Risk Of Attention Deficit Hyperactivity Disorder Research Articles

Two meta-analyses of the association between atopic diseases and core symptoms of attention deficit hyperactivity disorder

Studies in the field of neuroscience and psychology have hypothesized that a causal association exists between atopic diseases and attention-deficit/hyperactivity disorder (ADHD). Previous systematic reviews and meta-analyses have reported a higher risk of ADHD in children with atopic diseases; however, the relationship between ADHD symptoms and atopic diseases remains unclear. We systematically reviewed observational cross-sectional and longitudinal studies to investigate the relationship between atopic diseases and ADHD symptom severity (hyperactivity/impulsivity and inattention). The majority of studies showed a statistically significant association between atopic diseases and both ADHD symptoms, with substantial heterogeneity in the outcome of hyperactivity/impulsivity. Remarkably decreased heterogeneity and statistical significance were observed in the second meta-analysis of ADHD-related behavior symptoms in atopic patients without ADHD. Our study indicated that atopic diseases not only associated with ADHD but also ADHD symptoms severity. This association was even observed in children with subthreshold ADHD, indicating that atopic diseases may play a role in the spectrum of ADHD symptom severity. Trial registration: This study was registered on PROSPERO (registration ID: CRD42020213219).

Electroencephalogram aperiodic power spectral slope can be reliably measured and predicts ADHD risk in early development.

The aperiodic exponent of the electroencephalogram (EEG) power spectrum has received growing attention as a physiological marker of neurodevelopmental psychopathology, including attention-deficit/hyperactivity disorder (ADHD). However, its use as a marker of ADHD risk across development, and particularly in very young children, is limited by unknown reliability, difficulty in aligning canonical band-based measures across development periods, and unclear effects of treatment in later development. Here, we investigate the internal consistency of the aperiodic EEG power spectrum slope and its association with ADHD risk in both infants (n=69, 1-month-old) and adolescents (n=262, ages 11-17 years). Results confirm good to excellent internal consistency in infancy and adolescence. In infancy, a larger aperiodic exponent was associated with greater family history of ADHD. In contrast, in adolescence, ADHD diagnosis was associated with a smaller aperiodic exponent, but only in children with ADHD who had not received stimulant medication treatment. Results suggest that disruptions in cortical development associated with ADHD risk may be detectable shortly after birth via this approach. Together, findings imply a dynamic developmental shift in which the developmentally normative flattening of the EEG power spectrum is exaggerated in ADHD, potentially reflecting imbalances in cortical excitation and inhibition that could contribute to long-lasting differences in brain connectivity.

Polygenic risk for mental disorder reveals distinct association profiles across social behaviour in the general population

Many mental health conditions present a spectrum of social difficulties that overlaps with social behaviour in the general population including shared but little characterised genetic links. Here, we systematically investigate heterogeneity in shared genetic liabilities with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), bipolar disorder (BP), major depression (MD) and schizophrenia across a spectrum of different social symptoms. Longitudinally assessed low-prosociality and peer-problem scores in two UK population-based cohorts (4–17 years; parent- and teacher-reports; Avon Longitudinal Study of Parents and Children(ALSPAC): N ≤ 6,174; Twins Early Development Study(TEDS): N ≤ 7,112) were regressed on polygenic risk scores for disorder, as informed by genome-wide summary statistics from large consortia, using negative binomial regression models. Across ALSPAC and TEDS, we replicated univariate polygenic associations between social behaviour and risk for ADHD, MD and schizophrenia. Modelling variation in univariate genetic effects jointly using random-effect meta-regression revealed evidence for polygenic links between social behaviour and ADHD, ASD, MD, and schizophrenia risk, but not BP. Differences in age, reporter and social trait captured 45–88% in univariate effect variation. Cross-disorder adjusted analyses demonstrated that age-related heterogeneity in univariate effects is shared across mental health conditions, while reporter- and social trait-specific heterogeneity captures disorder-specific profiles. In particular, ADHD, MD, and ASD polygenic risk were more strongly linked to peer problems than low prosociality, while schizophrenia was associated with low prosociality only. The identified association profiles suggest differences in the social genetic architecture across mental disorders when investigating polygenic overlap with population-based social symptoms spanning 13 years of child and adolescent development.

