications during pregnancy. Studies on parental mental health conditions and autism that document the mother's symptoms and psychiatric medication use during pregnancy could enhance understanding of their contributions. Lastly, more research is needed on how to better support parents with mental health conditions in raising their children. Family-based interventions that focus on the emotional health of parents and children could provide a strong foundation for the child's social and emotional development, even when parents have existing mental health conditions.10Havighurst S.S. Radovini A. Hao B. Kehoe C.E. Emotion-focused parenting interventions for prevention and treatment of child and adolescent mental health problems: a review of recent literature.Curr Opin Psychiatry. 2020; 33: 586-601Crossref PubMed Scopus (41) Google Scholar Future research should take a holistic approach to identify potentially modifiable factors playing a role during and after pregnancy. Prenatal psychosocial interventions could help pregnant people reduce stress and manage symptoms during a critical period for child neurodevelopment. ZBK: conceptualisation, writing—original draft, and writing-review & editing. RJS: writing–review & editing. ZBK: No declarations of interest. RJS has received funding to support the MARBLES Study from the Simons Foundation. RJS consulted for the Beasley Law Firm and Linus Technology, Inc. RJS has received travel support to present at the 35th Annual Meeting of the Organization of Teratology Information Specialists (OTIS) and to serve on the Observational Study Monitoring Board (OSMB) for HEALthy Brain and Child Development (HBCD) Study, and has received compensation to serve on NIH Reviews. Association between parental psychiatric disorders and risk of offspring autism spectrum disorder: a Swedish and Finnish population-based cohort studyPsychiatric disorders in both parents conveyed the highest risk of offspring autism spectrum disorder, followed by mothers and then fathers. The risk increased with number of co-occurring disorders. All parental psychiatric disorders were associated with increased the risk of autism spectrum disorder. To reliably assess the risk of autism spectrum disorder in children, a comprehensive history incorporating the full range of parental psychiatric disorders is needed beyond solely focusing on familial autism spectrum disorder. Full-Text PDF Open Access