DSM-IV Attention-deficit/hyperactivity Disorder Research Articles

Ocular and neural genes jointly regulate the visuospatial working memory in ADHD children

ObjectiveWorking memory (WM) deficits have frequently been linked to attention deficit hyperactivity disorder (ADHD). Despite previous studies suggested its high heritability, its genetic basis, especially in ADHD, remains unclear. The current study aimed to comprehensively explore the genetic basis of visual-spatial working memory (VSWM) in ADHD using wide-ranging genetic analyses.MethodsThe current study recruited a cohort consisted of 802 ADHD individuals, all met DSM-IV ADHD diagnostic criteria. VSWM was assessed by Rey-Osterrieth complex figure test (RCFT), which is a widely used psychological test include four memory indexes: detail delayed (DD), structure delayed (SD), structure immediate (SI), detail immediate (DI). Genetic analyses were conducted at the single nucleotide polymorphism (SNP), gene, pathway, polygenic and protein network levels. Polygenic Risk Scores (PRS) were based on summary statistics of various psychiatric disorders, including ADHD, autism spectrum disorder (ASD), major depressive disorder (MDD), schizophrenia (SCZ), obsessive compulsive disorders (OCD), and substance use disorder (SUD).ResultsAnalyses at the single-marker level did not yield significant results (5E−08). However, the potential signals with P values less than E−05 and their mapped genes suggested the regulation of VSWM involved both ocular and neural system related genes, moreover, ADHD-related genes were also involved. The gene-based analysis found RAB11FIP1, whose encoded protein modulates several neurodevelopment processes and visual system, as significantly associated with DD scores (P = 1.96E−06, Padj = 0.036). Candidate pathway enrichment analyses (N = 53) found that forebrain neuron fate commitment significantly enriched in DD (P = 4.78E−04, Padj = 0.025), and dopamine transport enriched in SD (P = 5.90E-04, Padj = 0.031). We also observed a significant negative relationship between DD scores and ADHD PRS scores (P = 0.0025, Empirical P = 0.048).ConclusionsOur results emphasized the joint contribution of ocular and neural genes in regulating VSWM. The study reveals a shared genetic basis between ADHD and VSWM, with GWAS indicating the involvement of ADHD-related genes in VSWM. Additionally, the PRS analysis identifies a significant relationship between ADHD-PRS and DD scores. Overall, our findings shed light on the genetic basis of VSWM deficits in ADHD, and may have important implications for future research and clinical practice.

Hyperactivity and Inattention in Young Patients Born With an Atrial Septal or Ventricular Septal Defect.

Background: Patients with congenital heart defects have a well-established risk of neuropsychiatric comorbidities. Inattention and hyperactivity are three to four times more frequent in children with complex congenital heart defects. We have previously shown a higher burden of overall attention deficit/hyperactivity disorder (ADHD) symptoms in adults with simple congenital heart defects as well. However, it is unknown whether the higher burden of ADHD symptoms is mainly driven by hyperactivity, inattention, or both.Methods: The participants [simple congenital heart defect = 80 (26.6 years old), controls = 36 (25.3 years old)] and a close relative for each (n = 107) responded to the long version of the Conners' Adults ADHD Rating Scales questionnaire. Our primary and secondary outcomes are mean T-scores in the ADHD scores and symptom sub-scores.Results: Patients with simple congenital heart defects reported a higher mean T-score at all three DSM-IV ADHD scores (ADHD—combined: 52.8 vs. 44.9, p = 0.007, ADHD—inattention: 55.5 vs. 46.4, p = 0.002, and ADHD—hyperactivity: 49.4 vs. 44.0, p = 0.03) and in all four ADHD symptom sub-scores (inattention/memory problems: 50.3 vs. 44.2, p = 0.001, hyperactivity/restlessness: 49.7 vs. 45.9, p = 0.03, impulsivity/emotional lability: 50.0 vs. 41.3, p = 0.001, and self-esteem problems: 53.8 vs. 46.3, p = 0.003). The results were maintained after the removal of outliers (incongruent responses), albeit the hyperactivity/restlessness ADHD symptom sub-score lost significance. Self- and informant ratings differed significantly on the ADHD—inattention score for the congenital heart defect group, where informants rated the ADHD—inattention scores better than the congenital heart defect patients rated themselves.Conclusions: Patients with a simple congenital heart defect have a higher symptom burden across all ADHD scores and all symptom sub-scores. The higher burden of ADHD is driven by both inattention and hyperactivity symptoms, though the inattention symptoms seem more prominent. Close relatives were less aware of the inattention symptoms than the congenital heart defect patients themselves. Routine screening for ADHD symptoms may be warranted to facilitate adequate help and guidance as these symptoms are easily overlooked.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03871881.