Smoking During Pregnancy and Risk of Attention-deficit/Hyperactivity Disorder in the Third Generation.

Animal experiments indicate that environmental factors, such as cigarette smoke, can have multigenerational effects through the germline. However, there are little data on multigenerational effects of smoking in humans. We examined the associations between grandmothers' smoking while pregnant and risk of attention-deficit/hyperactivity disorder (ADHD) in her grandchildren. Our study population included 53,653 Nurses' Health Study II (NHS-II) participants (generation 1 [G1]), their mothers (generation 0 [G0]), and their 120,467 live-born children (generation 2 [G2]). In secondary analyses, we used data from 23,844 mothers of the nurses who were participants in the Nurses' Mothers' Cohort Study (NMCS), a substudy of NHS-II. The prevalence of G0 smoking during the pregnancy with the G1 nurse was 25%. ADHD was diagnosed in 9,049 (7.5%) of the grandchildren (G2). Grand-maternal smoking during pregnancy was associated with increased odds of ADHD among the grandchildren (adjusted odds ratio [aOR] = 1.2; 95% confidence interval [CI] = 1.1, 1.2), independent of G1 smoking during pregnancy. In the Nurses' Mothers' Cohort Study, odds of ADHD increased with increasing cigarettes smoked per day by the grandmother (1-14 cigarettes: aOR = 1.1; 95% CI = 1.0, 1.2; 15+: aOR = 1.2; 95% CI = 1.0, 1.3), compared with nonsmoking grandmothers. Grandmother smoking during pregnancy is associated with an increased risk of ADHD among the grandchildren.

Interrelationships among growth hormone, thyroid function, and endocrine-disrupting chemicals on the susceptibility to attention-deficit/hyperactivity disorder.

Abnormal growth hormones and thyroid function may be linked to pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Phthalates and bisphenol-A (BPA), two endocrine-disrupting chemicals (EDCs), may affect the human endocrine system. In this study, we aimed to perform a comprehensive investigation of whether growth hormone, thyroid function, and EDCs exhibited differential levels between ADHD patients and healthy controls. In total, 144 children with ADHD and 70 healthy control subjects were enrolled. Their endocrine systems were evaluated using the serum levels of insulin-like growth factor-1 (IGF-1), IGF-binding protein-3 (IGFBP-3), thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and Free T4. The urinary levels of EDCs, including monoethyl phthalate (MEP), mono-methyl phthalate (MMP), monoethylhexyl phthalate (MEHP), mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), and BPA, were also examined. Patients with ADHD had lower IGF-1 levels than healthy controls (p = 0.003), but we observed no significant difference in IGFBP-3, TSH, T3, T4, or Free T4. Compared to the control group, patients with ADHD demonstrated higher MEHP levels (p = 0.043), MnBP (p = 0.033), and MBzP (p = 0.040). Furthermore, MEHP levels (p < 0.001) and BPA levels (p = 0.041) were negatively correlated with IGF-1 levels, while IGF-1 levels were negatively correlated with principal components consisting of ADHD clinical symptoms and neuropsychological performance variables. We suggest that MEHP exposure may be associated with decreased serum levels of IGF-1 and increased risk of ADHD. The mechanism underlying this association may be important for protecting children from environmental chemicals that adversely affect neurodevelopment.

Maternal infection during pregnancy and the risk of attention-deficit/hyperactivity disorder in the offspring: A systematic review and meta-analysis.

The effects of maternal infection during pregnancy on the risk of attention-deficit/hyperactivity disorder (ADHD) in the offspring are unclear, and no overview is available. We searched the PubMed and EMBASE databases for relevant studies and performed a systematic review and meta-analysis of the literature. We found that that maternal infection during pregnancy was associated with a small increase in the risk of ADHD (OR 1.25, 95% CI 1.09, 1.44, P<0.0001; I2 = 92.9%, p<0.0001) in the offspring. In subgroup analyses, the association remained for maternal genitourinary (GU) infection (OR, 1.19, 1.12, 1.27, P<0.001; I2 = 0%; p=0.517). However, there was no significant association when we pooled data from siblings from other pregnancies (OR = 1.06, 95% CI, 0.99-1.13, P=0.084; I2 = 0%; p=0.859), implying that the association was due to confounding. The statistically significant association between maternal infection during pregnancy and ADHD in the offspring can be partially explained by unmeasured confounding.

