Neurodevelopmental multimorbidity and educational outcomes of Scottish schoolchildren: A population-based record linkage cohort study

Autoři: Michael Fleming aff001;  Ehsan E. Salim aff001;  Daniel F. Mackay aff001;  Angela Henderson aff001;  Deborah Kinnear aff001;  David Clark aff002;  Albert King aff003;  James S. McLay aff004;  Sally-Ann Cooper aff001;  Jill P. Pell aff001
Působiště autorů: Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom aff001;  Information Services Division, Edinburgh, United Kingdom aff002;  ScotXed, Scottish Government, Edinburgh, United Kingdom aff003;  Department of Child Health, University of Aberdeen, Aberdeen, United Kingdom aff004
Vyšlo v časopise: Neurodevelopmental multimorbidity and educational outcomes of Scottish schoolchildren: A population-based record linkage cohort study. PLoS Med 17(10): e32767. doi:10.1371/journal.pmed.1003290
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003290



Neurodevelopmental conditions commonly coexist in children, but compared to adults, childhood multimorbidity attracts less attention in research and clinical practice. We previously reported that children treated for attention deficit hyperactivity disorder (ADHD) and depression have more school absences and exclusions, additional support needs, poorer attainment, and increased unemployment. They are also more likely to have coexisting conditions, including autism and intellectual disability. We investigated prevalence of neurodevelopmental multimorbidity (≥2 conditions) among Scottish schoolchildren and their educational outcomes compared to peers.

Methods and findings

We retrospectively linked 6 Scotland-wide databases to analyse 766,244 children (390,290 [50.9%] boys; 375,954 [49.1%] girls) aged 4 to 19 years (mean = 10.9) attending Scottish schools between 2009 and 2013. Children were distributed across all deprivation quintiles (most to least deprived: 22.7%, 20.1%, 19.3%, 19.5%, 18.4%). The majority (96.2%) were white ethnicity. We ascertained autism spectrum disorder (ASD) and intellectual disabilities from records of additional support needs and ADHD and depression through relevant encashed prescriptions. We identified neurodevelopmental multimorbidity (≥2 of these conditions) in 4,789 (0.6%) children, with ASD and intellectual disability the most common combination. On adjusting for sociodemographic (sex, age, ethnicity, deprivation) and maternity (maternal age, maternal smoking, sex-gestation–specific birth weight centile, gestational age, 5-minute Apgar score, mode of delivery, parity) factors, multimorbidity was associated with increased school absenteeism and exclusion, unemployment, and poorer exam attainment. Significant dose relationships were evident between number of conditions (0, 1, ≥2) and the last 3 outcomes. Compared to children with no conditions, children with 1 condition, and children with 2 or more conditions, had more absenteeism (1 condition adjusted incidence rate ratio [IRR] 1.28, 95% CI 1.27–1.30, p < 0.001 and 2 or more conditions adjusted IRR 1.23, 95% CI 1.20–1.28, p < 0.001), greater exclusion (adjusted IRR 2.37, 95% CI 2.25–2.48, p < 0.001 and adjusted IRR 3.04, 95% CI 2.74–3.38, p < 0.001), poorer attainment (adjusted odds ratio [OR] 3.92, 95% CI 3.63–4.23, p < 0.001 and adjusted OR 12.07, 95% CI 9.15–15.94, p < 0.001), and increased unemployment (adjusted OR 1.57, 95% CI 1.49–1.66, p < 0.001 and adjusted OR 2.11, 95% CI 1.83–2.45, p < 0.001). Associations remained after further adjustment for comorbid physical conditions and additional support needs. Coexisting depression was the strongest driver of absenteeism and coexisting ADHD the strongest driver of exclusion. Absence of formal primary care diagnoses was a limitation since ascertaining depression and ADHD from prescriptions omitted affected children receiving alternative or no treatment and some antidepressants can be prescribed for other indications.


Structuring clinical practice and training around single conditions may disadvantage children with neurodevelopmental multimorbidity, who we observed had significantly poorer educational outcomes compared to children with 1 condition and no conditions.

