Clinical profile of headache attributed to anxiety and depressive disorder: an observational study

Clinical profile of headache attributed to anxiety and depressive disorder: an observational study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical profile of headache attributed to anxiety and depressive disorder: an observational study Boyan Chen, Xinyu Yan, Jing Yang, Sailucao Zhang, Chunyu Wang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8492822/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Headache attributed to anxiety or depressive disorder was added to the appendix of the International Classification of Headache Disorders, 3rd edition (ICHD-3) in 2018. However, the clinical features have not been systematically characterized. This study aims to describe its clinical profile of headache attributed to anxiety and depressive disorders (HA-ADD). Methods An observational study was performed between March 2024 and June 2025 in a Chinese headache center. A total of 101 patients diagnosed with HA-ADD were enrolled after excluding primary headaches and other secondary causes. Clinical data were collected through structured face-to-face interviews. Results Headache experienced by majority of the participants was bilateral (72.3%), dull type (92.1%) and of moderate-to-severe intensity (96.1%). The most frequently locations of headache were the temporal (47.5%), parietal (35.6%) regions. 60.4% of attacks lasted for less than 4h. Common accompanying symptoms were phonophobia (79.2%), restlessness and agitation (58.4%), dizziness (57.4%), and nausea (51.5%). Emotional fluctuations (71.3%), poor sleep (57.4%) were the most common triggering factors. 73.2% of patients reported severe headache impact on daily life. Conclusions Headache attributed to anxiety and depressive disorders has distinct clinical characteristics that may aid in its early clinical recognition. Neurobiology of Disease Headache Attributed to Anxiety and Depressive Disorder Clinical Profile Comorbidity Anxiety Depression Figures Figure 1 Figure 2 Figure 3 Introduction Anxiety and depression often coexist with primary headache disorders, particularly with migraine and tension headache [ 1 ] . In some patients, anxiety and depression are the only identifiable cause of headache [ 2 ] . Headache attributed to anxiety or depressive disorder was added to the appendix in 2018 ICHD-3. However, its clinical features have not been systematically characterized, hindering accurate early recognition and leading to delayed diagnosis and suboptimal treatment. A key diagnostic issue is how to determine whether the headache is a secondary headache attributable to anxiety and depressive disorder (HA-ADD), or a primary headache comorbid with anxiety and depressive disorder. According to the diagnostic criteria of ICHD-3, the crucial distinction lies in the presence of a temporal causal relationship—specifically, whether the headache occurs exclusively during the active phase of the anxiety-depressive disorder. In practice, patients often struggle to accurately recall and describe the temporal relationship between the onset and fluctuations of their anxiety–depressive symptoms and their headache episodes. This substantially limits the clinical applicability of this core diagnostic criterion. Consequently, the current diagnosis of HA-ADD largely relies on a "therapeutic diagnosis" or "post-hoc verification" approach, which means when the mood disorder is effectively treated and the headache symptoms subsequently improve or resolve, the headache is then considered attributable to the anxiety and depressive disorder. Anxiety and depression frequently co-occur. A cohort study found that among patients with depression, 67% had comorbid anxiety, and among those with anxiety, 63% had comorbid depression [ 3 ] . These findings suggest that the concurrent presence of both disorders is more common than either disorder occurring in isolation. Epidemiological data indicate that major depressive disorder (MDD) and persistent depressive disorder (PDD) are the most prevalent forms of depressive disorders [ 4 , 5 ] . Generalized anxiety disorder (GAD) is a highly chronic condition that is not dependent on specific triggers. Moreover, GAD and MDD exhibit particularly high rates of comorbidity. A large-scale epidemiological survey revealed that up to 65% of individuals with GAD concurrently meet criteria for MDD [ 6 ] . Given this strong bidirectional relationship, the present study focused on patients with GAD comorbid with MDD or PDD to characterize the clinical features of headache attributable to anxiety and depressive disorders. Methods Participants The study was carried out at Headache Center of the 940th Hospital, Joint Logistics Support Force of the PLA. From March 2024 to June 2025, patients provisionally diagnosed with HA-ADD were enrolled. Ethical approval was obtained from the Hospital Ethics Committee (Approval No. [2024KYLL198]), and all patients provided written informed consent prior to participation. Inclusion Criteria: (1) Age 18-65 years; (2) Meeting DSM-5 criteria for major depressive disorder or persistent depressive disorder (F32.x/F33.x, F34.1) co - occurring with generalized anxiety disorder (F41.1), with concomitant headache symptoms ; (3) Headache occurring after anxiety and depression; (4) Free of antidepressant or anxiolytic medications for at least one month prior to enrollment; (5) Documented reduction in headache frequency or severity following a confirmed alleviation of anxiety and depressive symptoms after a course of adequate pharmacotherapy. Exclusion Criteria: (1) Diagnosis meeting ICHD-3 criteria for primary headache disorders ( e.g., migraine, tension-type headache); (2) Headaches attributed to other underlying causes; (3) Diagnosis of other primary or secondary psychiatric disorders per DSM-5 criteria (e.g., substance use disorders, psychiatric conditions due to medical conditions); (4) Absence of significant headache improvement after 6 months of adequate antidepressant/anxiolytic therapy; (5) Pregnancy or lactation; (6) Severe systemic disease. Procedures At the initial consultation, a headache specialist performed a detailed clinical interview and physical examination. Demographic and headache characteristics were recorded, including age, sex, onset time, pain location, quality, intensity, duration, monthly frequency, triggers, relieving factors, associated symptoms, and current medications. Features of mood disorders were also documented, encompassing core symptoms and severity. All patients completed a series of standardized assessments to quantify mood symptoms and headache impact. The final diagnosis of HA-ADD was established through multidisciplinary discussion between at least one experienced headache specialist and one psychiatrist, according to DSM-5 criteria for anxiety and depression and ICHD-3 criteria for headache disorders. To exclude secondary causes, all patients underwent appropriate ancillary investigations, including brain CT/MRI and blood tests (liver and renal function, autoimmune antibodies, erythrocyte sedimentation rate, D-dimer, etc.). Patients with a provisional diagnosis of HA-ADD received antidepressant and anxiolytic medications. Follow-up assessments were conducted at 1, 3, and 6 months after treatment initiation, either in the outpatient clinic or via telephone, to evaluate changes in mood disorders and headache symptoms. Headache was attributable to the anxiety-depressive disorder if it resolved or markedly improved (in frequency, severity, or duration) following the alleviation of mood symptoms. A detailed flowchart of patient screening and enrollment is presented in Figure 1. Scale Assessment All participants were assessed using the following standardized scales. Research staff verified the completeness of all questionnaires. Scale data were entered by one investigator and independently double-checked by another. (1) Visual analog scale (VAS) was used to assess the maximum pain intensity (0-3: mild; 4-6: moderate ;7-10: severe). (2) The short-form headache impact test 6(HIT-6) [7] was employed to evaluate the impact of headache on daily life and work. Total scores were interpreted as: ≤49 (little or no impact); 50-55(moderate impact); 56-59(substantial impact); ≥60(very severe impact). (3) Patient health questionnaire 9 (PHQ-9) [8] was administered to assess the severity of depressive symptoms. Scores were classified as follows: 0-4(minimal or none); 5-9(mild); 10-14(moderate); 15-19(moderately severe); ≥20(severe). (4) Generalized Anxiety Disorder 7-item (GAD-7) Scale [9] was administered to assess the severity of anxiety symptoms. Scores were categorized as: 0-4(minimal or none); 5-9(mild); 10-14(moderate); ≥15(severe). (5) Pittsburgh sleep quality index (PSQI) was employed to assess sleep quality. A global score ≥7 indicates poor sleep quality (range: 0-21), with higher scores reflecting worse sleep. Treatment Protocol Patients with provisional diagnosis of HA-ADD received individualized pharmacotherapy prescribed by a psychiatrist, targeting their anxiety and depressive symptoms. The treatment goal was defined as reaching and maintaining each medication within its recommended effective dose range for a minimum of 4-6 weeks to ensure adequate efficacy, with subsequent adjustments based on individual response and tolerability. The pharmacological regimen included selective serotonin reuptake inhibitors (SSRIs, e.g., fluvoxamine maleate, escitalopram), non-benzodiazepine anxiolytics (e.g., buspirone, tandospirone), serotonin and norepinephrine reuptake inhibitors (SNRIs, e.g., duloxetine), and Chinese herbal formulations (e.g., Shuganjieyu Capsule, Wuling Capsule). Notably, venlafaxine and amitriptyline, both explicitly recommended in current guidelines for migraine and tension-type headache (TTH) prophylaxis [10–11] , were excluded from this study to avoid potential confounding of the treatment effect. Throughout the 6-month treatment and follow-up period, patients were permitted to use acute medications (such as nonsteroidal anti-inflammatory drugs or triptans) as needed for headache attacks. No other preventive medications were administered during the study. O utcome assessment The follow-up assessment protocol evaluated headache improvement using three standardized instruments: the PHQ-9 for depression, the GAD-7 for anxiety, and the HIT-6 for headache impact. Clinical improvement was defined as a reduction in total scores across all three scales, with each score dropping by at least one severity category (e.g., PHQ-9 from severe to moderate; HIT-6 from “very severe impact” to “substantial impact”). Statistical analysis The normality of continuous variables was assessed using the Shapiro-Wilk test. Non-normal variables were consequently reported as median and interquartile range (IQR). Categorical variables were presented as frequencies and percentages. Group comparisons employed the Mann-Whitney U test for continuous variables and the Chi-square test or Fisher's exact test for categorical variables. The association between anxiety and depressive was evaluated using Spearman's rank correlation. Furthermore, linear, logistic, and negative binomial regression models were used to examine the independent effects of anxiety and depression on headache outcomes. All analyses were performed in SPSS 25.0, with a two-sided p ＜0.05 considered statistically significant. Results Of the 132 Han Chinese patients initially enrolled with a provisional HA-ADD diagnosis, all received a full course of adequately dosed antidepressant/anxiolytic therapy. During the 6-month follow-up, 6 patients were lost to contact, 10 were excluded due to medication non-compliance, and 15 were excluded for showing no improvement headache symptoms, resulting in 101 patients included in the final analysis . This cohort was predominantly female (70.3% female vs. 29.7% male), with a median age of 36 years (IQR: 25.5-48.5). Notably, age distribution was skewed toward younger individuals, with the 18-27-year age group representing the largest proportion (37.6%), followed by a secondary peak in the 38-47-year age group (22.8%). Patients exhibited severe, moderate, and mild anxiety in 46.5%, 26.7%, and 26.7% of cases, respectively; the corresponding rates for depression were 64.3%, 23.8%, and 11.9%. No significant gender differences were found in symptom severity. Regarding sleep, 91.1% of patients had sleep disturbance (PSQI ≥7). Table 1 . Demographics of patients with HA-ADD. Demographics Male (n=30) Female (n=71) Total (n =101) P Age, Median (IQR) 27(25-47.5) 40(27-49) 36(25.5-48.5) 0.274 Age distribution 0.227 18-27y 16（53.3） 22（31.0） 38(37.6) 28-37y 3（10.0） 11（15.5） 14(13.9) 38-47y 4（13.3） 19（26.8） 23(22.8) 48-57y 4（13.3） 14（19.7） 18(17.8) 58-65y 3（10.0） 5（7.0） 8(7.9) Education level, n (%) 0.238 ≤Primary 4(13.3) 19(26.8) 23(22.8) Secondary 12(40.0) 19(26.8) 31(30.7) ≥College 14(46.7) 33(46.4) 47(46.5) Headache onset after anxiety/depression, n (%) 0.113 ≤6 months 15(50.0) 39(54.9) 54(53.4) 6-12 months 5(16.7) 2(2.8) 7(7.0) 1-2year 4(13.3) 10(14.1) 14(13.9) ≥2 year 6(20.0) 20(28.2) 26(25.7) Anxiety, n (%) 0.425 Mild 9(30.0) 18(25.3) 27(26.7) Moderate 10(33.3) 17(24.0) 27(26.7) Severe 11(36.7) 36(50.7) 47(46.5) Depression, n (%) 0.134 Mild 2(6.7) 10(14.1) 12(11.9) Moderate 11(36.7) 13(18.3) 24(23.8) Severe 17(56.6) 48(67.6) 65(64.3) PSQI score, n (%) 0.671 ＜7 1(3.3) 6(8.45) 7(7.0) ≥7 29(96.7) 65(91.5) 94(93.0) Abbreviations: HA-ADD, Headache attributed to anxiety and depressive disorder; IQR , interquartile range ; PSQI , P ittsburgh s leep q uality i ndex . Clinical features of headache In the study, m oderate headache was reported by 54 patients (53.5%), and severe headache by 43 patients (42.6%) . T he majority of headaches were bilateral (72.3%), with a gender difference in pain side distribution . The most frequently locations of headache were the temporal (47.5%), parietal (35.6%), occipital (29.7%), frontal (26.7%) regions, followed by the entire head (7.9%). Regarding pain quality , dull pain ( 92.1 %) was the predominant type of headache, followed by stabbing (17.8%) and t hrobbing (9.9%). The incidence of dull pain was significantly higher in females than in males ( 95.8 % vs. 8 3.3%, p =0.04 8 ) ( Table 2 ). Table 2 . Clinical features of HA-ADD patients. Features Male (n=30) Female (n=71) Total (n =101) P -Value Pain side, n (%) Bilateral 16(53.3) 57(80.3) 73(72.3) 0.004* Predominant right-side 6(20.0) 6(8.5) 12(11.9) 0.174 Predominant left-side 6(20.0) 6(8.5) 12(11.9) 0.174 Side-alternating 2(6.7) 2(2.8) 4(4.0) 0.58 Locations, n (%) Temporal 11(36.7) 37(52.1) 48(47.5) 0.635 Parietal 7(23.3) 29(40.8) 36(35.6) 0.093 Occipital 9(30.0) 21(29.6) 30(29.7) 0.966 Forehead 6(20.0) 21(29.6) 27(26.7) 0.320 Generalized 3(10.0) 5(7.0) 8(7.9) 0.691 Quality, n (%) Dull 25(83.3) 68(95.8) 93(92.1) 0.048* Stabbing 7 (23.3) 11(15.5) 18(17.8) 0.347 P ulling /tugging 3(10.0) 0(0.0) 3(3.0) 0.024* Throbbing 2(6.7) 8(11.3) 10(9.9) 0.719 Unclassifiable 2(6.7) 5(7.0) 7(6.9) 1.0 Electric shock-like 1(3.3) 1(1.4) 2(2.0) 0.508 Pressing 0(0.0) 1(1.4) 1(1.0) 1.0 VAS, n (%) 0.218 Mild 1(3.3) 3(4.2) 4(3.9) Moderate 20(66.7) 34(47.9) 54(53.5) Severe 9(30.0) 34(47.9) 43(42.6) Headache Impact (HIT-6), n (%) 0.001* No/little 0(0.0) 2(2.8) 2(2.0) Some 7(23.3) 2(2.8) 9(9.0) Substantial 10(33.3) 6(8.5) 16(15.8) Severe 13(43.3) 61(85.9) 74(73.2) * P < 0.05; HA-ADD: Headache attributed to anxiety and depressive disorder. 60.4% of patients reported that each headache episode lasted less than 4h, while 23.8% reported 4-12h, 5.9% reported 12-24h, 9.9% reported 24-72h. Concerning headache frequency, 28.7% of patients experienced fewer than 10 attacks per month, while 35.6% reported 10-20 attacks per month (Figure. 2). In total, over 60% of patients with HA - ADD had fewer than 20 episodes per month. There was a statistically significant difference in the overall distribution between genders. It is important to note that headache-related impact on daily life was highly prevalent in the study population. 73.2% of patients experienced a "severe" condition (HIT-6>60). This impairment has a more significant impact on female patients than on male patients (85.9% vs. 43.3%, p =0.001). Associated Symptoms Among the 101 HA-ADD patients, the most common associated symptoms were phonophobia (79.2%), restlessness/agitation (58.4%), dizziness (57.4%), and nausea (51.5%). Less frequent symptoms included photophobia (34.7%), vomiting (15.8%), and other manifestations such as sweating, lacrimation, and bitter taste (Figure 3). Dizziness was significantly more frequent in female patients compared with males (64.8% vs 40.0%, p =0.021). Triggers and relieving factors The most common reported triggers were emotional fluctuations (71.3%), poor sleep (57.4%), and irritability (56.4%). Significant gender differences were observed for emotional fluctuations (77.5% in females vs. 56.7% in males; p = 0.034) and irritability (63.4% vs. 40.0%; p = 0.030). The most effective relief factors were adequate sleep (39.6%) and lying down (38.6%). Massage was reported as effective significantly more often by females than males (21.2% vs. 0.0%; p = 0.004) ( Table 3 ) . Table 3 . Trigger and Relieving factors of HA-ADD. Factors Male (n=30) Female (n=71) Total (n =101) p- Value Trigger Factors Emotional fluctuations 17(56.7) 55(77.5) 72(71.3) 0.034* Poor sleep 14(46.7) 44(62.0) 58(57.4) 0.155 irritability 12(40.0) 45(63.4) 57(56.4) 0.030* Stress 6(20.0) 22(31.0) 28(27.7) 0.259 Fatigue 5(16.7) 20(28.1) 25(24.8) 0.221 Exposure to cold 3(10.0) 12(21.4) 15(17.4) 0.183 Physical activity 2(6.7) 9(12.7) 11(10.9) 0.499 Exposure to heat 2(6.7) 8(11.2) 10(9.9) 0.719 None 5(16.7) 4(5.6) 9(8.9) 0.128 Altered sleep-wake cycle 2(6.7) 3(4.2) 5(5.0) 0.632 Weather changes 2(6.7) 1(1.4) 3(3.0) 0.210 Menstruation 0(0.0) 4(5.6) 4(4.0) 0.315 Excessive work 1(3.3) 0(0.0) 1(1.0) 0.297 Relieving Factors Adequate sleep 9 (30.0) 31 (43.7) 40(39.6) 0.200 Lying down 8 (26.7) 31 (43.7) 39(38.6) 0.109 Quiet environment 8(26.7) 22(31.0) 30(29.7) 0.664 Outdoor walking 4(13.3) 12(17.0) 16(15.8) 0.771 Massage therapy 0(0.0) 15(21.2) 15(14.9) 0.004* None 3(10.0) 9(12.7) 12（11.9） 1.0 Removal from stimulating environments 2(6.7) 5(7.0) 7(7.0) 1.0 Shifting attention 1(3.3) 2(2.8) 3(3.0) 0.210 Standing 1(3.3) 1(1.4) 2(2.0) 0.508 Food intake 1(3.3) 0(0.0) 1(1.0) 0.297 * P < 0.05; HA-ADD: Headache attributed to anxiety and depressive disorder. The association of Anxiety and Depression Severity on headache Features To assess the associations of anxiety and depression severity with headache characteristics, separate regression models were conducted for headache intensity (VAS), headache impact (HIT-6), attack duration, and frequency. Neither anxiety nor depression severity was related to attack duration or pain intensity. In contrast, both were significantly associated with greater impact of headaches on normal daily activity. Furthermore, moderate depression specifically increased the risk of headache attacks (RR = 2.66, p = 0.007). Discussion To verify that the patients' headaches were attributable to anxiety and depression, we administered adequate pharmacological treatment for these mood disorders and conducted systematic follow-up assessments. Headaches were considered secondary to the underlying affective disorders when their severity decreased alongside the improvement of mood symptoms. We identified a distinct clinical profile of headache attributed to anxiety and depressive disorder, characterized by bilateral, dull pain predominantly localized in the temporal and parietal regions, of moderate to severe intensity, with attack duration typically under 4 hours, and frequently accompanied by symptoms such as phonophobia, dizziness, and restlessness. This distinct profile differentiates HA-ADD from common primary headache disorders and provides a valuable basis for its earlier clinical identification. The clinical features of HA-ADD contrast with those of migraine and TTH. While migraine is typically characterized by unilateral (56%) with throbbing (47%) or pressing quality (42%) [12] , and TTH is predominantly bilateral (90%) with a pressing or tightening sensation (78%) and generally mild to moderate intensity (99%) [13] , HA-ADD exhibits a consistent pattern of bilateral, dull, and moderate-to-severe pain. Beyond pain characteristics, associated symptoms offer further diagnostic clues. Patients with HA-ADD frequently reported phonophobia (79.2%)，and restlessness/agitation (58%), symptoms aligning more closely with somatic manifestations of anxiety than with typical TTH profiles [14] . In contrast, migraine is commonly associated with nausea (86.1%), phonophobia (69.5%), photophobia (61.0%), and vomiting (59.2%) [15] . Attack duration further distinguishes these disorders. Most HA-ADD episodes (60.4%) were brief (<4 hours), contrasting with the typical 4-72hour duration of untreated migraine and the 30-minute to 7-day range of TTH [16] . The pattern of frequent, short-duration attacks is a key temporal characteristic of HA-ADD. Trigger and relief factors also provide differential