FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313441493> ?p ?o ?g. }

• W4313441493 endingPage "16" @default.
• W4313441493 startingPage "14" @default.
• W4313441493 abstract "Back to table of contents Previous article Next article EditorialsFull AccessADHD: The Mammoth Task of Disentangling Genetic, Environmental, and Developmental Risk FactorsSarah Kittel-Schneider, M.D.Sarah Kittel-SchneiderSearch for more papers by this author, M.D.Published Online:1 Jan 2023https://doi.org/10.1176/appi.ajp.20220916AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail The first medical description of what is currently labeled attention deficit hyperactivity disorder (ADHD) was published as early as the 18th century. The German physician Melchior Adam Weikard and the Scottish physician Alexander Crichton described individuals suffering from attention deficit, increased distractibility, and reduced stamina (1). This symptom complex defines the attention deficit disorder subtype without hyperactivity in the currently used DSM-5 (2). However, George Frederick Still was the first physician to publish an article in a medical journal, the Lancet, about children with symptoms of attention deficit, self-regulation problems, and learning difficulties, in 1902. Charles Bradley then treated children who were described as hyperactive with amphetamine sulfate. Since 1978, ADHD has been recognized as a childhood disorder entity in ICD-9, and since 1992, ICD-10 has also recognized persisting ADHD into adulthood (3).The underlying causes of ADHD, however, were unclear for nearly 200 years. Since the beginning of the 21st century, it is largely validated that ADHD is a disorder with a heritability of about 80%, estimated from twin and family studies (4). However, the first genetic studies that investigated several candidate genes were disappointing in that there were hardly any gene candidates with high effect sizes for the risk of developing ADHD (4). Linkage studies and genome-wide association studies (GWASs) investigating common genetic variants such as single-nucleotide polymorphisms (SNPs) were conducted, and the findings hinted at several gene loci being associated with ADHD, but each risk variant conveyed only a rather small risk (5, 6). In the meantime, the first genome-wide significant genetic loci for ADHD have been reported, and meta-analysis of GWASs indicate that about 22% of genetic liability is caused by SNP heritability (7, 8).Polygenic risk scores (PRSs) summarize the risk alleles of an individual and weigh the effect size in an independent GWAS. Using PRSs seems to be useful to capture the synergistic effects of common risk variants of low effect sizes and to identify individuals carrying a higher genetic burden of those common variants (9). Moreover, more rare variants, such as copy number variants (CNVs), are also shown to play a role in ADHD pathogenesis, since there is a significantly increased burden in individuals with ADHD compared with the general population (10).However, not only genetic but also environmental and developmental risk factors and their interaction are suggested to contribute to the onset of ADHD (11). But the investigation of the causality of environmental and developmental risk factors in ADHD is even more complex. Earlier studies investigating, for example, the impact of smoking during pregnancy on ADHD risk in the exposed child often did not take the mother’s psychopathology or genetic risk into account (12). The same is true for the effect of breastfeeding on ADHD risk (13). Better-designed studies already hinted that the genetic risk of the mother might be the causal factor rather than the harmful effects of smoking in ADHD (14). Only few studies have been published so far looking at pregnant women with ADHD and mother-child interaction in early infancy in mothers (and fathers) with ADHD. Early data hint that women with ADHD are at a greater risk of smoking, drinking alcohol, and using illegal drugs as well as greater risk of pregnancy and birth complications, compared with the general population (15). Therefore, it is highly challenging to disentangle the genetic from the environmental and developmental risk factors.For example, preterm birth has been shown to have a relatively consistent association with an increased ADHD risk, but the direction of the effect is less clear (16). Does prematurity lead to ADHD symptoms, or do fetuses with a genetic ADHD risk tend to be born prematurely for unknown biological reasons? Or, as a third possibility, are mothers with ADHD more prone to give birth to premature infants