Polygenic risk of genes involved in the catecholamine and serotonin pathways for ADHD in children

It is general acknowledged that genes play a vital role in the etiology of attention deficit/hyperactivity disorder (ADHD). The relationship between the genes involved in catecholamine (dopamine, noradrenaline)/serotonin transmissions and ADHD has been widely described in medical literature. A pathway-based study was conducted in this study to test the association of gene-gene interaction and the cumulative effect of genetic polymorphisms within the dopamine, norepinephrine, and serotonin neurotransmitter pathways with ADHD susceptibility. A case-control study was conducted among Chinese children, and 168 ADHD patients and 233 controls were recruited using a combination diagnosis according to the DSM-IV ADHD rating scale. Classification and regression tree (CART) analysis was conducted to explore the gene-gene interaction, and logistic regression modal was applied to estimate the polygenic risk of the potential multiple genetic variants. The results of CART analyses indicated that the children carrying the combination of ADRA2A rs553668GG/GA and SLC6A4 rs6354 GG/GT genotypes displayed a 6.15-fold increased risk of ADHD, compared to those with the combination of ADRA2A rs553668 AA and ANKK1 rs1800497 AA genotypes. The unfavorable alleles of ADRA2A rs553668 G, DRD2 rs1124491 G and SLC6A4 rs6354 G showed cumulative effects on ADHD, and the OR for ADHD may increase by 1.42 times when the number of unfavorable allele number increased by one. Those findings reveal the importance of the gene-gene interactions and polygenic effects of many common variants to ADHD susceptibility, even the effect of each variant is very small.

Attention Deficit/Hyperactivity Disorder and Global Severity Profiles in Treatment-Seeking Patients with Substance Use Disorders

Introduction: Comorbid attention deficit/hyperactivity disorder (ADHD) is present in 15–25% of all patients seeking treatment for substance use disorders (SUDs). Some studies suggest that comorbid ADHD increases clinical severity related to SUDs, other psychiatric comorbidities, and social impairment, but could not disentangle their respective influences. Objectives: To investigate whether comorbid adult ADHD in treatment-seeking SUD patients is associated with more severe clinical profiles in these domains assessed altogether. Methods: Treatment-seeking SUD patients from 8 countries (N = 1,294: 26% females, mean age 40 years [SD = 11 years]) were assessed for their history of DSM-IV ADHD, SUDs, and other psychiatric conditions and sociodemographic data. SUD patients with and without comorbid ADHD were compared on indicators of severity across 3 domains: addiction (number of SUD criteria and diagnoses), psychopathological complexity (mood disorders, borderline personality disorder, lifetime suicidal thoughts, or behavior), and social status (education level, occupational and marital status, and living arrangements). Regression models were built to account for confounders for each severity indicator. Results: Adult ADHD was present in 19% of the SUD patients. It was significantly associated with higher SUD severity, more frequent comorbid mood or borderline personality disorder, and less frequent “married” or “divorced” status, as compared with the absence of comorbid ADHD. ADHD comorbidity was independently associated with a higher number of dependence diagnoses (OR = 1.97) and more psychopathology (OR = 1.5), but not marital status. Conclusions: In treatment-seeking SUD patients, comorbid ADHD is associated with polysubstance dependence, psychopathological complexity, and social risks, which substantiates the clinical relevance of screening, diagnosing, and treating ADHD in patients with SUDs.

Effects of 16 Weeks of Methylphenidate Treatment on Actigraph-Assessed Sleep Measures in Medication-Naive Children With ADHD.

