Pål Zeiner

Altered reinforcement mechanisms in attention-deficit/hyperactivity disorder.

The present study tested eight boys with attention-deficit/hyperactivity disorder (ADHD) and 12 normal boys (comparison group), aged 7-12 years, to investigate the hypothesis that ADHD is associated with a steeper and shorter delay-of-reinforcement gradient than is normal. A two-component schedule of reinforcement was used to deliver trinkets or coins as reinforcers in a game-like test. One component was marked by a signal. During this period reinforcers (coins or trinkets) were delivered every 30 s. This component is called a 30-s fixed interval (FI) schedule of reinforcement and measures changes in reactivity to reinforcers. The other component was in effect when the signal was turned off. Then no reinforcer was ever delivered. This is called an extinction (EXT) component and measures primarily sustained attention. The ADHD children gradually developed hyperactivity to a large extent consisting of bursts of responses with short interresponse times (IRTs) during both schedule components. The response bursts not only constituted a substantial portion of the ADHD overactivity, but may well be a key component of the behaviour commonly described as impulsiveness, the key behavioural characteristic of ADHD. In addition, the ADHD children showed behaviour during the extinction component that may well be described as a sustained-attention deficit: initially stopping when the signal was turned off and then resuming responding some time thereafter as if the signal had been turned on again. The comparison group ceased responding during extinction and did not show impulsiveness. The findings were in accordance with a steeper and shorter delay gradient in ADHD.

Comorbid oppositional defiant disorder and the risk of relapse during 9 months of atomoxetine treatment for attention- deficit/hyperactivity disorder

ObjectiveTo examine the influence of comorbid oppositional defiant disorder (ODD) on the relative risk (RR) of relapse during 9 months of treatment with atomoxetine for attention-deficit/hyperactivity disorder (ADHD).MethodFour hundred and sixteen children and adolescents with ADHD whose symptoms remitted during initial 10-week, open-label atomoxetine treatment were randomly assigned to continue with atomoxetine or placebo.ResultsIn all, 43% met criteria for comorbid ODD. A total of 17% of patients with comorbid ODD relapsed (CGI-Severity score ≥ 3 and ADHD Rating Scale total score of 90% or more of baseline at study entry on two consecutive visits) during atomoxetine treatment, compared with 26% of patients without comorbid ODD (RR 0.67, 95% CI 0.42–1.06). Mean time to relapse was not significantly different [mean (SE) days to relapse, ADHD/ +ODD: 215 (7.38); ADHD/–ODD: 211 (7.61); log rank p=0.08]. This finding is placed within the context of atomoxetine affording an overall protection against relapse compared with placebo (RR 0.59, 95% CI 0.43–0.80).ConclusionsComorbid ODD does not influence the rate of relapse of patients with ADHD during longer-term treatment with atomoxetine. Atomoxetine protects against the relapse of ADHD symptoms regardless of the presence or absence of comorbid ODD.

Response to methylphenidate in boys with attention‐deficit hyperactivity disorder

The response to methylphenidate was examined in 36 boys, aged 7–11 y, with attention‐deficit hyperactivity disorder (ADHD) in a double‐blind, placebo‐controlled, crossover design. Hyperactivity and conduct problems were significantly reduced during methylphenidate treatment. Stimulant medication was associated with improvements on tests of sustained attention, working memory and motor steadiness. When individual changes were studied, it was found that 83% showed a significant improvement in their hyperactivity at home or at school, and for 60% their levels of hyperactive behaviour were within the normal range. High levels of hyperactivity at school and relatively low age were significant predictors of normalization of hyperactivity in at least one setting. However, these predictors could only classify correctly 71% of the children. In clinical practice a trial with stimulants is indicated in ADHD children who show symptoms that are sufficiently severe to cause impairment at home and at school.