as a result of increased psychosocial stress and unhealthy lifestyle and the causal link is rather the transmission of the genetic risk variants? Finally, is there an interaction or interplay between those different risk factors?To make it even more complex, several potential environmental risk factors (in pregnancy or after birth) may also share genetic risk with ADHD, such as obesity, gestational diabetes mellitus, autoimmune disorders, allergic disorders, and so on, and there are hints that polygenic liability of ADHD is associated with an increased risk of exposure to environmental ADHD risk factors in individuals without an ADHD diagnosis as well.A 2019 study by Leppert et al. (17) investigated mothers without a clinical ADHD diagnosis but carrying risk alleles associated with ADHD, compared with mothers without those risk alleles. Of most interest was the fact that the mothers with ADHD risk alleles had increased lifestyle-related negative exposures, such as more mental health issues and pregnancy complications and increased markers of unhealthy nutritional status. However, that study was unable to show a significant association of preterm birth with maternal ADHD genetic risk or with ADHD risk genes in the exposed children.In this issue of the Journal, Brikell et al. (18) report on a study of the interaction between ADHD PRS, ADHD diagnosis, and environmental risk factors. They studied the association of 24 environmental and developmental risk factors and ADHD polygenic risk scores in a large cohort of 13,697 ADHD case subjects and 21,578 control subjects from a general population sample. There were three times more affected males than females in the sample, which needs to be mentioned, as we estimate that rates of adult ADHD are only 1.5 times higher in men compared with women in population-based studies. Brikell et al. included birth-related, somatic, and psychosocial risk factors, including parental mental disorder diagnoses, to evaluate potential gene-environment interactions. Not surprisingly, they could confirm a significant association of ADHD PRS with ADHD diagnosis. The higher the PRS burden, the greater the ADHD risk, which is confirmed in other studies (19). It is most interesting that in the general population sample, the authors could show a significant association of ADHD PRS with half of the 24 environmental risk factors. Small for gestational age, maternal autoimmune disorder, having had at least one infection, having had five or more infections, and a history of mild traumatic brain injury (TBI) were significantly associated. Furthermore, ADHD PRS was significantly associated with most of the psychosocial risk factors, such as income in the lowest quintile, low education level, living in a single-parent household during the first 5 years of life, being under age 20 at birth of index child, and parental history of mental disorder. Nineteen of the 24 risk factors were associated with a diagnosis of ADHD. The most significant associations were reported for low birth weight, epilepsy, and low parental education. Adjusting for ADHD PRS load and parental mental disorder diagnosis did not largely change the findings.Surprisingly, Brikell et al. only found a tendency of gene-environment interaction between ADHD PRS and four of the 24 risk factors, namely, maternal autoimmune disease, TBI, paternal unemployment, and lower paternal age at birth of index child. This suggests that individuals who are burdened with a higher ADHD PRS load and are additionally exposed to one of these four environmental risk factors might have a higher probability of developing ADHD. The only gene-environment interaction that survived false discovery rate correction for multiple comparison, however, was the interaction of maternal autoimmune disease and high ADHD PRS load.The results from the Brikell et al. study are very promising and point out the importance of what data should be included in future studies on the etiopathology of ADHD. They strengthen the evidence of the heterogeneity of ADHD disease mechanisms and point toward the possibility of disentangling genetic and environmental risk factors as well as studying their complex interplay and interactions. Recent studies give first hints as to how environmental factors can influence gene expression by changes in the epigenome, but this field is only in its infancy (20). More insight into ADHD pathomechanisms will reveal targetable risk factors that then can be addressed by interventions, and the causality will finally be proven in future interventional studies.Department of