ADHD and Neurodegenerative Disease Risk: A Critical Examination of the Evidence.

In this review, we undertake a critical appraisal of eight published studies providing first evidence that a history of attention-deficit/hyperactivity disorder (ADHD) may increase risk for the later-life development of a neurodegenerative disease, in particular Lewy body diseases (LBD), by up to five-fold. Most of these studies have used data linked to health records in large population registers and include impressive sample sizes and adequate follow-up periods. We identify a number of methodological limitations as well, including potential diagnostic inaccuracies arising from the use of electronic health records, biases in the measurement of ADHD status and symptoms, and concerns surrounding the representativeness of ADHD and LBD cohorts. Consequently, previously reported risk associations may have been underestimated due to the high likelihood of potentially missed ADHD cases in groups used as “controls”, or alternatively previous estimates may be inflated due to the inclusion of confounding comorbidities or non-ADHD cases within “exposed” groups that may have better accounted for dementia risk. Prospective longitudinal studies involving well-characterized cases and controls are recommended to provide some reassurance about the validity of neurodegenerative risk estimates in ADHD.

Analysis of Neurodevelopmental Disorders in Offspring of Mothers With Eating Disorders in Sweden

Despite indices of impaired neurodevelopment in children of mothers with eating disorders, it remains unclear whether these children are at increased risk of developing neuropsychiatric diseases. To evaluate the association between maternal eating disorders, whether preexisting or ongoing during pregnancy, and offspring neuropsychiatric disease risk. This population-based prospective cohort study used the Swedish Medical Birth Registry and identified singleton births registered between from January 1, 1990, and December 31, 2012. Children of exposed mothers with eating disorders were matched with comparator children of mothers without diagnoses of eating disorders. To adjust for unmeasured shared familial factors, a cluster of exposed children with full maternal cousin comparators was identified. Follow-up was completed on December 31, 2017. Data were analyzed from August 31, 2020, to April 30, 2021. Maternal eating disorder diagnosis. All children were followed up from 1 year of age for autism spectrum disorder (ASD) and from 3 years of age for attention-deficit/hyperactivity disorder (ADHD). The relative risk of ASD and ADHD was assessed among exposed children, stratified by eating disorder subtype and ongoing vs previous disease, adjusted for potential confounders, including parental socioeconomic status and comorbidities. Among the 52 878 children included in the analysis, maternal eating disorder exposure (n = 8813) was associated with an increased risk of ADHD (hazard ratio [HR] for anorexia nervosa, 1.42 [95% CI, 1.23-1.63]; HR for bulimia nervosa, 1.91 [95% CI, 1.43-2.54]; and HR for unspecified eating disorder, 2.00 [95% CI, 1.72-2.32]) and ASD (HR for anorexia nervosa, 2.04 [95% CI, 1.58-2.63]; HR for bulimia nervosa, 2.70 [95% CI, 1.68-4.32]; and HR for unspecified eating disorder, 1.95 [95% CI, 1.49-2.54]). After adjustment for parental confounders, the risk of ADHD remained significantly increased, whereas the risk of ASD in children to mothers with bulimia nervosa was no longer significant. Ongoing anorexia nervosa was associated with a significantly higher risk of ADHD (HR, 2.52 [95% CI, 1.86-3.42]) and ASD (HR, 3.98 [95% CI, 2.49-6.27]) compared with previous disease (HRs, 1.26 [95% CI, 1.06-1.48] and 1.81 [95% CI, 1.38-2.38], respectively). Results based on the family cluster were similar to those of the main analysis for maternal exposure to anorexia nervosa and bulimia nervosa. These findings suggest that children born to mothers with eating disorders, in particular disorders that were active during pregnancy, were at increased risk of developing ADHD and ASD. The association could not be fully explained by parental psychiatric comorbidities, and among children of mothers with anorexia nervosa and bulimia nervosa, it could not be explained by unmeasured familial confounding.

