Attention Deficit Hyperactivity Disorder Cases Research Articles

Environmental burden of disease related to pyrethroid-insecticide exposure and neurodevelopmental toxicity in Europe based on human biomonitoring

Abstract As indicated by human biomonitoring (HBM) studies, exposure to pyrethroids is widespread in Europe with significantly higher exposure observed in children compared to adults. Epidemiological, toxicological, and mechanistic studies raise concerns about potential health effects in humans and, particularly, behavioral disorders such as attention deficit hyperactivity disorder (ADHD) in children at low levels of exposure. Based on an exposure-response function from a single European study and on available quality-assured and harmonized HBM data collected in France, Germany, Iceland, Switzerland, and Israel, an initial estimate of the environmental burden of disease for ADHD associated with pyrethroid exposure (measured by the metabolite 3-phenoxybenzoic acid) was made for individuals aged 0-19 years. The estimated yearly number of prevalence-based disability-adjusted life years (DALYs) per million inhabitants due to ADHD were 34 DALYs for Israel, 26 DALYs for France, 14 DALYs for both Switzerland and Iceland, and 4 DALYs for Germany. Additionally, a substantial number of ADHD cases, averaging 18%, were associated with pyrethroid exposure. Yet, these figures should be interpreted with caution given the uncertainty of some input parameter. In addition to burden of disease estimates due to ADHD, the associated burden of autism-spectrum disorder (ASD) due to pyrethroid exposure and the health economic costs attributable to ADHD and ASD will also be investigated further. To ensure adequate follow-up of policy measures and more robust disease burden estimates, more HBM studies are recommended, along with increased efforts to harmonize the design of epidemiological studies to ensure more meaningful meta-analyses of exposure-response functions. This is particularly important for pyrethroids as more evidence on potential adverse health effects is continuously emerging.

A preliminary estimate of the environmental burden of disease associated with exposure to pyrethroid insecticides and ADHD in Europe based on human biomonitoring

Human biomonitoring (HBM) data indicate that exposure to pyrethroids is widespread in Europe, with significantly higher exposure observed in children compared to adults. Epidemiological, toxicological, and mechanistic studies raise concerns for potential human health effects, particularly, behavioral effects such as attention deficit hyperactivity disorder (ADHD) in children at low levels of exposure. Based on an exposure-response function from a single European study and on available quality-assured and harmonized HBM data collected in France, Germany, Iceland, Switzerland, and Israel, a preliminary estimate of the environmental burden of disease for ADHD associated with pyrethroid exposure was made for individuals aged 0–19 years. The estimated annual number of prevalence-based disability-adjusted life years (DALYs) per million inhabitants were 27 DALYs for Israel, 21 DALYs for France, 12 DALYs for both Switzerland and Iceland, and 3 DALYs for Germany; while the annual ADHD cases per million inhabitants attributable to pyrethroids were 2189 for Israel, 1710 for France, 969 for Iceland, 944 for Switzerland, and 209 for Germany. Direct health costs related to ADHD ranged between 0.3 and 2.5 million EUR yearly per million inhabitants for the five countries. Additionally, a substantial number of ADHD cases, on average 18%, were associated with pyrethroid exposure. Yet, these figures should be interpreted with caution given the uncertainty of the estimation. A sensitivity analysis showed that by applying a different exposure-response function from outside the EU, the population attributable fraction decreased from an average of 18 to 7%. To ensure more robust disease burden estimates and adequate follow-up of policy measures, more HBM studies are needed, along with increased efforts to harmonize the design of epidemiological studies upfront to guarantee meta-analysis of exposure-response functions. This is particularly important for pyrethroids as evidence of potential adverse health effects is continuously emerging.

ADHD and Risk of Precocious Puberty: Considering the Impact of MPH.

