Symptoms of Obsessive-Compulsive Disorder,Attention-Deficit/Hyperactivity Disorder,and Autism Spectrum Disorder in Children and Adolescents Attending a Headache Outpatient Clinic and School-Based Controls

Abstract

This case-control study assessed symptom severity and prevalence of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) in children attending a headache clinic compared to controls. We included 343 patients (5-19 years) and 130 controls (6-19 years; no prior headache diagnosis/medical contact for headache) between October 2018 and January 2024. Controls were divided into CH+ (experiencing headaches) and CH– (headache-free). Severity was assessed using scores from questionnaires, and prevalence was defined by prior diagnosis or symptom scores above clinical cutoffs, therefore indicating symptom burden over confirmed diagnoses. Patients had more severe symptoms of OCD, ADHD, and ASD than CH–. CH+ had the most severe symptoms of OCD and ADHD. OCD, ADHD, and ASD research diagnoses were present in 20.8%, 17.3%, and 10.1% in patients; 27.8%, 18.8%, and 4.4% in CH+; 1.7%, 7.0%, and 1.8% in CH–. Headache in youth, even in non-clinical settings, is linked to psychiatric symptoms; hence, routine screening is recommended.

Keywords

comorbidity migraine neurodevelopmental disorders psychiatric disorders screening recommendations tension-type headache

Headache symptoms and primary headache diagnoses are linked to psychiatric and neurodevelopmental disorders. The association between migraine and anxiety/depression in children and adolescents is well established.¹ However, evidence for a link between headache and obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism-spectrum disorder (ASD) is limited.

Adult studies suggest comorbidity between OCD and migraine, particularly chronic migraine and medication overuse headache.^2-6 In children and adolescents, the presence of OCD in children with headache has been examined in 2 studies.^7,8 One found obsessive-compulsive symptoms to be equally prevalent in patients receiving care for headaches in a pediatric outpatient clinic and in children from the background population with headaches who had not sought help in managing their symptoms.⁷ For both groups, OCD was more prevalent compared to controls without headache.⁷ Another study found no increased prevalence of OCD in children with primary headache disorders compared to controls but observed higher prevalence in children with migraine than in children with tension-type headache (TTH).⁸

Meta-analyses suggests an association between headache and both ADHD and ASD in children and adolescents.^9-11 However, most studies have examined children with ADHD and ASD, and not headache, as their primary diagnosis.^9-11 ADHD has been most strongly associated to migraine or headache in general, and not to TTH.^9,10 Although children with ASD have been shown to have higher odds of experiencing migraine/headaches than controls,¹¹ symptoms of ASD in children with headache disorders as their primary concern has not previously been investigated.

The causal relationship between psychiatric disorders and headache in childhood is unclear, but likely bidirectional: headache may be a symptom of an underlying psychiatric disorder, as seeking care for headache has been hypothesized to precede ASD diagnosis,¹² or headaches can cause symptoms resembling psychiatric disorders, such as attention deficit.¹³ They also co-occur, with evidence of a synergistic effect, as in adults where OCD symptoms increase with migraine frequency.⁴ Lastly, a shared pathophysiological link between headache (primarily migraine) and all 3 conditions has been suggested.^14-18

In the present study, we compared children and adolescents referred to a headache outpatient clinic with a control group drawn from the general population. Controls were not allowed to have a headache disorder or receive medical attention for headaches. However, because headache is highly prevalent in this age group—with Danish studies showing that up to 95% experience headache and 58% to 67% more report headache within the past 2 weeks^19,20—controls were not required to be completely headache-free.

To better explore the relationship between headache and psychiatric comorbidity, we divided the control group into 2 subgroups based on headache frequency: those with headaches (at least 1 headache in the past month) and those who were headache-free (no headaches in the past month). These groups we simply called controls with headache and headache-free controls. This allowed us to investigate whether psychiatric comorbidity is specific to children with a primary headache disorder, which might support a shared pathophysiology, or whether similar patterns are also present in children from the general population who experience headaches but have not sought help in managing their headaches, suggesting a broader or more complex relationship.

Identifying psychiatric comorbidities in children and adolescents with headaches is crucial, as these conditions may represent underlying causes or contributing factors to the headache itself. Early recognition and treatment of psychiatric comorbidities may therefore not only improve overall well-being but also address the root cause of the headache in some cases. Moreover, increased awareness of these associations may support the implementation of routine screening for these psychiatric comorbidities in children presenting with headaches, enabling early identification and intervention.

The primary aim of the study was to assess the prevalence and symptom severity of OCD, ADHD, and ASD in children and adolescents attending a headache outpatient clinic compared to controls with and without headache. Our secondary aim was to investigate the association between headache frequency and the symptom severity of these disorders.

Materials and Methods

This case-control study is outlined in Figure 1. Patients were recruited from the Headache Outpatient Clinic, Department of Pediatrics and Adolescents, Copenhagen University Hospital–Herlev and Gentofte, Denmark (“the clinic”), between October 2018 and April 2021. Patients were recruited through 2 approaches: (1) data collection in the clinic and (2) participation in a clinical research project. Inclusion criteria for both approaches were being a patient at the clinic, aged 5-19 years, and having sufficient proficiency in Danish to complete questionnaires. Symptom severity and research diagnosis of the conditions were based on screening instruments and prior diagnosis of the conditions.

Figure 1.

Study flow outlining methods, recruitment, missing data evaluation, and inclusion process. Figure 1 outlines key elements of the study design, including recruitment, inclusion, and sample sizes of the responses obtained. ADHD-RS, Attention-Deficit Hyperactivity Disorder Rating Scale Extended; OCI-R, Obsessive-Compulsive Inventory–Revised; REDCap, Research Electronic Data Capture tool; SRS-2, Social Responsiveness Scale 2. *See text for explanation.

In October 2018, the Attention-Deficit/Hyperactivity Disorder Rating Scale–Extended Version (ADHD-RS) was implemented in the clinic's routine initial assessment along with other questionnaires. All newly referred patients received this questionnaire on paper at their first visit as part of standard care. The completed questionnaire was scanned to the patient's medical record. We chose the questionnaires suitable for implementation based on the following rationale: there should be a limited number of questionnaires administered to avoid overwhelming the family; shorter questionnaires were favored²¹; and each questionnaire was expected to provide a clinical benefit, specifically, by addressing the expected association between headache and ADHD.

From April 2019, patients had the option of participating in a clinical research project. Beyond the questionnaires distributed as standard care, this included the Obsessive-Compulsive Inventory–Revised (OCI-R) and the Social Responsiveness Scale–Second Edition (SRS-2). Patients were informed of the project by their regular physician and, if interested, were recruited by a researcher over phone (Figure 1). They completed questionnaires using Research Electronic Data Capture tool (REDCap).^22,23

In February 2020, we conducted an interim analysis in the clinical research project showing a high prevalence of obsessive-compulsive symptoms. Screening for OCD proved to be highly clinically relevant, and therefore, OCI-R was subsequently incorporated into standard care along with ADHD-RS.

Data were collected through these 2 approaches until April 2021. Hereafter, the medical records of all patients who had attended the clinic from October 2018 to April 2021 (N = 800) were reviewed. Patients who had completed at least 1 of the mentioned questionnaires were identified and included in the final patient sample, along with all patients who had completed one of the questionnaires as part of the clinical research project. Because inclusion required completion of only 1 questionnaire, not all participants completed all questionnaires. The responses obtained for each questionnaire are presented in Figure 1.

Controls were intended to match patients on age, sex, and geographical location. They were recruited from schools across the Capital Region and Zealand Region between November 2022 and January 2024. Inclusion criteria were as follows: age 6-19 years, no headache diagnosis, no history of medical treatment for headache, sufficient proficiency in Danish to complete the questionnaires, provision of information on headache frequency, and completion of at least 1 study questionnaire. The lower age limit of 6 years was chosen both because only 2 patients were below this age and because formal schooling in Denmark begins at age 6 years. Questionnaires were completed in REDCap.^22,23 Controls were divided post hoc based on headache frequency into 2 groups: controls with headache (CH+) (≥1 headache in the past month) and headache-free controls (CH–) (no headaches in the past month).

Measurements and Variables

Obsessive-Compulsive Inventory Revised

Symptoms of OCD in the past month were measured with OCI-R, consisting of 18 items comprising 6 subscales and a total score.²⁴ The subscales are washing, obsessing, ordering, checking, neutralizing, and hoarding.^24,25 OCI-R was completed by the child/adolescent as self-report. OCI-R is validated as a screening instrument to be used in adolescents ≥16 years old.²⁶ It has been translated into Danish and is used across all age groups because of current practice and availability. The OCI-R is a valid and reliable measure, with high internal consistency and moderate to high test-retest reliability.^24,25,27-29 Participants received a research diagnosis of OCD if the total score was above the empirically derived cutoff score of 15.²⁷ The OCI-R total score was used to estimate symptom severity of OCD.

