Mental Health: Global Challenges Journal

https://www.sciendo.com/journal/MHGCJ

ISSN 2612-2138

Literature review

The association between Autism Spectrum Disorder

and Chronic Fatigue Syndrome. A Care Plan

Perspective

Nida Khubaib

Children & Young People Mental Health Services, Leeds Community Healthcare Trust, Leeds, England

Abstract

Introduction:

Autism spectrum disorder (ASD) is a neurodevelopmental condition that shares

clinical features with chronic fatigue syndrome (CFS), a condition affecting the neurological

and immune systems. Emerging evidence suggests a potential link between the two conditions,

including shared genetics and neuropathology. However, there is a paucity of data and lack of

conclusive evidence to draw any definite associations.

Purpose This review aims to gather available evidence to determine whether an association

exists between autism and CFS and to report on published findings.

Methodology:

The search was conducted on databases PUBMED, MEDLINE and Google

Scholar. Eligibility criteria included studies examining the association between autism spectrum

disorder (ASD) and chronic fatigue syndrome (CFS). Exclusion criteria included 1) studies that

reported on autism and chronic fatigue syndrome separately 2) studies that evaluated the

association of autism with conditions other than CFS and 3) and studies that looked at the

association of CFS with conditions other than autism. Non-Engl

ish language studies were

excluded.

Results: A total of eight articles were reviewed for the study and the reported findings indicates

the complex relationship between autism and co-morbid physical health conditions.

Conclusion: This study highlights the need for enhanced awareness among

mental health

practitioners regarding the complex interplay between autism and co-occurring physical health

conditions like CFS presenting in children and young people and appropriate management of

physical health symptoms as part of the overall care plan.

Keywords

Mental Health, autism, autism spectrum disorder, chronic fatigue syndrome, myalgic

encephalomyelitis, care plan.

Address for correspondence:

Nida Khubaib, MBBS, MSc Public Health, MRCPsych; Children & Young People Mental Health

Services, Leeds Community Healthcare Trust, Leeds, England

Address: Parkside Community Health Centre, Leeds, LS11 5LQ

E-mail: nida.khubaib@nhs.net

This work is licensed under a Creative Commons Attribution- 4.0 International License (CC

BY 4.0).

©Copyright: Khubaib, 2025

Publisher: Sciendo (De Gruyter)

DOI: https://doi.org/10.56508/mhgcj.v8i1.265

Submitted for publication:

01 May 2025

Revised: 16 June 2025

Accepted for publication:

23 June 2025

Mental Health: Global Challenges Journal

https://www.sciendo.com/journal/MHGCJ

ISSN 2612-2138

Introduction

Autism spectrum disorder (ASD) is a

neurodevelopmental condition, characterized by

social interaction and communication difficulties,

repetitive and restricted interests, and sensory

behaviours (DSM-5, 2013). On the other hand,

chronic fatigue syndrome (CFS), also referred to

as myalgic encephalomyelitis (ME), is a complex

disease involving widespread inflammation and

dysregulation of the central nervous system (CNS)

and immune system (Carruthers et al, 2011).

There is evidence to suggest that people with ASD

and CFS share overlapping clinical

characteristics, including fatigue, low mood,

anxiety, and reduced self-efficacy, which

impacts upon their overall functioning (Rogers et

al, 2017). It has been reported that unexplained

chronic fatigue and increased sensitivity to pain

are common in both ASD and CFS (Forde et al,

2022, Mariman et al, 2013 and Keville et al,

2021). In addition, sleep difficulties, brain fog and

variable deficits in emotional awareness have

also been observed in both groups (Maroti et al,

2017, Mariman et al, 2013, Devnani et al, 2015,

and Ocon, 2013).

However, some recent explorations have ruled

out a direct link between ASD and CFS

(Bileviciute-Ljungar et al, 2018). Although CFS and

ASD are distinct diagnoses, certain situations can

be challenging; for instance, when a person with

social interaction difficulties presents with

unexplained fatigue at a young age. Although

autism typically presents in early childhood (DSM-

5, 2013) and CFS usually affects middle-aged

adults (Chu et al, 2019 and Bakken et al, 2014), it

is not uncommon for a fatigued, emotionally

detached CFS patient to be referred for an ASD

assessment. On the other hand, patients with ASD

are often evaluated in physical health clinics to

assess for a CFS co-morbidity that could explain

their chronic mental and physical fatigue.

Purpose

There is currently very limited data on the

association between ASD and CFS. The aim of

this review is to gather evidence and examine

potential associations between autism and

chronic fatigue syndrome and explore the

possibility of shared genetic influences and similar

neuropathology between the two conditions.

