Background
Autistic people are more likely to experience a broad range of physical health issues [
1], including chronic disease and premature mortality [
2,
3] and have poorer general health outcomes [
4] than the wider population. However, the underlying mechanisms are not yet well established. One group of physical problems colloquially thought to be more prevalent in autistic people are ‘central sensitivity syndromes’ (CSS) including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia syndrome (FMS), migraine, irritable bowel syndrome (IBS) restless legs syndrome (RLS) and temporomandibular joint disorder (TMJD). CSS are thought to have central sensitisation, or augmented sensory signalling of the central nervous system, as a core component [
5]; symptoms include fatigue, chronic pain and sensory hypersensitivity. In the general population, prevalence estimates of CSS vary 0.2–20% [
6‐
12] depending on type of syndrome and country. For example, fibromyalgia is thought to be prevalent at between 0.2 and 6.6% in the general population [
6], but the global prevalence for IBS has been more difficult to ascertain, with ranges varying from 5.8% in the Middle East and Africa, up to 17.5% in Latin America [
10].
A core feature common to both autism [
13] and CSS [
14] is sensory sensitivity. While sensory research in autism has been more focussed on altered experience and heightened sensory sensitivity across all modalities [
15], CSS research has been centred around pain [
16]. Therefore, whilst CSS studies have acknowledged that general sensory sensitivity, and not just pain, is part of central sensitisation [
17‐
21], the mechanisms of individual differences in sensory sensitivity within this population, as well as the neurodivergent and general population, are still unclear [
22]. Studies on sensory differences in autism are plentiful [
13,
15,
23,
24] but research specifically on the autistic pain experience is more limited. Research on acute pain in autism, and quantitative sensory testing studies, has suggested that autistic people have a normal or hypersensitive physiological response to acute pain, but may express pain differently [
25‐
28] and also experience more pain-related anxiety [
29], but it has not yet been established whether this anxiety contributes to, or is caused by, altered pain sensitivity. Neural differences in the sustained pain response have also been found in autistic people [
30] but to date there have been no studies exploring the phenomenon of central sensitisation in the autistic population.
Sensory sensitivity is not the only commonality between autism and CSS. The autistic and CSS communities both experience psychosocial factors that can reduce their physical and mental wellbeing, including (but not limited to) poor mental health [
31‐
33], trauma [
34,
35], stigma and discrimination [
36‐
39], socioeconomic disparity [
40,
41] and poor access to or experiences with healthcare [
42,
43]. CSS have a troubled history in the research literature, with many clinicians still referring to them as somatoform disorders despite considerable evidence to the contrary [
44,
45]. Psychosocial factors have been shown to play a complex role in the development and maintenance of CSS and chronic pain [
46] however how these factors affect physical health in the autistic community is under-explored.
Research looking directly at an association between autism and CSS is limited. Paediatric studies have highlighted a higher incidence of neurodevelopmental disorders in children with chronic pain [
47,
48] and/or CSS [
49,
50], but there is little equivalent research in adults. There is, however, growing awareness of a link between autism and genetic connective tissue disorders, particularly joint hypermobility- related disorders [
51,
52] and the Ehlers-Danlos syndromes [
53]. These conditions often co-occur with CSS [
54‐
56], but more research is needed to determine whether this directly translates to an association between autism and CSS.
CSS are much more commonly diagnosed in women than in men [
57]. Women are also proposed to have greater pain sensitivity [
58,
59] and heightened central sensitisation [
60] although how much of this difference is truly gender specific [
61] and how much can be attributed to gender bias [
62,
63] is unclear. Gender is also an important predictor of an autism diagnosis and physical health in autism. Autism has historically been under recognised [
64] and diagnosed later [
65] in women, and autistic women appear to experience a greater range of co-occurring physical conditions than autistic men [
66]. Whether CSS are more common in autistic women has not been explored.
Our study aimed to investigate the rates of CSS and CSS symptoms in a sample of autistic adults. We first examined the dimensionality and reliability of the Central Sensitization Inventory (CSI), a widely used CSS measure [
67], in this autistic sample. We hypothesized that, given the link between autism and sensory sensitivity, and sensory sensitivity and central sensitisation, as well as the high incidence of co-occurring conditions in autism, CSS symptoms would be common in autistic adults and may be more prevalent than observed in the general population. We also hypothesized that, since high scores on measures of autistic traits correlate with autism diagnoses [
68], then autistic traits would be positively associated with CSS symptoms as measured through the CSI.
We also postulated that higher CSI scores would be associated with greater sensory sensitivity, higher anxiety and depression scores and poorer physical health and subjective well-being, and we predicted that autistic women would report greater sensory sensitivity and more CSS symptoms than autistic men. Lastly, as sensory sensitivity, anxiety and chronic pain have been linked together in previous studies [
29,
69] we considered whether sensory sensitivity or anxiety might mediate a relationship between autism and CSS.
Discussion
This is the first study, to our knowledge, that directly considers an association between autism, central sensitisation, and CSS. In our large sample of autistic adults, 21% reported a CSS diagnosis of FMS, ME/CFS, IBS, RLS or TMJD and 60% scored at or above the clinical cut-off for a CSS on the CSI, suggesting that CSS symptoms are very common in autistic people.
