Re-understanding autism: Fractionable symptoms and quantitative genetics

Yıl 2021, Cilt: 8 Sayı: 2, 186 - 198, 28.06.2021

Esra Zıvralı Yarar

https://doi.org/10.31682/ayna.734371

Öz

Autism spectrum disorder is diagnosed based on impairments in social interaction and communication and engagement in restricted and repetitive behaviors and interests. Understanding the etiology of autism and developing effective interventions can be challenging due to the disorder's complex and heterogeneous nature. The search for a single cause for autism may be the reason for limited progress in the relevant research. The “fractionable autism triad" hypothesis suggests that the symptom domains defining autism are largely independent of each other at behavioral, cognitive, neural, and genetic levels. This paper outlined the evidence for the hypothesis at the genetic level using quantitative genetic methods. Results suggested that genetic factors associated with autism symptoms may differ, giving support to the fractionable autism triad hypothesis. The phenotypical variance within monozygotic twin pairs, lack of plausible associations between the levels of core symptom domains, and differences in genetic and/or environmental factors contributing to different symptom groups indicated the independence of the triad. These findings, which were discussed with limitations and suggestions for future research, are illuminating the heterogeneity of the disorder and lead researchers to new directions for the development of interventions tailored to specific difficulties. This way, treatment protocols can be developed for individuals with difficulties in specific symptom groups and those who could not meet the diagnostic criteria but continue having related difficulties.

Anahtar Kelimeler

autism spectrum disorder, autism symptoms, fractionable autism triad, quantitative genetics

Otizmi Yeniden Anlamak: Parçalanabilir Belirtiler ve Nicel Genetik

Öz

Otizm spektrum bozukluğu, sosyal etkileşimde ve iletişimde güçlükler ile kısıtlı/tekrarlayan davranışlar ve ilgi alanları temelinde tanımlanmaktadır. Otizmin etiyolojisini anlamak ve etkili müdahale yolları üretmek, bozukluğun karmaşık doğası ve belirtilerin farklı şekillerde görülebilmesi gibi sebeplerden dolayı zorlayıcı olabilmektedir. Konu hakkında kısıtlı ilerlemenin sebeplerinden biri birbirinden oldukça farklı belirti gruplarını açıklayan tek bir sebep aranması olabilir. Parçalanabilir otizm üçlemesi hipotezi, otizmi karakterize eden belirti gruplarının davranışsal, bilişsel ve genetik düzeylerde büyük ölçüde birbirinden bağımsız olabileceğini önermektedir. Bu makale, söz konusu hipoteze kanıt teşkil edebilecek nicel genetik yöntemler ile elde edilen bulguları değerlendirmeyi amaçlamaktadır. Söz konusu bulgular, otizm belirtilerinin genetik temellerinin farklılık gösterebildiğine işaret etmekte ve parçalanabilir otizm üçlemesi hipotezini desteklemektedir. Tek yumurta ikizlerinde görülen fenotipik varyanslar, belirti grupları arasında yeterli düzeyde anlamlı ilişkinin bulunamayışı ve hem genetik hem de çevresel faktörlerin etkisi açısından tespit edilen farklılıklar otizm belirtilerinin birbirinden bağımsız değerlendirilebileceğine işaret etmektedir. Belirli kısıtlılıklar ve bunlara yönelik öneriler ışığında tartışılan bulgular otizmin heterojen yapısını anlamayı kolaylaştırmakta ve etkili müdahale teknikleri geliştirilebilmesi için yol göstermektedir. Böylece, belirli belirti gruplarında daha çok güçlüğü bulunan otizm tanısı almış bireyler kadar tanı kriterini karşılayacak kadar çeşitli belirtilere sahip olmayan ancak yoğun güçlük yaşayan bireyler için faydalı olacak müdahale protokollerinin oluşturulabileceğine dikkat çekilmiştir.

