BACKGROUND:Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder marked by persistent patterns of inattention, disorganization, hyperactivity, and impulsivity. Increasing evidence implicates immune-inflammatory processes in its etiology, with observed associations between ADHD and infectious diseases, allergic conditions, and recent findings involving SARS-CoV-2. This study investigated whether early-life inflammatory markers, as measured by routine complete blood counts (CBCs) in clinically healthy 1-year-old children, were associated with subsequent diagnoses of ADHD. METHODS:A retrospective case-control study was conducted using electronic medical records from Leumit Health Services, encompassing children under 18 years between January 1, 2006, and June 30, 2021. The sample included children who underwent routine CBC testing at age one during a well-child visit, without signs of acute illness. ADHD cases were identified based on ICD-9/10 criteria. Controls, free of any ADHD diagnosis, were randomly selected at a 1:2 ratio and matched for age, sex, socioeconomic status, and cultural sector. Analyses included white blood cell (WBC) subtypes and platelet counts, with the calculation of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR). RESULTS:Children who were subsequently diagnosed with ADHD demonstrated statistically significant elevated total WBC counts at age one, including higher neutrophil, eosinophil, and lymphocyte levels, and lower basophil counts compared to matched controls (all p < .05). No significant differences were observed in PLR between groups. CONCLUSIONS:Elevated inflammatory markers were detectable in clinically healthy 1-year-old children who were later diagnosed with ADHD. These findings suggest a potential preclinical inflammatory phenotype linked to ADHD risk, highlighting the need for further investigation into early immune dysregulation as a contributing factor in ADHD pathophysiology. Early identification of such biomarkers may inform preventive strategies and targeted interventions in high-risk pediatric populations.

Objective: Current data on the association between attention-deficit/hyperactivity disorder (ADHD) and essential hypertension (EH) in pediatric populations are very limited, as most research has focused on adults. This study investigated the long-term prevalence of EH in Israeli youth aged 5–18 years with ADHD, examining also trends in antihypertensive medication use. Methods: A retrospective cohort study was conducted using data from Leumit Health Services. The ADHD cohort (N = 18,558) was compared in a 1:2 ratio to controls (N = 37,116), who were strictly matched for age, gender, birth year and quarter, socioeconomic status (SES), sectors, region, and cumulative years of LHS membership up to the index date. Diagnoses of ADHD and EH were identified using ICD-9/10 codes, depending on the year of diagnosis. Logistic regression analyses were used to assess the associations between ADHD, EH and the use of antihypertensive medications over a 20-year follow-up. Results: ADHD-diagnosed children had a higher prevalence of EH, with odds ratios (ORs) of 3.17 (95% CI: 1.46–7.16, p = 0.0017) at 5 years, 2.94 (95% CI: 1.45–6.09, p = 0.0013) at 10 years, and 1.92 (95% CI: 1.26–2.93, p = 0.0015) at 20 years. ADHD patients showed a greater use of antihypertensive medications, including calcium channel blockers (OR 1.85, 95% CI: 1.02–3.35, p = 0.035), renin angiotensin system blockers (OR 2.20, 95% CI: 1.15–4.25, p = 0.013), and diuretics (OR 1.77, 95% CI: 1.21–2.60, p = 0.0028). Conclusions: These findings highlight an association between ADHD diagnosis and EH, suggesting regular cardiovascular monitoring of children with ADHD. Further studies are needed to uncover the role of stimulant medications and shared biological and behavioral factors involved in the pathogenesis.

BACKGROUND:Suicide is the second leading cause of death among adolescents. Although suicide attempts are most frequently associated with mood, sleep, and personality disorders, attention-deficit/hyperactivity disorder (ADHD) may also confer risk. We hypothesized that ADHD is independently associated with suicide attempts beyond the effects of psychiatric comorbidities. METHODS:We conducted a retrospective, population-based case-control study using electronic medical records from Clalit Health Services (N = 1,652,752) among adolescents aged 12-18 years. The study group comprised 1763 adolescents who presented to emergency departments for attempted suicide between 2010 and 2022. Diagnoses were based on ICD-10 and DSM-5 criteria. Logistic regression analyses assessed associations between ADHD and attempted suicide while adjusting for comorbid psychiatric disorders. RESULTS:Adolescents who attempted suicide exhibited a markedly higher female-to-male ratio (80%:20%) than the general population (51%:49%). Higher socioeconomic status among adolescents with ADHD was significantly associated with increased attempted suicide risk. Comorbidities, including major depressive disorder, anxiety, and personality disorders, were also linked to suicide attempts. Importantly, ADHD remained an independent risk factor for attempted suicide even after excluding significant psychiatric comorbidities (e.g., without depression: OR 2.12, 95% CI 1.91-2.35; without borderline personality disorder: OR 2.39, 95% CI 2.15-2.65). CONCLUSIONS:ADHD significantly increases the risk of suicide attempts in adolescents, independent of common psychiatric comorbidities. These findings underscore the need for targeted screening and prevention strategies in this high-risk population.