A factor analysis of the CSI [
70] was undertaken to test the measure’s construct validity in an autistic sample, as previous CSI studies have focussed on chronic pain and control groups [
67,
71,
82]. The results supported the bi-factor model [
82], and a highly internally consistent scale. Partial-metric equivalence was observed between genders with items 11 “I feel discomfort in my bladder and/or burning when I urinate” and 16 “I feel sad or depressed” identified as functioning differently between men and women. Given that the difference in loadings were relatively small (< 0.2), and that two out of 25 items were affected, the impact on the comparability of scores across males and females is likely to be small. It is unclear whether this observation is specific to autistic people or generalises to the population as a whole.
In our sample, the mean CSI score for those with a diagnosed CSS was 55.3, slightly higher than the mean score of 52.4 Neblett et al. [
67] found in their study of CSS patients establishing the clinical cut-off of 40 on the CSI. However, the mean CSI score for autistic participants without a diagnosed CSS was 40.6; a score far higher than that of Neblett’s control group (30.9) and closer instead to the mean score of 40.9 in Neblett’s non-CSS chronic pain patients. This suggests that CSS symptoms such as pain and fatigue are very common in autistic individuals and possibly more prevalent than in the general population.
There are many theoretical reasons why autism and CSS might be linked with each other. Sensory processing differences are a core feature of autism [
13] with autistic people reporting greater sensory sensitivity [
15] than the general population. People with CSS also experience sensory sensitivity [
14] but in this case it is more clearly associated with central sensitisation [
5]. Our results demonstrated that autistic people with greater sensory sensitivity also had more CSS symptoms. Whilst it is possible that this is due to an overlap of symptoms or traits between the CSI and the autistic experience, this also fits with recent research indicating that generalised or multi-sensory sensitivity may be a risk factor for developing central sensitisation or chronic pain [
86‐
89].
Our results also showed that, as predicted, higher scores on the CSI were associated with greater sensory sensitivity, greater anxiety and lower subjective well-being. Whilst higher scores on the CSI also appeared to be associated with higher autistic traits, the path analysis conducted suggested that sensory sensitivity and anxiety mediated this relationship. This suggests that sensory sensitivity and anxiety may increase vulnerability to CSS, rather than autism per se.
The finding that anxiety acted as a mediator in this model is in line with previous research on pain in autism that identified anxiety as a contributor to pain levels [
29,
69]. CSS research also suggests that anxiety may contribute to both the development of central sensitisation and the severity of symptoms [
90,
91]. Although we only considered anxiety in our exploratory analyses, existing research suggests that many mental health conditions could affect the incidence of CSS symptoms in autistic people; high anxiety [
33], chronic stress [
92] and PTSD [
33,
93] have all been associated with CSS, and are also more common in the autistic community [
29,
31,
34,
94] than the general population. Other psychological factors could also be important; for example, some research suggests chronic illness severity might be affected by illness beliefs and coping mechanisms [
95] and how these relate to autism has not been explored.
Just as previously reported in the general population [
57,
67], there were clear gender differences in this study, with women over-represented for both CSS diagnoses and number and severity of CSS symptoms. Women also showed greater sensory sensitivity and reported greater anxiety, depression and lower subjective wellbeing. Previous research into sensory sensitivity in autism has been mixed when considering gender differences [
15,
96]. Recent studies on the SPQ, both on data within the Netherlands Autism Register (of which this dataset is also a subsample) and outside, found that autistic women had higher sensory sensitivity than both autistic men [
72] and non-autistic women [
24]. Research within the general population also suggests that women may be more sensitive than men across a range of modalities [
58,
97], with hormones thought to play a key role [
98]. However consideration needs to be given to issues like gender bias [
63]. The results of this study suggest that autistic women might be more likely to experience central sensitisation and related CSS than autistic men.
Whilst not a focus of our study, it is also possible that our results could be explained by neuroimmune and genetic differences in the autistic population. Recent research into joint hypermobility, hypermobility spectrum disorders and the Ehlers-Danlos syndromes (EDS) [
52,
56,
99‐
102] as well as mast cell activation syndrome (MCAS) [
103,
104] and dysautonomia [
105,
106] has suggested that autistic people, and people with ADHD, are over-represented in these conditions. HSD and EDS are also associated with chronic pain, and are often found to co-occur with, or underly, CSS diagnoses [
56]. We did not include questions on joint hypermobility in this study, but future research might consider including these conditions.
Whilst our results show quite clearly that autistic people experience a lot of symptoms associated with central sensitisation, how these symptoms translate to CSS diagnoses is more difficult to establish. Firstly, not all conditions considered to be a CSS were included in our analysis; for example, migraine was not included in our list of CSS, and only 733 of the 973 participants that completed CSI Part A also completed the co-occurring conditions section. This means that the number of participants with a diagnosed CSS is likely to be understated in the current sample. We also did not have CSS diagnosis dates available in our data so cannot examine whether autistic people with CSS were diagnosed with CSS before or after their autism diagnosis. This is important because there are many nuanced difficulties that may exist around diagnosis. For example, autistic people are more likely to experience difficulties accessing healthcare [
42,
107], communicating with clinicians [
108,
109], and also express pain differently to the general population [
29,
110]. There is also a danger of diagnostic overshadowing, where symptoms of CSS may be incorrectly attributed to an existing autism diagnosis; research shows that clinicians are often uninformed about co-occurring conditions in autism [
111]. In addition, fatigue may be attributed to autistic masking [
112] or burnout [
113] by health professionals or the autistic person themselves, when actually it is a sign of an underlying CSS.