Anahtar Kelimeler

otizm spektrum bozukluğu, otizm belirtileri, parçalanabilir otizm üçlemesi, nicel genetik

Kaynakça

• American Psychiatric Association (APA). (2013). Diagnostic and statistical manual of mental disorders (5. Baskı). Washington, DC: Author.
• Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E. ve Rutter, M. (1995). Autism as a strongly genetic disorder: Evidence from a British twin study. Psychological Medicine, 25(01), 63–77. https://doi.org/10.1017/S0033291700028099
• Bargiela, S., Steward, R. ve Mandy, W. (2016). The experiences of late-diagnosed women with autism spectrum conditions: An investigation of the female autism phenotype. Journal of Autism and Developmental Disorders, 46(10), 3281–3294. https://doi.org/10.1007/s10803-016-2872-8
• Bolton, P., Macdonald, H., Pickles, A., Rios, P., Goode, S., Crowson, M., Bailey, A. ve Rutter, M. (1994). A case-control family history study of autism. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 35(5), 877–900. https://doi.org/10.1111/j.1469-7610.1994.tb02300.x
• Bruder, C. E., Piotrowski, A., Gijsbers, A. A., Andersson, R., Erickson, S., de Ståhl, T. D., ... Crowley, M. (2008). Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. The American Journal of Human Genetics, 82(3), 763–771. https://doi.org/10.1016/j.ajhg.2007.12.011
• Brunsdon, V. E. ve Happé, F. (2014). Exploring the ‘fractionation’of autism at the cognitive level. Autism, 18(1), 17–30. https://doi.org/10.1177/1362361313499456
• DeFries, J. C. ve Fulker, D. W. (1985). Multiple regression analysis of twin data. Behavior Genetics, 15(5), 467–473. https://doi.org/10.1007/BF01066239
• Dworzynski, K., Happé, F., Bolton, P. ve Ronald, A. (2009). Relationship between symptom domains in autism spectrum disorders: A population based twin study. Journal of Autism and Developmental Disorders, 39(8), 1197–1210. https://doi.org/10.1007/s10803-009-0736-1
• Folstein, S. ve Rutter, M. (1977). Genetic influences and infantile autism. Nature, 265(5596), 726–728. https://doi.org/10.1038/265726a0
• Frith, U. (2003). Autism explaining the enigma (3. Baskı). Oxford: Blackwell.
• Happé, F. ve Frith, U. (2020). Annual research review: Looking back to look forward–changes in the concept of autism and implications for future research. Journal of Child Psychology and Psychiatry, 61(3), 218–232. https://doi.org/10.1111/jcpp.13176
• Happé, F. ve Ronald, A. (2008). The “fractionable autism triad”: A review of evidence from behavioural, genetic, cognitive and neural research. Neuropsychology Review, 18(4), 287– 304. https://doi.org/10.1007/s11065-008-9076-8
• Happé, F., Ronald, A. ve Plomin, R. (2006). Time to give up on a single explanation for autism. Nature Neuroscience, 9(10), 1218–1220. https://doi.org/10.1038/nn1770
• Kim, S. H. ve Lord, C. (2012). Combining information from multiple sources for the diagnosis of autism spectrum disorders for toddlers and young preschoolers from 12 to 47 months of age. Journal of Child Psychology and Psychiatry, 53(2), 143–151. https://doi.org/10.1111/j.1469-7610.2011.02458.x
• Kolevzon, A., Smith, C. J., Schmeidler, J., Buxbaum, J. D. ve Silverman, J. M. (2004). Familial symptom domains in monozygotic siblings with autism. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics, 129(1), 76–81. https://doi.org/10.1002/ajmg.b.30011
• Le Couteur, A., Bailey, A., Goode, S., Pickles, A., Gottesman, I., Robertson, S. ve Rutter, M. (1996). A broader phenotype of autism: The clinical spectrum in twins. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 37(7), 785–801. https://doi.org/10.1111/j.1469- 7610.1996.tb01475.x
• Loomes, R., Hull, L. ve Mandy, W. P. L. (2017). What is the male-to-female ratio in autism spectrum disorder? A systematic review and meta-analysis. Journal of the American Academy of Child and Adolescent Psychiatry, 56(6), 466–474. https://doi.org/10.1016/j.jaac.2017.03.013