Psychiatry, Psychotherapy, and Psychosomatics, University Hospital Würzburg, Würzburg, Germany.Send correspondence to Dr. Kittel-Schneider ([email protected]).The author has received authorship and speaking honoraria from Takeda and Medice Arzneitmittel Püter GmbH & Co.KG.References1. Barkley RA, Peters H: The earliest reference to ADHD in the medical literature? Melchior Adam Weikard’s description in 1775 of “attention deficit” (Mangel der Aufmerksamkeit, Attentio Volubilis). J Atten Disord 2012; 16:623–630Crossref, Medline, Google Scholar2. Baird G: Classification of diseases and the neurodevelopmental disorders: the challenge for DSM-5 and ICD-11. Dev Med Child Neurol 2013; 55:200–201Crossref, Medline, Google Scholar3. Mahone EM, Denckla MB: Attention-deficit/hyperactivity disorder: a historical neuropsychological perspective. J Int Neuropsychol Soc 2017; 23:916–929Crossref, Medline, Google Scholar4. Cortese S, Coghill D: Twenty years of research on attention-deficit/hyperactivity disorder (ADHD): looking back, looking forward. Evid Based Ment Health 2018; 21:173–176Crossref, Medline, Google Scholar5. Neale BM, Lasky-Su J, Anney R, et al.: Genome-wide association scan of attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 2008; 147B:1337–1344Crossref, Medline, Google Scholar6. Lasky-Su J, Neale BM, Franke B, et al.: Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations. Am J Med Genet B Neuropsychiatr Genet 2008; 147B:1345–1354Crossref, Medline, Google Scholar7. Demontis D, Walters RK, Martin J, et al.: Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nat Genet 2019; 51:63–75Crossref, Medline, Google Scholar8. Brikell I, Burton C, Mota NR, et al.: Insights into attention-deficit/hyperactivity disorder from recent genetic studies. Psychol Med 2021; 51:2274–2286Crossref, Medline, Google Scholar9. Zheutlin AB, Ross DA: Polygenic risk scores: what are they good for? Biol Psychiatry 2018; 83:e51–e53Crossref, Medline, Google Scholar10. Williams NM, Zaharieva I, Martin A, et al.: Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet 2010; 376:1401–1408Crossref, Medline, Google Scholar11. Palladino VS, McNeill R, Reif A, et al.: Genetic risk factors and gene-environment interactions in adult and childhood attention-deficit/hyperactivity disorder. Psychiatr Genet 2019; 29:63–78Crossref, Medline, Google Scholar12. Langley K, RiceF, van den Bree MBM, et al.: Maternal smoking during pregnancy as an environmental risk factor for attention deficit hyperactivity disorder behaviour: a review. Minerva Pediatr 2005; 57:359–371Medline, Google Scholar13. Bar S, Milanaik R, Adesman A: Long-term neurodevelopmental benefits of breastfeeding. Curr Opin Pediatr 2016; 28:559–566Crossref, Medline, Google Scholar14. Thapar A, Rice F, Hay D, et al.: Prenatal smoking might not cause attention-deficit/hyperactivity disorder: evidence from a novel design. Biol Psychiatry 2009; 66:722–727Crossref, Medline, Google Scholar15. Kittel-Schneider S, Quednow BB, Leutritz AL, et al.: Parental ADHD in pregnancy and the postpartum period: a systematic review. Neurosci Biobehav Rev 2021; 124:63–77Crossref, Medline, Google Scholar16. McCoy BM, Rickert ME, Class QA, et al.: Mediators of the association between parental severe mental illness and offspring neurodevelopmental problems. Ann Epidemiol 2014; 24:629–634 e1Crossref, Medline, Google Scholar17. Leppert B, Havdahl A, Riglin L, et al.: Association of maternal neurodevelopmental risk alleles with early-life exposures. JAMA Psychiatry 2019; 76:834–842Crossref, Medline, Google Scholar18. Brikell I, Wimberley T, Albiñana C, et al.: Interplay of ADHD polygenic liability with birth-related, somatic, and psychosocial factors in ADHD: a nationwide study. Am J Psychiatry 2023; 180:73–88Link, Google Scholar19. Green, A., et al.: Examining the impact of ADHD polygenic risk scores on ADHD and associated outcomes: a systematic review and meta-analysis. J Psychiatr Res, 2022. 155:49–67 Crossref, Medline, Google Scholar20. Rovira P, Sanchez-Mora C, Pagerols M, et al.: Epigenome-wide association study of attention-deficit/hyperactivity disorder in adults. Transl Psychiatry 2020; 10:199Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byChildhood- and Neurodevelopment-Related Psychiatric DisordersNed H. Kalin, M.D.1 January 2023 | American Journal of Psychiatry, Vol. 180, No. 1 Volume 180Issue 1 January 01, 2023Pages 14-16 Metrics KeywordsNeurodevelopmental DisordersADHDGenetics / GenomicsEnvironmental Risk FactorsPDF download History Accepted 4 November 2022 Published online 1 January 2023 Published in print 1 January 2023" @default.