Methylphenidate (MPH) improves behavioral symptoms of attention-deficit/hyperactivity disorder (ADHD). Its effects on sleep, however, are insufficiently known, as trials with MPH in medication-naive children were so far restricted to relatively short trial durations. Here, we assessed effects of prolonged MPH treatment on sleep in medication-naive boys in a 16-weeks double-blind, placebo controlled, multicenter clinical trial with immediate-release MPH (ePOD-MPH trial, NTR3103). Seventy-five medication-naive boys, aged 10–12 years, were screened for eligibility using ADHD DSM-IV criteria. Sleep was assessed using actigraphy, diaries and questionnaires prior to randomization, in week 8, and 1 week after trial end. Fifty boys (mean age 11.4y, SD 0.9) were randomized to MPH or placebo. Linear mixed model analysis demonstrated a significant time-by-treatment interaction effect (p = 0.007) on sleep efficiency. Post-hoc analyses demonstrated that the two groups did not differ from each other (p = 0.94) during treatment (week 8), but that sleep efficiency was significantly improved in the MPH (p = 0.005), but not placebo group (p = 0.87) 1 week after trial end. The lack of MPH's negative effects on sleep during treatment differ from most previous studies and could be explained by the relatively long trial duration in our study and the medication-naive status of our sample; suggesting that evaluating sleep problems only shortly after treatment onset presents an incomplete picture, because it might not be representative for sleep quality after longer treatment periods. Our findings of improved sleep after trial end could be due to rebound effects or longer-term effects of MPH treatment and therefore require replication.Clinical Trial RegistrationCentral Committee on Research Involving Human Subjects (an independent registry, identifier NL34509.000.10) before enrollment of the first subject and The Netherlands National Trial Register, identifier NTR3103.

Attention deficit hyperactivity disorder in children and adolescents

To evaluate the level of adaptive functioning in patients with attention deficit hyperactivity disorder (ADHD). One hundred children and adolescents with ADHD (79 male and 21 female) were examined using M. Weiss functional impairment rating scale (WFIRS). The total score on the ADHD-DSM-IV was at least 24 and ADHD severity was rated as «Moderately ill» or «Markedly ill» on CGI-S-ADHD scale. Typical for ADHD difficulties with adaptive functioning in «Family», «Learning and school», «Life skills», «Social activities» domains are more pronounced in «Markedly ill» patients compared to «Moderately ill» and increase during the transition from childhood to adolescence. Comorbid disorders (oppositional defiant disorder and anxiety disorders) lead to a significant increase in adaptive functioning impairments in most domains of daily life, including «Family», «Learning and school», «Child's self concept», «Social activities» and «Risky activities». It is necessary not only to assess core symptoms in the follow-up of patients with ADHD, but also evaluate comorbid disorders and the level of functional impairment across the main domains of daily life.

Effects of prenatal exposure to particulate matter air pollution on corpus callosum and behavioral problems in children

ObjectiveAir pollution (AP) may affect neurodevelopment, but studies about the effects of AP on the growing human brain are still scarce.We aimed to investigate the effects of prenatal exposure to AP on lateral ventricles (LV) and corpus callosum (CC) volumes in children and to determine whether the induced brain changes are associated with behavioral problems. MethodsAmong the children recruited through a set of representative schools of the city of Barcelona, (Spain) in the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) study, 186 typically developing participants aged 8–12 years underwent brain MRI on the same 1.5 T MR unit over a 1.5-year period (October 2012–April 2014). Brain volumes were derived from structural MRI scans using automated tissue segmentation. Behavioral problems were assessed using the Strengths and Difficulties Questionnaire (SDQ) and the criteria of the Attention Deficit Hyperactivity Disorder DSM-IV list. Prenatal fine particle (PM2.5) levels were retrospectively estimated at the mothers’ residential addresses during pregnancy with land use regression (LUR) models. To determine whether brain structures might be affected by prenatal PM2.5 exposure, linear regression models were run and adjusted for age, sex, intracranial volume (ICV), maternal education, home socioeconomic vulnerability index, birthweight and mothers’ smoking status during pregnancy. To test for associations between brain changes and behavioral outcomes, negative binomial regressions were performed and adjusted for age, sex, ICV. ResultsPrenatal PM2.5 levels ranged from 11.8 to 39.5 μg/m3 during the third trimester of pregnancy. An interquartile range increase in PM2.5 level (7 μg/m3) was significantly linked to a decrease in the body CC volume (mm3) (β = −53.7, 95%CI [-92.0, −15.5] corresponding to a 5% decrease of the mean body CC volume) independently of ICV, age, sex, maternal education, socioeconomic vulnerability index at home, birthweight and mothers’ smoking status during the third trimester of pregnancy. A 50 mm3 decrease in the body CC was associated with a significant higher hyperactivity subscore (Rate Ratio (RR) = 1.09, 95%CI [1.01, 1.17) independently of age, sex and ICV. The statistical significance of these results did not survive to False Discovery Rate correction for multiple comparisons. ConclusionsPrenatal exposure to PM2.5 may be associated with CC volume decrease in children. The consequences might be an increase in behavioral problems.

