Attention-deficit/hyperactivity Disorder Cohort Research Articles

Risk factors associated with newly diagnosed attention-deficit/hyperactivity disorder in adults: a retrospective case-control study

BackgroundKnowledge of risk factors for attention-deficit/hyperactivity disorder (ADHD) may facilitate early diagnosis; however, studies examining a broad range of potential risk factors for ADHD in adults are limited. This study aimed to identify risk factors associated with newly diagnosed ADHD among adults in the United States (US).MethodsEligible adults from the IQVIA PharMetrics® Plus database (10/01/2015-09/30/2021) were classified into the ADHD cohort if they had ≥ 2 ADHD diagnoses (index date: first ADHD diagnosis) and into the non-ADHD cohort if they had no observed ADHD diagnosis (index date: random date) with a 1:3 case-to-control ratio. Risk factors for newly diagnosed ADHD were assessed during the 12-month baseline period; logistic regression with stepwise variable selection was used to assess statistically significant association. The combined impact of selected risk factors was explored using common patient profiles.ResultsA total of 337,034 patients were included in the ADHD cohort (mean age 35.2 years; 54.5% female) and 1,011,102 in the non-ADHD cohort (mean age 44.0 years; 52.4% female). During the baseline period, the most frequent mental health comorbidities in the ADHD and non-ADHD cohorts were anxiety disorders (34.4% and 11.1%) and depressive disorders (27.9% and 7.8%). Accordingly, a higher proportion of patients in the ADHD cohort received antianxiety agents (20.6% and 8.3%) and antidepressants (40.9% and 15.8%). Key risk factors associated with a significantly increased probability of ADHD included the number of mental health comorbidities (odds ratio [OR] for 1 comorbidity: 1.41; ≥2 comorbidities: 1.45), along with certain mental health comorbidities (e.g., feeding and eating disorders [OR: 1.88], bipolar disorders [OR: 1.50], depressive disorders [OR: 1.37], trauma- and stressor-related disorders [OR: 1.27], anxiety disorders [OR: 1.24]), use of antidepressants (OR: 1.87) and antianxiety agents (OR: 1.40), and having ≥ 1 psychotherapy visit (OR: 1.70), ≥ 1 specialist visit (OR: 1.30), and ≥ 10 outpatient visits (OR: 1.51) (all p < 0.05). The predicted risk of ADHD for patients with treated anxiety and depressive disorders was 81.9%.ConclusionsMental health comorbidities and related treatments are significantly associated with newly diagnosed ADHD in US adults. Screening for patients with risk factors for ADHD may allow early diagnosis and appropriate management.

Patient Outcomes following Septoplasty in Patients with Attention-deficit/Hyperactivity Disorder

Summary: Recent research has indicated that daytime manifestations of sleep-disordered breathing, frequently caused by deviated septum, can mimic many characteristic symptoms of attention-deficit/hyperactivity disorder (ADHD) and could indicate intermittent hypoxia or hypercarbia as factors in the development of ADHD. To investigate the differences in outcomes following septoplasty between patients with ADHD and deviated septum, we used a retrospective cohort design to compare outcomes in patients diagnosed with deviated septa between June 1, 2002 and June 1, 2022. We then separated these patients into four total groups based on the presence or absence of ADHD diagnosis and the presence or absence of septoplasty. After matching cohorts to create insignificant differences in age, sex, and race, we analyzed various outcomes associated with ADHD, such as conduct disorders, anxiety disorders, fractures, and substance abuse disorders. Septoplasty reduces the risk for nearly all outcomes in patients with deviated septum, with statistically significant results present in 11 of 15 outcomes in both ADHD and non-ADHD groups. The effect of septoplasty was up to 10 times greater for the ADHD cohort. Patients with ADHD who receive septoplasty display a plethora of beneficial effects, with significantly reduced risk of common sequelae such as depression, obsessive-compulsive disorder, anxiety, and addictive disorders. The difference in outcomes indicates future prospective studies into outcomes of septoplasty in patients with ADHD.