insights. Emotional fluctuations (71.3%), upset (56.4%), and poor sleep (57.4%) were core trigger factors for HA-ADD. In contrast, stress and sleep disturbance are well-established triggers of migraines and TTH [14,15, 17,18 ] . A comparative summary of clinical features is presented in Table 4. In this study, we observed that HA-ADD share several clinical features with migraines, including a higher prevalence among women, moderate to severe pain intensity, and accompanying symptoms such as nausea and phonophobia. These findings suggest that HA-ADD may involve overlapping biological mechanisms with migraines. A large-scale population-based follow-up study demonstrated there was a bidirectional association between anxiety and depression and migraine. Anxiety and depression increase the risk of migraines (RR 1.8-2.0). Vice versa, the risk of having anxiety and depression was increased for migraine (RR 1.3-1.6) [19] . Several factors, such as dysregulation of neurotransmitter systems and dysfunction in sensory processing, have been common proposed to contribute to both migraine and anxiety and depression [20-22] . In addition, our results demonstrate that depression is linked to increased headache frequency, whereas anxiety shows no significant correlation with headache frequency, duration, or severity. This finding contrasts with prior evidence indicating that both anxiety and depression are associated with the frequency and severity of migraine attacks [23-25] . The relationship between anxiety and depression level and headache characteristics needs further research to confirm. Table 4 Comparison of clinical features among HA-ADD, migraine and TTH HA-ADD Migraine Tension-Type Headache Pain type Dull Throbbing Pressing/tightening Location Bilateral (temporoparietal) Often Unilateral Bilateral (frontal/temporal/occipital) Severity Moderate to Severe Moderate to Severe Mild to Moderate Duration Predominantly <4 hours 4-72 hours 30 minutes-7 days Associated Symptoms phonophobia , dizziness, restlessness/agitation Photophobia, phonophobia, nausea, vomiting. No more than one of Photophobia or phonophobia Limitations This study has several limitations. First, the single-center design and absence of a control group may limit the specificity of the identified features. The female predominance may be influenced by selection bias, which is consistent with the higher prevalence of anxiety and depressive disorders in women in the general population, but may still affect generalizability. Second, headache characteristics were primarily obtained from patients’ retrospective self-reports of symptoms over the 3 months preceding the initial assessment, which may be subject to recall bias. Finally, analyzing "anxiety-depressive disorder" as a unified entity without subgroup analysis (e.g., by DSM-5 subtypes) limits insights into potential phenotypic variations. Future studies should examine whether different subtypes (e.g., GAD vs different depressive disorders; DSM-5 codes F41.1, F32–F34) are associated with distinct headache profiles. Conclusion This research offers the initial systematic characterization of the clinical profile of HA - ADD, defining its core phenotype as bilateral, moderate - to - severe dull pain in the temporoparietal regions, associated with phonophobia, restlessness, and agitation. These features differentiate HA-ADD from both migraine and tension-type headache and may facilitate earlier recognition and more precise management of this secondary headache disorder. Abbreviations ICHD-3: The 3rd edition of international classification of headache disorders; DSM-5: Fifth version of the Diagnostic and Statistical Manual of Mental Disorders; GAD: Generalized anxiety disorder; HA-ADD: Headache attributed to anxiety and depressive disorders; HIT-6: Headache impact test; IQR: Interquartile range; MDD: major depressive disorder; PDD: Persistent depressive disorder; PHQ-9: Patient health questionnaire; PSQI: Pittsburgh sleep quality index; SSRIs: Selective serotonin reuptake inhibitors; TTH: Tension type of headache; RR: Risk ratio; SNRIs: serotonin and norepinephrine reuptake inhibitors; SSRIs: selective serotonin reuptake inhibitors; VAS: Visual analog scale. Declarations Acknowledgements We would like to extend our gratitude to the patients who contributed to this research. Authors’ contributions BY.C. and XY.Y. collected the data, analyzed and interpreted the results. J.Y. and SLC.Z. participated in data collection. B.Y. drafted the manuscript. DJ.W. and CY.W. designed the study and revised manuscript. All authors read and approved the final manuscript. Funding This research received no specific grant from any funding agency in the public or commercial sectors. Availability of data and materials Part of the dataset of this article is available on request to the corresponding author. Ethics approval and consent to participate This study was approved by the Ethics Committee of the 940th Hospital, Joint Logistics Support Force of the PLA. The approval number was 2024KYLL198. The participants have given written informed consent. Consent for publication Not applicable. Competing interests The authors declared no conflict of interest. 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BMC Neurol 12:82. https://doi.10.1186/1471-2377-12-82. Giri S, Tronvik EA, Hagen K (2022) The bidirectional temporal relationship between headache and affective disorders: longitudinal data from the HUNT studies. J Headache Pain 23(1):14. https://doi.10.1186/s10194-022-01388-x. Viudez-Martínez A, Torregrosa AB, Navarrete F, et al (2024) Understanding the Biological Relationship between Migraine and Depression. Biomolecules 14(2):163. https://doi.10.3390/biom14020163. Johnson M, Filali Y, Adegboyo A,et al (2025) Mechanistic intersections between migraine and major depressive disorder. J Headache Pain 26(1):157. https://doi.10.1186/s10194-025-02097-x. Amaro-Díaz L, Montoro CI, Fischer-Jbali LR, et al (2022) Chronic Pain and Emotional Stroop: A Systematic Review. J Clin Med 11(12):3259. https://doi.10.3390/jcm11123259. Chu HT, Liang CS, Lee JT, et al (2018) Associations Between Depression/Anxiety and Headache Frequency in Migraineurs: A Cross-Sectional Study. Headache 58(3):407-415. https://doi.10.1111/head.13215. Jafari E, Kazemizadeh H, Togha M, et al (2022) The influence of anxiety and depression on headache in adolescent migraineurs: a case-control study. Expert Rev Neurother 22(11-12):1019-1023. https://doi.10.1080/14737175.2022.2154657. Oh K, Cho SJ, Chung YK, et al (2014) Combination of anxiety and depression is associated with an increased headache frequency in migraineurs: a population-based study. BMC Neurol 14:238. https://doi.10.1186/s12883-014-0238-4. Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8492822","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":567958710,"identity":"46a1b09c-3404-49cb-b507-66c937ed5471","order_by":0,"name":"Boyan Chen","email":"","orcid":"","institution":"Department of Neurology, the 940th Hospital of Joint Logistics Support Force of the PLA","correspondingAuthor":false,"prefix":"","firstName":"Boyan","middleName":"","lastName":"Chen","suffix":""},{"id":567958711,"identity":"b6ad1806-23f5-42d4-9daf-66643b5a4721","order_by":1,"name":"Xinyu Yan","email":"","orcid":"","institution":"Department of 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13:40:23","extension":"html","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":104165,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8492822/v1/e7c0592fcb0e6002556387be.html"},{"id":99691861,"identity":"4eb0256b-038e-423a-a3ec-28d040dde578","added_by":"auto","created_at":"2026-01-07 10:29:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":156082,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of patient screening and enrollment\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8492822/v1/08fcb56f61ece83fa31f0a46.png"},{"id":99691862,"identity":"01894631-c079-432e-b976-8513845a04ee","added_by":"auto","created_at":"2026-01-07 10:29:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":55584,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHeadache attack duration and frequency in HA-ADD Patients. A \u003c/strong\u003eDistribution of headache attack duration. The majority of patients experienced attacks lasting \u003cstrong\u003eless than 4\u003c/strong\u003e hours. \u003cstrong\u003eB\u003c/strong\u003eDistribution of headache attack frequency per month. Most patients experienced 0-20 attacks per month.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8492822/v1/e4b13ff56cb52e69cd0b44e5.png"},{"id":99691863,"identity":"6ec1ba79-0dfe-4627-b9e7-70e9c04c4ee1","added_by":"auto","created_at":"2026-01-07 10:29:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":340474,"visible":true,"origin":"","legend":"\u003cp\u003eAssociated Symptoms in patients with HA-ADD. *\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8492822/v1/81799d683136624532f582c0.png"},{"id":99805148,"identity":"e2cc2fb1-9abb-46a5-9bd8-37dc78f87e2d","added_by":"auto","created_at":"2026-01-08 14:15:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1511659,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8492822/v1/4477627d-7e07-4c01-973b-42012a83ac44.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eClinical profile of headache attributed to anxiety and depressive disorder: an observational study\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAnxiety and depression often coexist with primary headache disorders, particularly with migraine and tension headache \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. In some patients, anxiety and depression are the only identifiable cause of headache \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Headache attributed to anxiety or depressive disorder was added to the appendix in 2018 ICHD-3. However, its clinical features have not been systematically characterized, hindering accurate early recognition and leading to delayed diagnosis and suboptimal treatment. A key diagnostic issue is how to determine whether the headache is a secondary headache attributable to anxiety and depressive disorder (HA-ADD), or a primary headache comorbid with anxiety and depressive disorder. According to the diagnostic criteria of ICHD-3, the crucial distinction lies in the presence of a temporal causal relationship\u0026mdash;specifically, whether the headache occurs exclusively during the active phase of the anxiety-depressive disorder. In practice, patients often struggle to accurately recall and describe the temporal relationship between the onset and fluctuations of their anxiety\u0026ndash;depressive symptoms and their headache episodes. This substantially limits the clinical applicability of this core diagnostic criterion. Consequently, the current diagnosis of HA-ADD largely relies on a \"therapeutic diagnosis\" or \"post-hoc verification\" approach, which means when the mood disorder is effectively treated and the headache symptoms subsequently improve or resolve, the headache is then considered attributable to the anxiety and depressive disorder.