The complex association between attention-deficit/hyperactivity disorder (ADHD) and methylphenidate (MPH) with precocious puberty (PP) is still unclear. This study aims to investigate the association between ADHD, MPH, and PP. This is a nationwide cohort study including a total of 3,342,077 individuals, 186,681 with ADHD and 3,155,396 without. First, we compared the risk of PP between ADHD cases and non-ADHD cases. Second, we compared the risk of PP between MPH users and non-MPH users in patients with ADHD. Patients with ADHD were at a greater risk of PP (adjusted hazard ratio [aHR], 2.01 [95% CI, 1.91-2.11]). In our moderation analyses, the female gender was a positive additive effect modifier of the association between ADHD and PP, whereas tics and intellectual disability were negative effect modifiers. In patients with ADHD, MPH users had a significantly lower risk of PP (aHR, 0.63 [95% CI 0.57-0.70]), and females had a negative effect modification on the association between MPH and PP. Our study found that children with ADHD were at a greater risk of PP. Girls with ADHD were a group particularly vulnerable to PP. Comorbid tics or intellectual disability was associated with a lower risk of PP. Among patients with ADHD, MPH was protective against PP, especially in girls. However, these preliminary results need further validation due to the nature of them being from an electronic database study. Unmeasured confounding factors might affect the association between MPH and PP.

Post-COVID-19 Yearly Pattern Changes and Gender Variations in Attention Deficit Hyperactivity Disorder Patients at an Urban Mental Health Clinic in Alabama, USA.

Introduction The COVID-19 era has seen an increased trend in attention deficit hyperactivity disorder (ADHD) diagnoses. Historically, males have been diagnosed with ADHD more frequently than females during childhood. Studies have indicated a higher use of stimulant medications among male ADHD cases compared to females. This study examines ADHD cases from 2021 to 2023 to analyze yearly trends following the initial COVID-19 spike and explores gender and age differences between ADHD-positive and ADHD-negative cases. Methods This retrospective study was conducted using data from an urban outpatient mental health clinic in Alabama. Data were extracted from Electronic Health Records (EHR) for patients seen from January 1, 2021, to December 31, 2023. The Institutional Review Board (IRB) approved the study under the exempt research category. Data were analyzed using Microsoft Excel (Microsoft® Corp., Redmond, WA, USA) and the StatisticalPackage for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 26.0, Armonk,NY). Diagnoses were based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, and clinical diagnoses and medication information were obtained from the EHR. Results The study included 1,422 patients, of whom 881 (62%) were diagnosed with ADHD. Females with ADHD had significantly higher comorbid conditions, such as major depressive disorder, generalized anxiety disorder, panic disorder, and post-traumatic stress disorder, compared to males with ADHD. Gender differences in ADHD diagnoses were seen over the years, though no significant age differences were observed. Conclusions The study indicates a sustained high rate of ADHD diagnoses even after the initial COVID-19 spike. Females showed a higher ADHD diagnoses compared to males, but stimulant medication use remained consistent across genders. No significant age differences were observed between males and females with ADHD. Further research is needed to explore the reasons behind these gender differences and to evaluate their implications.

High level of immunoglobulin G targeting mycoplasma or cytomegalovirus in the newborn increases risk of ADHD

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder typically detected in childhood. Although ADHD has been demonstrated to have a strong genetic component, environmental risk factors, such as maternal infections during pregnancy, may also play a role. We therefore measured the immunological response to 5 abundant microorganisms (Toxoplasmosis Gondii, cytomegalovirus (CMV), Herpes Simplex Virus 1, Epstein Barr Virus and mycoplasma pneumoniae) in newborn heel prick samples of 1679 ADHD cases and 2948 matching controls as part of the iPSYCH Danish case-cohort study. We found an association between high anti-CMV (OR 1.30, 95 % CI [1.09,1.55], p = 0.015) and anti-mycoplasma (OR 1.30, 95 % CI [1.07,1.59], p = 0.037) signal and those newborns later being diagnosed with ADHD. The risk estimate remained increased when controlling for ADHD polygenic risk score as well as penicillin prescriptions. We saw a dose–response association with the amount of positive anti-microorganism titers increasing the risk of being diagnosed with ADHD later in life (p = 0.01 for the trend), suggesting that the more activated the immune system is prior to or at birth, the higher the risk is for a later diagnosis with ADHD. If the associations are causal, they emphasize the importance of a healthy life style during pregnancy to reduce the risk of infections when pregnant and the associated risks for the child.

