Childhood neurodivergent traits, inflammation and chronic disabling fatigue in adolescence: a longitudinal case–control study 2024 Quadt et al

Authors:

1. Lisa Quadt1,
2. Jenny Csecs2,
3. Rod Bond3,
4. Neil A Harrison4,
5. Hugo D Critchley1,
6. Kevin A Davies5,
7. Jessica Eccles1

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.

Open access, https://bmjopen.bmj.com/content/14/7/e084203

 

"Chronic disabling fatigue and depression at age 18 years

Chronic disabling fatigue and depression were assessed at age 18 years using the self-administered computerised version of the CIS-R.62 We included a measure of depression to test for potential confounding effects of depressed mood. Participants were classified as experiencing ‘chronic disabling fatigue’ as defined by Collin et al 65 if they met the following criteria: (1) they had been lacking energy and getting tired during the last month, (2) they responded ‘yes’ to more than two of the following four items: (a) feeling tired or lacking energy for 4 days within the past 7 days; (b) feeling tired of lacking energy for more than 3 hours in total on any day in the past 7 days; (c) feeling so tired or lacking in energy that they had to push themselves to get things done on one or more occasions in the past 7 days; (d) feeling tired or lacking energy when doing things they enjoy in the past 7 days, (3) their fatigue lasted longer than 6 months, (4) their fatigue was not explained by exercise or medication, (5) their fatigue was not alleviated by rest and (6) their fatigue was worse after exercise.65 We use the term ‘chronic disabling fatigue’ instead of ME/CFS to indicate that this was based on self-report instead of a clinical assessment by a physician following a diagnosis of ME/CFS.66"

 

I'm wondering about the reverse causation.

Can having a chronic illness lead to traits that resemble the concept of neurodivergence?

For example, chronic illness can easily lead to loneliness. Prolonged loneliness would be expected to lead to a decay of social skills, which might include skills such as understanding what others are thinking and feeling, or communicating one's inner world to another person.

Having little contact with broader society would also lead to the person having less understanding of social norms, and being more likely to develop their own norms.

Socializing is a form of activity and living with fatigue means having less capacity to socialize. This might look like a lack of interest in socializing.

The experience of having a poorly understood, neglected and disrespected illness would lead to patients feeling not included in society, not feeling part of it, and different in a way that might be hard to put into words. It would make it harder to form and maintain friendships.

I could go on. There are probably many examples one can come up with.