Motor Function and Physiology in Youth With Neurofibromatosis Type 1

BackgroundNeurofibromatosis type 1 (NF1) is a genetic neurocutaneous disorder commonly associated with motor and cognitive symptoms that greatly impact quality of life. Transcranial magnetic stimulation (TMS) can quantify motor cortex physiology, reflecting the basis for impaired motor function as well as, possibly, clues for mechanisms of effective treatment. We hypothesized that children with NF1 have impaired motor function and altered motor cortex physiology compared to typically developing (TD) control children and children with attention-deficit/hyperactivity disorder (ADHD). MethodsChildren aged 8-17 years with NF1 (n = 21) were compared to children aged 8-12 years with ADHD (n = 59) and TD controls (n = 88). Motor development was assessed using the Physical and Neurological Examination for Subtle Signs (PANESS) scale. The balance of inhibition and excitation in motor cortex was assessed using the TMS measures short-interval cortical inhibition (SICI) and intracortical facilitation (ICF). Measures were compared by diagnosis and tested using bivariate correlations and regression for association with clinical characteristics. ResultsIn NF1, ADHD severity scores were intermediate between the ADHD and TD cohorts, but total PANESS scores were markedly elevated (worse) compared to both (P < 0.001). Motor cortex ICF (excitatory) was significantly lower in NF1 than in TD and ADHD (P < 0.001), but SICI (inhibitory) did not differ. However, in NF1, better PANESS scores correlated with lower SICI ratios (more inhibition; ρ = 0.62, P = 0.003) and lower ICF ratios (less excitation; ρ = 0.38, P = 0.06). ConclusionsTMS-evoked SICI and ICF may reflect processes underlying abnormal motor function in children with NF1.

The Oregon ADHD-1000: A new longitudinal data resource enriched for clinical cases and multiple levels of analysis

The fields of developmental psychopathology, developmental neuroscience, and behavioral genetics are increasingly moving toward a data sharing model to improve reproducibility, robustness, and generalizability of findings. This approach is particularly critical for understanding attention-deficit/hyperactivity disorder (ADHD), which has unique public health importance given its early onset, high prevalence, individual variability, and causal association with co-occurring and later developing problems. A further priority concerns multi-disciplinary/multi-method datasets that can span different units of analysis. Here, we describe a public dataset using a case-control design for ADHD that includes: multi-method, multi-measure, multi-informant, multi-trait data, and multi-clinician evaluation and phenotyping. It spans > 12 years of annual follow-up with a lag longitudinal design allowing age-based analyses spanning age 7–19 + years with a full age range from 7 to 21. Measures span genetic and epigenetic (DNA methylation) array data; EEG, functional and structural MRI neuroimaging; and psychophysiological, psychosocial, clinical and functional outcomes data. The resource also benefits from an autism spectrum disorder add-on cohort and a cross sectional case-control ADHD cohort from a different geographical region for replication and generalizability. Datasets allowing for integration from genes to nervous system to behavior represent the “next generation” of researchable cohorts for ADHD and developmental psychopathology.

Altered cortical gyrification, sulcal depth, and fractal dimension in the autism spectrum disorder comorbid attention-deficit/hyperactivity disorder than the autism spectrum disorder.

Autism spectrum disorder (ASD) frequently occurs accompanied by attention-deficit/hyperactivity disorder (ADHD), which catches increasing attention. The comorbid diagnosis of ASD with ADHD (ASD + ADHD) is permitted in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). However, compared to autism spectrum disorder without other symptoms (ASD-only), the special neural underpinnings in ASD+ADHD remain unclear. Therefore, this study aimed to uncover the differences in cortical complexity between ASD + ADHD and ASD-only patients. A total of 114 ASD participants (i.e. containing 40 ASD + ADHD and 74 ASD-only participants) with T1-weighted magnetic resonance images were collected from the Autism Brain Imaging Data Exchange II. Afterward, a surface-based morphometry method was carried out to compare the cortical complexity (i.e. gyrification index, fractal dimension, and sulcal depth) between the ASD + ADHD and ASD-only cohorts. Results showed the increased fractal dimension in the right fusiform gyrus of the ASD + ADHD cohort in comparison to the ASD-only cohort. Moreover, the ASD + ADHD cohort exhibited increased sulcal depth in the left middle temporal gyrus/inferior temporal gyrus and right middle temporal gyrus compared to the ASD-only cohort. Last but not least, the increased gyrification index in the insula/postcentral gyrus was observed in the ASD + ADHD cohort in comparison to the ASD-only cohort. Overall, the present study contributes to the delineation of particular structural abnormalities in ASD + ADHD than ASD-only, enriching the evidence of the combined phenotype of ASD + ADHD.