Rare de novo damaging DNA variants are enriched in attention-deficit/hyperactivity disorder and implicate risk genes

Research demonstrates the important role of genetic factors in attention-deficit/hyperactivity disorder (ADHD). DNA sequencing of families provides a powerful approach for identifying de novo (spontaneous) variants, leading to the discovery of hundreds of clinically informative risk genes for other childhood neurodevelopmental disorders. This approach has yet to be extensively leveraged in ADHD. We conduct whole-exome DNA sequencing in 152 families, comprising a child with ADHD and both biological parents, and demonstrate a significant enrichment of rare and ultra-rare de novo gene-damaging mutations in ADHD cases compared to unaffected controls. Combining these results with a large independent case-control DNA sequencing cohort (3206 ADHD cases and 5002 controls), we identify lysine demethylase 5B (KDM5B) as a high-confidence risk gene for ADHD and estimate that 1057 genes contribute to ADHD risk. Using our list of genes harboring ultra-rare de novo damaging variants, we show that these genes overlap with previously reported risk genes for other neuropsychiatric conditions and are enriched in several canonical biological pathways, suggesting early neurodevelopmental underpinnings of ADHD. This work provides insight into the biology of ADHD and demonstrates the discovery potential of DNA sequencing in larger parent-child trio cohorts.

Attention Deficit / Hyperactivity Disorder and Paediatric Dentistry

Aim: Attention Deficit/Hyperactivity Disorder (ADHD) restlessness one of the most frequently diagnosed neurodevelopmental and neurobehavioral disorders in children, with a higher incidence observed in boys compared to girls. The fundamental characteristics of ADHD include three main symptoms: pronounced lack of attention, excessive hyperactivity, and impulsive behaviour. Materials and Methods: The diagnostic process for ADHD is complex and multidimensional, involving a thorough analysis of behaviour, collection of extensive and detailed information, comprehensive evaluation of the child’s developmental history, and intensive collaboration between various specialists, including educators, psychologists, paediatricians, dentists as well as active participation of parents or guardians. With the increasing number of diagnosed cases of ADHD globally, it becomes increasingly important to timely recognize the symptoms and symptomatology of the disorder and to apply appropriate therapeutic strategies and treatment methods tailored to the individual needs of each child. Results: Dental care requires special attention in the context of ADHD. Children with ADHD face greater challenges in maintaining oral hygiene, leading to an increased risk of dental caries, more frequent oral traumas, and generally poorer oral health conditions. Conclusion: It is crucial to ensure a tailored approach during dental treatment, which may include establishing special communication and techniques adapted to the child, as well as increasing the frequency of preventive check-ups and interventions to preserve and enhance oral health.

Environmental Risk Factors Associated with Behavioral Problems among Children with Attention Deficit Hyperactivity Disorder: Maternal Perceptions

OBJECTIVE This study aims to identify environmental risk factors associated with behavioral problems in children and adolescents with attention deficit hyperactivity disorder (ADHD). METHODS A case-control study was conducted in children aged 4-15 years comprising 92 children diagnosed with ADHD and 92 controls without ADHD. Stratified sampling was used to select 184 participants residing in Chiang Mai and Lamphun provinces, Thailand. Data were collected from the mothers of the participants using a self-report questionnaire between May and August 2022. The questionnaire consisted of three parts: child characteristics (gender, age, underlying diseases, past illness history), mother’s characteristics (age, income, occupational status, history of cigarette smoking and alcohol drinking), and maternal perceptions about caring for the child and the child’s behavioral problems (exposure to chemicals/toxicants, frequent punishment, excessive use of digital media and games). Data were analyzed using descriptive statistics, chi-squared test, odds ratio (OR) and logistic regression using SPSS version 21. RESULTS Most of participants were males (86.96%) while 13.04% were females. The results showed that the ADHD cases were significantly more likely than the controls to have underlying diseases such as G6PD, allergy, and asthma (p = 0.006). There was also a statistically significant correlation with smoking history in the mothers of ADHD cases (OR = 2.64; 95% CI: 1.36-5.13 p = 0.004). In terms of maternal perceptions, the mothers of ADHD children were significantly more likely than the controls to have frequently punished the child (OR = 6.26; 95% CI: 3.24-12.07; p < 0.001), to have children who were exposed to chemicals (pesticides and fertilizer) or toxicants (passive smoking) (OR = 4.14; 95%CI: 1.76-9.73; p = 0.001), and to have allowed their child to use digital media and play video games excessively (OR = 2.82; 95% CI: 1.55-5.16; p = 0.001). After adjustment for other environmental risk factors, frequent child punishment (ORadj = 4.32; 95% CI: 2.13-8.78; p < 0.001) and exposure of the child to chemicals/toxicants (ORadj = 2.66; 95% CI: 1.00-7.02; p = 0.049) were found to be significantly related with ADHD. CONCLUSIONS Frequent child punishment was the most significant environmental risk factor related to behavioral problems among children with ADHD. This indicates the importance of healthcare providers developing strategies and/or interventions to enhance knowledge and awareness in mothers of ADHD which can improve treatment outcomes. KEYWORDS ADHD, risk factors, behavioral problems, maternal percep- tions