Genome-Wide Analysis of Attention Deficit Hyperactivity Disorder in Norway

Background Attention deficit hyperactivity disorder (ADHD) is a highly heritable neuropsychiatric condition, but it has been difficult to identify genes underlying this disorder. This study aimed to explore genetics of ADHD in an ethnically homogeneous Norwegian population by means of a genome-wide association (GWA) analysis followed by examination of candidate loci. Materials and Methods Participants were recruited through Norwegian medical and birth registries as well as the general population. Presence of ADHD was defined according to DSM-IV criteria. Genotyping was performed using Illumina Human OmniExpress-12v1 microarrays. Statistical analyses were divided into several steps: (1) genome-wide association in the form of logistic regression in PLINK and follow-up pathway analyses performed in DAPPLE and INRICH softwares, (2) SNP-heritability calculated using genome-wide complex trait analysis (GCTA) tool, (3) gene-based association tests carried out in JAG software, and (4) evaluation of previously reported genome-wide signals and candidate genes of ADHD. Results In total, 1.358 individuals (478 cases and 880 controls) and 598.384 autosomal SNPs were subjected to GWA analysis. No single polymorphism reached genome-wide significance. The strongest signal was observed at rs9949006 in the ENSG00000263745 gene (OR=1.51, 95% CI 1.28–1.79, p=1.38E-06). Pathway analyses of the top SNPs implicated genes involved in the regulation of gene expression, cell adhesion and inflammation. Among previously identified ADHD candidate genes, prominent association signals were observed for SLC9A9 (rs1393072, OR=1.46, 95% CI = 1.21–1.77, p=9.95E-05) and TPH2 (rs17110690, OR = 1.38, 95% CI = 1.14–1.66, p=8.31E-04). Conclusion This study confirms the complexity and heterogeneity of ADHD etiology. Taken together with previous findings, our results point to a spectrum of biological mechanisms underlying the symptoms of ADHD, providing targets for further genetic exploration of this complex disorder.

Reliability of triclosan measures in repeated urine samples from Norwegian pregnant women

Triclosan (TCS) is a synthetic antibacterial chemical that is used in personal care products and is measurable in urine. Urinary TCS has been associated with allergy in children in Norway and the United States. A reasonable degree of temporal reliability of TCS urinary concentrations has been reported among US children as well as for Puerto Rican pregnant women. We examined the reliability of TCS measures in urine among Norwegian pregnant women. TCS was measured in spot urine samples collected in gestational weeks 17, 23, and 29 from 45 women in The Norwegian Mother and Child Cohort Study (MoBa) enrolled in 2007 and 2008. Spearman’s rank correlation coefficient (rs) and intraclass correlation coefficient (ICC) statistics were calculated. Fifty-six percent of the 45 women had a least one sample with a value above the method limit of detection (2.3 μg/l). The correlation coefficients were 0.61 for TCS concentrations at 17 and 23 weeks and 0.49 for concentrations at 17 and 29 weeks. For the three time points, the ICC was 0.49. The reliability of TCS concentrations in repeated urine samples from pregnant Norwegian women was reasonably good, suggesting a single urine sample can adequately represent TCS exposure during pregnancy.

Measurement of Total and Free Urinary Phenol and Paraben Concentrations over the Course of Pregnancy: Assessing Reliability and Contamination of Specimens in the Norwegian Mother and Child Cohort Study.

Background Exposures to environmental phenols and parabens may be harmful, especially in utero. Prior studies have demonstrated high within-person variability of urinary concentrations across pregnancy. Objectives We sought to measure phenol and paraben biomarker concentrations for the Norwegian Mother and Child Cohort (MoBa) study, assess within-person variability, and investigate any possible external phenol or paraben contamination of specimens. Methods We collected three spot urine samples at approximately 17, 23, and 29 weeks gestation in a hospital setting and added a preservative containing ethyl paraben. We measured urinary concentrations and within-person variability for phenols and parabens in a MoBa sample (n = 45), including a subgroup of 15 participants previously randomly selected for a bisphenol A (BPA) exposure study who had unusually high total BPA concentrations. Additionally, we compared reliability results for total, conjugated, and free concentrations of phenolic compounds. Results We detected total and free BPA, butyl paraben, propyl paraben, and methyl paraben in 100% of samples, total benzophenone-3 in 95% of samples, and infrequently detected free benzophenone-3 and total and free 2,4-dichlorophenol and 2,5-dichlorophenol. Intraclass correlation coefficients (ICCs) for total, conjugated, and free concentrations ranged from relatively low for BPA to moderate for propyl paraben. ICCs were generally similar overall and by subgroup. Conclusions Using conjugated concentrations improved reliability estimates only for BPA. Measuring total and free concentrations, an approach that may be useful for future studies, allowed us to identify likely BPA and butyl paraben contamination of archived MoBa urine specimens. Citation Guidry VT, Longnecker MP, Aase H, Eggesbø M, Zeiner P, Reichborn-Kjennerud T, Knudsen GP, Bertelsen RJ, Ye X, Calafat AM, Engel SM. 2015. Measurement of total and free urinary phenol and paraben concentrations over the course of pregnancy: assessing reliability and contamination of specimens in the Norwegian Mother and Child Cohort Study. Environ Health Perspect 123:705–711; http://dx.doi.org/10.1289/ehp.1408325

Response to atomoxetine in boys with high-functioning autism spectrum disorders and attention deficit/hyperactivity disorder

Aim:  To study the efficacy and tolerability of atomoxetine in high‐functioning boys with autism spectrum disorders (ASD) and comorbid attention deficit/hyperactivity disorder (AD/HD).