Attention-Deficit/Hyperactivity Disorder Rating Scale Extended Version

The ADHD-RS was used to assess symptoms of ADHD within the last six months.³⁰ The ADHD-RS is a revised 26-item version of the ADHD-RS-IV, including items on the subscales inattention, hyperactivity/impulsivity and Oppositional Defiant Disorder.^31-33 It is validated as a screening instrument in children ages 4-17 years. The parent-report version was completed by the child's caregiver/parent. The ADHD-RS is a valid and reliable tool, with high internal consistency, good to really good test-retest reliability, and excellent predictive ability for ADHD.^30,34,35 Danish national norm scores exist, with rater-, sex-, and age-dependent cutoff scores for each subscale (Appendix A, Table A.1).^30,36 A research diagnosis of ADHD was assigned if the participant scored above the national norm score on either one or both subscales for inattention and hyperactivity/impulsivity. ADHD symptom severity was measured with the total score.

Social Responsiveness Scale–Second Edition

SRS-2 was used to quantify symptoms of the ASD within the past month.^37-39 The scale has 65 items and five subscales: social awareness, social cognition, social communication, social motivation, and restricted interests and repetitive behavior. It is validated as a screening instrument for children ages 4-18 years, and the parent-report version was completed by the child's caregiver/parent. The SRS-2 is reliable, with high internal consistency, good interrater and test-retest reliability, and good validity.^38,40-43 When scoring, the scores are converted to rater-, sex- and age-specific T scores. A research value for the total T score of 65 is recommended and applied to assign a research diagnosis of ASD.⁴⁰ Symptom severity of ASD was estimated with the total T score.

Research Diagnosis of Psychiatric Comorbidity

A research diagnosis of OCD, ADHD, and ASD was given to participants who either had a prior clinical diagnosis given by a child and adolescent psychiatrist or who met research diagnostic criteria based on their questionnaire scores. Data on prior diagnosis was collected during the medical record review for patients and as self-report in controls. Participants with a prior diagnosis were considered to have the condition irrespective of their questionnaire results, reflecting the expectation that effective management may reduce symptoms below the diagnostic threshold for a research diagnosis. Throughout this study, the term prevalence therefore refers to individuals with either a prior diagnosis or symptom scores above established clinical cutoffs.

Headache Diagnosis

For patients, medical records were reviewed manually and headache diagnosis assigned according to the International Classification of Headache Disorders–III criteria (ICHD-3).⁴⁴ This approach was chosen over relying on diagnoses assigned in clinic, ensuring homogeneity of the symptoms experienced within each diagnostic group and to improve comparability with other research. Patients were classified as follows: All Patients (regardless of headache diagnosis), Migraine group (including both migraine with and without aura), TTH group, Mixed group (patients with both migraine and TTH), and Unclassified Headache group (patients who did not fully meet ICHD-3 criteria). Patients with secondary or cluster headaches were included only in the All Patients group. The All Patients group was intended to represent the entire clinical population typically seen in a headache outpatient clinic, while the subgroup analyses provided insight into whether associations with psychiatric symptoms were specific to primary headache types or also present among patients with unclassified headache.

Headache Frequency

Headache frequency (past month) was obtained from medical records for patients and from self-report questionnaires for controls. Headache frequency was categorized into daily (≥15 days per month), weekly (4-14 days per month), monthly (1-3 days per month), and less than monthly headache. This categorization differs from the frequency categories defined by ICHD-3, as the available data only reflected headaches in the past month, whereas ICHD-3 considers a longer duration. However, a cutoff of ≥15 days per month is consistent with the ICHD-3 criteria for chronic headache.

Confounders

Confounders included age (continuous and categorized as child <12 years or adolescent ≥12 years), sex (biological sex assigned at birth), and socioeconomic status (SES). SES was determined by the education and occupation of the parent and graded using a scale by the Danish National Centre for Social Research.⁴⁵ The highest SES among the parents was chosen, assuming the child primarily benefits from the parent with the higher SES, irrespective of the other parent's standing.

Bias

The approach of introducing questionnaires in the routine initial assessment in clinic was chosen to reduce selection bias, which might otherwise favor families with the time and resources to participate in a clinical study. Support from a registered nurse was available if needed, helping to ensure broad representation among patients participating through this approach. However, as not all study questionnaires could be integrated into the routine initial assessment, patients were recruited through 2 approaches. This may have introduced different selection biases, depending on the approach. In terms of resources and patient motivation, those completing questionnaires as part of standard care likely represent a more heterogeneous group, whereas participants in the clinical research project may reflect a smaller, more motivated sample with greater family resources. The 2 approaches may also have reduced statistical power because of the smaller sample size in approach (2).

When recruiting controls for a headache study, there was an inherent risk of attracting participants who experience headaches more frequently than the general population. To minimize this risk, we emphasized the recruitment of “healthy” participants—defined as children without a headache diagnosis and no prior medical care for headache—in both the written information materials and verbally throughout the recruitment process.

Study Size

No formal sample size calculation was performed, as the study was designed to include all eligible patients attending the clinic during the recruitment period. The sample size was thus determined by the clinic's annual intake, which is a minimum of 200 newly referred patients. We aimed to recruit approximately 400 patients, with 100 individuals in each diagnostic group. In addition, we aimed to recruit at least 100 controls to enable group comparisons.

Ethics

Danish Regional Scientific Ethics Committee (reference: H-19003374) and the Danish Data Protection agency (reference: VD-2019-222 and R-22069732) have approved the study. Before participation, signed and informed consent was obtained from all adults with parental custody.

Statistical Methods

Analysis was performed with R version 4.2.2 (Vienna, Austria: R Foundation for Statistical Computing).⁴⁶ The analysis followed a stepwise approach. (1) To address the primary aim, we analyzed across groups, comparing the All Patients, Migraine, TTH, Mixed, and Unclassified group to both CH+ and CH–. (2) To address the secondary aim, we analyzed across headache frequency. This was done by pooling all participants (patients and controls), which we divided according to headache frequency. Comparisons were then made across the headache frequency groups, using those with the least frequent headaches (ie, “less than monthly”) as the reference category. (3) To further investigate the relationship between headache and psychiatric symptoms, we examined the association between symptom severity and headache frequency within each group (see below).

Missing data were managed as follows: For the OCI-R, ADHD-RS, and SRS-2, a questionnaire was considered “complete” if all items within at least 1 subscale had been answered. Total and subscale scores were calculated only when all items within the respective scale were completed. Because of variations in sample size across measures (resulting from the study design), the sample size for each analysis is reported in the tables to ensure transparency.

Descriptive statistics were analyzed. Age and SES (scored 1-5, with 1 indicating highest SES) followed a non-normal distribution, and was reported with median and IQR. Sex and headache frequency were reported with frequencies. Age was compared across groups using the Kruskal-Wallis test, whereas sex, SES, and headache frequency were compared using pairwise Fisher exact tests.

Symptom severity was assessed by comparing total questionnaire scores between groups. Scores were treated as count data: negative binomial regression was used for the OCI-R and ADHD-RS, and quasi-Poisson regression for the SRS-2. All models were adjusted for age and sex. OCI-R and ADHD-RS scores were non-normally distributed and are presented as median (IQR), whereas SRS-2 scores followed a normal distribution and are reported as mean ± SD. Subscale scores are reported in Appendix B.

Prevalence of comorbidity (OCD, ADHD, and ASD) was assessed using binomial regression with a logit link. This approach was chosen over log-binomial models because of its greater numerical stability while allowing adjustment for age and sex. Results are presented with percentages and odds ratios with 95% CIs.

To assess the association between symptom severity and headache frequency, the same regression models were used (negative binomial for OCI-R and ADHD-RS; quasi-Poisson for SRS-2), comparing symptom severity across headache frequency groups, using the group with the least frequent headaches as the reference.

To assess the association between symptom severity and headache frequency within each group, analyses were conducted within each group, stratifying for headache frequency, again using the group with the least frequent headaches as the reference. For this analysis, control participants were included as a combined group, with CH– (less than monthly headaches) serving as the reference category. These results are provided in Appendix C.

For all analyses, model checks were performed to assess model fit and adequacy. The significance level was set at P <.05.

Results

Descriptive Statistics

A total of 343 patients with headache and 130 controls were included: 72 in the CH+ group and 58 in the CH– group (Figure 1). Of the 343 patients, 86 were diagnosed with migraine, 101 with TTH, 81 with mixed, 1 with cluster, and 21 with secondary headache, and 53 remained unclassified. Headache frequency was obtained for 459 participants: 116 had daily, 154 had weekly, 108 had monthly, and 81 had less than monthly headaches. In Table 1, the descriptive statistics of patients and controls are presented.

Table 1.