Autism diagnostic issues might also explain why an association between autism and central sensitisation has thus far been largely overlooked. Historically, autism has been classified as a social and communication disorder [
114], with sensory issues only included in the most recent DSM criteria [
115]. An autism diagnosis is still predominantly based on behaviour in childhood, with a considerable gender bias such that women tend to be underdiagnosed [
64] or diagnosed later [
65]. Increased understanding of the lived experience of autism has improved awareness of the many co-occurring health issues autistic people experience [
116] but this is not reflected in the current diagnostic criteria [
115,
117] or in measures aiming to assess autistic traits, such as the AQ [
74], where large dimensions of the autistic experience are excluded [
118]. It could be the case that the CSI has captured physical features that have always been common in the autistic population, but not recognised because they were not obvious to the external observer.
Clinically, this study has important implications. We found that the relationship between autistic traits and CSS symptoms was fully mediated by anxiety and sensory sensitivity. Autistic people often struggle to access mental health support or occupational therapy, particularly in adulthood [
119,
120]. Our research suggests that increased anxiety and sensory sensitivity could have wider physical health implications, and longitudinal research could explore further whether interventions focussed on these aspects might mitigate the risk of autistic people developing a CSS later in life.
Limitations
A strength of this study is that these data were reported as part of an ongoing data collection in the NAR volunteer register, with participants not explicitly primed as to the aims of the CSI data collection. Therefore, it is unlikely that these findings are inflated due to selection or attrition bias.
In terms of limitations, firstly, although we were able to include a large sample of autistic participants, we did not have a control or CSS only group. Future research including these groups would add additional power and allow for a greater exploration of the relationships between the main variables in the wider population. Our sample was also predominantly Dutch, with very few reporting to be a member of an ethnic minority. Future studies should try to recruit a more ethnically diverse sample.
Secondly, the variable ‘gender’ was assessed by asking participants to check one of three boxes (man/woman/other). Participants could have interpreted this as either ‘sex assigned at birth’ or as ‘gender of identification’. In many cases sex and gender will overlap but we know this will not apply to everyone. Participants indicating their gender as “other” were excluded due to the small sample size and this field was referred to throughout the study as “gender”. Since central sensitisation seems to be linked to sex and hormones [
57,
98] in the research literature, and that autistic individuals are less likely to identify with their assigned sex at birth [
121‐
123], it is important that further research is undertaken in which assigned sex at birth, gender, and hormonal influences are clearly delineated.
Another important limitation involves the wording of the CSI [
70]. It is possible that the association between autism and CSS identified in this study relates more to an overlap of traits (particularly sensory sensitivity) than a true co-occurrence. It is also possible that central sensitisation is directly related to sensory sensitivity [
86]. Furthermore, whilst the AQ is a widely used and reliable measure [
68], its ability to capture the essence of what autism is, and measure this quantitatively, is limited [
118,
124]. Further studies could utilise different illness-specific instruments and alternative instruments to the CSI and AQ to establish whether a relationship between autistic traits and CSS can be identified in different conditions.
There are many other aspects that may influence a possible association between autism and CSS that we were unable to measure in this study. For example, the SPQ [
15] does not measure interoception, but research indicates interoceptive awareness is altered in autistic people [
125] and also people with chronic pain [
126]. Similarly, we did not include an alexithymia measure in our analyses, however alexithymia has been indicated in chronic pain [
127], and is very common in autistic people [
128]. Future research on autism and CSS would need to consider these phenomena.
In this study, CSS diagnoses were self-reported and not independently verified. It is possible that participants may have indicated conditions that were not formally clinically diagnosed. Diagnosis of CSS can be particularly difficult, with clinician bias, misdiagnosis and diagnostic inconsistency a continuing problem [
129,
130]. Future studies could recruit via health services or incorporate additional questions to confirm CSS diagnoses. It is also possible that CSS diagnoses were underestimated in this study, partly due to not all participants completing sections on co-occurring conditions, and partly due to not including the ‘migraine’ diagnosis as this field also included ‘headache’ (see “
Measures” for more details). It is also important to note that the concept of central sensitisation as a unifying underlying feature of CSS, often also referred to as “chronic overlapping pain conditions” (COPCs), is still relatively new, and research is still evolving in terms of which health conditions are considered to come under this umbrella [
46,
131], therefore conditions that were included as a CSS in this study may change category in the future. Finally, as a cross-sectional study, this research is limited when exploring cause and effect, such as through the regression and path analyses, and any inferences drawn need to be treated with caution. Longitudinal studies may be able to shed more light on how and why autism and CSS might be related.
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