Quality of Life in Adults Aged 50+ With ADHD

Objective: To study the quality of life in adults aged 50+ with ADHD. Method: An anonymous questionnaire survey was performed on 148 adults aged 50+ with ADHD. Quality of life was assessed with EuroQol and the Satisfaction With Life Scale. Age-matched Norwegian and Danish population samples served as reference groups. Results: Mean age of participants was 55.7 years, and mean age when diagnosed with ADHD was 50.2 years, while mean Adult ADHD Self-Report Scale Screener score was 15.2. Adults with ADHD reported significantly reduced health-related quality of life and reduced satisfaction with life compared with population norms. Nonemployment and severe ADHD were associated with poor quality of life. Conclusion: Adults aged 50+ with ADHD diagnosed in late adulthood reported significantly reduced quality of life when compared with population norms. The negative impact of ADHD persists into late adulthood.

Inhibition and working memory in young preschool children with symptoms of ADHD and/or oppositional-defiant disorder.

Background: Early symptoms of attention deficit/hyperactivity disorder (ADHD) and oppositional-defiant disorder (ODD) are associated with deficits in cognitive self-regulatory processes or executive functions (EF)s. However, the hypothesis that neurocognitive deficits underlying the two disorders are already evident during early preschool years still has limited empirical support. The present study investigated associations between symptoms of ADHD and/or ODD and two core EFs, inhibition and working memory, in a large nonclinical sample of 3-year old children. Method: Participants were 1045 children (554 boys, age 37–47 months), recruited from the population based Norwegian Mother and Child Cohort Study (MoBa). Relations between behavioral symptoms and measures of inhibition and working memory were studied both categorically and dimensionally. Results: Children with co-occurring symptoms of ADHD and ODD performed at a significantly lower level than typically developing children in 4 out of 5 EF measures. Symptoms of ADHD, both alone and in combination with ODD, were associated with reduced performance on tests of inhibition in the group comparisons. Dimensional analyses showed that performance within both EF domains contributed to variance primarily in ADHD symptom load. The associations between test results and behavioral symptoms remained significant after gender and verbal skills had been controlled. Conclusion: Young preschoolers show the same pattern of relations between EF and behavioral symptoms of ADHD and/or ODD as previously described in older children diagnosed with ADHD and/or ODD. Effect sizes were generally small, indicating that measures of EF have limited clinical utility at this stage in development.

Four-year outcome in psychopharmacologically treated adults with attention-deficit/hyperactivity disorder: a questionnaire survey.

OBJECTIVE In adults with attention-deficit/hyperactivity disorder (ADHD), pharmacotherapy is a recommended treatment option. However, research on long-term outcome with such treatment has been scarce. METHOD A questionnaire survey was completed by adults with ADHD, diagnosed according to ICD-10/DSM-IV criteria and approved for pharmacotherapy during 2003 to 2005, living in southeastern Norway. The questionnaire was conducted from November 2008 to April 2009. Of an eligible number of 1,096 subjects, 1,080 remained at follow-up; 371 subjects (34.4%) agreed to participate, and 368 of these reported having ever been treated with ADHD medication. Baseline characteristics and self-reported outcome were studied by time on psychopharmacologic treatment. Primary outcome measures were the Adult ADHD Self-Report Scale version 1.1 (ASRS) Screener and the Mental Health Index-5 (MHI-5). Based on cutoff scores for these instruments, 2 groups (favorable outcome vs others) were created to study possible predictors of outcome status. RESULTS Self-reported baseline ADHD symptoms and impairment did not differ between participants and nonparticipants. Mean observation time was 4.5 years (range, 3.5-6.0 years). At follow-up, mean age was 36.5 years. Altogether, 270 patients (73.4%) had been treated for more than 24 months. They reported better outcome on all measures compared to those treated for 24 months or less (mean values: ASRS Screener score: 12.8 vs 15.3; MHI-5 score: 63.7 vs 57. 7). The favorable outcome group consisted of 79 participants (21.5%). Comorbidity at baseline predicted poorer outcome than did no comorbid illness. CONCLUSIONS In adults with ADHD, pharmacologic treatment for more than 2 years was associated with better functioning than treatment for 2 years or less. Comorbidity at baseline predicted poorer outcome.