Descriptive Statistics by Headache Diagnostic Group for Patients and Controls.^a

						Controls
	All Patients	Migraine	TTH	Mixed	Unclassified	CH+	CH–
n	343^b	86	101	81	53	72	58
Age, y, median (IQR); P value
	13.2 (10.6-15.5); <.001	12.1 (10.0-14.1);.002	14.2 (11.6-16.1); <.001	14.2 (12.2-15.9); <.001	12.5 (10.0-14.7); .003	12.4 (9.8-16.3); <.001	9.2 (8.0-12.0); Ref
Age group, n (%)
Child <12 y old	124 (36.2)	40 (46.5)	30 (29.7)	20 (24.7)	25 (47.2)	34 (47.2)	43 (74.1)
Adolescent ≥12 y old	219 (63.8)	46 (53.5)	71 (70.3)	61 (75.3)	28 (52.8)	38 (52.8)	15 (25.9)
P value	<.001	.001	<.001	<.001	.006	.002	Ref
Sex: female, n (%); P value
	204 (59.5); .006	40 (46.5); .416	73 (72.3); <.001	49 (60.5); .016	29 (54.7); .114	42 (58.3); .035	23 (39.7); Ref
SES, median score (IQR); P value
	2.0 (1.0-3.0); .120	2.0 (1.0-3.0); .058	2.0 (1.0-3.0); .392	2.0 (1.0-3.0); .273	2.0(1.0-3.0); .163	1.5 (1.0-3.0); .370	2.0 (1.0-2.0); Ref
Headache frequency, %
Daily	33.1	3.7	59.0	31.6	14.9	5.4
Weekly	38.3	30.5	31.0	53.2	48.9	21.5
Monthly	21.6	51.2	9.0	12.7	21.3	28.5
Less	7.0	14.6	1.0	2.5	14.9	44.6
P value	<.001	<.001	<.001	<.001	<.001	Ref

Abbreviations: CH+, controls with headache; CH–, headache-free controls; SES, socioeconomic status; TTH, tension-type headache.

Significant P values are in bold, with the significance level set at P <.05.

One patient with cluster headache and 21 patients with secondary headache are only included in the All Patients group.

The CH– group was significantly younger than all other groups, with a median age of 9.2 years (IQR 8.0-12.0) compared with 13.2 years (IQR 10.6-15.5, P < .001) in All Patients and 12.4 years (IQR 9.8-16.3, P < .001) in CH+. They were also predominantly male, with only 39.7% females compared with 46.5% to 72.3% in the other groups (Table 1). Patients reported more frequent headaches than the combined control group (Table 1). Headache frequency in the control group was comparable to, although slightly lower than, a large non-representative study of Danish schoolchildren from several municipalities (55.4% ≥ 1 day/month and 26.9% ≥ 4 days vs. 58%-67% ≥ 1 headache in 2 weeks).^19,20

Symptom Severity

Symptom severity of OCD, ADHD, and ASD was assessed using total scores from the screening questionnaires, reported in Table 2. The All Patients and CH+ groups consistently reported more severe symptoms of all 3 comorbidities than the CH– group (Table 3). In the patient subgroups, only patients with migraine had more severe OCD symptoms; both patients with migraine and unclassified headache had more severe ADHD symptoms; and only patients with TTH had more severe ASD symptoms than the CH– group (Table 3). OCD symptoms increased with age, whereas ADHD symptoms decreased, and ASD symptoms showed no association with age (Table 2). Only symptoms of ADHD were associated to sex, with higher severity in males than in females (Table 2). In Table 2, we also compare symptom severity between patients and the CH+ group. We found that only OCD scores differed significantly, with the All Patients, TTH, and Mixed Headache groups reporting lower symptom severity than the CH+ group.

Table 2.

Association of Psychiatric Symptom Severity to Group, Age, and Sex.^a

	OCD Symptom Severity	ADHD Symptom Severity	ASD Symptom Severity
	IRR (95% CI); P value	IRR (95% CI); P value	IRR (95% CI); P value
Age
Child	Ref	Ref	Ref
Adolescent	1.4 (1.1-1.8); .008	0.8 (0.7-0.9); .009	1.0 (1.0-1.0); .468
Sex
Female	Ref	Ref	Ref
Male	0.6 (0.5-0.8); .001	1.2 (1.0-1.4); .033	1.0 (0.91.0); .206
Group
CH–	Ref	Ref	Ref
All Patients	1.5 (1.1-2.2); .013	1.3 (1.0-1.7); .019	1.0 (1.0-1.1); .029
Migraine	1.7 (1.1-2.6); .011	1.4 (1.0-1.9); .024	1.0 (1.0-1.1); .384
TTH	1.5 (1.0-2.2); .074	1.3 (0.9-1.7); .135	1.1 (1.0-1.1); .015
Mixed	1.5 (1.0-2.3); .067	1.2 (0.9-1.6); .223	1.1 (1.0-1.1); .071
Unclassified	1.4 (0.8-2.3); .200	1.5 (1.1-2.0); .021	1.1 (1.0-1.1); .113
CH+	2.2 (1.5-3.3); .001	1.4 (1.1-2.0); .018	1.1 (1.0-1.1); .025
Group
CH+	Ref	Ref	Ref
All Patients	0.7 (0.5-0.9); .010	0.9 (0.7-1.2); .506	1.0 (1.0-1.0); .847
Migraine	0.8 (0.5-1.1); .162	1.0 (0.7-1.3); .826	1.0 (0.9-1.0); .257
TTH	0.7 (0.5-1.0); .028	0.9 (0.7-1.1); .287	1.0 (1.0-1.1); .499
Mixed	0.7 (0.5-1.0); .034	0.8 (0.6-1.1); .207	1.0 (0.9-1.0); .954
Unclassified	0.6 (0.4-1.0); .050	1.0 (0.7-1.4); .913	1.0 (0.9-1.1); .877

Abbreviations: ADHD, attention-deficit hyperactivity disorder; ASD, autism spectrum disorder; CH+, controls with headache; CH–, headache-free controls; IRR, incidence rate ratio; OCD, obsessive-compulsive disorder; TTH, tension-type headache.

Significant P values are in bold, with the significance level set at P <.05.

Table 3.

Observed Symptom Severity of OCD, ADHD, and ASD in All Groups.^a

	OCD Symptom Severity			ADHD Symptom Severity			ASD Symptom Severity
Group	Median (IQR)	P value	n	Median (IQR)	P value	n	Mean ± SD	P value	n
All Patients	4.5 (2.0-12.0)	.013	200	4.0 (4.0-16.0)	.019	328	48.0 ± 6.2	.029	131
Migraine	4.0 (2.0-9.0)	.011	53	9.0 (5.0-17.0)	.024	81	46.7 ± 6.6	.384	40
TTH	5.0 (2.0-14.0)	.074	58	8.0 (4.0-15.0)	.135	96	49.2 ± 5.9	.015	38
Mixed	5.0 (2.0-12.0)	.067	54	9.0 (4.0-15.0)	.223	79	48.1 ± 6.1	.071	37
Unclassified	4.0 (2.0-7.0)	.200	27	11.5 (5.3-17.0)	.021	50	48.5 ± 6.3	.113	15
CH+	8.5 (2.0-16.0)	<.001	72	12.0 (5.0-18.0)	.018	69	48.3 ± 6.1	.025	68
CH–	3.0 (1.0-6.0)	ref	58	8.0 (4.0-16.0)	ref	57	45.9 ± 5.0	ref	57

Abbreviations: ADHD, attention-deficit hyperactivity disorder; ASD, autism spectrum disorder; CH+, controls with headache; CH–, headache-free controls; OCD, obsessive-compulsive disorder; TTH, tension-type headache.

Symptom severity was defined as the total scores from the psychiatric screening questionnaires. Symptom severity of OCD is from the Obsessive-Compulsive Inventory–Revised; of ADHD from the ADHD-Rating Scale Extended; ASD from the Social Responsiveness Scale 2. Significant P values are in bold, with the significance level set at P <.05.

Symptom Severity and Headache Frequency

We found that psychiatric symptoms were associated to headache frequency (Table 4). For all 3 comorbidities, higher headache frequency was in some way associated with greater symptom severity. ASD symptoms consistently became more severe as headache frequency increased (Table 4). In contrast, the associations for OCD and ADHD were less consistent: weekly headache was associated with higher symptom severity for ADHD, whereas both weekly and monthly headache were associated with higher severity for OCD (Table 4).

Table 4.

Symptom Severity in Headache Frequency Groups.^a

	OCD Symptom Severity			ADHD Symptom Severity			ASD Symptom Severity
Headache frequency	Median (IQR)	P value	n	Median (IQR)	P value	n	Mean ± SD	P value	n
Daily	5.0 (2.0-12.3)	.467	72	7.0 (4.0-13.0)	.203	110	49.8 ± 6.7	.003	47
Weekly	2.0 (2.0-14.5)	.002	103	13.0 (6.0-19.0)	<.001	148	48.1 ± 6.5	.024	75
Monthly	5.0 (1.8-10.3)	.036	80	9.0 (5.0-17.0)	.097	105	47.3 ± 5.3	.125	68
Less than monthly	3.0 (1.0 -6.0)	Ref	72	8.0 (4.0-13.5)	Ref	80	45.8 ± 5.0	Ref	64

Abbreviations: ADHD, attention-deficit hyperactivity disorder; ASD, autism spectrum disorder; OCD, obsessive-compulsive disorder.