Healthcare utilization and comorbidity shortly before suicide mortality in patients with attention-deficit/hyperactivity disorder: a nested case-control study.

Few studies have analyzed healthcare utilization before suicide among individuals with attention-deficit/hyperactivity disorder (ADHD). This study examined the pattern of healthcare utilization and comorbidities shortly before death among patients with ADHD who died by suicide and compared these data with those of living controls. This study used Taiwan's National Health Insurance Research Database to identify patients with ADHD (N = 379,440) between January 1, 2001, and December 31, 2016. Subsequently, the researchers identified 159 suicide decedents by linking each patient with the National Mortality Database. By conducting a nested case-control study with risk-set sampling from the ADHD cohort, the researchers selected 20 age- and sex-matched controls (n = 3180) for each patient who died by suicide (cases). The researchers then applied conditional logistic regression to investigate differences in healthcare utilization as well as psychiatric and physical comorbidities between case patients and controls. Case patients had higher healthcare utilization within 3months before suicide, particularly in the psychiatry, emergency, internal medicine, neurosurgery, and plastic surgery departments. These patients also had higher risks of psychiatric comorbidities, including schizophrenia, bipolar disorder, depressive disorder, and sleep disorder, as well as physical comorbidities such as hypertension and other forms of heart disease. Among patients with ADHD, suicide decedents had increased healthcare utilization and higher risks of specific psychiatric and physical comorbidities than living controls. Thus, for suicide prevention among individuals with ADHD, suicide risk must be detected early and comorbidities should be adequately managed.

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.

Predicting the Adult Clinical and Academic Outcomes in Boys With ADHD: A 7- to 10-Year Follow-Up Study in China.

Background: Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood and causes adverse effects on social functioning. The present study aimed to widely investigate the predictors, particularly childhood intelligence quotient (IQ) and family environment factors, on adult clinical and academic outcomes in boys with ADHD.Methods: A total of 101 boys with ADHD in a Chinese Han ADHD cohort were followed up 7–10 years later. Baseline ADHD symptoms were evaluated using the parent version of the ADHD Rating Scale-IV (ADHD-RS-IV) and the Chinese version of the Conners' Parent Rating Scale-Revised (CPRS-48). The intelligence of the child was tested by the China-Wechsler Intelligence Scale for Children (C-WISC), and family function was assessed by the Family Environment Scale-Chinese Edition (FES-CV). Adult ADHD persistence was defined using DSM-IV criteria for ADHD, and academic outcome fell into two categories: higher academic level group (studying in senior middle school or above) and lower academic level group (studying in vocational secondary schools or below).Results: Stepwise multiple logistic regression analysis revealed that the father's character, impulsive–hyperactive index as measured by the CPRS-48, and intellectual–cultural index as measured by the FES-CV independently predicted clinical outcomes in adults, with an AUC of 0.770 (p < 0.001, 95% CI = 0.678–0.863). The corresponding sensitivity and specificity were 0.743 and 0.727, respectively. The father's education level, family economic level, and verbal IQ (VIQ) on the C-WISC independently predicted adult academic outcomes, with an AUC of 0.870 (p < 0.001, 95% CI = 0.796–0.944). The corresponding sensitivity and specificity were 0.813 and 0.783, respectively.Conclusion: Initial ADHD symptom severity and IQ, father's character and education level, and family atmosphere and function affect adult clinical and academic outcomes. Addressing these areas early may help to improve the prognosis of ADHD into adulthood.

