Executive functioning in children with autism and Tourette syndrome

The main aims of this study were to investigate if children with high-functioning autism (HFA) and children with Tourette syndrome (TS) can be differentiated in their executive functioning (EF) profile compared to normal controls (NCs) and compared to each other and to investigate whether children with HFA or children with TS and a comorbid group of children with both disorders are distinct conditions in terms of EF. Four groups of children participated in this study: HFA, TS, comorbid HFA + TS, and a NC group. All children were in the age range of 6 to 13 years. The groups were compared on five major domains of EF: inhibition, visual working memory, planning, cognitive flexibility, and verbal fluency. Children with HFA scored lower than NC children on all the EFs measured. Children with TS and NC children showed the same EF profile. The HFA group scored lower than the TS group for inhibition of a prepotent response and cognitive flexibility. Children with HFA performed poorer than children with comorbid HFA + TS on all functions, with the exception of inhibiting an ongoing response, interference control, and verbal fluency. Children with TS and children with comorbid HFA + TS could not be differentiated from one another in terms of EF. This study indicates that EF deficits are highly characteristic of children with HFA in comparison to children with TS and NC. The results suggest that for the comparison between HFA and TS groups, it is important to take into account comorbidity. A reevaluation of the EF hypothesis in children with TS is suggested. Copyright © 2005 Cambridge University Press

White matter hyperintensities and working memory: an explorative study

Contains fulltext : 73317.pdf (publisher's version ) (Closed access)White matter hyperintensities (WMH) are commonly observed in elderly people and may have the most profound effect on executive functions, including working memory. Surprisingly, the Digit Span backward, a frequently employed working memory task, reveals no association with WMH. In the present study, it was investigated whether more detailed analyses of WMH variables and study sample selection are important when establishing a possible relationship between the Digit Span backward and WMH. To accomplish this, the Digit Span backward and additional working memory tests, WMH subscores, and cardiovascular risk factors were examined. The results revealed that performance on the Digit Span backward test is unrelated to WMH, whereas a relationship between other working memory tests and WMH was confirmed. Furthermore, a division between several white matter regions seems important; hyperintensities in the frontal deep white matter regions were the strongest predictor of working memory performance.16 p

Are motor inhibition and cognitive flexibility dead ends in ADHD?

Contains fulltext : 53518.pdf (publisher's version ) (Closed access)Executive dysfunction has been postulated as the core deficit in ADHD, although many deficits in lower order cognitive processes have also been identified. By obtaining an appropriate baseline of lower order cognitive functioning light may be shed on as to whether executive deficits result from problems in lower order and/or higher order cognitive processes. We examined motor inhibition and cognitive flexibility in relation to a baseline measure in 816 children from ADHD and control families. Multiple children in a family were tested in order to examine the familiality of the measures. No evidence was found for deficits in motor inhibition or cognitive flexibility in children with ADHD or their nonaffected siblings: Compared to their baseline speed and accuracy of responding, children with ADHD and their (non)affected siblings were not disproportionally slower or inaccurate when demands for motor inhibition or cognitive flexibility were added to the task. However, children with ADHD and their (non)affected siblings were overall less accurate than controls, which could not be attributed to differences in response speed. This suggests that inaccuracy of responding is characteristic of children having (a familial risk for) ADHD. Motor inhibition and cognitive flexibility as operationalized with mean reaction time were found to be familial. It is concluded that poorer performance on executive tasks in children with ADHD and their (non)affected siblings may result from deficiencies in lower order cognitive processes and not (only) from higher order cognitive processes/executive functions