Klíčová slova:

ADHD – Autism spectrum disorder – Depression – Children – Labor and delivery – Schools – Intellectual disability – Scottish people


1. The Academy of Medical Sciences. Multimorbidity: a priority for global health research. [cited 2020 Sep 17].

2. Rimal H, Pokharel A. Prevalence of Attention Deficit Hyperactivity Disorder among School Children and Associated Co-morbidities—A Hospital Based Descriptive Study. Kathmandu Univ Med J. 2016;14(55):226–230. 28814683

3. Biederman J, Newcorn J, Sprich S. Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders. Am J Psychiatry. 1991;148(5):564–77. doi: 10.1176/ajp.148.5.564 2018156

4. Kraut AA, Langner I, Lindemann C, Banaschewski T, Petermann U, Petermann F et al. Comorbidities in ADHD children treated with methylphenidate: a database study. BMC Psychiatry. 2013; 13(11) doi: 10.1186/1471-244X-13-11 23294623

5. Carlsson LH, Norrelgen F, Kjellmer L, Westerlund J, Gillberg C, Fernell E. Coexisting disorders and problems in preschool children with autism spectrum disorders. The Scientific World Journal. 2013; 213979. doi: 10.1155/2013/213979 23737708

6. Zaboski BA, Storch EA. Comorbid autism spectrum disorder and anxiety disorders: a brief review. Future Neurol. 2018; 13(1): 31–37 doi: 10.2217/fnl-2017-0030 29379397

7. Van Steensel FJ, Bögels SM, Perrin S. Anxiety disorders in children and adolescents with autistic spectrum disorders: a meta-analysis. Clin Child Fam Psychol Rev. 2011;14(3):302–317. doi: 10.1007/s10567-011-0097-0 21735077

8. White SW, Oswald D, Ollendick T, Scahill L. Anxiety in children and adolescents with autism spectrum disorders. Clin Psychol Rev. 2009; 29(3): 216–229 doi: 10.1016/j.cpr.2009.01.003 19223098

9. Axelson DA, Birmaher B. Relation between anxiety and depressive disorders in childhood and adolescence. Depress Anxiety. 2001;14(2):67–78. doi: 10.1002/da.1048 11668659

10. Melton TH, Croarkin PE, Strawn JR, McClintock SM. Comorbid anxiety and depressive symptoms in children and adolescents: A systematic review and analysis. J Psychiatr Pract. 2016; 22(2): 84–98 doi: 10.1097/PRA.0000000000000132 27138077

11. Schuchardt K, Fischbach A, Balke-Melcher C, Mahler C. The comorbidity of learning difficulties and ADHD symptoms in primary-school-age children. Z Kinder Jugendpsychiatr Psychother. 2015; 43(3): 185–193. doi: 10.1024/1422-4917/a000352 26098006

12. Einfeld SL, Ellis LA, Emerson E. Comorbidity of intellectual disability and mental disorder in children and adolescents: a systematic review. J Intellect Dev Disabil. 2011; 36(2): 137–43. doi: 10.1080/13668250.2011.572548 21609299

13. Sahoo MK, Biswas H, Padhy SK. Psychological Co-morbidity in Children with Specific Learning Disorders. J Family Med Prim Care. 2015; 4(1): 21–25 doi: 10.4103/2249-4863.152243 25810984

14. Gillberg C. The ESSENCE in child psychiatry: Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations. Res Dev Disabil. 2010; 31(6): 1543–51. doi: 10.1016/j.ridd.2010.06.002 20634041

15. Biederman J, Ball SW, Monuteaux MC, Mick E, Spencer TJ, McCreary M et al. New insights into the comorbidity between ADHD and major depression in adolescent and young adult females. J Am Acad Child Adolesc Psychiatry. 2008; 47(4): 426–434. doi: 10.1097/CHI.0b013e31816429d3 18388760

16. Gillberg C, Gillberg IC, Rasmussen P, Kadesjo B, Soderstrom H, Rastam M et al. Co-existing disorders in ADHD—implications for diagnosis and intervention. Eur Child Adolesc Psychiatry. 2004; 13 (Suppl 1): 180–92. doi: 10.1007/s00787-004-1008-4

17. Spencer T, Biederman J, Wilens T: Attention-deficit/hyperactivity disorder and comorbidity. Pediatr Clin North Am. 1999; 46(5): 915–27. doi: 10.1016/s0031-3955(05)70163-2 10570696

18. Moreno-De-Luca A, Myers SM, Challman TD, Moreno-De-Luca D, Evans DW, Ledbetter DH. Developmental brain dysfunction: revival and expansion of old concepts based on new genetic evidence. Lancet Neurol. 2013; 12(4): 406–14 doi: 10.1016/S1474-4422(13)70011-5 23518333

19. Royal College of Psychiatrists. A competency-based curriculum for specialist core training in psychiatry. Core training in psychiatry CT1-CT3. [cited 2020 Sep 17].

20. Royal College of Psychiatrists. A competency-based curriculum for specialist training in psychiatry. Specialists in child and adolescent psychiatry. [cited 2020 Sep 17].