Whole-brain modelling of resting state fMRI differentiates ADHD subtypes and facilitates stratified neuro-stimulation therapy

Recent advances in non-linear computational and dynamical modelling have opened up the possibility to parametrize dynamic neural mechanisms that drive complex behavior. Importantly, building models of neuronal processes is of key importance to fully understand disorders of the brain as it may provide a quantitative platform that is capable of binding multiple neurophysiological processes to phenotype profiles. In this study, we apply a newly developed adaptive frequency-based model of whole-brain oscillations to resting-state fMRI data acquired from healthy controls and a cohort of attention deficit hyperactivity disorder (ADHD) subjects. As expected, we found that healthy control subjects differed from ADHD in terms of attractor dynamics. However, we also found a marked dichotomy in neural dynamics within the ADHD cohort. Next, we classified the ADHD group according to the level of distance of each individual's empirical network from the two model-based simulated networks. Critically, the model was mirrored in the empirical behavior data with the two ADHD subgroups displaying distinct behavioral phenotypes related to emotional instability (i.e., depression and hypomanic personality traits). Finally, we investigated the applicability and feasibility of our whole-brain model in a therapeutic setting by conducting in silico excitatory stimulations to parsimoniously mimic clinical neuro-stimulation paradigms in ADHD. We tested the effect of stimulating any individual brain region on the key network measures derived from the simulated brain network and its contribution in rectifying the brain dynamics to that of the healthy brain, separately for each ADHD subgroup. This showed that this was indeed possible for both subgroups. However, the current effect sizes were small suggesting that the stimulation protocol needs to be tailored at the individual level. These findings demonstrate the potential of this new modelling framework to unveil hidden neurophysiological profiles and establish tailored clinical interventions.

Diagnostic Classification for Human Autism and Obsessive-Compulsive Disorder Based on Machine Learning From a Primate Genetic Model.

Psychiatric disorders commonly comprise comorbid symptoms, such as autism spectrum disorder (ASD), obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD), raising controversies over accurate diagnosis and overlap of their neural underpinnings. The authors used noninvasive neuroimaging in humans and nonhuman primates to identify neural markers associated with DSM-5 diagnoses and quantitative measures of symptom severity. Resting-state functional connectivity data obtained from both wild-type and methyl-CpG binding protein 2 (MECP2) transgenic monkeys were used to construct monkey-derived classifiers for diagnostic classification in four human data sets (ASD: Autism Brain Imaging Data Exchange [ABIDE-I], N=1,112; ABIDE-II, N=1,114; ADHD-200 sample: N=776; OCD local institutional database: N=186). Stepwise linear regression models were applied to examine associations between functional connections of monkey-derived classifiers and dimensional symptom severity of psychiatric disorders. Nine core regions prominently distributed in frontal and temporal cortices were identified in monkeys and used as seeds to construct the monkey-derived classifier that informed diagnostic classification in human autism. This same set of core regions was useful for diagnostic classification in the OCD cohort but not the ADHD cohort. Models based on functional connections of the right ventrolateral prefrontal cortex with the left thalamus and right prefrontal polar cortex predicted communication scores of ASD patients and compulsivity scores of OCD patients, respectively. The identified core regions may serve as a basis for building markers for ASD and OCD diagnoses, as well as measures of symptom severity. These findings may inform future development of machine-learning models for psychiatric disorders and may improve the accuracy and speed of clinical assessments.

Shared polygenic risk for ADHD, executive dysfunction and other psychiatric disorders

