Kazan medical journalKazan medical journalКазанский медицинский журнал0368-48142587-9359Eco-Vector1555710.17816/KMJ2019-689ReviewsОбзорыReview ArticleSomatic disorders in autism as one of the factors of behavioral and social interaction disordersСоматические нарушения при аутизме как один из факторов нарушения поведения и социального взаимодействияIvanovaD VИвановаДарья Викторовнаauziganshin@gmail.comSeminaI IСёминаИрина Ивановнаauziganshin@gmail.comZiganshinA UЗиганшинАйрат Усмановичauziganshin@gmail.comKazan State Medical UniversityКазанский государственный медицинский университет3107201910046896943107201931072019Copyright ©; 2019, Ivanova D.V., Semina I.I., Ziganshin A.U.Copyright ©; 2019, Иванова Д.В., Сёмина И.И., Зиганшин А.У.2019Ivanova D.V., Semina I.I., Ziganshin A.U.Иванова Д.В., Сёмина И.И., Зиганшин А.У.http://creativecommons.org/licenses/by-nc-sa/4.0https://kazanmedjournal.ru/kazanmedj/article/view/15557

Autism is a pressing global problem in a number of medical and related scientific disciplines. For autism, a polysystemic feature is typical, and neurological changes are usually accompanied by somatic ones, most often affecting the intestine, pancreas, and often lungs, pelvic organs, kidneys, adrenal glands and other organs. It is not surprising that the mortality from somatic causes in such children exceeds the mortality of healthy children of the same age groups by 3–10 or more times (depending on the severity of autism). Many studies report a high prevalence of gastrointestinal symptoms in autistic people. The most common of these is chronic constipation (22% on average). The functional interaction of the gastrointestinal tract and the central nervous system is due to the presence of various connections and includes the autonomic nervous, immune and neuroendocrine systems. Of particular importance in gastrointestinal disorders and the pathogenesis of autism is the intestinal microbiota, a complex bacterial community located in the gastrointestinal tract. Under the influence of external and internal factors, the microbiota changes the permeability of the intestinal and blood-brain barriers, and the metabolites produced by the altered microbiota can enter the bloodstream and the central nervous system, disrupting its functioning. It was proven that there are pronounced differences between the intestinal microbiota of healthy children and autistic children, and directed individual correction often leads to normalization or significant improvement in social and communicative behavior and other deviations typical of children with autism. Thus, violations in the somatic sphere can increase the severity of the clinical presentation of autism, causing various behavioral and communication disorders. Identification of the spectrum of these disorders, as well as the study of the mechanisms of their development and interrelationship, is an urgent problem, the solution of which may be important for determining the tactics of complex therapy of patients with autism spectrum disorders.

Аутизм — актуальная проблема мирового масштаба по ряду медицинских и сопряжённых с ними научных дисциплин. Для аутизма типична полисистемность нарушений, причём неврологические изменения, как правило, сопровождаются соматическими, чаще всего затрагивающими кишечник, поджелудочную железу, нередко — лёгкие, тазовые органы, почки, надпочечники и другие органы. Не удивительно, что смертность от соматических причин у таких детей в 3–10 раз и более (в зависимости от тяжести аутизма) превышает смертность здоровых детей тех же возрастных групп. Во многих исследованиях сообщают о высокой распространённости желудочно-кишечных симптомов у аутичных людей. Наиболее частый из них — хронический запор (в среднем 22%). Функциональное взаимодействие желудочно-кишечного тракта и центральной нервной системы обусловлено наличием различных связей и включает вегетативную нервную, иммунную и нейроэндокринную системы. Особое значение в желудочно-кишечных нарушениях и патогенезе аутизма имеет микробиота кишечника — сложное бактериальное сообщество, расположенное в желудочно-кишечном тракте. Под воздействием внешних и внутренних факторов микробиота меняет проницаемость кишечного и гематоэнцефалического барьеров, а метаболиты, вырабатываемые изменённой микробиотой, могут попадать в кровоток и центральную нервную систему, нарушая её функционирование. Доказано, что между микробиотами кишечника здоровых детей и детей-аутистов существуют ярко выраженные различия, а направленная индивидуальная коррекция зачастую ведёт к нормализации или существенному улучшению социально-коммуникативного поведения и других девиаций, типичных для детей с аутизмом. Таким образом, нарушения в соматической сфере могут увеличивать тяжесть клинической картины аутизма, вызывая различные поведенческие и коммуникативные нарушения. Выявление спектра этих нарушений, а также изучение механизмов их развития и взаимосвязи — актуальная проблема, решение которой может иметь значение при определении тактики комплексной терапии пациентов с расстройствами аутистического спектра.