Using polygenic scores in combination with symptom rating scales to identify attention-deficit/hyperactivity disorder

BackgroundThe inclusion of biomarkers could improve diagnostic accuracy of attention-deficit/hyperactivity disorder (ADHD). One potential biomarker is the ADHD polygenic score (PGS), a measure of genetic liability for ADHD. This study aimed to investigate if the ADHD PGS can provide additional information alongside ADHD rating scales and examination of family history of ADHD to distinguish between ADHD cases and controls.MethodsPolygenic scores were calculated for 576 adults with ADHD and 530 ethnically matched controls. ADHD PGS was used alongside scores from the Wender-Utah Rating Scale (WURS) and the Adult ADHD Self-Report Scale (ASRS) as predictors of ADHD diagnosis in a set of nested logistic regression models. These models were compared by likelihood ratio (LR) tests, Akaike information criterion corrected for small samples (AICc), and Lee R². These analyses were repeated with family history of ADHD as a covariate in all models.ResultsThe ADHD PGS increased the variance explained of the ASRS by 0.58% points (pp) (R2ASRS = 61.11%, R2ASRS + PGS=61.69%), the WURS by 0.61pp (R2WURS = 77.33%, R2WURS + PGS= 77.94%), of ASRS and WURS together by 0.57pp (R2ASRS + WURS=80.84%, R2ASRS + WURS+PGS=81.40%), and of self-reported family history by 1.40pp (R2family = 28.06%, R2family + PGS=29.46%). These increases were statistically significant, as measured by LR tests and AICc.ConclusionWe found that the ADHD PGS contributed additional information to common diagnostic aids. However, the increase in variance explained was small, suggesting that the ADHD PGS is currently not a clinically useful diagnostic aid. Future studies should examine the utility of ADHD PGS in ADHD prediction alongside non-genetic risk factors, and the diagnostic utility of the ADHD PGS should be evaluated as more genetic data is accumulated and computational tools are further refined.

Association of prenatal and postnatal exposure to air pollution with clinically diagnosed attention deficit hyperactivity disorder: a systematic review

Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder in children, originates from a multifaceted interplay of genetic, neurological, and environmental factors. Recent studies have increasingly concentrated on environmental determinants, notably air pollution, and their impact on the risk of developing ADHD. Additionally, previous research has often conflated clinically diagnosed ADHD cases with instances of mere ADHD-like symptoms, a methodology that can introduce bias and obscure the true relationship between environmental factors and ADHD. To address this oversight, our systematic review meticulously investigates the relationship between both prenatal and postnatal exposures to particular air pollutants and strictly clinically diagnosed ADHD. Our comprehensive review encompassed 801 studies from PubMed, Cochrane Library, Web of Science, and Embase databases, out of which eight met our rigorous inclusion criteria. The Newcastle-Ottawa Scale (NOS) was utilized to gauge quality and bias. Our review found substantiated the connection between prenatal exposure to PM2.5 and NOx and a heightened risk of ADHD, while exposure to PM10 during the prenatal stage was not associated with ADHD. These findings hint at varied health impacts from different particulate matters and the prospect of gender-specific susceptibilities to such exposures. We also identified an association between postnatal exposure to PM2.5, PM10, and NO2 and an increased ADHD risk, underlining the potential neurodevelopmental harms from early exposure to these pollutants. These relationships, seemingly intricate and potentially dose-dependent, underscore the need for more detailed scrutiny. The unique value of our review is in its detailed exploration of the association between specific air pollution exposures and clinically diagnosed ADHD. Our findings offer much-needed clarity in this complex domain and emphasize the importance of future research to standardize exposure and outcome metrics, probe potential mechanisms, and reduce bias and heterogeneity.