\u003c/p\u003e \u003cp\u003eAnxiety and depression frequently co-occur. A cohort study found that among patients with depression, 67% had comorbid anxiety, and among those with anxiety, 63% had comorbid depression \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. These findings suggest that the concurrent presence of both disorders is more common than either disorder occurring in isolation. Epidemiological data indicate that major depressive disorder (MDD) and persistent depressive disorder (PDD) are the most prevalent forms of depressive disorders \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Generalized anxiety disorder (GAD) is a highly chronic condition that is not dependent on specific triggers. Moreover, GAD and MDD exhibit particularly high rates of comorbidity. A large-scale epidemiological survey revealed that up to 65% of individuals with GAD concurrently meet criteria for MDD \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Given this strong bidirectional relationship, the present study focused on patients with GAD comorbid with MDD or PDD to characterize the clinical features of headache attributable to anxiety and depressive disorders.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eParticipants\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was carried out at Headache Center of the 940th Hospital, Joint Logistics Support Force of the PLA. From March 2024 to June 2025, patients provisionally diagnosed with HA-ADD were enrolled. Ethical approval was obtained from the Hospital Ethics Committee (Approval No. [2024KYLL198]), and all patients provided written informed consent prior to participation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion Criteria:\u003c/strong\u003e(1) Age 18-65 years; (2) Meeting DSM-5 criteria for major depressive disorder or persistent depressive disorder (F32.x/F33.x, F34.1)\u0026nbsp;co\u003cstrong\u003e-\u003c/strong\u003eoccurring with\u0026nbsp;generalized anxiety disorder (F41.1),\u0026nbsp;with concomitant\u003cstrong\u003e\u0026nbsp;headache symptoms\u003c/strong\u003e; (3) Headache occurring after anxiety and depression; (4) Free of antidepressant or anxiolytic medications for at least one month prior to enrollment; (5) Documented reduction in headache frequency or severity following a confirmed alleviation of anxiety and depressive symptoms after a course of adequate pharmacotherapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExclusion Criteria:\u003c/strong\u003e(1) Diagnosis meeting ICHD-3 criteria for primary headache disorders ( e.g., migraine, tension-type headache); (2) Headaches attributed to other underlying causes; (3) Diagnosis of other primary or secondary psychiatric disorders per DSM-5 criteria (e.g., substance use disorders, psychiatric conditions due to medical conditions); (4) Absence of significant headache improvement after 6 months of adequate antidepressant/anxiolytic therapy; (5) Pregnancy or lactation; (6)\u0026nbsp;Severe systemic disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProcedures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt the initial consultation, a headache specialist performed a detailed clinical interview and physical examination. Demographic and headache characteristics were recorded, including age, sex, onset time, pain location, quality, intensity, duration, monthly frequency, triggers, relieving factors, associated symptoms, and current medications. Features of mood disorders were also documented, encompassing core symptoms and severity. All patients completed a series of standardized assessments to quantify mood symptoms and headache impact. The final diagnosis of HA-ADD was established through multidisciplinary discussion between at least one experienced headache specialist and one psychiatrist, according to DSM-5 criteria for anxiety and depression and ICHD-3 criteria for headache disorders. To exclude secondary causes, all patients underwent appropriate ancillary investigations, including brain CT/MRI and blood tests (liver and renal function, autoimmune antibodies, erythrocyte sedimentation rate, D-dimer, etc.).\u003c/p\u003e\n\u003cp\u003ePatients with a provisional diagnosis of HA-ADD received antidepressant and anxiolytic medications. Follow-up assessments were conducted at 1, 3, and 6 months after treatment initiation, either in the outpatient clinic or via telephone, to evaluate changes in mood disorders and headache symptoms. Headache was attributable to the anxiety-depressive disorder if it resolved or markedly improved (in frequency, severity, or duration) following the alleviation of mood symptoms. A detailed flowchart of patient screening and enrollment is presented in Figure 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eScale Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants were assessed using the following standardized scales. Research staff verified the completeness of all questionnaires. Scale data were entered by one investigator and independently double-checked by another. (1) Visual analog scale (VAS) was used to assess the maximum pain intensity (0-3: mild; 4-6: moderate ;7-10: severe). (2) The short-form headache impact test 6(HIT-6) \u003csup\u003e[7]\u003c/sup\u003e\u0026nbsp;was employed to evaluate the impact of headache on daily life and work.\u0026nbsp;Total scores\u0026nbsp;were\u0026nbsp;interpreted as: \u0026le;49\u0026nbsp;(little\u0026nbsp;or\u0026nbsp;no impact); 50-55(moderate impact); 56-59(substantial impact); \u0026ge;60(very severe impact).\u0026nbsp;(3) Patient\u0026nbsp;health\u0026nbsp;questionnaire\u0026nbsp;9 (PHQ-9)\u0026nbsp;\u003csup\u003e[8]\u0026nbsp;\u003c/sup\u003ewas administered to assess the severity of depressive symptoms. Scores were classified as follows:\u0026nbsp;0-4(minimal or none); 5-9(mild); 10-14(moderate); 15-19(moderately severe); \u0026ge;20(severe).\u0026nbsp;(4)\u0026nbsp;Generalized\u0026nbsp;Anxiety\u0026nbsp;Disorder 7-item (GAD-7)\u0026nbsp;Scale\u0026nbsp;\u003csup\u003e[9]\u003c/sup\u003e was administered to assess the severity of anxiety symptoms. Scores were categorized as: 0-4(minimal or none); 5-9(mild); 10-14(moderate); \u0026ge;15(severe). (5) Pittsburgh sleep quality index (PSQI) was employed to assess sleep quality. A global score \u0026ge;7 indicates poor sleep quality (range: 0-21), with higher scores reflecting worse sleep.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment Protocol\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients with provisional diagnosis of HA-ADD received individualized pharmacotherapy prescribed by a psychiatrist, targeting their anxiety and depressive symptoms. The treatment goal was defined as reaching and maintaining each medication within its recommended effective dose range for a minimum of 4-6 weeks to ensure adequate efficacy, with subsequent adjustments based on individual response and tolerability. The pharmacological regimen included selective serotonin reuptake inhibitors (SSRIs, e.g., fluvoxamine maleate, escitalopram), non-benzodiazepine anxiolytics (e.g., buspirone, tandospirone), serotonin and norepinephrine reuptake inhibitors (SNRIs, e.g., duloxetine), and Chinese herbal formulations (e.g., Shuganjieyu Capsule, Wuling Capsule). \u0026nbsp;Notably, venlafaxine and amitriptyline, both explicitly recommended in current guidelines for migraine and tension-type headache (TTH) prophylaxis \u003csup\u003e[10\u0026ndash;11]\u003c/sup\u003e, were excluded from this study to avoid potential confounding of the treatment effect. Throughout the 6-month treatment and follow-up period, patients were permitted to use acute medications (such as nonsteroidal anti-inflammatory drugs or triptans) as needed for headache attacks. No other preventive medications were administered during the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eO\u003c/strong\u003e\u003cstrong\u003eutcome\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eassessment\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe follow-up assessment protocol evaluated headache improvement using three standardized instruments: the PHQ-9 for depression, the GAD-7 for anxiety, and the HIT-6 for headache impact. Clinical improvement was defined as a reduction in total scores\u0026nbsp;across all three scales, with each score dropping by at least one severity category (e.g., PHQ-9 from severe to moderate; HIT-6 from \u0026ldquo;very severe impact\u0026rdquo; to \u0026ldquo;substantial impact\u0026rdquo;).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe normality of continuous variables was assessed using the Shapiro-Wilk test. Non-normal variables were consequently reported as median and interquartile range (IQR). Categorical variables were presented as frequencies and percentages. Group comparisons employed the Mann-Whitney U test for continuous variables and the Chi-square test or Fisher\u0026apos;s exact test for categorical variables. The association between anxiety and depressive was evaluated using Spearman\u0026apos;s rank correlation. Furthermore, linear, logistic, and negative binomial regression models were used to examine the independent effects of anxiety and depression on headache outcomes. All analyses were performed in SPSS 25.0, with a two-sided \u003cem\u003ep\u003c/em\u003e＜0.05 considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOf the 132 Han Chinese patients initially enrolled with a provisional HA-ADD diagnosis, all received a full course of adequately dosed antidepressant/anxiolytic therapy. During the 6-month follow-up, 6 patients were lost to contact,\u0026nbsp;10 were excluded due to medication non-compliance,\u0026nbsp;and 15 were excluded for showing no improvement headache symptoms, resulting in 101 patients included in the final analysis\u003cstrong\u003e.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThis cohort was predominantly female\u0026nbsp;(70.3%\u0026nbsp;female vs.