A novel genetic variant potentially altering the expression of MANBA in the cerebellum associated with attention deficit hyperactivity disorder in Han Chinese children

Objectives To obtain additional insight into the genetic factors of attention deficit hyperactivity disorder (ADHD). Methods First, we performed a transcriptome-wide association study (TWAS) integrating human cerebellum-specific variant-expression/splicing correlations to identify ADHD susceptibility genes. Then, the associations between expression/splicing quantitative trait loci (eQTLs/sQTLs) of the transcriptome-wide significant genes and ADHD were observed in a case-control study of Han Chinese children. Furthermore, dual luciferase reporter gene assays were performed to validate the regulatory function of ADHD risk variants. Additionally, the transcription level of target genes in blood was detected by real-time quantitative polymerase chain reaction (RT-qPCR) assay. Results TWAS identified that the genetically regulated expression of MANBA in the cerebellum was significantly associated with ADHD risk. Furthermore, we observed a higher risk of ADHD and more severe clinical symptoms in subjects harbouring heterozygous (TC) or mutant homozygous (TT) genotypes of MANBA rs1054037 than CC carriers. The dual luciferase reporter gene assay revealed that the mutation of rs1054037(C > T) potentially upregulated MANBA expression by eliminating the binding site for hsa-miR-5591-3P. Finally, RT-qPCR showed that MANBA expression in blood samples of patients was significantly higher than that of controls. Conclusions Taken together, these results suggest a role of MANBA in the development of ADHD.

Comorbidity of ADHD and allergic diseases in early adolescence: The role of parental smoking at home.

A growing body of research suggests an association between attention deficit hyperactivity disorder (ADHD) and allergic disorders, but little work has been done to explore the role of external factors such as parental smoking at home in the development of comorbid ADHD and allergic disorders. This study aimed to examine the association between allergic diseases and ADHD adjusted for exposure to parental smoking at home in early adolescents. We recruited 250 male (41.7%) and 350 female (58.3%) adolescents (mean [SD] age, 13.29 [0.52] years) via chain-referral sampling. Their ADHD symptoms were assessed by the parent proxy-report version of the Chinese Strengths and Weaknesses of Attention-Deficit/Hyperactivity-symptoms and Normal-behaviours (SWAN) rating scale. Data on the participants’ history of clinician-diagnosed allergic diseases, family socio-demographics, and parental smoking habit were collected using a parent-completed questionnaire. Regression analyses were performed to examine the associations of interest. The levels of ADHD symptoms were comparable between allergic and non-allergic participants after controlling for child and family demographics and parental smoking at home. Notably, the risk of probable ADHD was particularly high in participants with food allergies (odd ratio = 4.51, p = 0.011) but not in those with allergic rhinitis after adjusting for parental smoking at home. Our findings suggest that second-hand smoke exposure at home is a potential risk factor underlying the link between ADHD and allergic diseases. Current management guidelines should emphasize the importance of early identification and cessation of tobacco smoke exposure for prevention of comorbidity of ADHD and allergic disorders.Clinical Trial Registration (if any): NA.

Early-Life Injuries and the Development of Attention-Deficit/Hyperactivity Disorder.