Additionally, the study also aims to review recent

findings around the possible role of anti-

inflammatory drugs in the treatment of ASD and

CFS considering the role of inflammatory

processes involved in the pathogenesis of both

conditions.

Methodology

Literature search was performed on

databases PUBMED, MEDLINE and Google

Scholar. Eligibility criteria included all studies that

looked at the association between autism

spectrum disorder (ASD) and chronic fatigue

syndrome (CFS). Exclusion criteria included 1)

studies that reported on autism and chronic

fatigue syndrome separately 2) studies that

evaluated the association of autism with

conditions other than CFS and 3) and studies that

looked at the association of CFS with conditions

other than autism. Studies published in a

language other than English were also excluded.

On PUBMED, searching with MeSH terms

"autism"[MeSH] AND "chronic fatigue

syndrome"[MeSH] yielded 47 articles. After

applying filters for English language, full text

availability and search field (abstract/title), 28

articles were short listed. Out of those, only 4

articles met the eligibility criteria. Full text was not

available for 1 article. This completed the search

with 3 articles. Further advanced search on

PUBMED using key words “autism spectrum

disorder”, “autism spectrum condition” and

“myalgic encephalomyelitis” did not yield any

additional results. On MEDLINE, search was

conducted using the key words “autism” AND

“chronic fatigue syndrome”. The initial search

yielded 26 results. After applying the

inclusion/exclusion criteria, search was narrowed

down to 3 articles, out of which only 2 were new

searches. Google Scholar was searched using

key words “autism spectrum condition” AND

“chronic fatigue syndrome”. Initial search yielded

79 results. No additional articles were retrieved

after searching with MeSH terms “autism”[MeSH]

AND “myalgic encephalomyelitis”[MeSH] and

after applying advanced search filters for time

(anytime), relevance, and type of articles (any

type). 7 articles were shortlisted after excluding

books and applying inclusion/exclusion criteria.

Out of these, 4 were new searches, and full text

was available for only 3 articles, which were

added to the search. This concluded the

literature search with a total of 8 articles for review

(see Figure 1. Flow chart). No systematic reviews

or meta-analyses on the topic of interest were

identified during the literature search.

Ethical considerations

The review was conducted in a responsible

and respectful manner, ensuring transparency,

honesty and integrity of the research process.

Although no direct patient data was collected for

the purpose of this review, all efforts were made

to ensure that the publicly available data and

published papers were collected and reviewed

ethically.

Mental Health: Global Challenges Journal

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ISSN 2612-2138

Figure 1: Search strategy for selection of studies

Flowchart

PUBMED

n=47

(Filters applied)

English

language n= 47

Full text n= 47

Title/Abstract containing

meSH terms

“autism”

and

“CFS”

n= 28

Full text available for new

searches n=3

n=3

n=4

Old searches

New searches

Old searches n=1

New

searches n=2

Full text available n=3

After applying inclusion/

exclusion criteria

n= 3

After applying inclusion/

exclusion criteria

n= 3

After applying inclusion/

exclusion criteria (books

were excluded)

n= 7

MEDLINE n= 26

(Filters applied)

English Language n= 26

Studies on humans n=26

Abstract available n=26

Full text available n=4

Google Scholar n= 79

(Advanced Search filters

applied)

Articles containing MeSH terms

“autism and CFS” n=79

Articles containing MeSH terms

“autism and ME” n=79

Time: anytime

Type of articles: any type

Sort by relevance

PUBMED

n= 47

MEDLINE n= 26

Google Scholar n= 79

Total number of articles

n= 8

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ISSN 2612-2138

Results

A total of eight articles explored the

association between autism spectrum disorder

and chronic fatigue syndrome. Research

indicates that autistic individuals have a higher

prevalence of co-occurring medical conditions

compared to the general population (Grant et al,

2022), however, the underlying mechanisms are

not well understood. There is evidence to suggest

that central sensitivity syndromes (CSS), which

include chronic fatigue syndrome (CFS), are

more prevalent among people with autism

(Grant et al, 2022). Grant et al (2022) investigated

the occurrence of CSS diagnoses and symptoms

in autistic individuals using a Central Sensitization

Inventory (CSI). They reported that in a large

sample of 973 participants, about 4.5% of

people with autism reported a co-occurring

diagnosis of CFS. Although higher scores on the

CSI appeared to be related to stronger autistic

traits, the path analysis suggested that this

relationship was mediated by sensory sensitivity

and anxiety, implying that these two variables

could increase the vulnerability to conditions like

CFS, rather than autism per se (Grant et al, 2022).