ADHD symptoms in the adult general population are associated with factors linked to ADHD in adult patients

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder in children and adults. It is characterized by inappropriate levels of inattention (IA) and/or hyperactivity and impulsivity (HI). The ADHD diagnosis is hypothesized to represent the extreme of a continuous distribution of ADHD symptoms in the general population. In this study, we investigated whether factors linked to adult ADHD as a disorder are associated with adult ADHD symptoms in the general population. Our population-based sample included 4987 adults (mean age 56.1 years; 53.8% female) recruited by the Nijmegen Biomedical Study (NBS). Participants completed the Dutch ADHD DSM-IV Rating Scale for current and childhood ADHD symptoms, the Symptom Check List-90-R (SCL-90-R) anxiety subscale, and the Eysenk Personality Questionnaire (EPQR-S). Partial Spearman correlation and Hurdle negative binomial regression analysis were used to assess how age, sex, childhood ADHD symptoms, anxiety symptoms, and personality traits (neuroticism, extraversion, and psychoticism) are associated with current IA and HI symptoms. Increasing age was associated with a lower proportion of participants reporting HI symptoms and with reduced levels of HI; IA levels remained fairly stable over the age-range, but the probability of reporting IA symptoms increased throughout middle/late adulthood. Females were more likely to report IA symptoms than males. Childhood ADHD symptoms, neuroticism, and psychoticism were positively associated with current IA and HI symptoms, while extraversion had an opposite association with these symptom domains. Anxiety symptoms affected HI symptoms in females. Our results indicate that factors associated with categorical ADHD are also correlated with ADHD symptoms in the adult population.

Depression and ADHD-Related Risk for Substance Use in Adolescence and Early Adulthood: Concurrent and Prospective Associations in the MTA.

Childhood attention-deficit/hyperactivity disorder (ADHD) is prospectively linked to substance use and disorder. Depression emerging in adolescence is an understudied risk factor that may explain some of this risk. In the present study, we considered mediating and moderating roles of adolescent depression in explaining this association by using longitudinal data from the prospective 16-year follow-up of the Multimodal Treatment Study of ADHD (MTA). Participants were 547 children diagnosed with DSM-IV ADHD Combined Type, and 258 age- and sex-matched comparison children. In adolescence, depressive symptoms did not exacerbate effects of childhood ADHD on any substance use. For both groups, time-varying and average depressive symptoms were associated with more frequent use of all substances. Prospectively, we found no evidence of depression mediation to adult substance use. However, adolescent depression moderated the association between childhood ADHD and adult marijuana use. Although adults without ADHD histories used marijuana more frequently if they had elevated depressive symptoms in adolescence, marijuana use by adults with ADHD histories was independent of their adolescent depression. In adulthood, depression diagnoses and ADHD persistence continued to operate as independent, additive correlates of substance use risk. Our findings suggest a circumscribed role for depression in substance use risk that adds to, but does not alter or explain, ADHD-related risk.

Attention deficit hyperactivity disorder (ADHD) in children with epilepsy.