\u0026nbsp;29.7%\u0026nbsp;male), with a median age of 36 years (IQR: 25.5-48.5). Notably, age distribution\u0026nbsp;was\u0026nbsp;skewed toward younger\u0026nbsp;individuals, with the 18-27-year\u0026nbsp;age\u0026nbsp;group representing the largest proportion (37.6%), followed by a secondary peak in the 38-47-year\u0026nbsp;age\u0026nbsp;group (22.8%).\u003c/p\u003e\n\u003cp\u003ePatients exhibited severe, moderate, and mild anxiety in 46.5%, 26.7%, and 26.7% of cases, respectively; the corresponding rates for depression were 64.3%, 23.8%, and 11.9%. No significant gender differences were found in symptom severity. Regarding sleep, 91.1% of patients had sleep disturbance (PSQI \u0026ge;7).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Demographics of patients with HA-ADD.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eDemographics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003eMale (n=30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003eFemale (n=71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eTotal (n =101)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eAge, Median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e27(25-47.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e40(27-49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e36(25.5-48.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.274\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eAge distribution\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.227\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e18-27y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e16（53.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e22（31.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e38(37.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e28-37y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e3（10.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e11（15.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e14(13.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e38-47y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e4（13.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e19（26.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e23(22.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e48-57y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e4（13.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e14（19.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e18(17.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e58-65y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e3（10.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e5（7.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e8(7.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eEducation level, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.238\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026le;Primary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e4(13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e19(26.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e23(22.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eSecondary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e12(40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e19(26.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e31(30.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026ge;College\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e14(46.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e33(46.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e47(46.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eHeadache onset after anxiety/depression, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.113\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026le;6 months\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e15(50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e39(54.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e54(53.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e6-12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e5(16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2(2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e7(7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e1-2year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e4(13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e10(14.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e14(13.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026ge;2 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e6(20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e20(28.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e26(25.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eAnxiety, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.425\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e9(30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e18(25.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e27(26.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e10(33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e17(24.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e27(26.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e11(36.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e36(50.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e47(46.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eDepression, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.134\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e2(6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e10(14.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e12(11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e11(36.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e13(18.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e24(23.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e17(56.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e48(67.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e65(64.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003ePSQI score, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.671\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e＜7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e1(3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e6(8.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e7(7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026ge;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e29(96.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e65(91.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e94(93.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: HA-ADD, Headache attributed to anxiety and depressive disorder; \u003cstrong\u003eIQR\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;interquartile range\u003c/strong\u003e\u003cstrong\u003e;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePSQI\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;P\u003c/strong\u003e\u003cstrong\u003eittsburgh\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003es\u003c/strong\u003e\u003cstrong\u003eleep\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eq\u003c/strong\u003e\u003cstrong\u003euality\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ei\u003c/strong\u003e\u003cstrong\u003endex\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical features of headache\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIn the study, m\u003c/strong\u003e\u003cstrong\u003eoderate headache\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ewas reported by\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e54 patients (53.5%), and severe\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eheadache by\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;43 patients (42.6%)\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eT\u003c/strong\u003ehe majority of headaches were bilateral (72.3%),\u0026nbsp;with a\u0026nbsp;gender difference in pain side distribution\u003cstrong\u003e.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThe most frequently locations\u0026nbsp;of headache\u0026nbsp;were the temporal (47.5%), parietal (35.6%), occipital\u0026nbsp;(29.7%), frontal (26.7%)\u0026nbsp;regions,\u0026nbsp;followed by the\u0026nbsp;entire head (7.9%). Regarding pain quality\u003cstrong\u003e, dull pain (\u003c/strong\u003e\u003cstrong\u003e92.1\u003c/strong\u003e\u003cstrong\u003e%) was the predominant\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003etype of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eheadache, followed by stabbing\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(17.8%) and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003et\u003c/strong\u003e\u003cstrong\u003ehrobbing (9.9%).\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eThe incidence of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003edull\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;pain was significantly higher in females than in males (\u003c/strong\u003e\u003cstrong\u003e95.8\u003c/strong\u003e\u003cstrong\u003e% vs.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e8\u003c/strong\u003e\u003cstrong\u003e3.3%,\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e=0.04\u003c/strong\u003e\u003cstrong\u003e8\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e\u003cstrong\u003e).\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e.\u0026nbsp;Clinical features of HA-ADD patients.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"547\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003eFeatures\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eMale (n=30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eFemale (n=71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003eTotal (n =101)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePain side,\u003c/strong\u003e n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eBilateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e16(53.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e57(80.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e73(72.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.004*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003ePredominant right-side\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e6(20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e6(8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e12(11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.174\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003ePredominant left-side\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e6(20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e6(8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e12(11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.174\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eSide-alternating\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e2(6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e2(2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e4(4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLocations,\u003c/strong\u003e n (%)\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eTemporal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e11(36.