Kentrou et al (2024) explored the frequency of

perceived psychiatric misdiagnoses in autistic

individuals before receiving an autism diagnosis.

They reported that about 4% of autistic individuals

who had received a diagnosis of CFS prior to

autism diagnosis, perceived it as a misdiagnosis.

It is interesting to note that most patients were

diagnosed with autism after the age of 18; this

was attributed to autistic traits being potentially

misinterpreted as symptoms of other conditions

like anxiety disorders, CFS/burnout-related

disorders and fibromyalgia etc (Kentrou et al,

2024).

Keville et al captured the mothers’

experiences of co-occurring fatigue in children

with autism spectrum disorder (Keville et al, 2021).

They analyzed semi-structured interviews from

mothers of children with ASD aged 4–19 who also

had severe levels of co-occurring fatigue.

Mothers reported that their children’s fatigue was

mostly a result of culmination of everyday life,

social interactions and sensory demands (Keville

et al, 2021). It is interesting to note that even

when the child had a formal diagnosis of CFS,

their mother continued to seek their own

explanations for fatigue and did not agree with

the diagnosis (Keville et al, 2021). The study

reported that children with ASD experienced

excessive tiredness and intense day time fatigue

which was more unusual than the general

population and significantly affected the

children’s ability to function (Keville et al, 2021).

They argued that the autistic fatigue was different

from the fatigue seen in CFS and that individuals

diagnosed with CFS (in the absence of a known

medical explanation for fatigue) did not show

autistic traits (Bileviciute-Ljungar et al,2018 and

Keville et all, 2021).

Bileviciute-Ljungar et al (2018) examined

whether there was an association between ASD

and CFS and whether individuals with CFS would

score higher on the autism-spectrum quotient

(AQ) when compared to healthy controls. They

found that patients with ASD scored significantly

higher on the AQ as compared to the CFS and

control groups. However, no differences in AQ

scores were found between patients with CFS

and healthy controls (Bileviciute-Ljungar et al,

2018).

Konyenburg (2006), on the other hand,

studied the genetic susceptibility and similarities

between autism and CFS including shared

immune response pathways. He reported that

glutathione metabolism, through its impact on

redox environment, exerts a significant impact on

neuroinflammation and neural apoptosis in both

ASD and CFS, thus providing a link between both

conditions and glutathione depletion. Similar

findings have been validated by other studies

(Bjørklund et al, 2020 and Paul et al, 2021).

Theoharides and Tsilioni (2018) also studied the

neuroimmune and genetic link between ASD and

CFS and aimed to explore the inflammatory

processes involved in the pathogenesis of both

conditions. They reported that ASD and CFS both

involve focal inflammation in hypothalamus and

amygdala which could explain most symptoms

in both conditions (Theoharides and Tsilioni, 2018).

They reported that neuropeptides and cytokine

stimulation of mast cells and microglia during

early development adversely affects the brain in

ASD and that similar neuroimmune dysfunction

and neuroinflammation has also been proposed

in CFS (Theoharides and Tsilioni, 2018). Since

intranasal administration of anti-inflammatory

drugs has shown to reduce inflammation in mice

models (Sun et al, 2010 and Zhuang et al, 2011),

they proposed treatment with

tetramethoxyluteolin, a mast-cell inhibitor, which

could potentially reduce inflammation by directly

reaching the diencephalon through the cribriform

plexus. Theoharides and Tsilioni (2018) also

reported that tetramethoxyluteolin has shown to

improve attention and sociability in children with

ASD. They quoted evidence that treatment with

flavonoids/luteolin has improved symptoms of

ASD in children (Taliou et al, 2013) and has also

shown to reduce symptoms of CFS in

experimental models (Sachdeva et al, 2009 and

Kuo et al, 2009). However, because of limited

data on its use in humans, they did not draw

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definite conclusions rather suggested it as an

area of further research in future.

Lintas et al (2011) and Satterfield et al (2010)

aimed to explore the association between

xenotropic murine leukaemia virus-related virus

(XMRV), CFS and autism. They based their study

on the evidence that XMRV had been implicated

in chronic fatigue syndrome (Lombardi et al,

2009) and queried whether XMRV could be found

in individuals with ASD, establishing a link between

the two conditions. They screened blood samples

from autistic children born to mothers with CFS

using PCR and antibody assays but none of the

samples found any evidence of XMRV infection in

blood cells from patients (Satterfield et al, 2010).

