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

Andy

Andy

Retired committee member
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.
 
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The link between ADHD and chronic fatigue is illuminated by a new study that suggests higher levels of inflammation in neurodivergent kids may be to blame.

Children with ADHD or autism are twice as likely to experience chronic disabling fatigue by the age of 18, even when controlling for comorbid depression, according to a new study published in the journal BMJ Open. Researchers point to the high levels of inflammation (often resulting from elevated stress levels) found among research subjects as a possible explanation for this association.1

While previous research has demonstrated a high prevalence of chronic fatigue in patients with ADHD,2 this is the first study to investigate potential mechanisms underlying the association.

Data from The Avon Longitudinal Study of Parents and Children (ALSPAC) was analyzed to assess whether children who scored above the threshold for ADHD or autism at ages 7 and 9 had an increased risk of chronic disabling fatigue at age 18. Mediation analyses were performed to investigate whether an inflammatory marker (IL-6) at age 9 was linked to fatigue and neurodivergence.

In fact, it did. IL-6 levels at age 9 were associated with a higher likelihood of chronic disabling fatigue at age 18. Though the causes of inflammation are myriad, it is often exacerbated by elevated stress levels, common among neurodivergent children.

“Research shows that neurodivergent children experience higher levels of loneliness, and are more likely to experience bullying,” the authors of the study explain. “Neurodivergent children are also more vulnerable to experience pain.”

In addition to chronic fatigue, adults with ADHD suffer in higher numbers with many different physical conditions. In fact, a recent study found that adults with ADHD are at elevated risk for 34 of 35 conditions studied, including nervous system, respiratory, musculoskeletal, metabolic, circulatory, gastrointestinal, genitourinary, and skin conditions. 3 These include:

  • ulcer or chronic gastritis
  • pulmonary disease
  • Type 2 diabetes
  • epilepsy
  • heart failure
  • kidney infections
  • spinal conditions
  • eczema
The mechanisms of action underlying the association between ADHD and its comorbid physical conditions are not yet known, but this study brings us one step closer to understanding a complex and critically important picture, the authors of the study explain.

“Children who are suspected to be or diagnosed as neurodivergent should routinely be screened for physical and mental health concerns,” they urge. “Earlier integration of brain-body concerns in a holistic framework can facilitate tailored support and improve quality of life of neurodivergent individuals.”

Putting a Spotlight on Chronic Fatigue
“When you think of hyperactivity, you think of talking non-stop, fidgeting, interrupting, distractible,” says Walt Karniski, M.D., a developmental pediatrician. “Lethargy is the last thing you would think about.” Yet, Karniski says he has seen an increase in pediatric patients who present with lethargy as one of the most problematic symptoms. A slightly different approach is needed to treat ADHD patients dealing with chronic fatigue, he adds.

The authors of the study assessed the presence of “chronic disabling fatigue” (defined broadly as lacking energy and getting tired during the last month) rather than the presence of myalgic encephalomyelitis/chronic fatigue syndrome because up to 91% of ME/ CFS cases go undiagnosed. “Despite its evident detrimental impact on quality of life, prolonged or chronic fatigue as a medical symptom is frequently described as an ‘unexplained’ symptom, and patients regularly report being dismissed about their experience,” the study’s authors write.

The symptoms of ME/ CFS include chronic widespread pain, unrefreshing sleep and rest, and dysfunction in the areas of memory, attention, and cognition — many of the same symptoms as ADHD.

“Neurodivergence and chronic fatigue are conditions with complex individual neurodevelopmental pathways,” the researchers explain. “It is therefore likely that inflammation is not the only mediating or moderating factor […] Additional mechanistic insights are needed to disentangle the intricacies of this relationship.”

As is the case with all ADHD comorbidities, optimized treatment is a byproduct of comprehensive diagnostic care and a holistic picture of each individual’s conditions. When diagnoses are missed, patients suffer.

“For years I have struggled with chronic fatigue syndrome, going in cycles of boom and bust. I would work successfully for years, energetic and committed to what I was doing. Eventually, I could no longer sustain the pace and would crash, taking months to recover, unable to work,” explains Cathy, an ADDitude reader in the United Kingdom. “Only recently have I realized that I also have ADHD and begun my journey to a formal diagnosis.”
Click to expand...

https://www.additudemag.com/link-between-adhd-chronic-fatigue/

mixing chronic fatigue with ME/CFS again.
also using 'chronic disabling fatigue' a term frequently used by Crawley.

eta:
study in BMJ here
https://bmjopen.bmj.com/content/14/7/e084203
 
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I sometimes do an exercise of turning the causation around, e.g. Children with neurodivergent traits suffer from higher levels of childhood inflammation …

Because they struggle to communicate that they are feeling unwell and symptoms that are not obvious to parents could go untreated.

Or because the standard of healthcare is generally lower for patients who struggle with conventional communication, especially when medical staff are tired and rushed, or lack training in that area.
 
Some autistic children (and adults) have self-soothing/'stimming' habits such as skin picking and/or difficulties with hygiene routines that mean they are more likely to have repeated infections. I wonder if dietary differences might play a role too.
 
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