autismautism spectrum disordersgastrointestinal tractsomatic problemsаутизмрасстройства аутистического спектражелудочно-кишечный трактсоматические проблемыРабота частично выполнена при финансовой поддержке РФФИ и Правительства Республики Татарстан в рамках научных проектов №18-44-160009 и 18-00-01658-КОМФИ.Baranov A.A., Maslova O.I., Namazova-Baranova L.S. Ontogenesis of the neurocognitive development of a child. Vestnik RAMN. 2012; (8): 26–34. (In Russ.)Баранов А.А., Маслова О.И., Намазова-Баранова Л.С. Онтогенез нейрокогнитивного развития ребёнка. Вестн. РАМН. 2012; (8): 26–34. DOI: 10.15690/vramn.v67i8.346.Maslova O.I., Baranov A.A., Namazova-Baranova L.S. et al. Current aspects of the study of the cognitive sphere in child development. Pediatricheskaya farmakologiya. 2012; 9 (6): 61–72. (In Russ.)Маслова О.И., Баранов А.А., Намазова-Баранова Л.С. и др. Современные аспекты изучения когнитивной сферы в развитии ребёнка. Педиатрич. фармакол. 2012; 9 (6): 61–72.Karkashadze G.A., Maslova O.I., Namazova-Baranova L.S. Actual problems of diagnosing and treating mild cognitive impairment in children. Pediatricheskaya farmakologiya. 2011; 8 (5): 37–41. (In Russ.)Каркашадзе Г.А., Маслова О.И., Намазова-Баранова Л.С. Актуальные проблемы диагностики и лечения лёгких когнитивных нарушений у детей. Педиатрич. фармакол. 2011; 8 (5): 37–41.Chakrabarti S., Fombonne E. Pervasive developmental disorders in preschool children: confirmation of high prevalence. Am. J. Psychiatry. 2005; 162: 1133–1141. DOI: 10.1176/appi.ajp.162.6.1133.Fombonne E. Is there an epidemic of autism? Pediatrics. 2001; 107 (2): 411–412. DOI: 10.1542/peds.107.2.411.Mulvihill B., Wingate M., Kirby R.S. et al. Preva­lence of autism spectrum disorders — Autism and deve­lopmental disabilities monitoring network, United States, 2006. MMWR Surveill Summ. 2009; 58 (10): 1–20. PMID: 20023608.Simashkova N.V., Koval’-Zaytsev A.A., Zvereva N.V., Khromov A.I. Cognitive deficit in the structure of autism spectrum disorders. Psykhiatriya. 2010; (6): 5–15. (In Russ.)Симашкова Н.В., Коваль-Зайцев А.А., Зверева Н.В., Хромов А.И. Когнитивный дефицит в структуре расстройств аутистического спектра. Психиатрия. 2010; (6): 5–15.Simashkova N.V. Rasstroystva autisticheskogo spektra u detey. (Disorders of the autism spectrum in children.) Moscow: Avtorskaya akademiya. 2013; 8–30. (In Russ.)Симашкова Н.В. Расстройства аутистического спектра у детей. М.: Авторская академия. 2013; 8–30.Tiganov A.S. Psikhiatriya. (Psychiatry.) Guide for doctors. Moscow: Miditsina. 2012; 12–36. (In Russ.)Тиганов А.С. Психиатрия. Рук-во для врачей. М.: Медицина. 2012; 12–36.Simashkova N.V., Makushkin E.V. Rasstroystva autisticheskogo spektra: diagnostika, lechenie, nablyudenie. (Autism Spectrum Disorders: diagnosis, treatment, observation.) Clinical recommendations (treatment protocol). 2015; 50 р. (In Russ.)Симашкова Н.В., Макушкин Е.В. Расстройства аутистического спектра: диагностика, лечение, наблюдение. Клинические рекомендации (протокол лечения). 2015; 50 c.Diagnostic and statistical manual of mental disorders. Fifth edition. Arlington: American Psychiatric Association. 2013. DOI: 10.1176/appi.books.9780890425596.Poletaev A., Poletaeva A., Pukhalenko A. et al. Adaptive maternal immune deviations as a ground for autism spectrum disorders development in the child. Folia Med. 2014; 56 (2): 73–80. DOI: 10.2478/folmed-2014-0011.Rossignol D.A., Frye R.E. A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Mol. Psychiatry. 