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e37(52.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e48(47.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.635\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eParietal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e7(23.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e29(40.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e36(35.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.093\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eOccipital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e9(30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e21(29.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e30(29.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.966\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eForehead\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e6(20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e21(29.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e27(26.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.320\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eGeneralized\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e3(10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e5(7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e8(7.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.691\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQuality,\u003c/strong\u003e n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eDull\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e25(83.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e68(95.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e93(92.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.048*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eStabbing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e7 (23.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e11(15.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e18(17.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.347\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003cstrong\u003eulling\u003c/strong\u003e/tugging\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e3(10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e3(3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.024*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eThrobbing\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e2(6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e8(11.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e10(9.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.719\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eUnclassifiable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e2(6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e5(7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e7(6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eElectric shock-like\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1(3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e1(1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e2(2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.508\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003ePressing\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e1(1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e1(1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVAS,\u0026nbsp;\u003c/strong\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.218\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eMild\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e1(3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e3(4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e4(3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e20(66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e34(47.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e54(53.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e9(30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e34(47.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e43(42.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHeadache Impact (HIT-6),\u0026nbsp;\u003c/strong\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eNo/little\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e2(2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e2(2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eSome\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e7(23.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e2(2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e9(9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eSubstantial\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e10(33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e6(8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e16(15.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eSevere\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e13(43.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003e61(85.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e74(73.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05; HA-ADD: Headache attributed to anxiety and depressive disorder.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e60.4% of patients reported that each headache episode lasted less than 4h, while 23.8% reported 4-12h, 5.9% reported 12-24h, 9.9% reported 24-72h. Concerning headache frequency, 28.7% of patients experienced fewer than 10 attacks per month, while 35.6% reported 10-20 attacks per month (Figure. 2). In total, over 60% of patients with HA - ADD had fewer than 20 episodes per month. There was a statistically significant difference in the overall distribution between genders.\u003c/p\u003e\n\u003cp\u003eIt is important to note that headache-related impact on daily life was highly prevalent in the study population. 73.2% of patients experienced a \u0026quot;severe\u0026quot; condition (HIT-6\u0026gt;60). This impairment has a more significant impact on female patients than on male patients (85.9% vs. 43.3%, \u003cem\u003ep\u003c/em\u003e=0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociated Symptoms\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 101 HA-ADD patients, the most common associated symptoms were phonophobia (79.2%), restlessness/agitation (58.4%), dizziness (57.4%), and nausea (51.5%). Less frequent symptoms included photophobia (34.7%), vomiting (15.8%), and other manifestations such as sweating, lacrimation, and bitter taste (Figure 3). Dizziness was significantly more frequent in female patients compared with males (64.8% vs 40.0%, \u003cem\u003ep\u003c/em\u003e=0.021).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTriggers and relieving factors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe most common reported triggers were emotional fluctuations (71.3%), poor sleep (57.4%), and irritability (56.4%). Significant gender differences were observed for emotional fluctuations (77.5% in females vs. 56.7% in males; \u003cem\u003ep\u003c/em\u003e = 0.034) and irritability (63.4% vs. 40.0%; \u003cem\u003ep\u003c/em\u003e= 0.030). The most effective relief factors were adequate sleep (39.6%) and lying down (38.6%). Massage was reported as effective significantly more often by females than males (21.2% vs. 0.0%; \u003cem\u003ep\u003c/em\u003e = 0.004) \u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e. Trigger and Relieving factors of HA-ADD.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eFactors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eMale (n=30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eFemale (n=71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eTotal (n =101)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003ep- Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTrigger Factors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eEmotional fluctuations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e17(56.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e55(77.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e72(71.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.034*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003ePoor sleep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e14(46.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e44(62.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e58(57.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.155\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eirritability\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e12(40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e45(63.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e57(56.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.030*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eStress\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e6(20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e22(31.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e28(27.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.259\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eFatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e5(16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e20(28.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e25(24.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.221\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eExposure to cold\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e3(10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e12(21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e15(17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.183\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003ePhysical activity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2(6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e9(12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e11(10.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.499\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eExposure to heat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2(6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e8(11.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e10(9.