ObjectivesTo estimate phenotypic and familial association between early-life injuries and attention deficit/hyperactivity disorder (ADHD) and the genetic contribution to the association using polygenic risk score for ADHD (PRS-ADHD) and genetic correlation analyses.MethodsChildren born in Denmark 1995-2010 (n=786,543) were followed from age five until a median age of 14 (IQR: 10–18 years). Using ICD-10 diagnoses, we estimated hazard ratios (HRs) and absolute risks of ADHD by number of hospital/emergency ward treated injuries by age five. In a subsample born 1995 to 2005 with genetic data available (n=16,580), we estimated incidence rate ratios (IRR) for the association between PRS-ADHD and number of injuries before age five and the genetic correlation between ADHD and any injury before age five.ResultsInjuries were associated with ADHD (HR=1.61; 95% CI 1.55-1.66), in males (HR=1.59; 1.53-1.65) and females (HR=1.65; 1.54-1.77), with a dose-response relationship with number of injuries. The absolute ADHD risk by age 15 was 8.4% (3+ injuries) vs. 3.1% (no injuries).ADHD was also associated with injuries in relatives, stronger in 1st- than 2nd-degree relatives. PRS-ADHD was marginally associated with the number of injuries in the general population (IRR=1.06; 1.00-1.14), with a genetic correlation of 0.53 (0.21-0.85).ConclusionsEarly-life injuries in individuals and their relatives were associated with a diagnosis of ADHD. However, even in children with the most injuries, more than 90% were not diagnosed with ADHD by age 15. Despite a low positive predictive value and that the impact of unmeasured factors such as parental behaviour remains unclear, results indicate that the association is partly explained by genetics, suggesting that early-life injuries may represent or herald early behavioral manifestations of ADHD.

Comorbidity of Attention-Deficit Hyperactivity Disorder and Autism Spectrum Disorders: Current Status and Promising Directions.

High rates of co-occurring Attention-Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD) suggest common causal pathways, which await elucidation. What is well-established, however, is the negative impact of comorbid ADHD and ASD on outcomes for everyday living, particularly in social interaction and communication and on broader psychopathology. Neurocognitive approaches suggest correlates of comorbidity are rooted in functional connectivity networks associated with executive control. There is support for familial origins, with molecular-genetic studies suggesting a causal role of pleiotropic genes. Further investigation is needed to elucidate fully how genetic risk for ADHD and ASD affects neurodevelopment and to identify structural and functional neural correlates and their behavioral sequelae. Identification of intermediate phenotypes is necessary to advance understanding, which requires studies that include the full spectrum of ASD and ADHD symptom severity, use longitudinal designs and multivariate methods to probe broad constructs, such as executive and social function, and consider other sources of heterogeneity, such as age, sex, and other psychopathology. Randomized efficacy trials targeting comorbid symptomatology are needed to mitigate negative developmental outcomes.

A novel cis-regulatory variant modulating TIE1 expression associated with attention deficit hyperactivity disorder in Han Chinese children

BackgroundThe genetic factors of attention deficit hyperactivity disorder (ADHD) are far from fully elucidated. This study aims to get additional insight into the genetic structure of ADHD. MethodsFirst, a transcriptome-wide association study and summary data-based Mendelian randomization analysis were performed to identify ADHD susceptibility genes. Then, genetic variants influencing the expression of the identified susceptibility genes were tested for association with ADHD risk in a sample of Han Chinese children (543 cases and 560 controls). Dual-luciferase reporter gene assays and electrophoretic mobility shift assays were performed to verify the transcriptional regulatory functions of the identified ADHD-associated variants. Additionally, real-time quantitative polymerase chain reaction was applied to quantify the expression levels of target genes in blood samples. ResultsBoth TIE1 and MED8 were identified as ADHD susceptibility genes. Furthermore, we first found the G allele of rs3768046 was significantly associated with an increased risk of ADHD (recessive model: GG vs AA+AG, OR= 1.659, 95% CI= (1.262, 2.181); additive model: GG vs GA vs AA, OR= 1.493, 95% CI= (1.179, 1.890)). Additionally, in vitro functional experiments revealed that rs3768046 might alter TIE1 expression by affecting the binding sites of transcription factors. Moreover, the expression level of TIE1 in the blood samples of patients was significantly higher than that of controls. LimitationsGiven the moderate statistical power of this study, it is necessary to verify our findings in other larger samples. ConclusionsTogether, this study presents the first systematic evidence of TIE1 with potential implications for the genetic basis of ADHD.