Further subgroup analysis revealed the association between frequency and psychiatric symptoms to be primarily driven by the control group (Appendix C). Thus, a strong association between headache frequency and OCD, ADHD, and ASD symptoms was found in the control group (Appendix C, Table C.1-C.3). The association also persisted in the Mixed Headache group for OCD symptoms, and in the Migraine and All Patients group for ADHD symptoms (Tables C.1 and C.2).

Prevalence

Prevalence rates of participants receiving a research diagnosis of OCD, ADHD, and ASD are shown in Table 5 and Figure 2. We compared prevalence rates with reference to both the CH– and the CH+ groups. OCD was significantly more prevalent in the All Patients (20.8%), Migraine (20.8%), TTH (27.1%), Mixed (20.4%), and CH+ (27.8%) groups, compared with CH– (1.7%). ADHD was significantly more prevalent in the All Patients (17.3%), Migraine (18.1%), Unclassified (26.4%), and CH+ (18.8%) groups compared with CH– (7.0%). ASD was significantly more prevalent only in the Unclassified group compared with CH– (17.6% vs 1.8%). There were no significant differences in the prevalence of any of the 3 comorbidities when comparing patient groups with CH+.

Figure 2.

Bar plot of the observed prevalence of OCD, ADHD, and ASD in the groups. ADHD, attention-deficit hyperactivity disorder; ASD, autism spectrum disorder; CH+, controls with headache; CH–, headache-free controls; OCD, obsessive-compulsive disorder; TTH, tension-type headache.

Table 5.

Prevalence of OCD, ADHD, and ASD in the Groups.^a

Group	Clinical Diagnosis, n	Research Diagnosis, n	Observed Prevalence, % (95% CI)	Compared to CH–, OR (95% CI); P value	Compared to CH+, OR (95% CI); P value
OCD
All Patients	7	35	20.8 (15.5-27.2)	10.1 (2.0- 184); .026	0.6 (0.3-1.2); .144
Migraine	0	11	20.8 (10.8-34.1)	13.5 (2.4- 255); .016	0.8 (0.3-2.0); .665
TTH	2	14	27.1 (16.3-40.3)	11.4 (2.1-212); .023	0.7 (0.3-1.5); .370
Mixed	5	6	20.4 (10.6-33.5)	9.10 (1.6- 173); .042	0.6 (0.2-1.3); .190
Unclassified	0	2	7.4 (0.9-24.3)	3.8 (0.3-85.6); .288	0.2 (0.0-0.9); .066
CH+	0	20	27.8 (17.9-39.6)	16.4 (3.2-303); .008	Ref
CH–	0	1	1.7 (0.04-9.2)	Ref
ADHD
All Patients	15	43	17.3 (13.5-21.9)	3.4 (1.3, 11.8); .025	1.0 (0.5-1.9); .884
Migraine	6	9	18.1 (10.5-28.0)	3.3 (1.1-12.2); .046	0.9 (0.4-2.2); .878
TTH	2	12	14.3 (8.0-22.8)	2.8(0.9-10.4); .096	0.8 (0.3-1.8); .568
Mixed	2	8	12.7 (6.2-22.0)	2.4(0.7-9.4); .167	0.7 (0.3-1.7); .410
Unclassified	3	11	26.4 (15.3-40.3)	5.4 (1.8-20.6); .006	1.6 (0.7-3.7); .321
CH+	1	12	18.8 (10.4-30.1)	3.5 (1.2-13.2); .039	Ref
CH–	0	4	7.0 (1.9-17.0)	Ref
ASD
All Patients	11	3	10.1 (5.7-16.4)	6.4 (1.2-120); .083	2.5 (0.8-11.1); .172
Migraine	2	2	9.8 (2.7-23.1)	6.0 (0.8-122); .118	2.4 (0.5-13.1); .276
TTH	4	0	9.5 (2.7-22.6)	5.5 (0.7-117); .152	2.2 (0.4-12.2); .332
Mixed	2	1	8.1 (1.7-21.9)	4.8 (0.5-102); .197	1.9 (0.3-11.0); .454
Unclassified	3	0	17.6 (3.8-43.4)	11.9 (1.4-252); .038	4.8 (0.8-28.4); .079
CH+	2	1	4.4 (0.9-12.4)	2.5 (0.3-52.1); .436	Ref
CH–	1	0	1.8 (0.0-9.4)	Ref

Significant P values are in bold, with the significance level set at P <.05.

Discussion

We aimed to measure the symptom severity and prevalence of OCD, ADHD, and ASD in children and adolescents attending a headache outpatient clinic, compared to controls with and without headache (the CH+ and CH– groups). Findings were based on screening instruments and thus reflect symptom burden rather than confirmed clinical diagnoses. To our knowledge, this is the first study to evaluate ASD symptoms in children whose primary diagnosis is headache. We found a high prevalence—based on research diagnoses—of all 3 comorbidities, and surprisingly, these comorbidities were not limited to our patients but also prominent in our CH+ group. The CH+ group, surprisingly, had the most severe symptoms of all 3 conditions, when measured with total scores on the questionnaires, and had the highest research-based prevalence of OCD—suggesting a broader association between headache and psychiatric symptoms.

We also examined the relationship between symptom severity and headache frequency. In the control group, we observed a strong association between higher headache frequency and increased symptoms of OCD, ADHD, and ASD. This association is supported by existing literature.^2,4,47

Obsessive-Compulsive Disorder

One in 5 of All Patients received a research diagnosis of OCD compared with 1 in 4 of CH+, and 1 in 59 of CH–. Among patient subgroups, TTH had the highest prevalence, surpassing that of patients with migraine (27.1% vs 20.8%). In line with previous research, we replicated the finding that both patients and CH+—who had not sought help in managing their symptoms—experienced a significantly higher symptom burden of OCD than CH–.⁷ Contrary to existing literature, however, we found a higher prevalence of OCD in patients with TTH compared to those with migraine.⁸

It is important to note that the high prevalence may reflect an important limitation of our methodology—that we used a self-report questionnaire validated for use only in individuals ≥16 years, with cutoff scores based on adult data.^26,27 The validity of this instrument for use in younger children is uncertain. Nevertheless, OCD symptoms experienced by children are similar to those reported by adults,⁴⁸ and although the questionnaire might not be appropriate for diagnosing OCD in children, it may still provide a meaningful indication of overall symptom burden.

Attention Deficit/Hyperactivity Disorder

A research diagnosis of ADHD was given in 1 in 6 of All Patients, 1 in 5 of CH+, and 1 in 14 of CH–. Here, among patient subgroups, patients with unclassified headache had the highest prevalence, followed by patients with migraine and then patients with TTH (26.4% vs 18.8% vs 14.3%). We are the first to compare prevalence of ADHD in patients to both CH+ and CH– simultaneously. However, our findings are not unexpected. Previous clinical studies (eg, in pediatric headache outpatient clinics) have also reported more ADHD symptoms in patients with primary headache compared to CH–.^49-51 Contrary to us, however, they found that patients with TTH had similar⁵¹ or higher^49,52 prevalence/symptom severity than patients with migraine. Results from population-based studies are mixed: some report an association between frequent headaches or headache disorders (based on self- or parent-reported symptoms) and ADHD,^53-56 whereas others do not support this association.^57,58 This mirrors our comparison between the CH+ and CH− groups.

What stands out is the particularly high prevalence of ADHD in the Unclassified Headache group, where nearly one-third of participants received a research diagnosis. First, we raise the question of why these children fall in the Unclassified Headache category. It may reflect our methodological choice to manually assign headache diagnoses based on medical record review, rather than relying on clinically assigned headache diagnoses. The ICHD-3 criteria are adult-based,⁵⁹ and in clinical practice, neuropediatricians may adapt them to account for age-specific headache presentations,^60,61 such as shorter migraine duration. As a result, clinical diagnoses are not always strictly ICHD-3 compliant. For research purposes, however, strict adherence to the diagnostic criteria is paramount, allowing us to ensure homogeneity within groups and comparability across studies. However, this approach can result in a subset of patients being categorized as “unclassified” because of incomplete information in their medical records or because their symptoms do not strictly meet ICHD-3 criteria.

However, the high prevalence of ADHD offers an important new perspective. Although hypothetical, it raises the possibility that, for some children, the headache symptoms could be secondary to or influenced by an underlying ADHD condition. Notably, 11 of 14 children in this group received their ADHD research diagnosis based on their scores on the screening questionnaire. The diagnosis is not confirmed by a child and adolescent psychiatrist in this study; however, this could indicate that some children have ADHD symptoms that have previously gone unrecognized, warranting further exploration of whether they could benefit from psychiatric evaluation. These findings may support a possible bidirectional relationship between ADHD and headache.