Increased risk of attention-deficit/hyperactivity disorder in adolescents with high salivary levels of copper, manganese, and zinc

Exposure to toxic heavy metals has been associated with the development of attention-deficit/hyperactivity disorder (ADHD). However, fewer studies have examined the associations between abnormal levels of essential trace metals and ADHD, and none have done so using saliva. We investigated whether salivary metals were associated with ADHD in adolescents aged 12 from the Family Life Project (FLP) using a nested case–control study design that included 110 adolescents who met diagnostic criteria for inattentive (ADHD-I), hyperactive-impulsive (ADHD-H), or combined type ADHD (ADHD-C) (cases) and 173 children who did not (controls). We used inductively coupled plasma optical emission spectrophotometry to measure chromium, copper, manganese, and zinc in saliva samples. We employed logistic regression models to examine associations between quartile levels of individual metals and ADHD outcomes by subtype. Salivary copper levels were significantly associated with increased odds of any ADHD diagnosis (OR = 3.31, 95% CI: 1.08–10.12; p = 0.04) and with increased odds of ADHD-C diagnosis (OR = 8.44, 95% CI: 1.58–45.12; p = 0.01). Salivary zinc levels were significantly associated with increased odds of ADHD-C diagnosis (OR = 4.06, 95% CI: 1.21–13.69; p = 0.02). Salivary manganese levels were also significantly associated with increased odds of ADHD-C diagnosis (OR = 5.43, 95% CI: 1.08–27.27, p = 0.04). This is the first study using saliva to assess metal exposure and provide a potential link between salivary levels of copper, manganese, and zinc and ADHD diagnoses in adolescents. Public health interventions focused on metal exposures might reduce ADHD incidence in low-income, minority communities.

Prevalence of attention-deficit hyperactivity disorder in children, adolescents and adults in the Middle East and North Africa region: a systematic review and meta-analysis

ObjectivesTo systematically estimate the overall prevalence of attention-deficit hyperactivity disorder (ADHD) in children, adolescents and adults across the Middle East and North Africa (MENA) region.DesignSystematic review and meta-analysis conducted according...

Attention‐deficit/hyperactivity disorder in old age and the risk of dementia: A national cohort study in Israel

AbstractBackgroundEvidence of the association between Attention‐Deficit/Hyperactivity Disorder (ADHD) and the risk of dementia is scarce, inconsistent, and subject to potential sources of bias that are as yet unconsidered. Our objective was to examine the association between ADHD and dementia risk.MethodA prospective national cohort study born 1933‐1952, without a dementia diagnosis for two years, were followed up for incident dementia from 2002‐2020. Information was from electronic health records in a healthcare maintenance organization in Israel. ADHD diagnosis was classified as present from the age of the first diagnosis, otherwise absent. Competing risk Cox regression models were fit to quantify the risk of incident dementia with the Hazard Ratio (HR) and their associated 95% Confidence Intervals (CI) with inverse probability weights, age as the underlying time‐scale, unadjusted and, in the primary analysis, adjusted by 18 covariates.ResultOf 110,196 participants aged 50‐70 years in 2002, 56,914 (51.6%) were female. During follow‐up there were a total of 746 (0.7%) cases of ADHD, and 8,339 (7.6%) of incident dementia. The percentage of incident dementia was 13.1% (N = 98) among those with ADHD present and 7.5% (N = 8,241) among those with ADHD absent. In the primary analysis, the group with ADHD was statistically significantly (P<.05) associated with a higher risk of dementia (unadjusted: HR = 3.57, CI = 2.89, 4.42; adjusted HR = 2.73, CI = 2.04, 3.65) compared to the group with ADHD absent. Eight of ten sensitivity analyses replicated the statistically significant association observed in the primary analysis. Psychostimulant medication offset the association between ADHD and dementia risk to null, and evidence of reverse causation was mild.ConclusionADHD is associated with increased dementia risk. Policymakers, caregivers, patients, and clinicians may wish to monitor ADHD in old age reliably.

Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a complex disorder that manifests variability in long-term outcomes and clinical presentations. The genetic contributions to such heterogeneity are not well understood. Here we show several genetic links to clinical heterogeneity in ADHD in a case-only study of 14,084 diagnosed individuals. First, we identify one genome-wide significant locus by comparing cases with ADHD and autism spectrum disorder (ASD) to cases with ADHD but not ASD. Second, we show that cases with ASD and ADHD, substance use disorder and ADHD, or first diagnosed with ADHD in adulthood have unique polygenic score (PGS) profiles that distinguish them from complementary case subgroups and controls. Finally, a PGS for an ASD diagnosis in ADHD cases predicted cognitive performance in an independent developmental cohort. Our approach uncovered evidence of genetic heterogeneity in ADHD, helping us to understand its etiology and providing a model for studies of other disorders.

A systematic review of the association between lead levels in hair and urine in children with attention deficit hyperactivity disorder (ADHD)

Attention deficit hyperactivity disorder (ADHD), characterised by inattentiveness, hyperkinetic behaviour, and impulsivity in childhood, leads to decreased academic performance and learning in general. Among the environmental factors, lead (Pb) in the environment is considered a crucial public health issue associated with ADHD. This study assessed the existing literature for the association of hair and urine lead levels with ADHD. The studies included in this systematic review were case-control observational and prevalence studies of a place or population. For hair Pb levels, out of 478 participants, 89 were ADHD cases and 389 controls showed a pooled effect of a standardised mean difference of 0.30 (0.03–0.57). The overall effect Z was 2.16, which was statistically significant (P = 0.03). For urine Pb levels, there were 196 ADHD cases and 423 healthy controls. The pooled effect of the standardised mean difference was 0.34 (0.13–0.56). The overall effect Z was 3.12, which was statistically significant (P = 0.002). Pb estimations can reduce the disease burden of ADHD by non-invasive methods such as in hair and urine, which have better acceptance by parents.

Screening for Attention Deficit Hyperactivity Disorder in Young Autistic Adults: The Diagnostic Accuracy of Three Commonly Used Questionnaires.

Attention Deficit Hyperactivity Disorder (ADHD) is a common co-occurring condition in autistic individuals. ADHD is sometimes first recognised in young adulthood because ADHD symptoms may be misattributed to autism due to superficial overlap in presentation and diagnostic overshadowing. It should be investigated whether ADHD questionnaires are accurate in screening symptoms in young adults with autism. The current study examined this. Participants were autistic young adults (N = 119) who took part in the Special Needs and Autism Project (SNAP), a population-based cohort. ADHD research diagnoses were obtained through the parent-informed Young Adult Psychiatric Assessment. Parents and young adults (self-report sample N = 71) completed ADHD questionnaires (Aberrant Behavior Checklist hyperactivity/non-compliance subscale, Conners Adult ADHD Rating Scales ADHD Index, and Strengths and Difficulties Questionnaire ADHD subscale). Receiver operating characteristic analyses were conducted to explore if the questionnaires discriminated ADHD cases from non-cases. To assess whether results varied by intellectual functioning, subgroup analyses were completed for those with an IQ ≥ 70 vs. <70. Weighted ADHD rates were high. Overall although the measures were performing at or close to adequate levels (area under the curve was 0.66 to 0.79 for parent-report and 0.70 to 0.65 for self-report), no single measure met adequate thresholds for sensitivity and specificity simultaneously. Tool performance was not different for those with an IQ ≥ 70 vs. <70. No single measure reported adequate performance for distinguishing ADHD from non-ADHD cases in this sample of young autistic adults. Use of current thresholds may lead to under-diagnosis.

