Childhood Neurodivergent Traits, Inflammation and Chronic Disabling Fatigue in Adolescence: a Longitudinal Case-control Study

Overview

Journal BMJ Open

Specialty General Medicine

Date 2024 Jul 22

PMID 39038862

Authors

Lisa Quadt

Jenny Csecs

Rod Bond

Neil A Harrison

Hugo D Critchley

Kevin A Davies

Jessica Eccles

Affiliations

Soon will be listed here.

Abstract

Objectives: To test whether inflammatory processes link the expression of childhood neurodivergent traits to chronic disabling fatigue in adolescence.

Design: Longitudinal case-control study.

Setting: We analysed data from The Avon Longitudinal Study of Parents and Children (ALSPAC).

Participants: 8115 and 8036 children of the ALSPAC cohort at ages 7 and 9 years, respectively, 4563 of whom also completed self-report measures at age 18 years.

Primary And Secondary Outcome Measures: We assessed if children scoring above screening threshold for autism/attention deficit hyperactivity disorder (ADHD) at ages 7 and 9 years had increased risk of chronic disabling fatigue at age 18 years, computing ORs and CIs for effects using binary logistic regression. Mediation analyses were conducted to test if an inflammatory marker (interleukin 6 (IL-6)) at age 9 years linked neurodivergent traits to chronic disabling fatigue at age 18 years.

Results: Children with neurodivergent traits at ages 7 and 9 years were two times as likely to experience chronic disabling fatigue at age 18 years (likely ADHD OR=2.18 (95% CI=1.33 to 3.56); p=0.002; likely autism OR=1.78 (95% CI=1.17 to 2.72); p=0.004). Levels of IL-6 at age 9 were associated with chronic disabling fatigue at age 18 (OR=1.54 (95% CI=1.13 to 2.11); p=0.006). Inflammation at age 9 years mediated effects of neurodivergent traits on chronic disabling fatigue (indirect effect via IL-6: ADHD b=1.08 (95% CI=1.01 to 1.15); autism b=1.06; (95% CI=1.03 to 1.10)). All effects remained significant when controlling for the presence of depressive symptoms.

Conclusions: Our results indicate higher risk of chronic disabling fatigue for children with neurodivergent traits, likely linked to higher levels of inflammation. The implementation of transdiagnostic screening criteria to inform support strategies to counteract risk early in life is recommended.

References

Fletcher-Watson S . Transdiagnostic research and the neurodiversity paradigm: commentary on the transdiagnostic revolution in neurodevelopmental disorders by Astle et al. J Child Psychol Psychiatry. 2022; 63(4):418-420. PMC: 9303713. DOI: 10.1111/jcpp.13589. View

Buie T, Campbell D, Fuchs 3rd G, Furuta G, Levy J, Vandewater J . Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics. 2010; 125 Suppl 1:S1-18. DOI: 10.1542/peds.2009-1878C. View

Bileviciute-Ljungar I, Maroti D, Bejerot S . Patients with chronic fatigue syndrome do not score higher on the autism-spectrum quotient than healthy controls: Comparison with autism spectrum disorder. Scand J Psychol. 2018; 59(4):428-432. DOI: 10.1111/sjop.12451. View

Potts B, Smith N, Malamateniou C . Respectful language in autism research: In response to Abdelrahman et al. 'Exploration of radiographers' knowledge, attitudes, and practices in delivering healthcare to children with autism spectrum disorder.'. Radiography (Lond). 2024; 30(2):702-703. DOI: 10.1016/j.radi.2024.02.003. View

Goodman R . Psychometric properties of the strengths and difficulties questionnaire. J Am Acad Child Adolesc Psychiatry. 2001; 40(11):1337-45. DOI: 10.1097/00004583-200111000-00015. View

Appelman B, Charlton B, Goulding R, Kerkhoff T, Breedveld E, Noort W . Muscle abnormalities worsen after post-exertional malaise in long COVID. Nat Commun. 2024; 15(1):17. PMC: 10766651. DOI: 10.1038/s41467-023-44432-3. View

Bauminger N, Kasari C . Loneliness and friendship in high-functioning children with autism. Child Dev. 2000; 71(2):447-56. DOI: 10.1111/1467-8624.00156. View

Lim E, Ahn Y, Jang E, Lee S, Lee S, Son C . Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). J Transl Med. 2020; 18(1):100. PMC: 7038594. DOI: 10.1186/s12967-020-02269-0. View

Sacchetti G, Lefler E . ADHD Symptomology and Social Functioning in College Students. J Atten Disord. 2014; 21(12):1009-1019. DOI: 10.1177/1087054714557355. View

10.

Sukocheva O, Maksoud R, Beeraka N, Madhunapantula S, Sinelnikov M, Nikolenko V . Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome. J Adv Res. 2022; 40:179-196. PMC: 8619886. DOI: 10.1016/j.jare.2021.11.013. View

11.

Theoharides T, Perlman A, Twahir A, Kempuraj D . Mast cell activation: beyond histamine and tryptase. Expert Rev Clin Immunol. 2023; 19(6):639-654. DOI: 10.1080/1744666X.2023.2200936. View

12.

Theoharides T, Stewart J, Panagiotidou S, Melamed I . Mast cells, brain inflammation and autism. Eur J Pharmacol. 2015; 778:96-102. DOI: 10.1016/j.ejphar.2015.03.086. View

13.

Kerekes N, Sanchez-Perez A, Landry M . Neuroinflammation as a possible link between attention-deficit/hyperactivity disorder (ADHD) and pain. Med Hypotheses. 2021; 157:110717. DOI: 10.1016/j.mehy.2021.110717. View

14.

Theoharides T, Kavalioti M, Tsilioni I . Mast Cells, Stress, Fear and Autism Spectrum Disorder. Int J Mol Sci. 2019; 20(15). PMC: 6696098. DOI: 10.3390/ijms20153611. View

15.

Bundgaard-Nielsen C, Knudsen J, Leutscher P, Lauritsen M, Nyegaard M, Hagstrom S . Gut microbiota profiles of autism spectrum disorder and attention deficit/hyperactivity disorder: A systematic literature review. Gut Microbes. 2020; 11(5):1172-1187. PMC: 7524304. DOI: 10.1080/19490976.2020.1748258. View

16.

Hoover D, Kaufman J . Adverse childhood experiences in children with autism spectrum disorder. Curr Opin Psychiatry. 2017; 31(2):128-132. PMC: 6082373. DOI: 10.1097/YCO.0000000000000390. View

17.

Young J, Redmond J . Fibromylagia, chronic fatigue, and adult attention deficit hyperactivity disorder in the adult: a case study. Psychopharmacol Bull. 2007; 40(1):118-26. View

18.

Raymaker D, Teo A, Steckler N, Lentz B, Scharer M, Delos Santos A . "Having All of Your Internal Resources Exhausted Beyond Measure and Being Left with No Clean-Up Crew": Defining Autistic Burnout. Autism Adulthood. 2020; 2(2):132-143. PMC: 7313636. DOI: 10.1089/aut.2019.0079. View

19.

Ferencova N, Visnovcova Z, Ondrejka I, Hrtanek I, Bujnakova I, Kovacova V . Peripheral Inflammatory Markers in Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder at Adolescent Age. Int J Mol Sci. 2023; 24(14). PMC: 10380731. DOI: 10.3390/ijms241411710. View

20.

Skuse D, Mandy W, Scourfield J . Measuring autistic traits: heritability, reliability and validity of the Social and Communication Disorders Checklist. Br J Psychiatry. 2005; 187:568-72. DOI: 10.1192/bjp.187.6.568. View