Many psychiatric disorders are associated with impaired executive functioning (EF). The associated EF component varies by psychiatric disorders, and this variation might be due to genetic liability. We explored the genetic association between five psychiatric disorders and EF in clinically-recruited attention deficit hyperactivity disorder (ADHD) children using polygenic risk score (PRS) methodology. Genome-wide association study (GWAS) summary data for ADHD, major depressive disorder (MDD), schizophrenia (SZ), bipolar disorder (BIP) and autism were used to calculate the PRSs. EF was evaluated by the Stroop test for inhibitory control, the trail-making test for cognitive flexibility, and the digital span test for working memory in a Chinese ADHD cohort (n = 1147). Exploratory factor analysis of the three measures identified one principal component for EF (EF-PC). Linear regression models were used to analyze the association between each PRS and the EF measures. The role of EF measures in mediating the effects of the PRSs on ADHD symptoms was also analyzed. The result showed the PRSs for MDD, ADHD and BIP were all significantly associated with the EF-PC. For each EF component, the association results were different for the PRSs of the five psychiatric disorders: the PRSs for ADHD and MDD were associated with inhibitory control (adjusted P = 0.0183 and 0.0313, respectively), the PRS for BIP was associated with working memory (adjusted P = 0.0416), and the PRS for SZ was associated with cognitive flexibility (adjusted P = 0.0335). All three EF measures were significantly correlated with ADHD symptoms. In mediation analyses, the ADHD and MDD PRSs, which were associated with inhibitory control, had significant indirect effects on ADHD symptoms through the mediation of inhibitory control. These findings indicate that the polygenic risks for several psychiatric disorders influence specific executive dysfunction in children with ADHD. The results helped to clarify the relationship between risk genes of each mental disorder and the intermediate cognitive domain, which may further help elucidate the risk genes and motivate efforts to develop EF measures as a diagnostic marker and future treatment target.

Attention-Deficit/Hyperactivity Disorder and Suicidal Risk in Major Depression: Analysis of 141,530 Adolescent Hospitalizations.

ObjectivesWe conducted a cross-sectional study to understand the differences in demographics and psychiatric comorbidities in adolescents with major depressive disorder (MDD) and assess the risk of suicidality due to comorbid attention-deficit/hyperactivity disorder (ADHD).MethodsWe included 141,530 adolescents (age, 12 to 18 years) with a primary diagnosis of MDD from the nationwide inpatient sample (NIS, 2012-2014), and grouped by a comorbid diagnosis of ADHD (N = 22,665, 16%). Logistic regression analysis was used to measure the demographic predictors for ADHD in adolescents with MDD, and to measure the suicidal risk in ADHD versus non-ADHD.ResultsComorbid ADHD was prevalent in whites (71.9%), and males had two times higher odds (95% CI 2.25-2.41) compared to females. The most prevalent comorbidities seen in ADHD-cohort were anxiety disorders (46.3%) and substance abuse (20.1%) with 1.3 times higher odds of substance abuse (95% CI 1.41-1.65) compared to non-ADHD. Suicidal behaviors were seen in a higher proportion of the ADHD cohort compared to the non-ADHD cohort (54.3% vs. 52.7%). ADHD and suicidal behaviors relationship was statistically significant but had a very small positive association (OR 1.04, 95% CI 1.01-1.08) after controlling for demographic confounders and comorbidities. There was a significant increase in the number of MDD hospitalization with ADHD for suicidal behaviors from 51.1% (N = 3,360) in 2012 to 58.2% (N = 5,115) in 2014.ConclusionThere exists a significant but small positive association between suicidal behaviors and comorbid ADHD in MDD adolescents. The suicide rate has increased by 52.2% during the study period in depressed adolescents with ADHD. This calls for early diagnosis and management of ADHD and early-onset depression in adolescents to prevent suicide risk.

Psychostimulants/Atomoxetine and Serious Cardiovascular Events in Children with ADHD or Autism Spectrum Disorder.