Genome-wide analysis of copy number variants in attention deficit hyperactivity disorder: the role of rare variants and duplications at 15q13.3.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Because of its multifactorial etiology, however, identifying the genes involved has been difficult. The authors followed up on recent findings suggesting that rare copy number variants (CNVs) may be important for ADHD etiology. The authors performed a genome-wide analysis of large, rare CNVs (100 kb in size, which segregated into 912 independent loci. Overall, the rate of rare CNVs >100 kb was 1.15 times higher in ADHD case subjects relative to comparison subjects, with duplications spanning known genes showing a 1.2-fold enrichment. In accordance with a previous study, rare CNVs >500 kb showed the greatest enrichment (1.28-fold). CNVs identified in ADHD case subjects were significantly enriched for loci implicated in autism and in schizophrenia. Duplications spanning the CHRNA7 gene at chromosome 15q13.3 were associated with ADHD in single-locus analysis. This finding was consistently replicated in an additional 2,242 ADHD case subjects and 8,552 comparison subjects from four independent cohorts from the United Kingdom, the United States, and Canada. Presence of the duplication at 15q13.3 appeared to be associated with comorbid conduct disorder. These findings support the enrichment of large, rare CNVs in ADHD and implicate duplications at 15q13.3 as a novel risk factor for ADHD. With a frequency of 0.6% in the populations investigated and a relatively large effect size (odds ratio=2.22, 95% confidence interval=1.5–3.6), this locus could be an important contributor to ADHD etiology.Novartis Shire Eli Lilly Elminda Janssen McNeil Fundacion Areces (Spain) Fundacion Dr. Manuel Camelo A.C., Medice Pharmaceuticals Spanish Child Psychiatry Association Shionogi Pharma Cipher Pharmaceuticals Janssen-Cilag Vifor Alcobra NIH R13MH059126 R01MH62873 R01MH081803 Pfizer Guilford Press Oxford University Press Affymetrix Power Award Wellcome Trust, U.K. Action Medical Research UK Radboud University Nijmegen Medical Center Deutsche Forschungsgemeinschaft KFO 125 SFB 581 GRK 1156 ME 1923/5-1 ME 1923/5-3 GRK 1389 Bundesministerium fur Bildung und Forschung (BMBF 01GV0605 Health Research Board Irelan

Peripheral electrical stimulation in Alzheimer's Disease: A randomized controlled trial on cognition and behavior

In a number of studies, peripheral electrical nerve stimulation has been applied to Alzheimer's disease (AD) patients who lived in a nursing home. Improvements were observed in memory, verbal fluency, affective behavior, activities of daily living and on the rest-activity rhythm and pupillary light reflex. The aim of the present, randomized, placebo-controlled, parallel-group clinical trial was to examine the effects of electrical stimulation on cognition and behavior in AD patients who still live at home. Repeated measures analyses of variance revealed no effects of the intervention in the verum group (n = 32) compared with the placebo group (n = 30) on any of the cognitive and behavioral outcome measures. However, the majority of the patients and the caregivers evaluated the treatment procedure positively, and applying the daily treatment at home caused minimal burden. The lack of treatment effects calls for reconsideration of electrical stimulation as a symptomatic treatment in A

The risk of eating disorders comorbid with attention-deficit/hyperactivity disorder:A systematic review and meta-analysis

Objective: There has been interest in whether people with Attention-Deficit/Hyperactivity Disorder (ADHD) are at higher risk of developing an Eating Disorder (ED). The aim of this study was estimate the size of this association with a meta-analysis of studies. Methods: We retrieved studies following PRISMA guidelines from a broad range of databases. Results: Twelve studies fitted our primary aim in investigating ED in ADHD populations (ADHD = 4,013/Controls = 29,404), and five exploring ADHD in ED populations (ED = 1,044/Controls = 11,292). The pooled odds ratio of diagnosing any ED in ADHD was increased significantly, 3.82 (95% CI:2.34–6.24). A similar level of risk was found across all ED syndromes [Anorexia Nervosa = 4.28 (95% CI:2.24–8.16); Bulimia Nervosa = 5.71 (95% CI: 3.56–9.16) and Binge Eating Disorder = 4.13 (95% CI:3–5.67)]. The risk was significantly higher if ADHD was diagnosed using a clinical interview [5.89 (95% CI:4.32–8.04)] rather than a self-report instrument [2.23 (95% CI:1.23–4.03)]. The pooled odds ratio of diagnosing ADHD in participants with ED was significantly increased, 2.57 (95% CI:1.30–5.11). Subgroup analysis of cohorts with binge eating only yielded a risk of 5.77 (95% CI:2.35–14.18). None of the variables examined in meta-regression procedures explained the variance in effect size between studies. Discussion: People with ADHD have a higher risk of comorbidity with an ED and people with an ED also have higher levels of comorbidity with ADHD. Future studies should address if patients with this comorbidity have a different prognosis, course and treatment response when compared to patients with either disorder alone. Resumen Objetivo: Ha habido interés en saber si la gente con Trastorno por Déficit de Atención e Hiperactividad (TDAH) están en mayor riesgo de desarrollar un Trastorno de la Conducta Alimentaria (TCA). El objetivo de este estudio fue estimar el tamaño de esta asociación con un meta-análisis de los estudios. Métodos: Recuperamos estudios de una amplia gama base de datos, que siguen los lineamientos PRISMA. Resultados: Doce estudios encajaron con nuestro objetivo primario de investigar los TCA en poblaciones con TDAH (TDAH = 4,013/Controles = 29,404), y 5 exploraron TDAH en poblaciones con TCA (TCA = 1,044/Controles = 11,292). El odds ratio (OR) agrupado de diagnosticar cualquier TCA en el TDAH se incrementó significativamente, 3.82 (95% CI:2.34–6.24). Un nivel de riesgo similar fue encontrado en todos los síndromes de TCA [Anorexia Nervosa = 4.28 (95% CI:2.24–8.16); Bulimia Nervosa = 5.71 (95% CI:3.56–9.16) y Trastorno por Atracón = 4.13 (95% CI: 3–5.67)]. El riesgo fue significativamente mayor si el TDAH fue diagnosticado utilizando una entrevista clínica [5.89 (95% CI:4.32–8.04)] en lugar de un instrumento de auto-reporte [2.23 (95% CI:1.23–4.03)]. El odds ratio (OR) agrupado de diagnosticar TDAH en participantes con TCA fue significativamente incrementado, 2.57 (95% CI:1.30–5.11). El análisis de los subgrupos de cohort con atracones solamente produjo un riesgo de 5.77 (95% CI:2.35–14.18). Ninguna de las variables examinadas en los procedimientos de meta-regresión explicaron la varianza en el tamaño del efecto entre los estudios. Discusión: La gente con TDAH tiene un mayor riesgo de comorbilidad con un TCA y la gente con un TCA también tiene niveles altos de comorbilidad con TDAH. Los estudios futuros deberán abordar si los pacientes con esta comorbilidad tienen diferente pronóstico, curso y respuesta a tratamiento cuando son comparados con pacientes que solamente tienen uno de los trastornos.</p

