Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions
Abstract Background Neurodevelopmental conditions such as intellectual disability (ID) and autism spectrum disorder (ASD) can stem from a broad array of inherited and de novo genetic differences, with marked physiological and behavioral impacts. We currently know little about the psychiatric phenoty...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Journal of Neurodevelopmental Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11689-024-09532-1 |
| _version_ | 1797199629364756480 |
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| author | Emily Neuhaus Hannah Rea Elizabeth Jones Hannah Benavidez Conor Miles Alana Whiting Margaret Johansson Curtis Eayrs Evangeline C. Kurtz-Nelson Rachel Earl Raphael A. Bernier Evan E. Eichler |
| author_facet | Emily Neuhaus Hannah Rea Elizabeth Jones Hannah Benavidez Conor Miles Alana Whiting Margaret Johansson Curtis Eayrs Evangeline C. Kurtz-Nelson Rachel Earl Raphael A. Bernier Evan E. Eichler |
| author_sort | Emily Neuhaus |
| collection | DOAJ |
| description | Abstract Background Neurodevelopmental conditions such as intellectual disability (ID) and autism spectrum disorder (ASD) can stem from a broad array of inherited and de novo genetic differences, with marked physiological and behavioral impacts. We currently know little about the psychiatric phenotypes of rare genetic variants associated with ASD, despite heightened risk of psychiatric concerns in ASD more broadly. Understanding behavioral features of these variants can identify shared versus specific phenotypes across gene groups, facilitate mechanistic models, and provide prognostic insights to inform clinical practice. In this paper, we evaluate behavioral features within three gene groups associated with ID and ASD – ADNP, CHD8, and DYRK1A – with two aims: (1) characterize phenotypes across behavioral domains of anxiety, depression, ADHD, and challenging behavior; and (2) understand whether age and early developmental milestones are associated with later mental health outcomes. Methods Phenotypic data were obtained for youth with disruptive variants in ADNP, CHD8, or DYRK1A (N = 65, mean age = 8.7 years, 40% female) within a long-running, genetics-first study. Standardized caregiver-report measures of mental health features (anxiety, depression, attention-deficit/hyperactivity, oppositional behavior) and developmental history were extracted and analyzed for effects of gene group, age, and early developmental milestones on mental health features. Results Patterns of mental health features varied by group, with anxiety most prominent for CHD8, oppositional features overrepresented among ADNP, and attentional and depressive features most prominent for DYRK1A. For the full sample, age was positively associated with anxiety features, such that elevations in anxiety relative to same-age and same-sex peers may worsen with increasing age. Predictive utility of early developmental milestones was limited, with evidence of early language delays predicting greater difficulties across behavioral domains only for the CHD8 group. Conclusions Despite shared associations with autism and intellectual disability, disruptive variants in ADNP, CHD8, and DYRK1A may yield variable psychiatric phenotypes among children and adolescents. With replication in larger samples over time, efforts such as these may contribute to improved clinical care for affected children and adolescents, allow for earlier identification of emerging mental health difficulties, and promote early intervention to alleviate concerns and improve quality of life. |
| first_indexed | 2024-04-24T07:18:47Z |
| format | Article |
| id | doaj.art-b6050b2ba59c433a8a4dd9640bcb0bcf |
| institution | Directory Open Access Journal |
| issn | 1866-1955 |
| language | English |
| last_indexed | 2024-04-24T07:18:47Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neurodevelopmental Disorders |