Autism Spectrum Disorder

ASD was present in 1 of 10 of All Patients, 1 in 23 of CH+, and 1 in 56 of CH–. In contrast to the other conditions, most individuals with ASD had a prior diagnosis, and only a few received a research diagnosis based on their questionnaire scores. Once again, the patient subgroup with unclassified headache had the highest prevalence, followed by migraine and TTH (17.6% vs 9.8% vs 9.5%). As our study provides novel data on the presence of ASD in patients with headache as their primary diagnosis, comparisons with previous research are limited. However, as mentioned, existing studies found that individuals with ASD have higher odds of experiencing migraine or headaches.^11,62 Although we observed numerically higher odds of ASD in patients with migraine compared with CH–, this difference did not reach statistical significance. This is likely due to a significant limitation of our ASD data: sample size.

The SRS-2 was the only questionnaire to be solely distributed through the clinical research project approach, making it the questionnaire with the lowest response rate. It was also the longest questionnaire, and with only 131 of 183 fully completed (76%), this introduced a potential non-response bias. It is possible that those who chose to respond were those who found the content more relevant or reflective of their own experiences. For instance, those who had a prior diagnosis of ASD may be more familiar and willing to complete the questionnaire, which could overestimate the symptom severity based on questionnaire scores reported in this study. However, an important counterpoint is that the majority diagnosed with ASD (14 of 18; 78%) had already received their diagnosis prior to participation in the study—for them, the research diagnosis given was not based on their questionnaire scores. This suggests that the potential bias from non-responders may have had limited influence on the reported prevalence. Therefore, despite the small sample size, a key strength of our ASD data is that most diagnoses were confirmed as they were given by a child psychiatrist. This supports the notion that ASD and headache disorders are comorbid conditions.^11,62

Another interesting finding was that the TTH group was the only patient group with significantly more severe ASD symptoms than the CH– group. This could suggest that neurologic traits observed in ASD—such as sensory sensitivity or altered pain processing^63,64—may also play a role in the development or maintenance of TTH. Such shared mechanisms could reflect overlapping neurobiologic pathways, for example. involving central sensitization or atypical sensory integration.^65-68

Evidence for a Bidirectional Relationship

The relationship between headache and psychiatric disorders is still being explored. One theory is that there are shared pathophysiological mechanisms behind the conditions. For example, migraine and anxiety disorders such as OCD both involve the limbic system, which plays a role in migraine's prodromal phase and in anxiety-related threat processing.^18,69,70 Neuronal hyperexcitability in migraine may sensitize limbic structures, increasing vulnerability to anxiety^18,71 Migraine and ADHD may also share mechanisms, such as dopamine dysregulation,^72,73 disrupted sleep-wake cycle,^72,74 and impaired brain iron metabolism.⁷² Similarly, links between migraine and autism have been proposed. These may be linked to minicolumnopathy, which leads to a hyperexcitable cortex and serotonergic imbalance,¹⁵ genetic calcium signaling anomalies,¹⁶ and a shared sensory hyperreactivity.¹⁷

Another theory is that patients with primary headache exhibit associated symptoms that resemble a psychiatric disorder. For instance, Villa et al⁷⁵ found impaired visual attention in children with migraine and proposed that altered levels of noradrenaline and dopamine may predispose these children to attentional difficulties. Similarly, children with migraine report challenges with concentration in school,⁷⁶ and a recent review concluded that children with primary headache can have altered neuropsychological functions, including reduced attention, slower processing speed, and impaired memory.¹³ This raises the possibility that some of the psychiatric symptoms observed in our study may, in fact, reflect associated symptoms of having headaches rather than distinct comorbid disorders. OCD and ADHD were primarily identified through research diagnoses, which required a high symptom load during assessment—unlike ASD, where only a few participants showed symptoms severe enough to meet the research diagnostic criteria. This may suggest that the psychological symptoms linked to headache more often resemble anxiety or attention-related difficulties, rather than social-communication challenges.

One of the most unexpected findings was the high prevalence of participants receiving a research diagnosis of ADHD and OCD in the CH+ group. This may support a third theory: that children with underlying psychiatric symptoms or difficulties may experience headaches as a manifestation of psychological stress–suggesting a reversed causal relationship. Some studies have found that headache can precede the diagnosis of psychiatric disorders.^12,77 In this view, greater psychiatric symptom severity could be expected to coincide with increased headache frequency. Consistent with this, we observed a strong association between all three psychiatric conditions and headache frequency among controls.

We did not observe the same consistent association between psychiatric symptom severity and headache frequency in the patient groups. One explanation for this may be that treatment and management within the health care system have reduced headache frequency, thereby obscuring the observed link.

Perspectives and Clinical Implications

Our prevalence rates for OCD, ADHD, and ASD in our sample were markedly higher than national for patients aged 10-24 years in Denmark (0.65%, 4.50%, and 2.17%, respectively).⁷⁸ This may reflect an increased burden of neuropsychiatric symptoms among children with headache. However, research-based diagnoses are not equivalent to clinical diagnoses, and longitudinal studies are needed to assess diagnostic trajectories. Still, high symptom scores may indicate underlying psychosocial vulnerability, even without a formal diagnosis.

Current headache management guidelines recommend systematic assessment of anxiety and depression in children with headache.^79,80 Based on our findings, we propose that this should be extended to include screening for OCD and ADHD. Screening for ASD, however, should be reserved for cases with clinical suspicion. Although we identified a high prevalence, most cases had already been diagnosed prior to participation. This supports a comorbid relationship between ASD and headache but suggests that routine screening may have limited utility, as children with ASD are likely to have already been identified.

As psychiatric comorbidities were also common in CH+, this points to a broader and more complex association between headache and psychiatric disorders. Recognizing this association is important—not only for health professionals but also for teachers, school nurses, and parents. When a child experiences frequent headaches, it may be a sign of underlying psychological strain. Awareness of this link can help ensure that attention is directed beyond the physical symptom, to better understand what might be going on beneath the surface.

Strengths and Limitations

Strengths in this study include employing broad eligibility criteria in our patients and manual assignment of the headache diagnosis, enabling analysis of both the entire patient cohort and specific diagnostic subgroups. Additionally, actively addressing selection bias increased the representativeness of the patients, and results are likely generalizable to other neuropediatric departments and headache outpatient clinics.

A post hoc division of the control group into headache (CH+) and headache-free (CH–) subgroups was motivated by the high prevalence of headache among controls and the observed association with psychiatric symptoms. The purpose was to present this pattern clearly. However, this data-driven approach may reduce generalizability and statistical power and carries a risk of overfitting. It may also complicate interpretation, as the CH+ group could represent a subset of controls sharing several characteristics with the patient group, thereby diluting the contrast between patients and controls. At the same time, this division may provide new insights. The CH+ group could represent an intermediate stage between headache-free individuals and patients who have sought medical care for their headaches. This perspective may also help clarify whether the observed differences are specific to patients in clinic or reflect broader associations with headache occurrence in the general population. The CH– subgroup was younger and more predominantly male. As headache prevalence increases with age^81-83 and is generally higher among females, particularly after the onset of puberty,^81-84 this distribution was expected. Although analyses were adjusted for age and sex, this may still have influenced the results.

A key limitation was using OCI-R, which is developed and validated for individuals aged 16 years and older. Although child versions exist,^85,86 a Danish translation was not available at the time of data collection, and it is common practice to apply the adult version across age groups. This may have contributed to higher OCD symptom scores, as behaviors that are developmentally appropriate in younger children—such as ritualistic behaviors or collecting objects⁸⁷—might be interpreted as obsessive-compulsive symptoms in older individuals. The child version of OCI-R includes similar content but with age-adapted wording, which substantially improves children's comprehension of the items.⁸⁸ Consequently, use of the adult OCI-R could have led to falsely inflated prevalence rates of OCD among our participants.

Another important limitation is that the prevalence of psychiatric comorbidity was based on research diagnoses derived from screening instruments rather than clinical assessments. Although screening instruments can indicate a greater risk of psychiatric disorders,^27,40,89,90 they cannot alone serve as the basis for a clinical diagnosis.^91-93 A clinical diagnosis requires a comprehensive evaluation by a child and adolescent psychiatrist, including contextual information about the child's everyday functioning.⁹⁴ Consequently, some participants who met research criteria for a psychiatric disorder might not have received a clinical diagnosis if assessed by a psychiatrist.