Background:Acute urticaria (AU) is characterized by the sudden onset of wheals, angioedema, or both, with symptoms resolving within 6 weeks. While the association between chronic urticaria and mental health disorders is well-documented, the relationship between AU and psychological conditions remains understudied. Objective:To investigate the association between AU and anxiety and personality disorders, and to explore the potential psychoneuroimmunological mechanisms underlying these relationships. Methods:We conducted a population-based case-control study using the comprehensive electronic health records database of Leumit Health Services in Israel. The study included 72,805 AU patients and 291,220 matched controls. Subjects were matched for gender, age, ethnicity, year of first documented visit, and socioeconomic status. We analyzed the 20-year prevalence of anxiety disorders, personality disorders, and various nonpsychotic mental disorders in both groups. Results:AU patients demonstrated significantly higher prevalence of anxiety disorders (7.02 % vs. 5.22 %, p < 0.001, OR = 1.37 [95 % CI: 1.33-1.42]), personality disorders (0.23 % vs. 0.134 %, p < 0.001, OR = 1.73 [95 % CI: 1.44-2.08]), and adjustment disorders (0.91 % vs. 0.67 %, p < 0.001, OR = 1.37 [95 % CI: 1.25-1.50]) compared to controls. Particularly notable were the associations with personality disorders characterized by persistent mood disturbances (OR = 1.91 [95 % CI: 1.53-2.38]) and adjustment disorders with depressive features (OR = 1.49 [95 % CI: 1.27-1.74]). Conclusions:Our findings reveal significant associations between AU and various mental health disorders, particularly anxiety and personality disorders. These associations suggest a complex bidirectional relationship mediated through psychoneuroimmunological pathways involving the HPA axis, mast cell activation, and inflammatory cytokines. We recommend implementing specific screening tools (HADS, GAD-7) and a stepped-care approach for integrated dermatological and psychological management of AU patients.

IntroductionAttention-Deficit/Hyperactivity Disorder (ADHD) in girls and women is under-recognised and under-researched, despite increasing awareness of clinical challenges and unmet needs. This review by the Eunethydis Special Interest Group on Female ADHD, addresses current knowledge and identifies research gaps for future work. Issues in women with ADHD across the lifespan such as late diagnosis, pubertal development, sexual health, hormonal birth control, executive function difficulties, and gynaecological disorders associated with ADHD are highlighted.MethodsThe review synthesises existing literature and self-reported experiences of women with ADHD to explore the impact of hormonal fluctuations [puberty, menstrual cycle, pregnancy, (peri)menopause] on ADHD symptoms and mood disturbances. It examines the interplay of oestrogen and progesterone with dopaminergic pathways, when periods of lower oestrogen may affect cognition, as well as the manifestation of executive function deficits, and the intersection of ADHD with reproductive health.ResultsHormonal transitions exacerbate ADHD symptoms and mood disturbances, yet pharmacological research and tailored treatments are lacking. Executive function deficits manifest differently in girls and women with ADHD and are influenced by neuropsychological and neurobiological profiles. Diagnostic practices and sociocultural factors contribute to delayed diagnoses, increasing the risk of comorbidities, impaired functioning, and diminished quality of life. Undiagnosed women have increased vulnerability to premenstrual dysphoric disorder, postpartum depression, and cardiovascular disease during perimenopause.DiscussionLongitudinal, sex-specific studies incorporating hormonal status and lived experience are needed. Individualised interventions should be developed to address the unique needs of girls and women with ADHD. Addressing these gaps will advance more equitable diagnosis, management, and support for girls and women with ADHD, improving outcomes across the female lifespan.