Dental Caries in Children with Attention Deficit/Hyperactivity Disorder: A Meta-Analysis

Objectives: The aim of the study was to evaluate whether children with attention deficit/hyperactivity disorder (ADHD) are more affected by dental caries than children without ADHD by means of a systematic review and meta-analysis. Design: Electronic searches were performed in 4 databases (PubMed, Embase, Scopus, and Web of Science) in July 2021. Grey literature search in OpenGrey, a search in Google Scholar, and searches in the reference list of included articles were also conducted. The eligibility criteria were observational studies in which children with ADHD were compared with children without ADHD with respect to the dental caries. Study selection, data extraction, and risk of bias assessment, applying the Joanna Briggs tool were performed by 2 reviewers independently. Meta-analysis and assessment of heterogeneity among studies were conducted with the meta-package of RStudio using the R programming language (R Core Team, Vienna, Austria). Results of meta-analysis were provided in mean difference (MD), odds ratio (OR), and confidence intervals (CIs). For assessment of heterogeneity, Baujat plot and influence analysis plot were obtained. Results: Thirteen studies were included and 10 were incorporated into meta-analyses. The meta-analysis showed that children with ADHD had a higher decayed, missing, and filled teeth (DMFT) index than their peers without ADHD (I² = 42%; MD = 0.75 [0.38–1.13]). For decayed, missing, and filled surfaces (I² = 0; MD = 0.39 [−0.02 to 0.80]) and decayed surfaces (ds) (I² = 0%; MD = 0.35 [−0.63 to 1.33]), no difference between groups was observed. In addition, children with ADHD had higher odds of having dental caries than their healthy peers (OR = 3.31 [1.25, 8.73]; I² = 0%). After assessment of heterogeneity among studies, sensitivity analysis was conducted for DMFT. One study was removed and the significant difference between groups remained. Children with ADHD had a significantly higher DMFT index than their peers without ADHD (MD = 0.98 [CI = 0.75, 1.20]; I² = 0%) Risk of bias ranged from low to high. Conclusion: The main shortcoming of the included studies is the high risk of bias regarding the strategies to deal with confounding factors. Within its limitations, this systematic review and meta-analysis demonstrated that children with ADHD were more likely to develop dental caries than their healthy counterparts. Funding: No funding. Registration: CRD42021238923.

Association between Marginally Low Birth Weight and Obesity-Related Outcomes and Indirect Effects via Attention-Deficit Hyperactivity Disorder and Abnormal Eating

Introduction: Evidence of the association between children born with marginally low birth weight (MLBW) and obesity-related outcomes was controversial, and our study aimed to examine the role of attention-deficit hyperactivity disorder (ADHD) and/or abnormal eating in these associations. Methods: A retrospective cohort study consisting of 677 Chinese children was conducted. Obesity-related outcomes (body mass index [BMI], waist circumference [WC], skinfold thickness [SF], body fat, blood pressure, lipids, and blood glucose), behaviour problems (ADHD and eating behaviour) and birth weight were collected. Mediation analyses were used to explore whether ADHD and/or abnormal eating was an intermediary factor in the MLBW-OB relationship. Results: Children with MLBW tended to have higher SF, triglycerides, fasting blood glucose, waistline, body fat, and abdominal obesity risks. Birth weight was negatively related to obesity-related outcomes, and the associations were mediated, partially, by the increased risk of ADHD or abnormal eating behaviour after adjustment for the BMI Z score. Furthermore, lower birth weight predicted higher WC indirectly through emotional overeating caused by ADHD (β: −0.10; 95% confidence interval: −0.19, −0.01). Conclusion: Our study suggests the hypothetical role of ADHD and abnormal eating as underlying mechanisms in the association between MLBW and obesity-related outcomes, providing novel scientific evidence for childhood development interventions.