BackgroundPsychostimulants and atomoxetine have been shown to increase blood pressure, heart rate, and QT interval in children and adolescents; however, based on current literature, it is unclear if these “attention-deficit/hyperactivity disorder (ADHD) medications” are also associated with serious cardiovascular (SCV) events. We addressed this question in commonly exposed groups of children and adolescents with either ADHD or autism spectrum disorder (ASD).MethodsUsing commercial (years 2000–2016) and Medicaid (years 2012–2016) administrative claims data from the United States (US), we conducted two case–control studies, nested within respective cohorts of ADHD and ASD children aged 3–18 years. We defined cases by a composite outcome of stroke, myocardial infarction, or serious cardiac arrhythmia. For each case, we matched ten controls on age, sex, and insurance type. We conducted conditional logistic regression models to test associations between SCV outcomes and a primary exposure definition of current ADHD medication use. Additionally, we controlled for resource use, cardiovascular and psychiatric comorbidities, and use of medications in a variety of sensitivity analyses.ResultsWe identified 2,240,774 children for the ADHD cohort and 326,221 children for the ASD cohort. For ADHD, 33.9% of cases (63 of 186) versus 32.2% of controls (598 of 1860) were exposed, which yielded an odds ratio (OR) and 95% confidence interval (CI) of 1.08 (0.78–1.49). For ASD, 12.5% of cases (6 of 48) versus 22.1% of controls (106 of 480) were exposed [OR 0.49 (0.20–1.20)]. Covariate-adjusted results and results for individual outcomes and other exposure definitions were consistent with no increased risk of SCV events.ConclusionUsing large US claims data, we found no evidence of increased SCV risk in children and adolescents with ADHD or ASD exposed to ADHD medications.Electronic supplementary materialThe online version of this article (10.1007/s40263-019-00686-4) contains supplementary material, which is available to authorized users.

Inconsistency in Abnormal Functional Connectivity Across Datasets of ADHD-200 in Children With Attention Deficit Hyperactivity Disorder.

Many studies have shown abnormal functional connectivity in children with attention deficit hyperactivity disorder (ADHD) by using resting-state functional magnetic resonance imaging (rs-fMRI). However, few studies illustrated that to what extent these findings were consistent across different datasets. The present study aimed to assess the consistency of abnormal functional connectivity in children with ADHD across the four datasets from a public-assess rs-fMRI ADHD cohort, namely, ADHD-200. We employed the identical analysis process of previous studies and examined a few factors, including connectivity with the seed regions of the bilateral dorsal anterior cingulate cortex, bilateral inferior frontal gyrus, and bilateral middle frontal gyrus; connectivity between default mode network and executive control network; stringent and lenient statistical thresholds; and the ADHD subtypes. Our results revealed a high inconsistency of abnormal seed-based connectivity in children with ADHD across all datasets, even across three datasets from the same research site. This inconsistency could also be observed with a lenient statistical threshold. Besides, each dataset did not show abnormal connectivity between default mode network and executive control network for ADHD, albeit this abnormal connectivity between networks was intensively reported in previous studies. Importantly, the ADHD combined subtype showed greater consistency than did the inattention subtype. These findings provided methodological insights into the studies on spontaneous brain activity of ADHD, and the ADHD subtypes deserve more attention in future studies.

Attention-Deficit/Hyperactivity Disorder in Childhood and Adolescence and the Risk of Crime in Young Adulthood in a Danish Nationwide Study.

To determine the risk of long-term conviction and incarceration associated with childhood attention-deficit/hyperactivity disorder (ADHD), and to identify risk and protective factors including associations with active treatment with ADHD medication. All participants with ADHD who were 4 to 15 years of age during 1995 to 2005 were matched by year of birth and sex to a random sample of participants without ADHD from the Danish population using nationwide registers. Using Cox proportional hazard models, we estimated the risk of conviction and incarceration associated with ADHD in childhood and estimated associations with active treatment and outcome. The ADHD cohort were followed up at a mean of 22.0 (SD= 5.8) years. Of 4,231 individuals with ADHD, 1,355 (32.0%) had received at least one conviction, compared to 3,059 (15.6%) of the 19,595 participants without ADHD (p< 0.001). ADHD was significantly associated with conviction (hazard ratio [HR]= 2.4, 95% CI= 2.3-2.6) and incarceration (HR= 3.0, 95% CI= 2.8-3.3). Subsequent to adjustment for various risk factors, ADHD exposure was still significantly related to conviction (HR= 1.6, 95% CI= 1.5-1.8) and incarceration (HR= 1.7, 95% CI= 1.5-1.9). Comorbidity with substance use disorder, oppositional-defiant disorder/conduct disorder, low family socioeconomic status, parental incarceration, and parental relationship status all significantly increased the risk of conviction and incarceration. Crime rates increased with the number of associated risks but were reduced during periods of taking ADHD medication. In addition to ADHD, a broad range of individual, familial, and social factors increase the risk of antisocial development. The findings imply that ADHD medication may contribute to crime prevention.