Objectives This nationwide cohort study investigated the association between attention-deficit/hyperactivity disorder (ADHD) and various types of urticarial diseases.Methods We conducted a population-based cohort study using data from Leumit Health Services (LHS), a health maintenance organisation in Israel. The study population consisted of all members of LHS between 1 January 2002 and 30 November 2022 aged 5–18 years. Diagnoses of ADHD and urticarial diseases were based on International Classification of Diseases, 9th Edition codes. The study group consisted of subjects with ADHD, while matched controls were randomly selected non-ADHD subjects (2:1 ratio).Findings Demographic characteristics of ADHD (n=18 558) and control (n=37 116) groups were well-matched, with no significant socio-demographic differences. A significantly higher prevalence of various subtypes of urticarial diseases was found in the ADHD group compared with the control group. Specifically, urticaria (5.00% vs 4.22%, OR (95% CI) 1.19 (1.10 to 1.30), p<0.001), allergic urticaria (3.26% vs 2.73%, OR (95% CI) 1.20 (1.08 to 1.33), p<0.001). Inducible forms of urticaria did not show significant differences between the groups. The ADHD group had a higher use of systemic and topical antihistamines and systemic corticosteroids.Conclusions Various urticarial diseases are more prevalent in individuals with ADHD, possibly due to shared genetic factors, immune system dysfunction, or environmental triggers.Clinical implications This study suggests an association between ADHD and some urticaria subtypes. Physicians should be aware of this association and its public health implications.

OBJECTIVE:Previous studies indicate that national traumatic events, particularly terror attacks, have a broad impact on the general population, including individuals not directly exposed. However, research on how such events affect inattention and hyperactivity/impulsivity symptoms in individuals with ADHD remains limited. METHOD:This study examined the impact of the October 7 terror attack in Israel on ADHD-related symptoms. Young adults with and without ADHD (43 ADHD and 42 control) completed assessments of current and childhood ADHD symptoms, as well as anxiety, at two time-points: before and after the national traumatic event. Participants also reported their level of exposure to the October 7 attack and the subsequent war. RESULTS:The control group showed a substantial increase in inattention and hyperactivity/impulsivity symptoms after the attack, whereas the ADHD group exhibited no such increase and instead showed a slight reduction in symptom severity. Changes in symptoms in both groups were not influenced by direct exposure to an immediate threat. The increase in symptom severity tended to decline over time and was positively correlated with heightened anxiety symptoms. CONCLUSION:These results suggest that national traumatic events can temporarily increase inattention and hyperactivity/impulsivity symptoms among young adults without an ADHD diagnosis, even if they were not directly exposed to the events. This increase tends to return to baseline over time. Conversely, individuals diagnosed with ADHD did not experience a worsening of symptoms and instead showed a slight reduction in severity, particularly in inattention, following the traumatic event. Future research should further explore the functional capabilities of individuals with ADHD under acute stress to deepen the understanding of this relationship.

Background Mood disorders (MD) are multifactorial disorders. Identifying new biomarkers for the early diagnosis of MD and predicting response to treatment is currently a significant research topic. Both eosinopenia and MD are associated with increased activity of the hypothalamic-pituitary-adrenal axis. The present study, therefore, used a clear definition of chronic idiopathic eosinopenia (CIE) to determine the rate of MD in a large cohort of individuals with CIE. Methods This retrospective population-based, case-control study uses data of seven consecutive years from the database of Leumit Health Services (LHS) - a nationwide health maintenance organization in Israel. Results Participants were 13928 LHS members with CIE and 27858 negative controls. The CIE group exhibited significantly higher rates of MD than the control group throughout the whole study period, except for atypical depressive disorder at baseline. Conclusions CIE might be associated with a higher prevalence of MD. Further basic research should elucidate the pathophysiologic mechanisms linking CIE and MD.

Background: Pediatric pain significantly affects children’s lives, leading to school absenteeism, impaired social interactions, and psychological distress. The perception of sensory signals as pain is influenced by the brain’s noradrenergic system, and recent evidence suggests that chronic pain may impact cognitive functioning and emotional regulation. Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with alterations in the dopaminergic/noradrenergic systems, which could affect pain perception. Pain-associated conditions and frequent analgesic use in childhood may be linked to ADHD development and could serve as early indicators, yet data on this potential association remain limited. Study Aim: This population-based case-control study in Israel aimed to assess the prevalence of pain-related diagnoses prior to ADHD diagnosis in children aged 5 to 18. The study included children registered with Leumit Health Services (LHS) between 1 January 2006, and 30 June 2021. Children diagnosed with ADHD were compared to matched controls, selected based on age, gender, socioeconomic status, and other sociodemographic factors, who were never diagnosed with ADHD during the study period. Results: Children with ADHD (N = 18,756) and controls (N = 37,512) were precisely matched for sociodemographic characteristics. Individuals with ADHD exhibited significantly higher frequencies of diverse pain conditions, including those associated with illness [headache, earaches, and throat pain (odds ratios [OR] = 1.156 [95%CI 1.085, 1.232], 1.295 [95%CI 1.217, 1.377], and 1.080 [95%CI 1.019, 1.145], respectively; p < 0.01)] and injury [sprains and strains (OR = 1.233 [95% CI 1.104,1.376)]. Analgesics were more frequently purchased by individuals with ADHD, particularly paracetamol (OR = 1.194 [95%CI 1.152, 1.237], p < 0.001) and ibuprofen (OR = 1.366 [95%CI 1.318, 1.416], p = 0.001). Conclusions: This study highlights a potential connection between ADHD and pediatric pain. The elevated rates of pain diagnoses and analgesic usage among children with ADHD underscore the need for further research.