2012; 17: 389–401. DOI: 10.1038/mp.2011.165.Medical comorbidities in аutism spectrum disorders. nationalautismassociation.org/pdf/MedicalComorbiditiesinASD2013.pdf (access date: 01.06.2019).Maljaars J., Noens I., Scholte E, van Berckelaer-Onnes I. Evaluation of the criterion and convergent validity of the Diagnostic Interview for Social and Communication Disorders in young and low-functioning children. Autism. 2012; 16 (5): 487–497. DOI: 10.1177/­1362361311402857.Tsuji S., Yuhi T., Furuhara K. et al. Salivary oxytocin concentrations in seven boys with autism spectrum disorder received massage from their mothers: a pilot study. Front. Psychiatry. 2015; (6): 58. DOI: 10.3389/fpsyt.2015.00058.Van der Meer J.M.J., Lappenschaar M.G.A., Hartman C.A. et al. Homogeneous combinations of ASD-ADHD traits and their cognitive and behavioral correlates in a popu­lation-based sample. J. Atten. Disord. 2017; 21 (9): 753–763. DOI: 10.1177/1087054714533194.Herbert M.R., Sage C. Autism and EMF? Plausibi­lity of a pathophysiological link. Part I. Pathophysiology. 2013; 3: 191–209. DOI: 10.1016/j.pathophys.2013.08.001.Poletaev A.B., Shenderov B.A. Autism: genetics or epigenetics? ARC J. Immun. Vaccines. 2016; 1 (2): 1–7.Poletaev A.B. About drunk and lost keys. Klinicheskaya patofiziologiya. 2017; (3): 3–13. (In Russ.)Полетаев А.Б. Про пьяного и потерянные ключи. Клин. патофизиол. 2017; (3): 3–13.Simeng L., Enyao L., Zhenyu S. et al. Altered gut microbiota and shortchain fatty acids in Chinese children with autism spectrum disorder. Sci. Reports. 2019; 9: 287. DOI: 10.1038/s41598-018-36430-z.Buie T., Campbell D.B., Fuchs G.J. et al. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics. 2010; 125 (Suppl. 1): 1–18. DOI: 10.1542/peds.2009-1878C.Holingue C., Newill C., Lee L. et al. Gastrointestinal symptoms in autism spectrum disorder: a review of the literature on ascertainment and prevalence. Autism Res. 2018; 11: 24–36. DOI: 10.1002/aur.1854.Campbell D.J., Chang J., Chawarska K. Early gene­ralized overgrowth in autism spectrum disorder: prevalence rates, gender effects, and clinical outcomes. J. Am. Acad. Child Adolesc. Psychiatry. 2014; 53 (10): 1063–1073.e5. DOI: 10.1016/j.jaac.2014.07.008.Coury D.L., Ashwood P., Fasano A. et al. Gastrointestinal conditions in children with autism spectrum di­sorder: developing a research agenda. Pediatrics. 2012; 130 (2): 160–168. DOI: 10.1542/peds.2012-0900N.Parracho H.M., Bingham M.O., Gibson G.R., ­McCartney A.L. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J. Med. Microbiol. 2005; 54 (Pt. 10): ­987–991. DOI: 10.1099/jmm.0.46101-0.McElhanon B.O., McCracken C., Karpen S., Sharp W.G. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014; 133 (5): ­872–883. DOI: 10.1542/peds.2013-3995.Buie T., Fuchs G.J., Furuta G.T. et al. Recommendations for evaluation and treatment of common gastrointestinal problems in children with ASDs. Pediatrics. 2010; 125 (Suppl. 1): 19–29. DOI: 10.1542/peds.2009-1878D.Shenderov B.A. Functional nutrition and its role in the prevention of metabolic syndrome. M.: DeLiprint. 2008; 319 р. (In Russ.)Шендеров Б.А. Функциональное питание и его роль в профилактике метаболического синдрома. М.: ДеЛипринт. 