Headache, migraine and autism spectrum disorder: is there a link?

Leonardo Massoni

Received : October 12, 2025 | Published : November 05, 2025

Citation: M Leonardo. Headache, migraine and autism spectrum disorders: is there a link?. J Med Clin Case Stu. 2025;1(1);1-3.

Abstract

Background: Autism spectrum disorder (ASD) is often associated with acute pain, such as headache and migraine, which, in turn, may sometimes be accompanied by irritability or psychomotor agitation.¹ A genetic basis of the association between ASD, headache, and migraine seems to come from the analysis of autistic individuals’ families and polygenic studies. From a clinical perspective, it may often be quite difficult for clinicians to detect headache and migraine among autistic subjects, as these individuals usually show difficulties in communicating feelings and emotions. Starting from these premises, it is fundamental to exclude a painful symptomatology in autistic patients showing irritability or psychomotor agitation. In this framework, the aim of this brief communication is to discuss some studies on the genetic basis of headache and migraine in ASD, give some insights into their diagnostic and clinical basis, and finally report some of the available therapeutic strategies.

Methods: To carry out this study, a literature search was conducted, mainly employing the PubMed Database from March to June 2025. The author focused on works dealing with the reciprocal relationship between headache, migraine, and ASD.

Results: It was found that both ASD and migraine share genetic mutations as well as neurotransmission and immune system dysregulation. Meanwhile, it seems that, given the communication difficulties of ASD subjects, migraine and headache diagnoses are quite hard to make among these individuals. Regarding therapeutic strategies, we may distinguish non-pharmacological strategies, including environmental modifications, and pharmacological ones, such as antipsychotics.

Conclusions: Migraine and headache among ASD subjects are frequently underdiagnosed. Further studies are needed to shed new light on pathophysiological mechanisms as well as on clinical aspects of these pathologies in ASD.

Introduction

It is known that ASD is often associated with other psychiatric conditions such as anxiety and somatic symptoms, which, in turn, may lead to depression and impair the quality of life.² Interestingly, it seems that somatic symptoms in ASD are related to physical and mental health conditions, female gender, alexithymia, and intolerance of uncertainty, regardless of autism status.³ Accordingly, it has been reported that subjects with somatic symptom disorder often present subclinical autistic traits.⁴ A study by Fulceri and colleagues pointed out that ASD subjects, except for anxiety and somatic symptoms, often showed gastrointestinal problems.⁵ Few data are now available about other somatic features, such as migraine and headache in ASD. The aim of this brief communication is to assess genetic, clinical, and therapeutic aspects of this somatic symptomatology in ASD.

Methods

In this study, we analyzed headache and migraine in ASD. We included (1) based on the type of article, original research and reviews; (2) works written in English; and (3) studies dealing with headache and migraine in ASD.

Literature search was carried out mainly by the “PubMed” database from March to June 2025. We employed the following keywords: “migraine,” “ASD,” “headache,” and “somatic symptoms.”

Results

The result section is divided into a first part where genetic and clinical features of migraine and headache in ASD are exposed^6-14, while the second part gives some insights into the therapeutic approaches.^15-19

Genetic and diagnostic aspects

Polygenic scores (PGS) studies pointed out a significant association between ASD and migraine with and without aura. Intriguingly, neuroticism, that is, the tendency to experience negative emotions, seems to mediate the association between ASD and PGS.⁶ In addition, impaired channelopathies, associated with mutations in calcium voltage-gated channel subunit alpha1 (SCNA1), sodium voltage-gated channel (e.g., SCN1A), and sodium/potassium pump gene (ATP1A2), have been found both in ASD and in migraine.⁷ The role of genetic factors for the relationship between ASD and migraine is also supported by evidence showing a higher risk of developing ASD in families whose members suffer from headaches⁸ as well as by studies reporting a higher prevalence of migraine among ASD children.⁹

In line with these premises, a review by Vetri (2020) deepened the association between autism and migraine from a biological point of view, suggesting that autism shares with migraine common pathophysiological changes, including neurotransmission dysregulation, altered immune response, anatomical abnormalities such as cortical mini column organization, and the dysfunctional gut–brain axis.¹⁰ Specifically, dysregulation of the serotonin system has been implicated both in ASD and in migraine.¹¹