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.719\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e5(16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e4(5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e9(8.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.128\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eAltered sleep-wake cycle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2(6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e3(4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e5(5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.632\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eWeather changes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2(6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e1(1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e3(3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.210\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eMenstruation\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e4(5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e4(4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.315\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eExcessive work\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1(3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e1(1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.297\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRelieving Factors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eAdequate sleep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e9 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e31 (43.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e40(39.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.200\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eLying down\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e8 (26.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e31 (43.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e39(38.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.109\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eQuiet environment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e8(26.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e22(31.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e30(29.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.664\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eOutdoor walking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e4(13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e12(17.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e16(15.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.771\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eMassage therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e15(21.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e15(14.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.004*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e3(10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e9(12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e12（11.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eRemoval from stimulating environments\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e2(6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e5(7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7(7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eShifting attention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e1(3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2(2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e3(3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.210\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eStanding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e1(3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1(1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e2(2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.508\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eFood intake\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e1(3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e1(1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.297\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05; HA-ADD: Headache attributed to anxiety and depressive disorder.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eassociation\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;of Anxiety\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eDepression Severity on\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eheadache\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Features\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo assess the associations of anxiety and depression severity with headache characteristics, separate regression models were conducted for headache intensity (VAS), headache impact (HIT-6), attack duration, and frequency. Neither anxiety nor depression severity was related to attack duration or pain intensity. In contrast, both were significantly associated with greater impact of headaches on normal daily activity. Furthermore, moderate depression specifically increased the risk of headache attacks (RR = 2.66, \u003cem\u003ep\u003c/em\u003e = 0.007).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo verify that the patients\u0026apos; headaches were attributable to anxiety and depression, we administered adequate pharmacological treatment for these mood disorders and conducted systematic follow-up assessments. Headaches were considered secondary to the underlying affective disorders when their severity decreased alongside the improvement of mood symptoms.\u003c/p\u003e\n\u003cp\u003eWe identified a distinct clinical profile of headache attributed to anxiety and depressive disorder, characterized by bilateral, dull pain predominantly localized in the temporal and parietal regions, of moderate to severe intensity, with attack duration typically under 4 hours, and frequently accompanied by symptoms such as phonophobia, dizziness, and restlessness. This distinct profile differentiates HA-ADD from common primary headache disorders and provides a valuable basis for its earlier clinical identification.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe\u0026nbsp;clinical features of HA-ADD contrast with those of migraine and TTH. While\u0026nbsp;migraine\u0026nbsp;is typically characterized by unilateral (56%) with throbbing (47%) or pressing quality (42%)\u0026nbsp;\u003csup\u003e[12]\u003c/sup\u003e, and TTH\u0026nbsp;is\u0026nbsp;predominantly bilateral (90%) with a pressing or tightening sensation (78%) and generally mild to moderate intensity (99%)\u0026nbsp;\u003csup\u003e[13]\u003c/sup\u003e,\u0026nbsp;HA-ADD exhibits a consistent pattern of bilateral, dull, and moderate-to-severe pain. Beyond pain characteristics, associated symptoms offer further diagnostic clues.\u0026nbsp;Patients\u0026nbsp;with\u0026nbsp;HA-ADD\u0026nbsp;frequently reported\u0026nbsp;phonophobia (79.2%)，and\u0026nbsp;restlessness/agitation (58%),\u0026nbsp;symptoms aligning more closely with somatic manifestations of anxiety than with typical TTH profiles\u003csup\u003e[14]\u003c/sup\u003e. In contrast,\u0026nbsp;migraine\u0026nbsp;is commonly associated\u0026nbsp;with nausea (86.1%), phonophobia (69.5%), photophobia (61.0%), and vomiting (59.2%)\u0026nbsp;\u003csup\u003e[15]\u003c/sup\u003e.\u0026nbsp;Attack duration further distinguishes these disorders.\u0026nbsp;Most HA-ADD episodes (60.4%) were brief (\u0026lt;4 hours), contrasting with the typical 4-72hour\u0026nbsp;duration of untreated migraine and the 30-minute to 7-day range of TTH\u0026nbsp;\u003csup\u003e[16]\u003c/sup\u003e.\u0026nbsp;The pattern of frequent, short-duration attacks is a key temporal characteristic of HA-ADD.\u0026nbsp;Trigger and relief factors also provide differential insights.\u0026nbsp;Emotional fluctuations (71.3%),\u0026nbsp;upset\u0026nbsp;(56.4%), and poor sleep (57.4%)\u0026nbsp;were\u0026nbsp;core trigger factors for HA-ADD.\u0026nbsp;In contrast, stress and sleep disturbance\u0026nbsp;are well-established triggers of migraines and TTH \u003csup\u003e[14,15,\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003csup\u003e17,18\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. A comparative summary of clinical features is presented in Table 4.\u003c/p\u003e\n\u003cp\u003eIn this study, we observed that\u0026nbsp;HA-ADD\u0026nbsp;share several clinical features with migraines, including a higher prevalence among women, moderate to severe pain intensity, and accompanying symptoms such as nausea and phonophobia. These findings suggest that\u0026nbsp;HA-ADD may involve overlapping biological mechanisms with migraines. A large-scale population-based follow-up study demonstrated there was a bidirectional association between\u0026nbsp;anxiety and depression and migraine. Anxiety and depression increase the risk of migraines (RR 1.8-2.0).\u0026nbsp;Vice versa, the risk of having anxiety and depression was increased for migraine (RR 1.3-1.6)\u003csup\u003e\u0026nbsp;[19]\u003c/sup\u003e. Several factors, such as dysregulation of neurotransmitter systems and dysfunction in sensory processing, have been common proposed to contribute to both migraine and anxiety and depression \u003csup\u003e[20-22]\u003c/sup\u003e. \u003c/p\u003e\n\u003cp\u003eIn addition, our results demonstrate that depression is linked to increased headache frequency, whereas anxiety shows no significant correlation with headache frequency, duration, or severity. This finding contrasts with prior evidence indicating that both anxiety and depression are associated with the frequency and severity of migraine attacks \u003csup\u003e[23-25]\u003c/sup\u003e. The relationship between anxiety and depression level and headache characteristics needs further research to confirm.