The OCI-R was completed by the children themselves, whereas ADHD-RS and SRS-2 were completed by a parent. For OCI-R, then, a limitation is that we could not determine or control the extent of the parent's involvement, as questionnaires were completed without study personnel present, potentially introducing bias. Younger participants likely received parental assistance—which is necessary and beneficial, as it would have improved response validity in the youngest participants.⁹⁵

Other limitations include patient recruitment through 2 approaches, which might have introduced different selection biases in patients (see subsection “Bias” above); dividing participants into groups, which decreased sample size, limiting statistical power and generalizability; being unable to match controls on age, despite targeted efforts, which—although adjusted for in the analysis—may still impact results; recruiting participants partly during the COVID-19 pandemic, which could have influenced the presence of headache and increased the level of psychiatric symptoms both during^96,97 and after^98,99 the pandemic; the time gap between examining patients and controls; and that clinical diagnosis of psychiatric comorbidity was collected through self-report in controls, potentially causing misclassification. We did not collect data on medication use, which—particularly for treating the psychiatric comorbidity—could confound severity of reported symptoms. To partly address this, we did not use questionnaire data from participants with a clinical diagnosis of psychiatric comorbidity when assigning a research diagnosis. However, medication use could still confound the estimated symptom severity. Furthermore, we did not collect detailed information on individuals who declined participation or did not complete the questionnaires in approach (1). Although approximately 800 patients were seen in the clinic during the study period, the number who attended an initial assessment and were offered the questionnaires was not recorded. Similarly, it was not possible to determine how many patients received a questionnaire but did not return it because of discharge or other reasons. This lack of registration limits the ability to assess potential selection bias. Also, in the analysis of headache frequency (Appendix C, Tables C.1-C.3), the reference group had the fewest observations, thereby reducing the likelihood of detecting differences. Because of the cross-sectional design, causal relationships cannot be established, and the findings should therefore be interpreted as associations only.

Conclusion

We found a high symptom burden and prevalence of research diagnoses of OCD, ADHD, and ASD among children and adolescents attending a headache outpatient clinic, as well as in controls with headache, compared with headache-free controls. In the control group, symptom severity consistently increased with headache frequency. This suggests that headache and psychiatric comorbidities are associated, regardless of whether the child has sought medical attention for their headaches.

OCD and ADHD emerged as particularly relevant conditions to screen for, and we therefore recommend routine screening for these disorders in children presenting with headache. In contrast, screening for ASD should be reserved for cases where there is clinical suspicion.

Supplemental Material

sj-docx-1-jcn-10.1177_08830738261456884 - Supplemental material for Symptoms of Obsessive-Compulsive Disorder, Attention-Deficit/Hyperactivity Disorder, and Autism Spectrum Disorder in Children and Adolescents Attending a Headache Outpatient Clinic and School-Based Controls

Supplemental material, sj-docx-1-jcn-10.1177_08830738261456884 for Symptoms of Obsessive-Compulsive Disorder, Attention-Deficit/Hyperactivity Disorder, and Autism Spectrum Disorder in Children and Adolescents Attending a Headache Outpatient Clinic and School-Based Controls by Amalie Akulenok Berring-Uldum, Lisa Ysrea Pann, Maria J. Miranda and Nanette Marinette Monique Debes in Journal of Child Neurology

Supplemental Material

sj-docx-2-jcn-10.1177_08830738261456884 - Supplemental material for Symptoms of Obsessive-Compulsive Disorder, Attention-Deficit/Hyperactivity Disorder, and Autism Spectrum Disorder in Children and Adolescents Attending a Headache Outpatient Clinic and School-Based Controls

Supplemental material, sj-docx-2-jcn-10.1177_08830738261456884 for Symptoms of Obsessive-Compulsive Disorder, Attention-Deficit/Hyperactivity Disorder, and Autism Spectrum Disorder in Children and Adolescents Attending a Headache Outpatient Clinic and School-Based Controls by Amalie Akulenok Berring-Uldum, Lisa Ysrea Pann, Maria J. Miranda and Nanette Marinette Monique Debes in Journal of Child Neurology

Footnotes

ORCID iD

Amalie Akulenok Berring-Uldum

Nanette Marinette Monique Debes

Author Contributions

Amalie Akulenok Berring-Uldum: Conceptualization, Methodology, Formal analysis, Investigation, Data curation, Writing - original draft, Visualization, Project administration, Funding acquisition; Lisa Pann: Investigation, Data curation, Writing - Review and editing; Maria J. Miranda: Resources, Writing - Review and Editing; Supervision; Nanette Mol Debes: Conceptualization, Methodology, Resources, Writing - Review and Editing, Supervision, Project administration.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Herlev and Gentofte University Hospital Research Grant; Tværspuljen—Sektion for Tværsektoriel Forskning (grant number: Pb-2023-1); King Christian the Tenth Foundation (grant number: 13-2024); Tømrermester Jørgen Holm og hustru Elisa f. Hansens Mindelegat (grant number: 24009).

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The data are available on request from the corresponding author. Unfortunately, they are not deposited in a research data deposit because of restrictions imposed by the ethical board.

Supplemental Material

Supplemental material for this article is available online.

References

Falla

Kuziek

Mahnaz

Noel

Ronksley

Orr

. Anxiety and depressive symptoms and disorders in children and adolescents with migraine: a systematic review and meta-analysis. JAMA Pediatr. 2022;176(12):1176-1187. doi:10.1001/jamapediatrics.2022.3940

Cupini

Murtas

Costa

, et al. Obsessive-compulsive disorder and migraine with medication-overuse headache. Headache J Head Face Pain. 2009;49(7):1005-1013. doi:10.1111/j.1526-4610.2009.01457.x

Curone

D’Amico

Bussone

. Obsessive-compulsive aspects as predictors of poor response to treatments in patients with chronic migraine and medication overuse. Neurol Sci. 2012;33(1):211-213. doi:10.1007/s10072-012-1070-5

Goulart

Santos

Brunoni

, et al. Migraine headaches and mood/anxiety disorders in the ELSA Brazil. Headache J Head Face Pain. 2014;54(8):1310-1319. doi:10.1111/head.12397

Jeyagurunathan

Abdin

Vaingankar

, et al. Prevalence and comorbidity of migraine headache: results from the Singapore Mental Health Study 2016. Soc Psychiatry Psychiatr Epidemiol. 2019;55:33–43. doi:https://doi.org/10.1007/s00127-019-01755-1.

Breslau

Davis

. Migraine, physical health and psychiatric disorder: a prospective epidemiologic study in young adults. J Psychiatr Res. 1993;27(2):211-221. doi:10.1016/0022-3956(93)90009-Q

Vulić-Prtorić

Galić

Renata

Marina

Lopižić

Patricija

. Anxiety in Children with Headaches. Psihologijske Teme. 2007;16(2):201–224.

Pavone

Rizzo

Conti

, et al. Primary headaches in children: clinical findings and the association with other conditions. Int J Immunopathol Pharmacol. 2012;25(4):1083-1091. doi:10.1177/039463201202500425

Salem

Vivas

Cao

Kazimi

Teixeira

Zeni

. ADHD is associated with migraine: a systematic review and meta-analysis. Eur Child Adolesc Psychiatry. 2018;27(3):267-277. doi:10.1007/s00787-017-1045-4

10.

Pan

Jonsson

Şahpazoğlu Çakmak

, et al. Headache in ADHD as comorbidity and a side effect of medications: a systematic review and meta-analysis. Psychol Med. 2022;52(1):14-25. doi:10.1017/S0033291721004141

11.

Pan

Bölte

Kaur

Jamil

Jonsson

. Neurological disorders in autism: a systematic review and meta-analysis. Autism Int J Res Pract. 2021;25(3):812-830. doi:10.1177/1362361320951370

12.

Alexeeff

Yau

Qian

, et al. Medical conditions in the first years of life associated with future diagnosis of ASD in children. J Autism Dev Disord. 2017;47(7):2067-2079. doi:10.1007/s10803-017-3130-4

13.

Tarantino

Checchi

Papetti

, et al. Interictal cognitive performance in children and adolescents with primary headache: a narrative review. Front Neurol. 2022;13:898626. doi:10.3389/fneur.2022.898626

14.

Paolino

Ferretti

Villa

Parisi

. Headache and ADHD in pediatric age: possible physiopathological links. Curr Pain Headache Rep. 2015;19(7):25. doi:10.1007/s11916-015-0494-z

15.

Casanova

. The minicolumnopathy of autism: a link between migraine and gastrointestinal symptoms. Med Hypotheses. 2008;70(1):73-80. doi:10.1016/j.mehy.2007.04.025

16.

Gargus

. Genetic calcium signaling abnormalities in the central nervous system: seizures, migraine, and autism. Ann N Y Acad Sci. 2009;1151(1):133-156. doi:10.1111/j.1749-6632.2008.03572.x

17.

Sullivan

Miller

Nielsen

Schoen

. The presence of migraines and its association with sensory hyperreactivity and anxiety symptomatology in children with autism spectrum disorder. Autism. 2014;18(6):743-747. doi:10.1177/1362361313489377

18.

Kumar

Asif

Bali

Dang

Gonzalez

. The development and impact of anxiety with migraines: a narrative review. Cureus. 2022;14(6):e26419. doi:10.7759/cureus.26419

19.

Jorgensen

McGirr

Korsgaard

Rathleff

. Translation and validation of the child and the adolescent HARDSHIP (headache-attributed restriction, disability, social handicap and impaired participation) questionnaire into Danish language. PeerJ. 2016;4:e1927. doi:10.7717/peerj.1927

20.

Foreningen BørnUngeLiv. 2023. Denmark.