• Mazefsky, C. A., Goin-Kochel, R. P., Riley, B. P. ve Maes, H. H. (2008). Genetic and environmental influences on symptom domains in twins and siblings with autism. Research in Autism Spectrum Disorders, 2(2), 320–331. https://doi.org/10.1016/j.rasd.2007.08.002
• Mazefsky, C. A., Oswald, D. P., Day, T. N., Eack, S. M., Minshew, N. J. ve Lainhart, J. E. (2012). ASD, a psychiatric disorder, or both? Psychiatric diagnoses in adolescents with high-functioning ASD. Journal of Clinical Child and Adolescent Psychology, 41(4), 516–523. https://doi.org/10.1080/15374416.2012.686102
• Newschaffer, C. J., Fallin, D. ve Nora, L. L. (2002). Heritable and nonheritable risk factors for autism spectrum disorders. Epidemiologic Reviews, 24(2), 137–153. https://doi.org/10.1093/epirev/mxf010
• Pickles, A., Starr, E., Kazak, S., Bolton, P. ve Papanikolaou, K. (2000). Variable expression of the autism broader phenotype: Findings from extended pedigrees. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 41(4), 491–502. https://doi.org/10.1111/1469-7610.00634
• Plomin, R., DeFries, J. C., Knopik, V. S. ve Neiderhiser, J. M. (2013). Behavioral genetics (6. Baskı). New York: Worth.
• Ritvo, E. R., Freeman, B. J., Mason-Brothers, A., Mo, A. ve Ritvo, A. M. (1985). Concordance for the syndrome of autism in 40 pairs of afflicted twins. American Journal of Psychiatry, 142(1), 74–77. https://doi.org/10.1176/ajp.142.1.74
• Robinson, E. B., Koenen, K. C., McCormick, M. C., Munir, K., Hallett, V., Happé, F., Plomin, R. ve Ronald, A. (2011). Evidence that autistic traits show the same etiology in the general population and at the quantitative extremes (5%, 2.5%, and 1%). Archives of General Psychiatry, 68(11), 1113–1121. https://doi.org/10.1001/archgenpsychiatry.2011.119
• Robinson, E. B., Koenen, K. C., McCormick, M. C., Munir, K., Hallett, V., Happé, F., Plomin, R. ve Ronald, A. (2012). A multivariate twin study of autistic traits in 12-year-olds: Testing the fractionable autism triad hypothesis. Behavior Genetics, 42(2), 245–255. https://doi.org/10.1007/s10519-011-9500-3
• Ronald, A., Happé, F., Bolton, P., Butcher, L. M., Price, T. S., Wheelwright, S., Baron-Cohen, S. ve Plomin, R. (2006a). Genetic heterogeneity between the three components of the autism spectrum: A twin study. Journal of the American Academy of Child and Adolescent Psychiatry, 45(6), 691–699. https://doi.org/10.1097/01.CHI.0000215325.13058.9D
• Ronald, A., Happé, F. ve Plomin, R. (2005). The genetic relationship between individual differences in social and nonsocial behaviours characteristic of autism. Developmental Science, 8(5), 444–458. https://doi.org/10.1111/j.1467-7687.2005.00433.x
• Ronald, A., Happé, F., Price, T. S., Baron-Cohen, S. ve Plomin, R. (2006b). Phenotypic and genetic overlap between autistic traits at the extremes of the general population. Journal of the American Academy of Child and Adolescent Psychiatry, 45(10), 1206–1214. https://doi.org/10.1097/01.chi.0000230165.54117.41
• Ronald, A. ve Hoekstra, R. A. (2011). Autism spectrum disorders and autistic traits: A decade of new twin studies. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 156(3), 255–274. https://doi.org/10.1002/ajmg.b.31159
• Ronald, A., Larsson, H., Anckarsäter, H. ve Lichtenstein, P. (2011). A twin study of autism symptoms in Sweden. Molecular Psychiatry, 16(10), 1039–1047. https://doi.org/10.1038/mp.2010.82
• Steffenburg, S., Gillberg, C., Hellgren, L., Andersson, L., Gillberg, I. C., Jakobsson, G. ve Bohman, M. (1989). A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. Journal of Child Psychology and Psychiatry, 30(3), 405–416. https://doi.org/10.1111/j.1469-7610.1989.tb00254.x
• Szatmari, P., MacLean, J. E., Jones, M. B., Bryson, S. E., Zwaigenbaum, G. B., Mahoney, W. J. ve Tuff, L. (2000). The familial aggregation of the lesser variant in biological and nonbiological relatives of PDD probands: A family history study. Journal of Child Psychology and Psychiatry, 41(05), 579–586. https://doi.org/10.1111/1469-7610.00644