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u003c/strong\u003e Comparison of clinical features among HA-ADD, migraine and TTH\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eHA-ADD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eMigraine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 175px;\"\u003e\n \u003cp\u003eTension-Type Headache\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003ePain type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eDull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eThrobbing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 175px;\"\u003e\n \u003cp\u003ePressing/tightening\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003eLocation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eBilateral\u0026nbsp;(temporoparietal)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eOften Unilateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 175px;\"\u003e\n \u003cp\u003eBilateral\u0026nbsp;(frontal/temporal/occipital)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003eSeverity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eModerate to Severe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eModerate to Severe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 175px;\"\u003e\n \u003cp\u003eMild to Moderate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eDuration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003ePredominantly\u0026nbsp;\u0026lt;4 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003e4-72 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 175px;\"\u003e\n \u003cp\u003e30 minutes-7 days\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003eAssociated Symptoms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ephonophobia\u003c/strong\u003e, dizziness, restlessness/agitation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003ePhotophobia, phonophobia, nausea, vomiting.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 175px;\"\u003e\n \u003cp\u003eNo more than one of Photophobia or phonophobia\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, the single-center design and absence of a control group may limit the specificity of the identified features. The female predominance may be influenced by selection bias, which is consistent with the higher prevalence of anxiety and depressive disorders in women in the general population, but may still affect generalizability. Second, headache characteristics were primarily obtained from patients\u0026rsquo; retrospective self-reports of symptoms over the 3 months preceding the initial assessment, which may be subject to recall bias. Finally, analyzing \u0026quot;anxiety-depressive disorder\u0026quot; as a unified entity without subgroup analysis (e.g., by DSM-5 subtypes) limits insights into potential phenotypic variations. Future studies should examine whether different subtypes (e.g., GAD vs different depressive disorders; DSM-5 codes F41.1, F32\u0026ndash;F34) are associated with distinct headache profiles.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis research offers the initial systematic characterization of the clinical profile of HA - ADD, defining its core phenotype as bilateral, moderate - to - severe dull pain in the temporoparietal regions, associated with phonophobia, restlessness, and agitation. These features differentiate HA-ADD from both migraine and tension-type headache and may facilitate earlier recognition and more precise management of this secondary headache disorder.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eICHD-3: The 3rd edition of international classification of headache disorders;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDSM-5: Fifth version of the Diagnostic and Statistical Manual of Mental Disorders;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGAD: Generalized anxiety disorder;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHA-ADD: Headache attributed to anxiety and depressive disorders;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHIT-6:\u0026nbsp;Headache\u0026nbsp;impact\u0026nbsp;test;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIQR: Interquartile range;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMDD: major depressive disorder;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePDD: Persistent depressive disorder;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePHQ-9:\u0026nbsp;Patient\u0026nbsp;health\u0026nbsp;questionnaire;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePSQI:\u0026nbsp;Pittsburgh\u0026nbsp;sleep\u0026nbsp;quality\u0026nbsp;index; SSRIs:\u0026nbsp;Selective serotonin reuptake inhibitors;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTTH: Tension type of headache;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRR:\u0026nbsp;Risk ratio;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSNRIs:\u0026nbsp;serotonin and norepinephrine reuptake inhibitors;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSSRIs:\u0026nbsp;selective serotonin reuptake inhibitors;\u003c/p\u003e\n\u003cp\u003eVAS: Visual analog scale.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eWe would like to extend our gratitude to the patients who contributed to this research.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions\u003c/p\u003e\n\u003cp\u003eBY.C. and XY.Y. collected the data, analyzed and interpreted the results. J.Y. and SLC.Z. participated in data collection. B.Y. drafted the manuscript. DJ.W. and CY.W. designed the study and revised manuscript. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFunding\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public or commercial sectors.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePart of the dataset of this article is available on request to the corresponding author.\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the 940th Hospital, Joint Logistics Support Force of the PLA.\u0026nbsp;The approval number was\u0026nbsp;2024KYLL198. The participants have given written informed consent.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declared no conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eGiri S, Tronvik EA, Hagen K (2022) The bidirectional temporal relationship between headache and affective disorders: longitudinal data from the HUNT studies. J Headache Pain 23(1):14. https://doi.10.1186/s10194-022-01388-x. \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRadat F, Milowska D, Valade D (2011) Headaches secondary to psychiatric disorders (HSPD): a retrospective study of 87 patients. Headache 51(5):789-95. https://doi.10.1111/j.1526-4610.2011.01883.x.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Lamers F, van Oppen P, Comijs HC, et al (2011) Comorbidity patterns of anxiety and depressive disorders in a large cohort study: the Netherlands Study of Depression and Anxiety (NESDA). J Clin Psychiatry 72(3):341-8. https://doi.10.4088/JCP.10m06176blu\u003cstrong\u003e.\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eKasyanov E, Yakovleva Y, Khobeysh M, et al (2025) Lifetime Prevalence of Recurrent and Persistent Depression: A Scoping Review of Epidemiological Studies. Clin Pract Epidemiol Ment Health 21: e17450179372815. https://doi.10.2174/0117450179372815250516102324.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eHuang Y, Wang Y, Wang H, et al (2019) Prevalence of mental disorders in China: a cross-sectional epidemiological study. Lancet Psychiatry 6(3):211-224. https://doi.10.1016/S2215-0366(18)30511-X.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eDruet-Cabanac A, Azzi J, Lucchino M, Simon V, et al (2025) Generalized anxiety disorder: epidemiology, burden, and comorbid depression. Curr Med Res Opin 41(6):1053-1064. https://doi.10.1080/03007995.2025.2529974.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e Houts CR, Wirth RJ, McGinley JS, et al (2020) Content validity of HIT-6 as a measure of headache impact in people with migraine: a narrative review. Headache 60(1):28-39.\u0026nbsp;https://doi.10.1111/head.13701.\u003c/li\u003e\n \u003cli\u003eKroenke K, Spitzer RL, Williams JB (2001) The PHQ-9: validity of a brief depression severity measure. 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Expert Rev Neurother 22(11-12):1019-1023.\u0026nbsp;https://doi.10.1080/14737175.2022.2154657.\u003c/li\u003e\n \u003cli\u003eOh K, Cho SJ, Chung YK, et al (2014) Combination of anxiety and depression is associated with an increased headache frequency in migraineurs: a population-based study. BMC Neurol 14:238. https://doi.10.1186/s12883-014-0238-4.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Department of Neurology, the 940th Hospital of Joint Logistics Support Force of the PLA","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Headache Attributed to Anxiety and Depressive Disorder, Clinical Profile, Comorbidity, Anxiety, Depression","lastPublishedDoi":"10.21203/rs.3.rs-8492822/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8492822/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eHeadache attributed to anxiety or depressive disorder was added to the appendix of the International Classification of Headache Disorders, 3rd edition (ICHD-3) in 2018. However, the clinical features have not been systematically characterized. This study aims to describe its clinical profile of headache attributed to anxiety and depressive disorders (HA-ADD).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eAn observational study was performed between March 2024 and June 2025 in a Chinese headache center. A total of 101 patients diagnosed with HA-ADD were enrolled after excluding primary headaches and other secondary causes. Clinical data were collected through structured face-to-face interviews.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eHeadache experienced by majority of the participants was bilateral (72.3%), dull type (92.1%) and of moderate-to-severe intensity (96.1%). The most frequently locations of headache were the temporal (47.5%), parietal (35.6%) regions. 60.4% of attacks lasted for less than 4h. Common accompanying symptoms were phonophobia (79.2%), restlessness and agitation (58.4%), dizziness (57.4%), and nausea (51.5%). Emotional fluctuations (71.3%), poor sleep (57.4%) were the most common triggering factors. 73.2% of patients reported severe headache impact on daily life.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eHeadache attributed to anxiety and depressive disorders has distinct clinical characteristics that may aid in its early clinical recognition.\u003c/p\u003e","manuscriptTitle":"Clinical profile of headache attributed to anxiety and depressive disorder: an observational study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-07 10:29:05","doi":"10.21203/rs.3.rs-8492822/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"300c18f7-0a92-4746-ad72-ec469bc8b204","owner":[],"postedDate":"January 7th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":60728816,"name":"Neurobiology of Disease"}],"tags":[],"updatedAt":"2026-01-07T10:29:05+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-07 10:29:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8492822","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8492822","identity":"rs-8492822","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}