2008; 319 с.Heijtz R.D., Wang S., Anuar F. et al. Normal gut microbiota modulates brain development and behavior. Proc. Natl. Acad. Sci. USA. 2011; 108 (7): 3047–3052. DOI: 10.1073/pnas.1010529108.Ogbonnaya E.S., Clarke G., Shanahan F. et al. Adult hippocampal neurogenesis is regulated by themicro­biome. Biol. Psychiatry. 2015; 78 (4): 7–9. DOI: 10.1016/j.biopsych.2014.12.023.Fung T.C., Olson C.A., Hsiao E.Y. Interactions between the microbiota, immune and nervous systems in health and disease. Nat. Neurosci. 2017; 20 (2): 145–155. DOI: 10.1038/nn.4476.Brookes S.J.H., Spencer N.J., Costa M., Zagorodnyuk V.P. Extrinsic primary afferent signalling in the gut. Nat. Rev. Gastroenterol. Hepatol. 2013; 10 (5): 286–296. DOI: 10.1038/nrgastro.2013.29.Li Q., Han Y., Dy A.B.C., Hagerman R.J. The gut microbiota and autism spectrum disorders. Front. Cell. Neurosci. 2017; 11: 120. DOI: 10.3389/fncel.2017.00120.Coury D.L., Ashwood P., Fasano A. et al. Gastrointestinal conditions in children with autism spectrum di­sorder: developing a research agenda. Pediatrics. 2012; 130 (Suppl. 2): 160–168. DOI: 10.1542/peds.2012-0900N.Asano Y., Hiramoto T., Nishino R. et al. Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2012; 303 (11): G1288–G1295. DOI: 10.1152/ajpgi.00341.2012.Strandwitz P. Neurotransmitter modulation by the gut microbiota. Brain Res. 2018; 1693 (Pt. B): 128–133. DOI: 10.1016/j.brainres.2018.03.015.De Palma G., Lynch M.D., Lu J. et al. Transplantation of fecal microbiota from patients with irritable bo­wel syndrome alters gut function and behavior in recipient mice. Sci. Transl. Med. 2017; 9 (379).pii: eaaf6397. DOI: 10.1126/scitranslmed.aaf6397.Kelly J.R., Borre Y., O’Brien C. et al. Transferring the blues: depression-associated gut microbiota induces neurobehavioral changes in the rat. J. Psychiatr. Res. 2016; 82: 109–118. DOI: 10.1016/j.jpsychires.2016.07.019.Ge X., Zhao W., Ding C. et al. Potential role of fecal microbiota from patients with slow transit constipation in the regulation of gastrointestinal motility. Sci. Reports. 2017; 7: 441. DOI: 10.1038/s41598-017-00612-y.Luczynski P., Tramullas M., Viola M. et al. Microbiota regulates visceral pain in the mouse. Elife. 2017; 6. pii: e25887. DOI: 10.7554/eLife.25887.001.Porges S.W. Cardiac vagal tone: a physiological index of stress. Neurosci. Biobehav. Rev. 1995; 19: 225–233. DOI: 10.1016/0149-7634(94)00066-A.Mazefsky C.A., Schreiber D.R., Olino T.M., Minshew N.J. The association between emotional and behavio­ral problems and gastrointestinal symptoms among children with high-functioning autism. Autism. 2014; 18 (5): 493–501. DOI: 10.1177/1362361313485164.Peeters B., Noens I., Philips E.M. et al. Autism spectrum disorders in children with functional defecation disorders. J. Pediatr. 2013; 163 (3): 873–878. DOI: 10.1016/j.jpeds.2013.02.028.Bal E., Harden E., Lamb D. et al. Emotion recognition in children with autism spectrum disorders: relations to eye gaze and autonomic state. J. Autism Dev. Disord. 