Infection and lockdowns resulting from COVID-19 have been suggested to increase the prevalence and treatment rates of Attention Deficit/Hyperactivity Disorder (ADHD). To accurately estimate the pandemic's effects, pre-pandemic data can be used to estimate diagnosis and treatment rates during the COVID-19 years as if the COVID-19 pandemic did not occur. However, accurate predictions require a broad dataset, both in terms of the number of cases and the pre-pandemic timeframe. In the current study, we modeled monthly ADHD diagnosis and treatment rates over the 18 years preceding the COVID-19 pandemic. The dataset included ∼3 million cases for individuals aged 6 to 18 from the Clalit Health Services' electronic database. Using a trained model, we projected monthly rates for post-lockdown and post-infection periods, enabling us to estimate the expected diagnosis and treatment rates without the COVID-19 pandemic. We then compared these predictions to observed data, stratified by age groups, gender, and socioeconomic status. Our findings suggest no influence of the COVID-19 pandemic on ADHD diagnosis or treatment rates. We show that a narrower timeframe for pre-COVID-19 data points can lead to incorrect conclusions that COVID-19 affected ADHD diagnosis rates. Findings are discussed, given the assumed impact of the COVID-19 pandemic on ADHD.

Background: Selective Immunoglobulin A Deficiency (SIgAD) is one of the most prevalent immunodeficiencies, characterized by an increased risk of mucosal infections. Attention deficit hyperactivity disorder (ADHD) is among the most common neurodevelopmental disorders and is associated with significantly higher rates of various infectious diseases, white blood cell abnormalities, and considerable morbidity. This study aimed to evaluate the prevalence of ADHD among patients with SIgAD. Methods: We conducted a retrospective, observational, population-based case–control study, within Leumit Health Services, by comparing individuals diagnosed with SIgAD to a matched control group. Data were extracted from electronic health records. Results: Of the >700,000 registered individuals, 772 aged ≥4 years with SIgAD were identified (mean age 22.0 ± 17.5 years; male/female ratio 1:1). The 5:1 matched control group consisted of 3860 subjects without SIgAD, with no significant differences between the groups regarding age, gender, ethnicity, and socioeconomic status. ADHD prevalence was significantly higher in the SIgAD group (16.2%) than in the control group (12.9%), with an odds ratio of 1.30 (95% confidence interval 1.05–1.61, p = 0.017), as was the use of methylphenidate (6.6% vs. 4%). Additionally, respiratory and intestinal infections were significantly more common in the SIgAD group (p < 0.001). Conclusion: A significantly higher prevalence of ADHD was observed in patients with SIgAD compared to strictly matched controls without SIgAD. These findings enhance our understanding of the pathophysiology of ADHD and its associated health complications.

Objectives: To determine ADHD research priorities from the perspective of ADHD professionals internationally. Method: A two-stage modified Delphi design was used. In Stage 1 (qualitative), participants listed research questions relating to ADHD that they perceived to be most important ( N = 132). In Stage 2 (quantitative), participants were then asked to rate each research question that was deemed appropriate (able to be researched and not already addressed by research) in terms of perceived importance ( N = 180). Results: Stage 1 generated 382 research questions with 10 broad areas identified for example, co-occurring conditions and treatment, etc. The top 20 most important questions related to ADHD in women/girls, long-term medication use, non-pharmacological interventions, ADHD measurement/rating scales, and efficacy of emotional regulation interventions. Conclusion: These results can inform an ADHD research agenda which represents the views of the individuals from major ADHD professional groups internationally. Parallel work is needed focusing on research priorities from the perspective of ADHD consumers.