Associated Factors of Attention-Deficit/Hyperactivity Disorder Diagnosis and Psychostimulant Use: A Nationwide Representative Study

BackgroundConnections between epidemiological findings and children's and adolescents' mental health policies have not been properly made in Brazil, and such nationwide studies are scarce. This epidemiological study (1) estimated the prevalence and predictors of parent-reported attention-deficit/hyperactivity disorder (ADHD) (ADHD-report), (2) estimated the probable diagnosis and risk of ADHD based on Diagnostic and Statistical Manual of Mental Disorders, 5th edition, criteria (ADHD-probable), and (3) estimated current psychostimulant use (ADHD-pst) in a representative nationwide sample of Brazilian school-aged children and adolescents. MethodsData were obtained from 7114 school-aged children (49.9% boys) from 87 cities in 18 Brazilian states. Parents and teachers were interviewed using psychometrically sound questionnaires. Data and codes are available. ResultsThe prevalence of ADHD-report, ADHD-probable, and ADHD-pst were 7.1%, 3.9%, and 1.9%, respectively. The agreement was low between ADHD-probable and ADHD-report (22.6%) and between ADHD-report and ADHD-pst (15.6%). Logistic regression revealed that predictors of all three categories were male gender (odds ratio [OR] = 1.71, 2.32, and 1.96, respectively), divorced parents (OR = 1.47, 1.65, and 1.68, respectively), and below-expectation school performance (OR = 3.1, 13.74, and 3.95, respectively). Socioeconomic status was a significant predictor of ADHD-report, and participants from lower classes were less frequently diagnosed with ADHD than their peers from upper classes (OR = 0.57, 95% confidence interval = 0.37-0.88, P = 0.012). ConclusionsThe present findings provide an accurate description of ADHD in Brazil. We suggest disparities in agreement between report, risk, and psychostimulant use among children and adolescents and discrepancies between socioeconomic classes concerning the prevalence of an ADHD diagnosis.

The Relationship Between Blood Lipid and Attention-Deficit/Hyperactivity Disorder (ADHD) in an Obese Population of Chinese Children: An Obesity-Stratified Cross-Sectional Study.

BackgroundAlthough obesity has been related to attention-deficit/hyperactivity disorder (ADHD), few studies have examined the relationship between blood lipid levels and ADHD in children. We aimed to evaluate whether increased blood lipid levels are associated with the prevalence of ADHD in children.MethodsA total of 1179 children were studied in the cross-sectional analysis. Multivariate logistic regression and linear regression analyses were performed to evaluate the association of blood lipid levels with the prevalence of ADHD in children.ResultsIn 1179 children, the average age was 10.4 years, and the percentage of boys was 50.3%. 97 (8.2%) of the children were diagnosed with ADHD. The logistic regression analysis demonstrated that elevated levels of total cholesterol (OR=2.001, 95% CI 1.247–3.541, P-trend=0.024), triglycerides (OR=1.776, 95% CI 1.448–2.187, P-trend=0.003) and LDL (low density lipoprotein; OR=2.016, 95% CI 1.335–3.966, P-trend<0.001) and reduced levels of HDL (high density lipoprotein; OR=0.577, 95% CI 0.298–0.948, P-trend=0.023) were associated with the prevalence of ADHD after adjustments were made for age, sex, body mass index (BMI), residence type, maternal smoking during pregnancy, breastfeeding and breastfeeding length, maternal and paternal educational levels, and marital status of parents in Model 3. The stratified analysis using “obese” as a covariate showed that elevated levels of total cholesterol, triglycerides and LDL and reduced levels of HDL were independently associated with an increased risk of ADHD in obese children.ConclusionIncreased blood lipid levels were associated with ADHD in obese children.

Comparing Copy Number Variations in a Danish Case Cohort of Individuals With Psychiatric Disorders