When dealing with migraine diagnosis in ASD, it should be considered that these individuals may have difficulties in communicating pain symptoms, including headaches. Consequently, headache is often underdiagnosed in ASD. That’s why clinicians should suspect a diagnosis of headache in the ASD population, especially in the presence of some symptoms like changes in facial expression, increased irritability and agitation, seeking isolation, avoiding stimuli, sleep pattern alteration, and changes in eating habits.¹² A study by Sullivan et al. (2014) investigated ASD individuals with and without migraine, revealing that migraine, headaches, sensory hyperreactivity, and anxiety symptomatology could be reciprocally connected in ASD, and, in turn, suggesting the idea of a common pathogenetic basis.¹³

From another perspective, Türkel et al. (2025) reported a high prevalence of autistic traits (AT) among individuals with migraine. Particularly, the authors suggested that AT could have an indirect effect on headache through anxiety sensitivity and sensory sensitivity, while a direct effect seems to be exerted on depressive symptoms.

Overall, it is important to detect AT in subjects with migraine and headache to improve their quality of life and define a valid therapeutic strategy.¹⁴

Therapeutic perspectives

Regarding therapeutic approaches, we can distinguish between pharmacological and non-pharmacological options. Among non-pharmacological strategies, there are environmental modifications, such as reducing background noise, relaxation techniques, biofeedback, and cognitive behaviour therapies.^15,16 A particular psychotherapeutic approach, the applied behaviour analysis (ABA), may be effective to target and ameliorate negative behaviours resulting from headaches.^13,17 In this framework, Emtiazy and Abrishamkar reported the usefulness of massage in pupils and massage therapy to reduce stress, pain, anger, and aggressiveness in ASD. Particularly, massage in pupils could have a good effect on blood circulation, breathing, growth, concentration, immune system functioning. In addition, this massage may reduce stress, pain, anger, and aggressiveness. Meanwhile, programs of collective pupil massage have been reported as useful tools to improve children’s capabilities.¹⁸ Also, neuromodulation techniques may be potentially effective for pain management in ASD, including headache and migraine.¹⁹

About pharmacological approaches, some benefits seem to come from antipsychotics such as risperidone and aripiprazole.¹²

Discussion

In this short communication, we briefly summarized some of the current evidence about the relationship between headache and ASD, pointing out the genetic basis of this overlap, namely SCNA1, SCN1A and ATP1A2 mutations.^7-12 Furthermore, the impairment in neurotransmission, immune system response, and anatomical abnormalities seem to suggest biological common aspects shared across the two disorders.^10,11 From a clinical point of view, it should be considered that ASD individuals may have some difficulties in communicating pain and headache. As a result, clinicians had better pay attention to detect AT in individuals with migraine or other pains.^12,13 Among pharmacological perspectives, we reported risperidone and aripiprazole as the main therapeutic strategies to improve negative behaviours resulting from headaches.¹² Other therapeutic strategies include environmental modifications, massage in pupils, and massage therapy to reduce negative symptoms.¹⁸

From a wider point of view, it seems that headache in autism could be linked with sensory hyperreactivity and anxiety symptomatology. Consequently, clinicians should always consider ASD as a multifaceted syndrome in which somatic symptomatology often overlaps with neuropsychiatric symptoms, including hyperreactivity and anxiety.¹³ Accordingly, autistic individuals may present, especially during adolescence, behavioural problems, such as aggression, self-injury, disruption, agitation, and tantrums, often due to organic causes, including psychiatric and non-psychiatric conditions.²⁰ Interestingly, we should also consider that headache could underlie other severe general medical conditions, as shown by a case report of a child with a headache unexpectedly developing meningitidis.²¹

What’s more, even migraine and headache treatment in ASD should consider comorbid developmental problems, including orthostatic dysregulation and psychosocial problems.²² In the framework of somatic symptoms in ASD, Zotti and colleagues pointed out the usefulness of personal and familiar dynamics for the management of these symptoms.²³ Furthermore, if we consider that somatic therapy is known to exert a beneficial effect on the emotions and behaviours of ASD subjects²⁴, it could be speculated that by ameliorating these symptoms, migraine and headache in ASD could be improved.

Conclusion

This short communication gave some insights into the relationship between acute pain, namely headaches, and autism. In fact, we stated that individuals with AT often show comorbidities such as headache and migraine. Meantime, it is important to find out AT among the general population with this kind of somatic symptomatology to establish as soon as possible a proper therapeutic strategy. Further studies are warranted to better assess the relationship between somatic symptoms and AT and to define a precise treatment.

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