2010; 40: 358–370. DOI: 10.1007/s10803-009-0884-3.Ming X., Julu P.O., Brimacombe M. et al. Reduced cardiac parasympathetic activity in children with autism. Brain Dev. 2005; 27: 509–516. DOI: 10.1016/j.braindev.2005.01.003.Van Hecke A.V., Lebow J., Bal E. et al. Electroencephalogram and heart rate regulation to familiar and unfamiliar people in children with autism spectrum disorders. Child Dev. 2009; 80: 1118–1133. DOI: 10.1111/j.1467-8624.2009.01320.x.Hirstein W., Iversen P., Ramachandran V.S. Autonomic responses of autistic children to people and objects. Proc. Biol. Sci. R. Soc. 2001; (268): 1883–1888. DOI: 10.1098/rspb.2001.1724.Rash J.A., Aguirre-Camacho A. Attention-deficit hyperactivity disorder and cardiac vagal control: a syste­matic review. Attent. Deficit Hyperact. Disord. 2012; (4): 167–177. DOI: 10.1007/s12402-012-0087-1.Marshall P.J., Fox N.A. The development of social engagement: Neurobiological perspectives. New York: Oxford University Press. 2006; 440.Porges S.W. The vagus: A mediator of behavioral and visceral features associated with autism. The Neurobiology of Autism. Baltimore, MD: John Hopkins University Press. 2004; 65–78.Di Palma S., Tonacci A., Narzisi A. et al. Moni­toring of autonomic response to sociocognitive tasks during treatment in children with autism spectrum disorders by wearable technologies: A feasibility study. Comput. Biol. Med. 2016; 85: 143–152. DOI: 10.1016/j.compbiomed.2016.04.001.Panju S., Brian J., Dupuis A. et al. Atypical sympathetic arousal in children with autism spectrum disorder and its association with anxiety symptomatology. Mol. Autism. 2015; 6: 64. DOI: 10.1186/s13229-015-0057-5.Savanovich I.I., Tretyak I.G. Impaired gluten and casein tolerance in children with autism spectrum disorders. Li­terature review. Psykhiatriya, psykhoterapiya, klinicheskaya psykhologiya. 2015; (1): 1–9. (In Russ.)Саванович И.И., Третьяк И.Г. Нарушение толерантности к глютену и казеину у детей с расстройствами аутистического спектра. Обзор литературы. Психиатрия, психотерап., клин. психол. 2015; (1): 1–9.Shattock P., Hooper M., Waring R. Opioid peptides and dipeptidyl peptidase in autism. Dev. Med. Child. Neurol. 2004; (46): 357. DOI: 10.1111/j.1469-8749.2004.tb00498.x.D'eufemia R., Celli M., Finocchiaro R. et al. Abnormal intestinal permeability in children with autism. Acta. Paediatr. 1996; 85: 1076–1079. DOI: 10.1111/j.1651-2227.1996.tb14220.x.Buie T. The relationship of autism and gluten. Clin. Ther. 2013; 35 (5): 578–583. DOI: 10.1016/j.clinthera.2013.04.011.Krakowiak P., Goines P.E., Tancredi D.J. et al. Neonatal cytokine profiles associated with autism spectrum disorder. Biol. Psychiatry. 2017; 81 (5): 442–451. DOI: 10.1016/j.biopsych.2015.08.007.Masi A., Quintana D.S., Glozier N. et al. Cytokine aberrations in autism spectrum disorder: a systema­tic review and meta-analysis. Mol. Psychiatry. 2015; 20 (4): 440–446. DOI: 10.1038/mp.2014.59.Moynihan J.A., Santiago F.M. Brain behavior and immunity: twenty years of T cells. Brain Behav. Immun. 2007; 21 (7): 872–880. DOI: 10.1016/j.bbi.2007.06.010.Chen M.-H., Su T.-P., Chen Y.-S. et al. Comorbidity of allergic and autoimmune diseases in patients with autism spectrum disorder: a nationwide population-based study. Res. Autism Spectr. Disord. 20113; 7 (2): 205–212. DOI: 10.1016/j.rasd.2012.08.008.Miyazaki C., Koyama M., Ota E. et al. Allergies in children with autism spectrum disorder: a systematic review and meta-analysis. Rev. J. Autism Develop. Disord. 2015; 2 (4): 374–401. DOI: 10.1007/s40489-015-0059-4.Schneider T., Przewlocki R. Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism. Neuropsychopharmacology. 2005; 30: 80–89. DOI: 10.1038/sj.npp.1300518.