The Association Between Attention-Deficit Hyperactivity Disorder, Injuries, and Methylphenidate.

Objective. To evaluate the relationship between attention-deficit hyperactivity disorder (ADHD) and injuries and to verify whether methylphenidate (MPH), is associated with decreasing the risk of injuries. Methods. A retrospective cohort study using the computerized database of Maccabi Healthcare Services. The ADHD cohort included all children between 12 and 20 years of age, newly diagnosed with ADHD between 2003 and 2013. The comparison cohort was composed of children who were not diagnosed with ADHD. The primary outcome was traumatic injuries. A Cox proportional hazard regression analysis was conducted to estimate ADHD effects on the risk of injuries. We also conducted a nested case-control study to examine how MPH influences this relationship. Results. A total of 59 798 children were included in the cohort study; 28 921 were classified as exposed (ADHD cohort) and 30 877 were unexposed. The traumatic injuries incidence in the exposed group was significantly higher (adjusted hazard ratio = 1.63 [95% confidence interval = 1.60-1.66]). Similar increased risk was documented also for severe injuries (adjusted hazard ratio = 1.72 [1.59-1.86]). MPH use was significantly associated with 28% lower injury events. Therapy groups were significantly associated with 29% to 40% lower injuries rate for medium- or long-acting MPH. The intensity of therapy was significantly associated with 29% to 33% lower injury rate when the intensity was lower than 0.69 mg/kg/day. Conclusion. Children with ADHD have a 60% increased odds of experiencing an injury. Treatment with MPH reduced the risk by up to 28%. The individual and financial cost secondary to injuries, underscores the public health significance of this problem. Injury prevention should be considered in clinical evaluation of MPH risks and benefits, beyond the conventional consideration of enhancing academic achievements.

The Role of Ultra-Rare Coding Variants In ADHD

Attention-Deficit Hyperactivity Disorder (ADHD) is a highly heritable childhood behavioural disorder affecting 3-6% of school-age children, and has a heritability of around 0.80. The SNP heritability, estimating the amount of risk attributed to common genetic variation, has been estimated to 0.22. The difference between SNP heritability and total heritability indicates that the genetic component of ADHD most likely also includes effects of rare variants. The role of ultra-rare deleterious variants has been established for schizophrenia and autism, but the role of these variants in ADHD remains unknown.Here we present results from whole exome sequencing of two cohorts of ADHD cases and controls. A Danish cohort consisting of samples identified in the Danish Newborn Screening Biobank (DNSB) consisting of ~3,170 ADHD cases and ~6,100 controls, and a sample consisting of ~1,200 clinical ascertained ADHD cases from Germany and the Netherlands, and a control group of ~3,000 individuals with German, Dutch and Danish ancestries, giving a grand total of 7,542 cases and 9,100 controls.Preliminary results from the analysis of the DNSB ADHD cohort demonstrate a significant overrepresentation of ultra-rare deleterious variants in evolutionary constrained genes in cases compared to controls (P = 8.21x10-10). We will present results from analyses of the impact of ultra-rare deleterious variation on ADHD risk based on the full sample of ADHD cases and controls. We will especially focus on the burden of these variants in ADHD cases compared to controls in highly evolutionary constrained genes as well as specific gene-sets relevant to ADHD, e.g. “synaptic genes”, “neurite outgrowth genes”, “genes bound by the fragile X mental retardation gene FMRP” and “genes with high brain expression”. Furthermore, we will evaluate, whether ADHD risk genes identified based on common variant analyses also carry an increased burden of ultra-rare deleterious variants, and conduct gene-based association analyses to identify top-ranking genes most frequently hit by rare deleterious variants in ADHD cases compared to controls.

Discriminating ADHD From Healthy Controls Using a Novel Feature Selection Method Based on Relative Importance and Ensemble Learning.