21. Crump C, Rivera D, London R, Landau M, Erlendson B, Rodriguez E. Chronic health conditions and school performance among children and youth. Ann Epidemiol. 2013; 23(4): 179–184. doi: 10.1016/j.annepidem.2013.01.001 23415278

22. Keen D, Webster A, Ridley G. How well are children with autism spectrum disorder doing academically at school? An overview of the literature. Autism. 2016; 20(3): 276–294. doi: 10.1177/1362361315580962 25948598

23. May T, Rinehart N, Wilding J, Cornish K. The role of attention in the academic attainment of children with autism spectrum disorder. J Autism Dev Disord. 2013; 43(9): 2147–2158. doi: 10.1007/s10803-013-1766-2 23378062

24. Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A et al. Educational and Health Outcomes of Children Treated for Attention-Deficit/Hyperactivity Disorder. JAMA Pediatr. 2017; 171(7): e170691. doi: 10.1001/jamapediatrics.2017.0691 28459927

25. Loe IM, Feldman HM. Academic and educational outcomes of children with ADHD. J Pediatr Psychol. 2007; 32(6): 643–654. doi: 10.1093/jpepsy/jsl054 17569716

26. Needham BL. Adolescent depressive symptomatology and young adult educational attainment: an examination of gender differences. J Adolesc Health. 2009; 45(2): 179–186 doi: 10.1016/j.jadohealth.2008.12.015 19628145

27. Fletcher JM. Adolescent depression: diagnosis, treatment, and educational attainment. Health Econ. 2008;17(11): 1215–1235. doi: 10.1002/hec.1319 18157910

28. Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A et al. Educational and health outcomes of children and adolescents receiving antidepressant medication: Scotland-wide retrospective record linkage cohort study of 766 237 schoolchildren. Int J Epidemiol. 2020; 19; dyaa002 doi: 10.1093/ije/dyaa002 32073627

29. Fusaro JA, Shibley IA, Wiley DA. Learning disabilities and performance on the Pennsylvania System of School Assessment. Percept Mot Skills. 2006; 102(3): 760–766. doi: 10.2466/pms.102.3.760-766 16916154

30. Hen M, Goroshit M. Academic procrastination, emotional intelligence, academic self-efficacy, and GPA: a comparison between students with and without learning disabilities. J Learn Disabil. 2014; 47(2): 116–124. doi: 10.1177/0022219412439325 22442254

31. Beckman L, Janson S, von Kobyletzki L. Associations between neurodevelopmental disorders and factors related to school, health, and social interaction in schoolchildren: Results from a Swedish population-based survey. Disabil Health J. 2016; 9(4): 663–672. doi: 10.1016/j.dhjo.2016.05.002 27343047

32. Blackman GL, Ostrander R, Herman KC. Children with ADHD and depression: a multisource, multimethod assessment of clinical, social, and academic functioning. J Atten Disord. 2005; 8(4): 195–207. doi: 10.1177/1087054705278777 16110050

33. Taanila A, Ebeling H, Tiihala M, Kaakinen M, Moilanen I, Hurtig T et al. Association between childhood specific learning difficulties and school performance in adolescents with and without ADHD symptoms: a 16-year follow-up. J Atten Disord. 2014; 18(1): 61–72. doi: 10.1177/1087054712446813 22751677

34. Fleming M. Using Scotland-wide record linkage to investigate the educational and health outcomes off children treated for chronic conditions. PhD thesis. 2017. [cited 2020 Sep 17].

35. Smith TJ, Adams G. The effect of comorbid ADHD and learning disabilities on parent-reported behavioural and academic outcomes of children. Learn Disabil Q. 2006; 29(2): 101–112 doi: 10.2307/30035538

36. Wood R, Clark D, King A, Mackay D, Pell J. Novel cross-sectoral linkage of routine health and education data at an all-Scotland level: a feasibility study. Lancet. 2013; 382: S10 doi: 10.1016/S0140-6736(13)62435-6

37. Scottish Credit and Qualifications Framework (SCQF). [cited 2020 Jan 6].

38. Twisk JWR. Applied longitudinal data analysis for epidemiology: a practical guide. 2nd ed. Cambridge: Cambridge University Press; 2013.

39. Cui J. QIC program and model selection in GEE analyses. Stata Journal. 2007; 7(2): 209–220. doi: 10.1177/1536867X0700700205

40. Loomes R, Hull L, Mandy WPL. What is the male-to-female ratio in Autism Spectrum Disorder? A systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry. 2017; 56(6): 466–474 doi: 10.1016/j.jaac.2017.03.013 28545751

41. Gould J, Ashton-Smith J. Missed diagnosis or misdiagnosis: girls and women on the autism spectrum. Good Autism Practice. 2011; 12(1):34–41.