Lintas et al (2011) also screened DNA samples

from ASD patients but no XMRV or other MLV-

related virus was detected in blood and brain

samples of ASD patients. Both studies reported

that infection with XMRV or other MLV-related

viruses was not related to either autism or CFS

pathogenesis (Lintas et al, 2011 and Satterfield et

al, 2010). Three European studies that tried to

validate Lombardi et al (2009) findings also failed

to find XMRV in blood or CSF samples (Erlwein et

al, 2010, Groom et al, 2010 and van Kuppeveld

et al, 2010), refuting the link between the XMRV

and CFS and autism. The primary study (Lombardi

et al, 2009) was later retracted from the

publishing journal because of concerns around

the validity of its results and failure to disclose

important information pertaining to study

methods.

Discussion

Previous research has shown clinical overlap

between autism and various psychiatric and

medical conditions (Kentrou et al, 2024). Grant et

al (2022) published that 21% of autistic individuals

in their study reported having a CSS diagnosis,

including CFS. There are several theoretical

explanations that link autism and CFS to each

other; a core feature common to both autism

and CFS is fatigue and sensory sensitivity (Maroti

et al, 2017, Grant et al, 2022 and Keville et al,

2021). Established evidence indicates that

sensory processing difficulties are a primary

feature of autism (Grant et al, 2022), while similar

sensory sensitivity/amplification is observed in

individuals with CFS (Geisser et al, 2008).

However, research indicates that there remains a

risk of diagnostic overshadowing as clinicians are

often uninformed about co-occurring conditions

in autism (Micai et al, 2021); unexplained fatigue

is often attributed to autistic masking (Pearson

and Rose, 2021) or burnout (Higgins et al, 2021)

when actually it could be a symptom of an

underlying condition like CFS (Grant et al, 2022).

On the other hand, some autistic individuals who

were diagnosed with a co-occurring medical

condition reported that their symptoms resulted

from the challenges of living with undiagnosed

autism rather than distinct co-occurring condition

(Baron-Cohen et al, 2001). The complex

relationship between autism and co-morbid

physical health conditions including CFS warrants

a thorough assessment of people with ASD to

ascertain whether the functional

impairment/fatigue is a part of autism itself or

could be attributed to a particular co-morbid

diagnosis.

On another note, there is growing evidence

around the possible role of neuroinflammation in

the pathogenesis of both ASD and CFS and the

role of anti-inflammatory drugs in treating the two

conditions (Theoharides & Tsilioni, 2018). There are

currently no FDA approved drugs to treat either

CFS or ASD (Tsilioni et al, 2015) however, research

has shown that naturally occurring flavonoids

have potent anti-inflammatory and

neuroprotective actions and have been

discussed as a possible treatment of ASD and

CFS (Theoharides & Tsilioni, 2018). Tailou et al

(2013) conducted an open label trial and

reported significant improvements in

communication, adaptive functioning and

overall behaviours in children with ASD treated

with luteolin capsules for 26 weeks. Another open

label trial replicated similar results and reported

significant improvements in adaptive functioning

in autistic children treated with dietary formulation

containing luteolin (Tsilioni et al, 2015). However,

this is an area of growing research and further

RCTs are needed to validate the reported results.

Limitations

In terms of hierarchy of evidence, reviewed

studies indicate low level of evidence (Melnyk et

al, 2023) and are of not sufficient significance to

make any recommendations or draw definite

conclusions around association between ASD

and CFS (see Table 1). The lack of randomized-

controlled trials contributes to the uncertainty

regarding the efficacy of emerging anti-

inflammatory treatments for ASD and CFS.

Practical Value

This review shows that there is a paucity of

data on the association between autism

spectrum disorder and chronic fatigue syndrome

despite the co-occurrence of physical health

conditions like CFS being increasingly seen in

autistic children and young people in clinical

practice. The review presents a comprehensive

overview of existing research on the topic

highlighting the need for more extensive and

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larger scale studies to further explore and

establish the association between the two

conditions.

Conclusions

The findings highlight the critical need for

enhanced training and awareness of mental

health practitioners regarding the presentation of

autism and the complex relationship between

ASD and co-occurring physical health conditions

like CFS. Physicians should be aware that these

conditions are common in autistic individuals and

recognizing and treating overlapping clinical

symptoms can significantly improve their quality

of life and wellbeing. Additional epidemiological

studies based on larger and more representative

samples of autistic individuals are needed to

replicate current findings and provide more

accurate estimates of association between

autism and CFS.

Funding statement

The author has no funding to declare. No

specific grant from any funding agency in the

public, commercial or not-for-profit sector was

received for this research. The publication fee

was personally covered by the author.

Conflict of interest

The author declares no conflict of interests

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