Differential effects of Atomoxetine on executive functioning and lexical decision in Attention-Deficit/Hyperactivity Disorder and Reading Disorder

Objective: The effects of a promising pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), atomoxetine, were studied on executive functions in both ADHD and reading disorder (RD) because earlier research demonstrated an overlap in executive functioning deficits in both disorders. In addition, the effects of atomoxetine were explored on lexical decision. Methods: Sixteen children with ADHD, 20 children with ADHD + RD, 21 children with RD, and 26 normal controls were enrolled in a randomized placebo-controlled crossover study. Children were measured on visuospatial working memory, inhibition, and lexical decision on the day of randomization and following two 28-day medication periods. Results: Children with ADHD + RD showed improved visuospatial working memory performance and, to a lesser extent, improved inhibition following atomoxetine treatment compared to placebo. No differential effects of atomoxetine were found for lexical decision in comparison to placebo. In addition, no effects of atomoxetine were demonstrated in the ADHD and RD groups. Conclusion: Atomoxetine improved visuospatial working memory and to a lesser degree inhibition in children with ADHD + RD, which suggests differential developmental pathways for co-morbid ADHD + RD as compared to ADHD and RD alone

Cotransmission of conduct problems with attention-deficit/hyperactivity disorder: familial evidence for a distinct disorder

Common disorders of childhood and adolescence are attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and conduct disorder (CD). For one to two cases in three diagnosed with ADHD the disorders may be comorbid. However, whether comorbid conduct problems (CP) represents a separate disorder or a severe form of ADHD remains controversial. We investigated familial recurrence patterns of the pure or comorbid condition in families with at least two children and one definite case of DSM-IV ADHDct (combined-type) as part of the International Multicentre ADHD Genetics Study (IMAGE). Using case diagnoses (PACS, parental account) and symptom ratings (Parent/Teacher Strengths and Difficulties [SDQ], and Conners Questionnaires [CPTRS]) we studied 1009 cases (241 with ADHDonly and 768 with ADHD + CP), and their 1591 siblings. CP was defined as >= 4 on the SDQ conduct-subscale, and T >= 65, on Conners' oppositional-score. Multinomial logistic regression was used to ascertain recurrence risks of the pure and comorbid conditions in the siblings as predicted by the status of the cases. There was a higher relative risk to develop ADHD + CP for siblings of cases with ADHD + CP (RRR = 4.9; 95%CI: 2.59-9.41); p < 0.001) than with ADHDonly. Rates of ADHDonly in siblings of cases with ADHD + CP were lower but significant (RRR = 2.9; 95%CI: 1.6-5.3, p < 0.001). Children with ADHD + CP scored higher on the Conners ADHDct symptom-scales than those with ADHDonly. Our finding that ADHD + CP can represent a familial distinct subtype possibly with a distinct genetic etiology is consistent with a high risk for cosegregation. Further, ADHD + CP can be a more severe disorder than ADHDonly with symptoms stable from childhood through adolescence. The findings provide partial support for the ICD-10 distinction between hyperkinetic disorder (F90.0) and hyperkinetic conduct disorder (F90.1).Medical Research Council; NIMH NIH HHS [R01MH062873