42. Lai MC, Lombardo MV, Pasco G, Ruigrok ANV, Wheelwright SJ, Sadek SA et al. A behavioural comparison of male and female adults with high functioning autism spectrum conditions. PLoS ONE. 2011; 6(6): e20835. doi: 10.1371/journal.pone.0020835 21695147

43. Nilsson EW, Gillberg C, Gillberg IC, Rastam M. Ten-year follow-up of adolescent-onset anorexia nervosa: personality disorders. J Am Acad Child Adolesc Psychiatry. 1999; 38(11): 1389–95. doi: 10.1097/00004583-199911000-00013 10560225

44. Rydén G, Rydén E, Hetta J. Borderline personality disorder and autism spectrum disorder in females—a cross-sectional study. Clin Neuropsychiatry. 2008; 5(1): 22–30.

45. Holliday-Willey L. Pretending to Be Normal: Living with Asperger’s syndrome. Jessica Kingsley Publishers; 1999.

46. Gillberg C, Coleman M. The Biology of the Autistic Syndromes. 3rd edition. Cambridge University Press; 2000.

47. Thapar A, Collishaw S, Pine DS, Thapar AK. Depression in adolescence. Lancet. 2012; 379(9820):1056–67 doi: 10.1016/S0140-6736(11)60871-4 22305766

48. Abela JRZ, Hankin BL. Handbook of depression in children and adolescents. New York: Guilford Press; 2008.

49. Rucklidge JJ. Gender differences in attention-deficit/hyperactivity disorder. Psychiatr Clin. 2010; 33(2): 357–73. doi: 10.1016/j.psc.2010.01.006 20385342

50. Lillemoen PK, Kjosavik SR, Hunskar S, Ruths S. Prescriptions for ADHD medication, 2004–08. Tidsskr Nor Laegeforen. 2012. 132(16):1856–60. doi: 10.4045/tidsskr.11.1270 22986969

51. Srivastava AK, Schwartz CE. Intellectual disability and autism spectrum disorders: Causal genes and molecular mechanisms. Neurosci Biobehav Rev. 2014; 46(2): 161–174 doi: 10.1016/j.neubiorev.2014.02.015 24709068

52. Robertson J, Hatton C, Emerson E, Baines S. Prevalence of epilepsy among people with intellectual disabilities: A systematic review. Seizure. 2015; 29: 46–62 doi: 10.1016/j.seizure.2015.03.016 26076844

53. Alabaf S, Gillberg C, Lundstrom S, Lichtenstein P, Kerekes N, Rastam M et al. Physical health in children with neurodevelopmental disorders. J Autism Dev Disord. 2019; 49: 83–95 doi: 10.1007/s10803-018-3697-4 30043349

54. Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A et al. Educational and health outcomes of children treated for type 1 diabetes: Scotland-wide record linkage study of 766,047 children. Diabetes Care. 2019; 42(9):1700–1707 doi: 10.2337/dc18-2423 31308017

55. Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A et al. Educational and health outcomes of children treated for asthma: Scotland-wide record linkage study of 683,716 children. Eur Respir J. 2019; 54(3) doi: 10.1183/13993003.02309-2018 31196949

56. Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A et al. Educational and health outcomes of children and adolescents receiving antiepileptic medication: Scotland-wide record linkage study of 766 244 schoolchildren. BMC Public Health. 2019; 19(1): 595 doi: 10.1186/s12889-019-6888-9 31101093

57. Sarginson J, Webb RT, Stocks SJ, Esmail A, Garg S, Ashcroft DM. Temporal trends in antidepressant prescribing to children in UK primary care, 2000–2015. J Affect Disord. 2017; 210: 312–318 doi: 10.1016/j.jad.2016.12.047 28068620

58. Schroder C, Dorks M, Kollhorst B, Blenk T, Dittmann RW, Garbe E et al. Outpatient antidepressant drug use in children and adolescents in Germany between 2004 and 2011. Pharmacoepidemiol Drug Saf. 2017; 26(2): 170–179 doi: 10.1002/pds.4138 27868277

59. John A, Marchant AL, Fone DL, McGregor JI, Dennis MS, Tan JOA et al. Recent trends in primary-care antidepressant prescribing to children and young people: an e-cohort study. Psychol Med. 2016; 46(16): 3315–3327 doi: 10.1017/S0033291716002099 27879187

60. Gardarsdottir H, Heerdink ER, Van Dijk L, Egberts AC. Indications for antidepressant drug prescribing in general practice in the Netherlands. J Affect Disord. 2007; 98(1–2): 109–115 doi: 10.1016/j.jad.2006.07.003 16956665

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PLOS Medicine

2020 Číslo 10

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