• W4313441493 created "2023-01-06" @default.
• W4313441493 creator A5063823796 @default.
• W4313441493 date "2023-01-01" @default.
• W4313441493 modified "2023-09-23" @default.
• W4313441493 title "ADHD: The Mammoth Task of Disentangling Genetic, Environmental, and Developmental Risk Factors" @default.
• W4313441493 cites W2014614243 @default.
• W4313441493 cites W2072639973 @default.
• W4313441493 cites W2108035383 @default.
• W4313441493 cites W2112041738 @default.
• W4313441493 cites W2113747602 @default.
• W4313441493 cites W2123858748 @default.
• W4313441493 cites W2145163559 @default.
• W4313441493 cites W2409075348 @default.
• W4313441493 cites W2775641245 @default.
• W4313441493 cites W2799563959 @default.
• W4313441493 cites W2802815532 @default.
• W4313441493 cites W2895924317 @default.
• W4313441493 cites W2917099287 @default.
• W4313441493 cites W2943360197 @default.
• W4313441493 cites W3036721578 @default.
• W4313441493 cites W3126475346 @default.
• W4313441493 cites W3143087457 @default.
• W4313441493 cites W4290098908 @default.
• W4313441493 cites W4297613935 @default.
• W4313441493 doi "https://doi.org/10.1176/appi.ajp.20220916" @default.
• W4313441493 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36587269" @default.
• W4313441493 hasPublicationYear "2023" @default.
• W4313441493 type Work @default.
• W4313441493 citedByCount "2" @default.
• W4313441493 countsByYear W43134414932023 @default.
• W4313441493 crossrefType "journal-article" @default.
• W4313441493 hasAuthorship W4313441493A5063823796 @default.
• W4313441493 hasConcept C127413603 @default.
• W4313441493 hasConcept C138496976 @default.
• W4313441493 hasConcept C15744967 @default.
• W4313441493 hasConcept C166957645 @default.
• W4313441493 hasConcept C180747234 @default.
• W4313441493 hasConcept C201995342 @default.
• W4313441493 hasConcept C205649164 @default.
• W4313441493 hasConcept C2780451532 @default.
• W4313441493 hasConcept C2780964940 @default.
• W4313441493 hasConcept C78458016 @default.
• W4313441493 hasConcept C86803240 @default.
• W4313441493 hasConceptScore W4313441493C127413603 @default.
• W4313441493 hasConceptScore W4313441493C138496976 @default.
• W4313441493 hasConceptScore W4313441493C15744967 @default.
• W4313441493 hasConceptScore W4313441493C166957645 @default.
• W4313441493 hasConceptScore W4313441493C180747234 @default.
• W4313441493 hasConceptScore W4313441493C201995342 @default.
• W4313441493 hasConceptScore W4313441493C205649164 @default.
• W4313441493 hasConceptScore W4313441493C2780451532 @default.
• W4313441493 hasConceptScore W4313441493C2780964940 @default.
• W4313441493 hasConceptScore W4313441493C78458016 @default.
• W4313441493 hasConceptScore W4313441493C86803240 @default.
• W4313441493 hasIssue "1" @default.
• W4313441493 hasLocation W43134414931 @default.
• W4313441493 hasLocation W43134414932 @default.
• W4313441493 hasOpenAccess W4313441493 @default.
• W4313441493 hasPrimaryLocation W43134414931 @default.
• W4313441493 hasRelatedWork W1968116410 @default.
• W4313441493 hasRelatedWork W2016713905 @default.
• W4313441493 hasRelatedWork W2030000401 @default.
• W4313441493 hasRelatedWork W2052460212 @default.
• W4313441493 hasRelatedWork W2064484569 @default.
• W4313441493 hasRelatedWork W2092756134 @default.
• W4313441493 hasRelatedWork W2150658094 @default.
• W4313441493 hasRelatedWork W2334446790 @default.
• W4313441493 hasRelatedWork W2727442597 @default.
• W4313441493 hasRelatedWork W4241181729 @default.
• W4313441493 hasVolume "180" @default.
• W4313441493 isParatext "false" @default.
• W4313441493 isRetracted "false" @default.
• W4313441493 workType "article" @default.