Although the association between several recurrent genomic copy number variants (CNVs) and mental disorders has been studied for more than a decade, unbiased, population-based estimates of the prevalence, disease risks and trajectories, fertility, and mortality to contrast chromosomal abnormalities and advance precision health care are lacking. To generate unbiased, population-based estimates of prevalence, disease risks and trajectories, fertility, and mortality of CNVs implicated in neuropsychiatric disorders. In a population-based case-cohort study, using the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) 2012 database, individuals born between May 1, 1981, and December 31, 2005, and followed up until December 31, 2012, were analyzed. All individuals (n = 57 377) with attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), schizophrenia (SCZ), autism spectrum disorder (ASD), or bipolar disorder (BPD) were included, as well as 30 000 individuals randomly drawn from the database. Data analysis was conducted from July 1, 2017, to September 7, 2021. Copy number variants at 6 genomic loci (1q21.1, 15q11.2, 15q13.3, 16p11.2, 17p12, and 17q12). Population-unbiased hazard ratio (HR) and survival estimates of CNV associations with the 5 ascertained psychiatric disorders, epilepsy, intellectual disability, selected somatic disorders, fertility, and mortality. Participants' age ranged from 1 to 32 years (mean, 12.0 [IQR, 6.9] years) during follow-up, and 38 662 were male (52.3%). Copy number variants broadly associated with an increased risk of autism spectrum disorder and ADHD, whereas risk estimates of SCZ for most CNVs were lower than previously reported. Comparison with previous studies suggests that the lower risk estimates are associated with a higher CNV prevalence in the general population than in control samples of most case-control studies. Significant risk of major depressive disorder (HR, 5.8; 95% CI, 1.5-22.2) and sex-specific risk of bipolar disorder (HR, 17; 95% CI, 1.5-189.3, in men only) were noted for the 1q21.1 deletion. Although CNVs at 1q21.1 and 15q13.3 were associated with increased risk across most diagnoses, the 17p12 deletion consistently conferred less risk of psychiatric disorders (HR 0.4-0.8), although none of the estimates differed significantly from the general population. Trajectory analyses noted that, although diagnostic risk profiles differed across loci, they were similar for deletions and duplications within each locus. Sex-stratified analyses suggest that pathogenicity of many CNVs may be modulated by sex. The findings of this study suggest that the iPSYCH population case cohort reveals broad disease risk for some of the studied CNVs and narrower risk for others, in addition to sex differential liability. This finding on genomic risk variants at the level of a population may be important for health care planning and clinical decision making, and thus the advancement of precision health care.

Antipsychotic use in pregnancy and risk of attention/deficit-hyperactivity disorder and autism spectrum disorder: a Nordic cohort study

BackgroundAntipsychotics are increasingly used among women of childbearing age and during pregnancy.ObjectiveTo determine whether children exposed to antipsychotics in utero are at increased risk of attention-deficit/hyperactivity disorder (ADHD) or autism...

Development of a risk calculator to predict attention-deficit/hyperactivity disorder in very preterm/very low birth weight newborns.

Very preterm/very low birth weight (VP/VLBW) newborns can have lifelong morbidities, as attention-deficit/hyperactivity disorder (ADHD). Clinicians have no markers to discriminate which among those individuals will develop later ADHD, based only on the clinical presentation at birth. Our aim was to develop an individualized risk calculator for ADHD in VP/VLBW newborns. This retrospective prognostic study included a consecutive sample of all VP/VLBW children (gestational age <32 weeks and/or birth weight <1.5 kg) born between 2010 and 2012 from a clinical cohort in a Brazilian tertiary care hospital. Children were clinically assessed at 6 years of age for ADHD using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). The least absolute shrinkage and selection operator (LASSO) method was used for model-building. Ninety-six VP/VLBW children were assessed at 6 years of age (92% follow-up), of whom 32 (33%) were diagnosed with ADHD. The area under the ROC curve (AUC) for ADHD prediction based on seven parameters (late-onset sepsis confirmed by blood culture, necrotizing enterocolitis, neonatal seizures, periventricular leukomalacia, respiratory distress syndrome, length of hospital stay, and number of maternal ADHD symptoms) was .875 (CI, 0.800-0.942, p < .001; AUC corrected for optimism with bootstrapping: .806), a performance that is comparable to other medical risk calculators. Compared to approaches that would offer early intervention to all, or intervention to none, the risk calculator will be more useful in selecting VP/VLBW newborns, with statistically significant net benefits at cost:benefits of around 1:2 to around 10:6 (range of ADHD risk thresholds of 32%-62%, respectively). It also showed specificity for ADHD compared to other prevalent child psychopathologies. The risk calculator showed good performance for early identification of VP/VLBW newborns at high risk of future ADHD diagnosis. External validity in population-based samples is needed to extend clinical usefulness.