Attention deficit hyperactivity disorder (ADHD) is a common comorbidity of childhood epilepsy. ADHD symptoms in children with epilepsy have been studied since 1970s in western countries. However, relative studies are still rather limited in China. To study the incidence rate of ADHD in children with epilepsy, and further analyze the relationship of epilepsy and ADHD in China. 206 children (age 6-16) with epilepsy and 58 healthy controls underwent assessment instruments (DSM-IV ADHD, ADHD Rating Scale-IV, and SNAP-IV Rating Scale). The prevalence of comorbid ADHD was significantly higher in children with epilepsy (24.76%) than that in controls (5.17%), and inattentive subtype (ADHD-I, 14.1%) was the most prevalent. ADHD in childhood epilepsy was associated with younger age, early first onset age, and high frequency of epileptic seizures. There was no significant difference of ADHD incidence rate regarding the seizure type and abnormal electroencephalogram (EEG) discharges. The ADHD comorbidity rate in children treated with antiepileptic drugs (AEDs) (27.6%) was higher than that without AEDs therapy (14.0%); multiple AEDs were associated with a higher rate of ADHD comorbidity as compared with single AEDs. The incidence of comorbid ADHD in epileptic children treated with traditional single AEDs was significantly higher than those treated with novel single AEDs. Children with epilepsy have more attention problems as compared with healthy controls. ADHD in childhood epilepsy is associated with male sex, younger age, early first onset age, high frequency of epileptic seizures, and multiple AEDs.

Suggestive diagnosis of attention-deficit/hyperactivity disorder in indigenous children and adolescents from the Brazilian Amazon

The prevalence of attention-deficit/hyperactivity disorder (ADHD) symptoms has been scarcely studied in indigenous cultures that preserve ancestral cultural characteristics. The objective of the study is to estimate the prevalence of suggestive diagnosis of ADHD among indigenous children and adolescents from villages in the Amazon. This is an analytical cross-sectional study using instruments to track ADHD symptoms (the Child Behaviour Checklist for ages 6–18: CBCL/6–18 and the teacher report form for ages 6–18: TRF/6–18) and to investigate their negative impact on the patients (using the Strengths and Difficulties Questionnaire—SDQ). The prevalence of a suggestive ADHD diagnosis according to the CBCL/TRF DSM-IV ADHD subscale without and with negative impact as assessed by the SDQ was 4.3% and 1.1%, respectively. Comorbid oppositional-defiant, conduct problems and anxious symptoms were present in all cases screening positive for ADHD. We also presented a case report as an illustration of the observed clinical presentation. ADHD is a recognizable disorder even in a culture that preserves millennial characteristics. Furthermore, the presence of ADHD symptoms was associated with significant impairment.

Sex and Pubertal Status Moderate the Association Between ADHD and Depression Symptoms: An Examination From Preadolescence Through Late Adolescence.

This study examines the effects of sex and pubertal status on the association between attention-deficit/hyperactivity disorder (ADHD) and depression symptoms in preadolescence through late adolescence. Participants were 472 youth from the Multimodal Treatment Study of Children With ADHD. The study sample included 308 youth with DSM-IV ADHD, recruited from 1993 through 1996, and 164 comparison youth who were recruited approximately 2 years later. Self-reported depression symptoms from the Children's Depression Inventory and pubertal status from the Tanner Self-Report Scale were collected, along with combined parent-teacher reports of ADHD. Regression analyses examined the impact of ADHD, sex, pubertal status, and their interactions on total depression symptoms and related subscales (ie, negative mood, interpersonal problems, ineffectiveness, anhedonia, and negative self-esteem) in preadolescence. Next, path models examined associations between ADHD, sex, and pubertal status on depression symptoms into middle and late adolescence. In preadolescence, significant ADHD × sex × puberty interactions emerged for total depression symptoms and anhedonia (P < .05). Higher levels of ADHD severity were associated with higher levels of depression in early maturing girls and later maturing boys. Effects appear to be driven by anhedonia. Longitudinal effects emerged showing that total depression symptoms and anhedonia in preadolescence predicted levels of each respective outcome into late adolescence. Sex and pubertal status meaningfully impact the association between ADHD and depression symptoms in youth and should be considered in future work and treatment.

