A recent study published in BMJ Open reports that neurodivergent traits in childhood increase the risk of chronic disabling fatigue (CDF) at 18 years.

Study: Childhood neurodivergent traits, inflammation and chronic disabling fatigue in adolescence: a longitudinal case–control study. Image Credit: Sharomka / Shutterstock.com

What is CDF?

CDF can accompany various medical conditions, such as myalgic encephalomyelitis (ME/CFS) or long coronavirus disease 2019 (COVID-19). To date, it remains unclear what risk factors may cause certain patients to be more susceptible to the development of chronic fatigue than others.

Current estimates indicate that neurodivergent conditions like autism and attention deficit hyperactivity disorder (ADHD) are present in up to 15% of the population. Neurodivergence is associated with an increased risk of both physical and mental health conditions, some of which include chronic pain, connective tissue disorders, gastrointestinal disorders, anxiety, and depression.

An overlap in symptoms has also been observed between CDF and autism or ADHD. Despite the shared risk of chronic fatigue in both autistic children and adults, most studies examining this association have only been conducted on adults.

Various inflammatory and immunological processes have been implicated in chronic fatigue, including mitochondrial, T-cell, B-cell, and natural killer cell (NK) cell dysfunction. Increased levels of pro-inflammatory interleukin 6 (IL-6) have also been observed in fatigue syndromes present in the general population.

Mast cell activation syndrome (MCAS) arises due to internal or external stimuli that lead to the overactivation of mast cell mediators. MCAS and chronic fatigue, both common in neurodivergent patients, share numerous symptoms and mechanisms, suggesting that inflammation may play a role in the chronic fatigue experienced by neurodivergent individuals.  

About the study

Data for the current study were obtained from the Avon Longitudinal Study of Parents and Children (ALSPAC), which initially obtained data on 14,541 live births in southwest England between April 1991 and December 1992. Two assessments were subsequently conducted when the children were seven and nine years of age, comprising 8,115 and 8,036 children, respectively. At the age of 18, a final evaluation was conducted using self-reported measures.

The researchers aimed to clarify whether an increased risk of CDF was observed at 18 years in children who tested positive for autism or ADHD at either childhood time point. IL-6 levels were also measured in blood samples obtained at the nine-year visit.

What did the study show?

Children with autistic or ADHD traits at seven or nine years of age, respectively, were at a two-fold increased risk of CDF by 18 years of age. Likewise, higher IL-6 levels at nine years of age were associated with a 1.5 times greater risk of experiencing CDF at the age of 18. These results remained significant when controlling for depression.

Mediation analyses showed the indirect impact of higher IL-6 levels in children with both autism and ADHD traits. Among those with these neurodivergent traits, each unit increase in IL-6 levels was associated with an 8% and 6% increased risk of CDF at 18 years of age, respectively.

The higher levels of inflammation could be due to the increased prevalence of gastrointestinal and dental issues observed in neurodivergent individuals. Higher levels of biopsychosocial stress present in neurodivergent children may also lead to increased inflammation and the subsequent experience of CDF. It is also possible that the blood draw itself induced stress to the study participants, particularly those with neurodivergent traits, thereby leading to higher IL-6 levels.

Conclusions

Our results indicate higher risk of chronic disabling fatigue for children with neurodivergent traits, likely linked to higher levels of inflammation.”

The current study provides important insights into the overlap between chronic fatigue, ADHD, and/or autism while also providing evidence on the role of inflammation in mediating the relationship between childhood neurodivergent traits and CDF. Nevertheless, additional research is needed to further examine the different mechanisms, aside from inflammation, that may mediate the relationship between chronic fatigue and neurodivergence.

Neurodivergent children are more vulnerable to physical and mental health conditions, necessitating frequent healthcare visits to monitor their health status. Clinicians are also advised to utilize a holistic approach for treating neurodivergent individuals that considers the brain-body relationship to ultimately improve their quality of life.