A Protective Role of Low Polygenic Risk Score in Healthy Individuals Carrying Attention-Deficit/Hyperactivity Disorder–Associated Copy Number Variations

BackgroundPrevious studies have implicated both rare copy number variations (CNVs) and common variants in liability for attention-deficit/hyperactivity disorder (ADHD). However, how common and rare genetic variants jointly contribute to individual liability requires further investigation in larger cohorts. MethodsThis study comprises 9385 participants of European descent and 7810 participants of African American ancestry who were recruited from the greater Philadelphia area by the Children’s Hospital of Philadelphia. The polygenic risk score (PRS) of each participant was estimated by linkage disequilibrium pruning and p-value thresholding (P + T) methods using PRSice-2. We investigated whether the risk of ADHD follows a polygenic liability threshold model wherein 1) the risk of ADHD requires less contribution from common variants in the presence of a rare CNV, and 2) control carriers of ADHD-associated CNVs have lower common risk allele burden than noncarriers. ResultsCNVs previously reported in ADHD cases were significantly associated with ADHD risk in both the European American cohort and the African American cohort. Healthy control participants carrying those same risk CNVs had lower PRSs than those without risk CNVs in the European American cohort. This result was replicated in the African American cohort. However, PRSs were not significantly different in case participants carrying risk CNVs versus those without risk CNVs. ConclusionsThese findings provide evidence in support of interactive effects of PRS and ADHD-associated CNVs on disease risk and add novel insights into the genetic basis of ADHD by highlighting a protective role of low PRS in ADHD.

Practitioner Review: Clinical utility of the QbTest forthe assessment and diagnosis of attention-deficit/hyperactivity disorder - a systematic review and meta-analysis.

Several computerised cognitive tests (e.g. continuous performance test) have been developed to support the clinical assessment of attention-deficit/hyperactivity disorder (ADHD). Here, we appraised the evidence-base underpinning the use of one of these tests - the QbTest - in clinical practice, by conducting a systematic review and meta-analysis investigating its accuracy and clinical utility. Based on a preregistered protocol (CRD42022377671), we searched PubMed, Medline, Ovid Embase, APA PsycINFO and Web of Science on 15th August 2022, with no language/type of document restrictions. We included studies reporting accuracy measures (e.g. sensitivity, specificity, or Area under the Receiver Operating Characteristics Curve, AUC) for QbTest in discriminating between people with and without DSM/ICD ADHD diagnosis. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). A generic inverse variance meta-analysis was conducted on AUC scores. Pooled sensitivity and specificity were calculated using a random-effects bivariate model in R. We included 15 studies (2,058 participants; 48.6% with ADHD). QbTest Total scores showed acceptable, rather than good, sensitivity (0.78 [95% confidence interval: 0.69; 0.85]) and specificity (0.70 [0.57; 0.81]), while subscales showed low-to-moderate sensitivity (ranging from 0.48 [0.35; 0.61] to 0.65 [0.52; 0.75]) and moderate-to-good specificity (from 0.65 [0.48; 0.78] to 0.83 [0.60; 0.94]). Pooled AUC scores suggested moderate-to-acceptable discriminative ability (Q-Total: 0.72 [0.57; 0.87]; Q-Activity: 0.67 [0.58; 0.77); Q-Inattention: 0.66 [0.59; 0.72]; Q-Impulsivity: 0.59 [0.53; 0.64]). When used on their own, QbTest scores available to clinicians are not sufficiently accurate in discriminating between ADHD and non-ADHD clinical cases. Therefore, the QbTest should not be used as stand-alone screening or diagnostic tool, or as a triage system for accepting individuals on the waiting-list for clinical services. However, when used as an adjunct to support a full clinical assessment, QbTest can produce efficiencies in the assessment pathway and reduce the time to diagnosis.

Estimated prevalence study of attention-deficit/hyperactivity disorder among eastern province children in the Kingdom of Saudi Arabia.