Genetic and environmental influences on attention-deficit/hyperactivity disorder symptoms in Chinese adolescents: a longitudinal twin study.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder. However, no study has examined genetic and environmental influences in the longitudinal developmental course of ADHD symptoms in a non-Western population. This study investigated changes of genetic and environmental influences and their contributions to the stability and change of ADHD symptoms of hyperactivity/impulsivity and inattention in Chinese adolescent twins. A prospective sample of 602 twin pairs (48% male) self-reported both DSM-IV ADHD symptom subscales three times at the approximate age of 12, 13, and 15years. Longitudinal multivariate genetic analyses through structural equation modelling examined genetic and environmental contributions to the developmental course of ADHD symptoms. From early (time 1 and 2) to middle adolescence (time 3), both symptoms showed modest and non-significant genetic influences that became substantial and significant, whereas shared environmental influences were substantial and significant and became modest and non-significant. The same genetic factors influenced ADHD symptoms throughout adolescence, while shared and non-shared environmental influences largely came from new emerging factors. In early adolescence, genetic factor contributed to the stability of inattention, whereas shared environmental factor contributed to the stability of hyperactivity/impulsivity. Genetic influences of ADHD tended to be smaller, whereas shared environmental influences tended to be larger in Chinese than in Western populations. Genetic factors played a large role in the stability of ADHD throughout adolescence, while shared and non-shared environment primarily contributed to its change. Findings highlight the importance of shared family, neighbourhood, and community experiences on child psychopathology in a collectivistic culture such as the Chinese society.

Prenatal fluoride exposure and attention deficit hyperactivity disorder (ADHD) symptoms in children at 6–12 years of age in Mexico City

BackgroundEpidemiologic and animal-based studies have raised concern over the potential impact of fluoride exposure on neurobehavioral development as manifested by lower IQ and deficits in attention. To date, no prospective epidemiologic studies have examined the effects of prenatal fluoride exposure on behavioral outcomes using fluoride biomarkers and sensitive measures of attention. ObjectiveWe aimed to examine the association between prenatal fluoride exposure and symptoms associated with attention-deficit/hyperactivity disorder (ADHD). Method213 Mexican mother-children pairs of the Early Life Exposures to Environmental Toxicants (ELEMENT) birth cohort study had available maternal urinary samples during pregnancy and child assessments of ADHD-like behaviors at age 6–12. We measured urinary fluoride levels adjusted for creatinine (MUFcr) in spot urine samples collected during pregnancy. The Conners' Rating Scales-Revised (CRS-R) was completed by mothers, and the Conners' Continuous Performance Test (CPT-II) was administered to the children. ResultsMean MUFcr was 0.85 mg/L (SD = 0.33) and the Interquartile Range (IQR) was 0.46 mg/L. In multivariable adjusted models using gamma regression, a 0.5 mg/L higher MUFcr (approximately one IQR higher) corresponded with significantly higher scores on the CRS-R for DSM-IV Inattention (2.84 points, 95% CI: 0.84, 4.84) and DSM-IV ADHD Total Index (2.38 points, 95% CI: 0.42, 4.34), as well as the following symptom scales: Cognitive Problems and Inattention (2.54 points, 95% CI: 0.44, 4.63) and ADHD Index (2.47 points; 95% CI: 0.43, 4.50). The shape of the associations suggested a possible celling effect of the exposure. No significant associations were found with outcomes on the CPT-II or on symptom scales assessing hyperactivity. ConclusionHigher levels of fluoride exposure during pregnancy were associated with global measures of ADHD and more symptoms of inattention as measured by the CRS-R in the offspring.

Predictive utility of childhood diagnosis of ICD-10 hyperkinetic disorder: adult outcomes in the MTA and effect of comorbidity.

Diagnostic guidelines differ between DSM attention-deficit/hyperactivity disorder (ADHD) and ICD hyperkinetic disorder (HKD). Only 145 of 579 children age 7-9 in the Multimodal Treatment Study of ADHD (the MTA) with combined-type DSM-IV ADHD met criteria for ICD-10 HKD, because major internalizing comorbidities and more stringent symptom count/pervasiveness requirements excluded most. The 145 HKD had significantly better 14-month medication response than the rest. We explored whether HKD had greater adult symptom persistence and/or impairment than other ADHD. Multi-informant assessments were done for 16 years. We used the 12/14/16-year assessments, in young adulthood. The post-attrition 109 with baseline HKD had no greater adult persistence of ADHD symptoms/impairment than 367 without HKD, but had more cumulative stimulant use, more job losses, lower emotional lability, and fewer car crashes. However, those excluded for internalizing comorbidity but otherwise meeting HKD criteria had significantly more persistence. Only 6 of the 109 (5.5%) with baseline HKD met ICD-10 criteria for HKD in adulthood, compared to 25 of 367 (6.8%) without a childhood HKD diagnosis. Despite greater initial symptom severity, HKD had no worse 16-year young adult outcome than others, except for job losses, balanced by less emotional lability and fewer crashes. Comorbid internalizing disorder seems to have worse prognosis than initial severity/pervasiveness of ADHD symptoms.