21.

Matza

Swensen

Flood

Secnik

Leidy

. Assessment of health-related quality of life in children: a review of conceptual, methodological, and regulatory issues. Value Health. 2004;7(1):79-92. doi:10.1111/j.1524-4733.2004.71273.x

22.

Harris

Taylor

Thielke

Payne

Gonzalez

Conde

. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377-381. doi:10.1016/j.jbi.2008.08.010

23.

Harris

Taylor

Minor

, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform. 2019;95:103208. doi:10.1016/j.jbi.2019.103208

24.

Foa

Huppert

Leiberg

, et al. The Obsessive-Compulsive Inventory: development and validation of a short version. Psychol Assess. 2002;14(4):485-496. doi:10.1037/1040-3590.14.4.485

25.

Huppert

Walther

Hajcak

, et al. The OCI-R: validation of the subscales in a clinical sample. J Anxiety Disord. 2007;21(3):394-406. doi:10.1016/j.janxdis.2006.05.006

26.

Piqueras Rodríguez

Martínez González

Hidalgo Montesinos

Fullana Rivas

MÁ

Mataix-Cols

Rosa Alcázar

. Psychometric properties of the Obsessive Compulsive Inventory-Revised in a non-clinical sample of late adolescents. Behav Psychol. 2009;17(3):561-572.

27.

Abramovitch

Abramowitz

Riemann

McKay

. Severity benchmarks and contemporary clinical norms for the Obsessive-Compulsive Inventory-Revised (OCI-R). J Obsessive-Compuls Relat Disord. 2020;27:100557. doi:10.1016/j.jocrd.2020.100557

28.

Hajcak

Huppert

Simons

Foa

. Psychometric properties of the OCI-R in a college sample. Behav Res Ther. 2004;42(1):115-123. doi:10.1016/j.brat.2003.08.002

29.

Williams

Davis

Thibodeau

Bach

. Psychometric properties of the Obsessive-Compulsive Inventory Revised in African Americans with and without obsessive-compulsive disorder. J Obsessive-Compuls Relat Disord. 2013;2(4):399-405. doi:10.1016/j.jocrd.2013.07.003

30.

Szomlaiski

Dyrborg

Rasmussen

Schumann

Koch

Bilenberg

. Validity and clinical feasibility of the ADHD rating scale (ADHD-RS): a Danish nationwide multicenter study. Acta Paediatr. 2009;98(2):397-402. doi:10.1111/j.1651-2227.2008.01025.x

31.

DuPaul

. Parent and teacher ratings of ADHD symptoms: psychometric properties in a community-based sample. J Clin Child Psychol. 1991;20(3):245-253. doi:10.1207/s15374424jccp2003_3

32.

DuPaul

Power

Anastopoulos

Reid

. ADHD Rating Scale-IV: Checklists, Norms, and Clinical Interpretation . Guilford; 1998.

33.

Barkley

Robin

. Defiant Teens, Second Edition: A Clinician’s Manual for Assessment and Family Intervention. Guilford; 2014.

34.

Ishibashi

Nishiyama

Makino

, et al. Psychometrics of rating scales for externalizing disorders in Japanese outpatients: the ADHD-rating scale-5 and the disruptive behavior disorders rating scale. Int J Methods Psychiatr Res. 2024;33(1):e2015. doi:10.1002/mpr.2015

35.

Zhang

Faries

Vowles

Michelson

. ADHD Rating scale IV: psychometric properties from a multinational study as a clinician-administered instrument. Int J Methods Psychiatr Res. 2005;14(4):186-201. doi:10.1002/mpr.7

36.

Makransky

Bilenberg

. Psychometric properties of the parent and teacher ADHD rating scale (ADHD-RS): measurement invariance across gender, age, and informant. Assessment. 2014;21(6):694-705. doi:10.1177/1073191114535242

37.

Constantino

. The Social Responsiveness Scale. Published online 2002.

38.

Constantino

Davis

Todd

, et al. Validation of a brief quantitative measure of autistic traits: comparison of the social responsiveness scale with the Autism Diagnostic Interview-Revised. J Autism Dev Disord. 2003;33(4):427-433. doi:10.1023/A:1025014929212

39.

Constantino

Gruber

. Social Responsiveness Scale Second Edition (SRS-2): Manual. 2nd edition. Western Psychological Services (WPS); 2012.

40.

Wang

Lee

Chen

Hsu

. Assessing autistic traits in a Taiwan preschool population: cross-cultural validation of the Social Responsiveness Scale (SRS). J Autism Dev Disord. 2012;42(11):2450-2459. doi:10.1007/s10803-012-1499-7

41.

Constantino

Gruber

. Social Responsiveness Scale (SRS) Manual. Los Angeles: Western Psychological Services. Western Psychological Services; 2005.

42.

Bölte

Poustka

Constantino

. Assessing autistic traits: cross-cultural validation of the social responsiveness scale (SRS). Autism Res. 2008;1(6):354-363. doi:10.1002/aur.49

43.

Constantino

Przybeck

Friesen

Todd

. Reciprocal social behavior in children with and without pervasive developmental disorders. J Dev Behav Pediatr JDBP. 2000;21(1):2-11. doi:10.1097/00004703-200002000-00002

44.

Gobel

. The International Classification of Headache Disorders. ICHD-3. Accessed February 19, 2024. https://ichd-3.org/

45.

Hansen

Andersen

. Socialforskningsinstituttets Socialgruppeinddeling. In: Et Sociologisk Værktøj. Introduktion Til Den Kvantitative Metode. Hans Reizels Forlag; 2000.

46.

R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2021. Accessed October 3, 2024. https://www.r-project.org/

47.

Arruda

Guidetti

Bigal

. ADHD is comorbid to migraine in childhood: a population-based study. J Atten Disord. 2020;24(7):990-1001. doi:10.1177/1087054717710767

48.

Kalra

Swedo

. Children with obsessive-compulsive disorder: are they just “little adults”? J Clin Invest. 2009;119(4):737-746. doi:10.1172/JCI37563

49.

Mazzone

Vitiello

Incorpora

Mazzone

. Behavioural and temperamental characteristics of children and adolescents suffering from primary headache. Cephalalgia. 2006;26(2):194-201. doi:10.1111/j.1468-2982.2005.01015.x

50.

Pavone

Rizzo

Conti

, et al. Primary headaches in children: clinical findings on the association with other conditions. Int J Immunopathol Pharmacol. 2012;25(4):1083-1091. doi:10.1177/039463201202500425

51.

Riva

Usilla

Aggio

Vago

Treccani

Bulgheroni

. Attention in children and adolescents with headache. Headache J Head Face Pain. 2012;52(3):374-384. doi:10.1111/j.1526-4610.2011.02033.x

52.

Genizi

Gordon

Kerem

Srugo

Shahar

Ravid

. Primary headaches, attention deficit disorder and learning disabilities in children and adolescents. J Headache Pain. 2013;14(1):54. doi:10.1186/1129-2377-14-54

53.

Jameson

Sheppard

Lateef

Vande Voort

Merikangas

. Medical comorbidity of attention-deficit/hyperactivity disorder in US adolescents. J Child Neurol. 2016;31(11):1282-1289. doi:10.1177/0883073816653782

54.

Arruda

. Psychological adjustment in children with episodic migraine: a population-based study. Psychol Neurosci. 2014;7(1):33-41. doi:10.3922/j.psns.2014.1.06

55.

Arruda

Guidetti

Galli

Albuquerque

RCAP

Bigal

. Migraine, tension-type headache, and attention-deficit/hyperactivity disorder in childhood: a population-based study. Postgrad Med. 2010;122(5):18-26. doi:10.3810/pgm.2010.09.2197

56.

Lateef

Merikangas

, et al. Headache in a national sample of American children: prevalence and comorbidity. J Child Neurol. 2009;24(5):536-543. doi:10.1177/0883073808327831

57.

Genizi

Marom

Srugo

Kerem

. The relations between attention deficit hyperactivity disorder and headaches in a non-clinical sample of adolescents. Acad J Pediatr Neonatol. 2016;2(2):29–32. doi:https://doi.org/10.19080/AJPN.2016.02.555583.

58.

Pitrou

Shojaei

Chan-Chee

Wazana

Boyd

Kovess-Masféty

. The associations between headaches and psychopathology: a survey in school children. Headache J Head Face Pain. 2010;50(10):1537-1548. doi:10.1111/j.1526-4610.2010.01781.x

59.

IHS Classification. ICHD-3 The International Classification of Headache Disorders 3rd edition. Accessed September 30, 2019. https://ichd-3.org/

60.

McAbee

Morse

Assadi

. Pediatric aspects of headache classification in the International Classification of Headache Disorders—3 (ICHD-3 beta version). Curr Pain Headache Rep. 2016;20(1):1-6. doi:10.1007/s11916-015-0537-5

61.

Özge

Faedda

Abu-Arafeh

, et al. Experts’ opinion about the primary headache diagnostic criteria of the ICHD-3rd edition beta in children and adolescents. J Headache Pain. 2017;18(1):109. doi:10.1186/s10194-017-0818-y

62.