Objective: We examined the association between the number, magnitude, and frequency of febrile episodes during the 0 to 4 years of life and subsequent diagnosis of ADHD. Methods: This population-based case-control study in an Israeli HMO, Leumit Health Services (LHS), uses a database for all LHS members aged 5 to 18 years between 1/1/2002 and 1/30/2022. The number and magnitude of measured fever episodes during the 0 to 4 years were recorded in individuals with ADHD ( N = 18,558) and individually matched non-ADHD controls in a 1:2 ratio ( N = 37,116). Results: A significant, independent association was found between the number and magnitude of febrile episodes during the 0 to 4 years and the probability of a later diagnosis of ADHD. Children who never had a measured temperature >37.5°C had a significantly lower rate of ADHD (OR = 0.834, 95% CI [0.802, 0.866], p < .0001). Conclusions: Febrile episodes during 0 to 4 years are associated with a significantly increased rate of a later diagnosis of ADHD in a doseresponse relationship.

Objective: There is growing evidence of involvement of inflammatory mechanisms in ADHD. Previous studies found significantly higher rates of ADHD among children with FMF. The present study examined the rate of exposure to FMF in children with a later (within a 5-year period) diagnosis of ADHD compared to non-ADHD children. Methods: A population-based case-control study of all children (<18 years) registered in Leumit Health Services during 01.01.2006 to 06.30.2021. All cases met ICD-9/10 criteria for ADHD. They were matched by age, sex, and socioeconomic status on a 1:2 rate to randomly selected non-ADHD controls. Results: Fifty-six (0.30%) children with ADHD ( N = 18,756) were previously diagnosed with FMF compared to 65 of 37,512 controls (0.17%). A significant, independent association existed between a preceding FMF diagnosis and a later ADHD diagnosis [OR = 1.72 (95% CI 1.18–2.51); p = .003]. Conclusions: The mechanisms underlying the association w between FMF and later ADHD diagnosis merit further elucidation.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, impacting 4.9% of the population and more prevalent in Mediterranean communities, is a common enzymopathy with potential relevance to Attention Deficit/Hyperactivity Disorder (ADHD). This study investigated this association. Methods: The clinical characteristics of 7473 G6PD-deficient patients and 29,892 matched case–controls (selected at a 1:4 ratio) from a cohort of 1,031,354 within the Leumit Health Services database were analyzed using Fisher’s exact test for categorical variables and the Mann–Whitney U test for continuous variables. Results: In total, 68.7% were male. The mean duration of follow-up was 14.3 ± 6.2 years at a mean age of 29.2 ± 22.3 years. G6PD deficiency was associated with an increased risk of being diagnosed with ADHD (Odds Ratio (OR) = 1.16 [95% CI, 1.08–1.25], p < 0.001), seeking care from adult neurologists (OR = 1.30 [95% CI, 1.22–1.38], p < 0.001), and consulting adult psychiatrists (OR = 1.12 [95% CI, 1.01–1.24], p = 0.048). The use of stimulant medications among G6PD-deficient individuals was 17% higher for the methylphenidate class of drugs (OR = 1.17 [95% CI, 1.08, 1.27], p < 0.001), and there was a 16% elevated risk for amphetamine use (OR = 1.16 [95% CI, 1.03, 1.37], p = 0.047). Conclusions: G6PD deficiency signals an increased risk of ADHD diagnosis, more severe presentations of ADHD and a greater need for psychiatric medications to treat ADHD.

There is a growing interest in examining the relationship between physical health issues and ADHD. This Symposium discusses the association between ADHD and variable health conditions in different age groups.

There are recent reports of increased prevalence of ADHD among people with Familial Mediterranean Fever (FMF). We examined the association between FMF and ADHD in a sample of 56,268, enriched for youth with ADHD. A population-based case-control study was based on electronic medical records (EMRs) of an Israeli Health Maintenance Organization, Leumit Health Services (LHS). The study population consisted of all individuals (5-18 years old) who were members of LHS between January 1, 2006 and June 30, 2021. Cases met the ICD-9/10 criteria for ADHD. Controls included randomly selected subjects without ADHD, matched individually by age, gender, sector, socioeconomic status (SES), and BMI in a 2:1 ratio. The rate of patients with FMF among children diagnosed with ADHD was compared to that of FMF patients among children without ADHD. A total of 18,765 cases and 37,512 matched controls were studied. BMI was omitted. The demographic variables were similar between the groups (p = .92-1.0). There was a significant association between ADHD in children and the diagnosis of FMF (p < .01; OR = 1.725 [95% CI, 1.184-2.506]). There is a significant association between ADHD in children and a prior diagnosis of FMF.