Behavioral adjustment to asymmetric reward availability among children with and without ADHD: effects of past and current reinforcement contingencies

Altered reinforcement sensitivity is hypothesized to underlie symptoms of attention deficit hyperactivity disorder (ADHD). Here we evaluate the behavioral sensitivity of Brazilian children with and without ADHD to a change in reward availability. Forty typically developing children and 32 diagnosed with DSM-IV ADHD completed a signal-detection task in which correct discriminations between two stimuli were associated with different frequencies of reinforcement. The response alternative associated with the higher rate of reinforcement switched, without warning, after 30 rewards were delivered. The task continued until another 30 rewards were delivered. Both groups of children developed a response bias toward the initially more frequently reinforced alternative. This effect was larger in the control group. The response allocation of the two groups changed following the shift in reward availability. Over time the ADHD group developed a significant response bias toward the now more frequently reinforced alternative. In contrast, the bias of the control group stayed near zero after an initial decline following the contingency change. The overall shift in bias was similar for the two groups. The behavior of both groups of children was sensitive to the asymmetric reward distribution and to the change in reward availability. Subtle group differences in response patterns emerged, possibly reflecting differences in the time frame of reward effects and sensitivity to reward exposure.

Risk of mild head injury in preschool children: relationship to attention deficit hyperactivity disorder symptoms.

To investigate whether there is an association between mild head injury (MHI) and attention deficit hyperactivity disorder (ADHD) symptoms in preschool children. The study included a patient group of 30 children aged 3-6years with mild head trauma and a control group of 30 healthy and age- and sex-matched children. The symptoms of ADHD were evaluated using the Conners' Parent Rating Scale-Revised Long (CPRS-RL) form. The mean age was 4.73 ± 1.13years in the patient group and 4.65 ± 0.99years in the control group. No significant differences were determined between the groups in terms of age, gender, parents' age and education (p > 0.05). The total subscale points as reported by the parents of the children with MHI were significantly higher than those for the control group in terms of the following subscales: oppositional, cognitive problems/inattention, hyperactivity, social problems, ADHD index, Conners' Global Index (CGI)-Irritability-Impulsiveness, CGI-Emotional Lability, CGI-Total and DSM-IV ADHD symptoms (p < 0.05). A history of previous trauma treated in emergency services was determined in eight of the 30 patients (26.7%). The findings of this study suggest that preschool children with MHI have more pre-injury ADHD symptoms and oppositional and emotional-behavioural symptoms than healthy children without trauma. Clinicians should screen children with MHI for ADHD symptoms and refer them for treatment when necessary. Evaluation of children presenting with MHI by a child psychiatrist may prevent repetition of injuries.

The Mixed Opioid Receptor Antagonist Naltrexone Mitigates Stimulant-Induced Euphoria: A Double-Blind, Placebo-Controlled Trial of Naltrexone.

Supratherapeutic doses of methylphenidate activate μ-opioid receptors, which are linked to euphoria. This study assessed whether naltrexone, a mixed μ-opioid antagonist, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential in subjects with attention-deficit/hyperactivity disorder (ADHD). We conducted a 6-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long-acting formulation of methylphenidate (January 2013 to June 2015). Spheroidal Oral Drug Absorption System methylphenidate (SODAS-MPH) was administered twice daily, was titrated to ~1 mg/kg/d over 3 weeks, and was continued for 3 additional weeks depending on response and adverse effects. Subjects were adults with ADHD preselected for having experienced euphoria with an oral test dose of 60 mg of immediate-release methylphenidate (IR-MPH). The primary outcome measure was Question 2 (Liking a Drug Effect) on the Drug Rating Questionnaire, Subject version, which was assessed after oral test doses of 60 mg of IR-MPH were administered after the third and sixth weeks of treatment with SODAS-MPH. Thirty-seven subjects who experienced stimulant-induced (mild) euphoria at a baseline visit were started in the open trial of SODAS-MPH and randomized to naltrexone 50 mg/d or placebo. Thirty-one subjects completed through week 3, and 25 completed through week 6. Naltrexone significantly diminished the euphoric effect of IR-MPH during the heightened-risk titration phase (primary outcome; first 3 weeks) (χ² = 5.07, P = .02) but not the maintenance phase (weeks 4-6) (χ² = 0.22, P = .64) of SODAS-MPH treatment. Preclinical findings are extended to humans showing that naltrexone may mitigate stimulant-associated euphoria. Our findings provide support for further studies combining opioid receptor antagonists with stimulants to reduce abuse potential. ClinicalTrials.gov identifier: NCT01673594.