| spelling | doaj.art-b6050b2ba59c433a8a4dd9640bcb0bcf2024-04-21T11:08:49ZengBMCJournal of Neurodevelopmental Disorders1866-19552024-04-0116111310.1186/s11689-024-09532-1Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditionsEmily Neuhaus0Hannah Rea1Elizabeth Jones2Hannah Benavidez3Conor Miles4Alana Whiting5Margaret Johansson6Curtis Eayrs7Evangeline C. Kurtz-Nelson8Rachel Earl9Raphael A. Bernier10Evan E. Eichler11Department of Psychiatry and Behavioral Sciences, University of Washington School of MedicineDepartment of Psychiatry and Behavioral Sciences, University of Washington School of MedicineDepartment of Psychiatry and Behavioral Sciences, University of Washington School of MedicineDepartment of Psychology, University of WashingtonDepartment of Psychiatry and Behavioral Sciences, University of Washington School of MedicineDepartment of Psychiatry and Behavioral Sciences, University of Washington School of MedicineDepartment of Psychiatry and Behavioral Sciences, University of Washington School of MedicineDepartment of Psychiatry and Behavioral Sciences, University of Washington School of MedicineDepartment of Pediatrics, Indiana University School of MedicineDepartment of Psychiatry and Behavioral Sciences, University of Washington School of MedicineDepartment of Psychiatry and Behavioral Sciences, University of Washington School of MedicineDepartment of Genome Sciences, University of Washington School of MedicineAbstract Background Neurodevelopmental conditions such as intellectual disability (ID) and autism spectrum disorder (ASD) can stem from a broad array of inherited and de novo genetic differences, with marked physiological and behavioral impacts. We currently know little about the psychiatric phenotypes of rare genetic variants associated with ASD, despite heightened risk of psychiatric concerns in ASD more broadly. Understanding behavioral features of these variants can identify shared versus specific phenotypes across gene groups, facilitate mechanistic models, and provide prognostic insights to inform clinical practice. In this paper, we evaluate behavioral features within three gene groups associated with ID and ASD – ADNP, CHD8, and DYRK1A – with two aims: (1) characterize phenotypes across behavioral domains of anxiety, depression, ADHD, and challenging behavior; and (2) understand whether age and early developmental milestones are associated with later mental health outcomes. Methods Phenotypic data were obtained for youth with disruptive variants in ADNP, CHD8, or DYRK1A (N = 65, mean age = 8.7 years, 40% female) within a long-running, genetics-first study. Standardized caregiver-report measures of mental health features (anxiety, depression, attention-deficit/hyperactivity, oppositional behavior) and developmental history were extracted and analyzed for effects of gene group, age, and early developmental milestones on mental health features. Results Patterns of mental health features varied by group, with anxiety most prominent for CHD8, oppositional features overrepresented among ADNP, and attentional and depressive features most prominent for DYRK1A. For the full sample, age was positively associated with anxiety features, such that elevations in anxiety relative to same-age and same-sex peers may worsen with increasing age. Predictive utility of early developmental milestones was limited, with evidence of early language delays predicting greater difficulties across behavioral domains only for the CHD8 group. Conclusions Despite shared associations with autism and intellectual disability, disruptive variants in ADNP, CHD8, and DYRK1A may yield variable psychiatric phenotypes among children and adolescents. With replication in larger samples over time, efforts such as these may contribute to improved clinical care for affected children and adolescents, allow for earlier identification of emerging mental health difficulties, and promote early intervention to alleviate concerns and improve quality of life.https://doi.org/10.1186/s11689-024-09532-1Neurodevelopmental conditionsAutismASDPhenotyping; geneticsADNPCHD8 |
| spellingShingle | Emily Neuhaus Hannah Rea Elizabeth Jones Hannah Benavidez Conor Miles Alana Whiting Margaret Johansson Curtis Eayrs Evangeline C. Kurtz-Nelson Rachel Earl Raphael A. Bernier Evan E. Eichler Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions Journal of Neurodevelopmental Disorders Neurodevelopmental conditions Autism ASD Phenotyping; genetics ADNP CHD8 |
| title | Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions |
| title_full | Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions |
| title_fullStr | Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions |
| title_full_unstemmed | Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions |
| title_short | Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions |
| title_sort | shared and divergent mental health characteristics of adnp chd8 and dyrk1a related neurodevelopmental conditions |
| topic | Neurodevelopmental conditions Autism ASD Phenotyping; genetics ADNP CHD8 |
| url | https://doi.org/10.1186/s11689-024-09532-1 |
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