Underwood

JFG

Kendall

Berrett

, et al. Autism spectrum disorder diagnosis in adults: phenotype and genotype findings from a clinically derived cohort. Br J Psychiatry J Ment Sci. 2019;215(5):647-653. doi:10.1192/bjp.2019.30

63.

Bogdanova

Bogdanov

Pizano

, et al. The current view on the paradox of pain in autism spectrum disorders. Front Psychiatry. 2022;13:910824. doi:10.3389/fpsyt.2022.910824

64.

Marco

Hinkley

LBN

Hill

Nagarajan

. Sensory processing in autism: a review of neurophysiologic findings. Pediatr Res. 2011;69(5 Pt 2):48R-54R. doi:10.1203/PDR.0b013e3182130c54

65.

Ashina

Mitsikostas

Lee

, et al. Tension-type headache. Nat Rev Dis Primer. 2021;7(1):24. doi:10.1038/s41572-021-00257-2

66.

Steel

Robertson

Whealy

. Current understanding of the pathophysiology and approach to tension-type headache. Curr Neurol Neurosci Rep. 2021;21(10):1-12. doi:10.1007/s11910-021-01138-7

67.

Bentivegna

Luciani

Paragliola

, et al. Recent advancements in tension-type headache: a narrative review. Expert Rev Neurother. 2021;21(7):793-803. doi:10.1080/14737175.2021.1943363

68.

Bendtsen

Fernández-de-la-Peñas

. The role of muscles in tension-type headache. Curr Pain Headache Rep. 2011;15(6):451-458. doi:10.1007/s11916-011-0216-0

69.

Dodick

. Migraine. Lancet. 2018;391(10127):1315-1330. doi:10.1016/S0140-6736(18)30478-1

70.

Giacobbe

Flint

. Diagnosis and management of anxiety disorders. Continuum (Minneap Minn). 2018;24(3):893-919. doi:10.1212/CON.0000000000000607

71.

Zarcone

Corbetta

. Shared mechanisms of epilepsy, migraine and affective disorders. Neurol Sci. 2017;38(S1):73-76. doi:10.1007/s10072-017-2902-0

72.

Parisi

Verrotti

Paolino

, et al. Headache and attention deficit and hyperactivity disorder in children: common condition with complex relation and disabling consequences. Epilepsy Behav. 2014;32:72-75. doi:10.1016/j.yebeh.2013.12.028

73.

Treister

Eisenberg

Demeter

Pud

. Alterations in pain response are partially reversed by methylphenidate (Ritalin) in adults with attention deficit hyperactivity disorder (ADHD). Pain Pract. 2015;15(1):4-11. doi:10.1111/papr.12129

74.

Paolino

Ferretti

Villa

Parisi

. Headache and ADHD in pediatric age: possible physiopathological links. Curr Pain Headache Rep. 2015;19(7):25. doi:10.1007/s11916-015-0494-z

75.

Villa

Moutran

Diaz

, et al. Visual attention in children with migraine: a controlled comparative study. Cephalalgia. 2009;29(6):631-634. doi:10.1111/j.1468-2982.2008.01767.x

76.

Canfora

Pallotto

Davis

, et al. More than a headache: lived experience of migraine in youth. Pediatr Neurol. 2023;146:79-84. doi:10.1016/j.pediatrneurol.2023.05.019

77.

Blaauw

Dyb

Hagen

, et al. The relationship of anxiety, depression and behavioral problems with recurrent headache in late adolescence—a Young-HUNT follow-up study. J Headache Pain. 2015;16(1):10. doi:10.1186/1129-2377-16-10

78.

Jeppesen

Obel

Lund

Madsen

Nielsen

Nordentoft

. Mental sundhed og sygdom hos børn og unge i alderen 10-24 år—forekomst, fordeling og forebyggelsesmuligheder. København Vidensråd Forebyggelse. 2020;1.359(1-359).

79.

Baglioni

Orecchio

Esposito

Faedda

Natalucci

Guidetti

. Tension-type headache in children and adolescents. Life. 2023;13(3):825. doi:10.3390/life13030825

80.

Orr

. Headache in children and adolescents. Contin Minneap Minn. 2024;30(2):438-472. doi:10.1212/CON.0000000000001414

81.

Philipp

Zeiler

Wöber

, et al. Prevalence and burden of headache in children and adolescents in Austria - a nationwide study in a representative sample of pupils aged 10-18 years. J Headache Pain. 2019;20(1):101. doi:10.1186/s10194-019-1050-8

82.

Zewde

Zebenigus

Demissie

, et al. The burden attributable to primary headache disorders in children and adolescents in Ethiopia: estimates from a national schools-based study. J Headache Pain. 2024;25(1):47. doi:10.1186/s10194-024-01743-0

83.

Karaaslan

Uygunoğlu

Şaşmaz

, et al. The prevalence of headache disorders in children and adolescents in Istanbul: a school-based study. Pediatr Neurol. 2023;149:100-107. doi:10.1016/j.pediatrneurol.2023.09.007

84.

Onofri

Pensato

Rosignoli

, et al. Primary headache epidemiology in children and adolescents: a systematic review and meta-analysis. J Headache Pain. 2023;24(1):8. doi:10.1186/s10194-023-01541-0

85.

Abramovitch

Abramowitz

McKay

, et al. The OCI-CV-R: a revision of the obsessive-compulsive inventory - child version. J Anxiety Disord. 2022;86:102532. doi:10.1016/j.janxdis.2022.102532

86.

Opakunle

Aloba

Akinsulore

. Obsessive compulsive inventory — child version (OCI-CV): confirmatory factor analysis, reliability, validity and correlates among Nigerian adolescents. Malawi Med J. 2018;30(4):262-269. doi:10.4314/mmj.v30i4.9

87.

Geller

Homayoun

Johnson

. Developmental considerations in obsessive compulsive disorder: comparing pediatric and adult-onset cases. Front Psychiatry. 2021;12:678538. doi:10.3389/fpsyt.2021.678538

88.

Uher

Heyman

Turner

Shafran

. Self-, parent-report and interview measures of obsessive-compulsive disorder in children and adolescents. J Anxiety Disord. 2008;22(6):979-990. doi:10.1016/j.janxdis.2007.10.001

89.

Poulsen

Jørgensen

Dalsgaard

Bilenberg

. Danish standardization of the attention deficit hyperactivity disorder rating scale. Ugeskr Laeger. 2009;171(18):1500-1504.

90.

Szomlaiski

Dyrborg

Rasmussen

Schumann

Koch

Bilenberg

. Validity and clinical feasibility of the ADHD rating scale (ADHD-RS) A Danish nationwide multicenter study. Acta Paediatr. 2009;98(2):397-402. doi:10.1111/j.1651-2227.2008.01025.x

91.

Wolraich

Hagan

Allan

, et al. Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2019;144(4):e20192528. doi:10.1542/peds.2019-2528

92.

Hyman

Levy

Myers

, et al. Identification, evaluation, and management of children with autism Spectrum disorder. Pediatrics. 2020;145(1):e20193447. doi:10.1542/peds.2019-3447

93.

Geller

March

. Practice parameter for the assessment and treatment of children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 2012;51(1):98-113. doi:10.1016/j.jaac.2011.09.019

94.

Mayall

Teoh

McDermott

Sadhu

Bosanquet

. Child and adolescent mental health multiaxial classification: a useful biopsychosocial framework for paediatrics? J Paediatr Child Health. 2022;58(7):1130-1135. doi:10.1111/jpc.16026

95.

Matza

Patrick

Riley

, et al. Pediatric patient-reported outcome instruments for research to support medical product labeling: report of the ISPOR PRO good research practices for the assessment of children and adolescents task force. Value Health. 2013;16(4):461-479. doi:10.1016/j.jval.2013.04.004

96.

Chawla

Tom

Sen

Sagar

. Psychological impact of COVID-19 on children and adolescents: a systematic review. Indian J Psychol Med. 2021;43(4):294-299. doi:10.1177/02537176211021789

97.

Panchal

Salazar de Pablo

Franco

, et al. The impact of COVID-19 lockdown on child and adolescent mental health: systematic review. Eur Child Adolesc Psychiatry. 2023;32(7):1151-1177. doi:10.1007/s00787-021-01856-w

98.

Kiviruusu

Ranta

Lindgren

, et al. Mental health after the COVID-19 pandemic among Finnish youth: a repeated, cross-sectional, population-based study. Lancet Psychiatry. 2024;11(6):451-460. doi:10.1016/S2215-0366(24)00108-1

99.

Haskell

Sigmarsdottir

Thorisdottir

, et al. Adolescent mental health before, during, and after the COVID-19 pandemic in Iceland: a repeated, cross-sectional, population-based study. Lancet Reg Health—Eur. 2025;53. doi:https://doi.org/10.1016/j.lanepe.2025.101301.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.03 MB

0.04 MB