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder that often persists into adulthood, resulting in adverse effects on work performance and social function. The current diagnosis of ADHD primarily depends on the judgment of clinical symptoms, which highlights the need for objective imaging biomarkers. In this study, we aim to classify ADHD (both children and adults [34/112]) from age-matched healthy controls (HCs [28/77]) with functional connectivity (FCs) pattern derived from resting-state functional magnetic resonance imaging (rs-fMRI) data. However, the neuroimaging classification of brain disorders often meets a situation of high dimensional features were presented with limited sample size. Thus an efficient method that is able to reduce original feature dimension into a much more refined subspace is highly desired. Here we proposed a novel Feature Selection method based on Relative Importance and Ensemble Learning (FS_RIEL). Compared with traditional feature selection methods, FS_RIEL algorithm improved the ADHD classification by about 15% in both child and adult ADHD classification, achieving 80-86% accuracy. Moreover, we found the most frequently selected FCs were mainly involved in frontoparietal network, default network, salience network, basal ganglia network and cerebellum network in both child and adult ADHD cohorts, which indicates that ADHD is characterized by a widely-impaired brain connectivity profile that may serve as potential biomarkers for its early diagnosis.

Economic Burden of Attention-Deficit/Hyperactivity Disorder among Pediatric Patients in the United States.

To determine the adjusted incremental total costs (direct and indirect) for patients (aged 3-17 years) with attention-deficit/hyperactivity disorder (ADHD) and the differences in the adjusted incremental direct expenditures with respect to age groups (preschoolers, 0-5 years; children, 6-11 years; and adolescents, 12-17 years). The 2011 Medical Expenditure Panel Survey was used as the data source. The ADHD cohort consisted of patients aged 0 to 17 years with a diagnosis of ADHD, whereas the non-ADHD cohort consisted of subjects in the same age range without a diagnosis of ADHD. The annual incremental total cost of ADHD is composed of the incremental direct expenditures and indirect costs. A two-part model with a logistic regression (first part) and a generalized linear model (second part) was used to estimate the incremental costs of ADHD while controlling for patient characteristics and access-to-care variables. The 2011 Medical Expenditure Panel Survey database included 9108 individuals aged 0 to 17 years, with 458 (5.0%) having an ADHD diagnosis. The ADHD cohort was 4.90 times more likely (95% confidence interval [CI] 2.97-8.08; P < 0.001) than the non-ADHD cohort to have an expenditure of at least $1, and among those with positive expenditures, the ADHD cohort had 58.4% higher expenditures than the non-ADHD cohort (P < 0.001). The estimated adjusted annual total incremental cost of ADHD was $949.24 (95% CI $593.30-$1305.18; P < 0.001). The adjusted annual incremental total direct expenditure for ADHD was higher among preschoolers ($989.34; 95% CI $402.70-$1575.98; P = 0.001) than among adolescents ($894.94; 95% CI $428.16-$1361.71; P < 0.001) or children ($682.71; 95% CI $347.94-$1017.48; P < 0.001). Early diagnosis and use of evidence-based treatments may address the substantial burden of ADHD.

Effects of dopaminergic genes, prenatal adversities, and their interaction on attention-deficit/hyperactivity disorder and neural correlates of response inhibition.

Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that individuals carrying the ADHD risk alleles of the dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) genes may be especially sensitive to their effects. Functional MRI data, information on prenatal adversities and genetic data were available for 239 adolescents and young adults participating in the multicentre ADHD cohort study NeuroIMAGE (average age 17.3 yr). We analyzed the effects of DRD4 and DAT1, prenatal exposure to alcohol and smoking and their interactions on ADHD severity, response inhibition and neural activity. We found no significant gene × environment interaction effects. We did find that the DRD4 7-repeat allele was associated with less superior frontal and parietal brain activity and with greater activity in the frontal pole and occipital cortex. Prenatal exposure to smoking was also associated with lower superior frontal activity, but with greater activity in the parietal lobe. Further, those exposed to alcohol had more activity in the lateral orbitofrontal cortex, and the DAT1 risk variant was associated with lower cerebellar activity. Retrospective reports of maternal substance use and the cross-sectional study design restrict causal inference. While we found no evidence of gene × environment interactions, the risk factors under investigation influenced activity of brain regions associated with response inhibition, suggesting they may add to problems with inhibiting behaviour.