Performance of the Adult ADHD Self-Report Scale-v1.1 in Adults with Major Depressive Disorder.

Attention deficit/hyperactivity disorder (ADHD) is an under-recognized comorbid disorder among patients with mood disorders. ADHD is an independent risk factor for suicidal ideation and behavior and contributes to many aspects of impaired function in adults. Diagnosis of ADHD in Major Depressive Disorder (MDD) patients is challenging due to the overlap in cognitive symptoms between the two disorders. The ADHD Self-Report Scale, version 1.1 (ASRS-v1.1) is a widely used screening instrument for ADHD in adults but its accuracy has not been evaluated previously in treatment-seeking MDD patients. We administered the ASRS-v1.1 to 55 healthy controls and 40 adults with a primary psychiatric diagnosis of MDD who were participating in clinical research studies. ADHD diagnosis was assessed via structured interview with the adult ADHD module of the Mini International Neuropsychiatric Interview Plus version 6.0.0 (MINI) along with a psychiatrist’s assessment. Overall, full-syndrome ADHD was diagnosed in 12.5% of the MDD patients. MDD patients endorsed all 18 items of the ASRS-v1.1 more frequently than the healthy controls and the number of ASRS-v1.1 items endorsed correlated with levels of anxiety in the MDD patients. The ASRS-v1.1 demonstrated fair performance for identifying full syndrome DSM-IV ADHD diagnosis, with sensitivity 60%, specificity: 68.6%, positive predictive value 21.4%, negative predictive value 92.3% and total classification accuracy of 67.5%. Positive predictive value improved substantially when the ADHD criterion requiring symptom onset before age 7 was omitted. In adult MDD patients, a negative ASRS-v1.1 screen strongly suggests the absence of ADHD but positive screen results require careful evaluation to determine whether self-reported ADHD symptoms simply emerge from depression or whether comorbid ADHD is present.

The Alpha-2A Adrenergic Receptor Gene -1291C/G Single Nucleotide Polymorphism is Associated with the Efficacy of Methylphenidate in Treating Taiwanese Children and Adolescents with Attention-Deficit Hyperactivity Disorder.

ObjectiveThe therapeutic effect of methylphenidate (MPH) in treating attention-deficit/hyperactivity disorder (ADHD) has been related to the alpha-2A adrenergic receptor (ADRA2A) gene -1291C/G single nucleotide polymorphism (SNP). We investigated the effect of MPH in treating Taiwanese children and adolescent with ADHD and its relation to the ADRA2A gene -1291C/G SNP. MethodsThe subjects with DSM-IV ADHD diagnosis underwent a titration period to find out the dose of MPH for maintenance treatment. After 4 weeks maintenance treatment, the effect of MPH was evaluated by the Swanson, Nolan and Pelham version IV total scores. The subjects with more than 25% score reduction were referred to responders and those with ≥50% improvement were considered as better responders. The -1291C/G variant of the ADRA2A gene was identified by DNA sequencing and what relevance it has to the MPH response was examined by binary logistic regression analysis. ResultsOf the 59 subjects, 44 (74.6%) were responsive to MPH treatment and the responsiveness was not shown to be associated with the ADRA2A gene -1291C/G SNP. As the responsive subjects were categorized as moderate responders and better responders and subjected to statistical analysis, the GG homozygotes showed a greater chance to have a better response to MPH treatment than CC homozygotes (p=0.02), with an odds ratio of 32.14 (95% CI=1.64–627.80). ConclusionThe ADRA2A gene -1291C/G SNP is associated with the efficacy of MPH for the treatment of ADHD in Taiwanese children and adolescents. The responsive subjects bearing homozygous -1291G allele are more likely to have a better response to MPH treatment.