Studying mental disorders in children is significantly important due to the huge suffering of educational and psychosocial impairments in adult life. Attention-deficit/hyperactivity disorder (ADHD) is considered the most common mental disorder in children, especially in early school-aged children. It manifests in about 8%-12% of children in the world. In Saudi Arabia, it affects 4%-12% of children. The study aimed to count the number of undiagnosed ADHD cases and the associated risk factors in Eastern Province in Kingdom of Saudi Arabia (KSA). A cross-sectional study was performed among girls' and boys' children aged 6-10 years old in Eastern Province in KSA with a random selection of parents. Sample size is equal to 1658. The assessment was done by an online questionnaire filled it by parents using Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnostic criteria and Connor's scale of ADHD excluding any developmental or mental disorder at the beginning of the questionnaire. After excluding the participants who were diagnosed with behavioral and growth developmental disorder, the remaining 1430 have been screened for ADHD based on Connor's scale. 185 of a child out of 1430 were suggested to have ADHD, of which 10 out of them show the signs of ADHD, 76 of them have moderately severe ADHD, and 99 out of them have atypical or severe ADHD based on Connor's scale of ADHD. The study shows that there is a significant relationship between the positive screening of ADHD and gender males (71.35%), females (28.64%), family history (20.5%), nervous system diseases (4.32%), brain damage from trauma (9.72%), smoking habit of the mother (8.64%), smoking during pregnancy (3.78%), mother exposure to second-hand smoking (42.16%), child exposure to a toxic substance like lead during the early life (1.62%), and the preterm labor (15.13%). However, the study shows there is no significant relationship between the positive screening of ADHD with age, drinking alcohol, and central nervous system infection. The prevalence of undiagnosed ADHD is slightly high. Also, it has many causes of ADHD including gender, smoking, parental psychiatric disorders, and obstetric and pregnancy problems.

Sleep problems at ages 8–9 and ADHD symptoms at ages 10–11: evidence in three cohorts from INMA study

Sleep problems and attention deficit hyperactivity disorder (ADHD) are interrelated during childhood and preadolescence. The objective of this work is assessing if sleep problems at ages 8–9 represent an alarm sign for presenting ADHD problems at ages 10–11 in three cohorts from INMA Study. Participants were 1244 children from Gipuzkoa, Sabadell, and Valencia cohorts. Sleep problems were assessed (ages 8–9) with the sleep items of the Child’s Behaviour Checklist (CBCL), and ADHD problems were collected through the Conner’s Parent Rating Scales-Revised: Short Form (CPRS-R:S) (age 10–11). Minimally and fully adjusted negative binomial models were fitted for each CPRS-R:S scale. Linearity of the relationship was assessed with generalized additive models (cubic smoothing splines with 2, 3, and 4 knots). For sensitivity analyses, children with previous symptoms, those born preterm and small for gestational age, and cases with extreme values, were excluded. Sleep problems presented IRR (95% CI) of 1.14 (1.10–1.19), 1.20 (1.14–1.26), 1.18 (1.11–1.25), and 1.18 (1.13–1.23) for opposition, inattention, hyperactivity, and ADHD scales, respectively. Fully adjusted models slightly decreased the IRR, but the association remained similar and significant. Sensitivity analyses showed similar results to fully adjusted models with only hyperactivity shown a slight decrease on significance (p = 0.051) when ADHD cases at age 9 were excluded. Conclusion: Sleep problems are an alarm sign for later neurodevelopment problems such as ADHD. Healthcare systems could take advantage implementing policies to pay special attention on the sleep habits and sleep hygiene. This could contribute to add evidence to public health programmes such as the Healthy Child Programme.What is Known:• Sleep problems and Attention Deficit Hyperactivity Disorder (ADHD) are common problems during childhood and preadolescence, with prevalences of 20-40% and 3.0-7.5%, respectively.• Sleep problems are even more common in children with ADHD condition.What is New:• Sleep problems at ages 8-9 increased the risk of ADHD symptoms at ages 10-11.• This association remained strong even when considering child’s previous (5 years) and concurrent (8-9 years) ADHD symptoms, and other clinical conditions, such as being born preterm or small for gestational age.