The role and validity of actigraphy in sleep medicine: An update

Quantitative genetic studies (i.e., twin and adoption studies) suggest that genetic influences contribute substantially to the development of attention deficit hyperactivity disorder (ADHD). Over the past 15 years, considerable efforts have been made to identify genes involved in the etiology of this disorder resulting in a large and often conflicting literature of candidate gene associations for ADHD. The first aim of the present study was to conduct a comprehensive meta-analytic review of this literature to determine which candidate genes show consistent evidence of association with childhood ADHD across studies. The second aim was to test for heterogeneity across studies in the effect sizes for each candidate gene as its presence might suggest moderating variables that could explain inconsistent results. Significant associations were identified for several candidate genes including DAT1, DRD4, DRD5, 5HTT, HTR1B, and SNAP25. Further, significant heterogeneity was observed for the associations between ADHD and DAT1, DRD4, DRD5, DBH, ADRA2A, 5HTT, TPH2, MAOA, and SNAP25, suggesting that future studies should explore potential moderators of these associations (e.g., ADHD subtype diagnoses, gender, exposure to environmental risk factors). We conclude with a discussion of these findings in relation to emerging themes relevant to future studies of the genetics of ADHD.

Candidate gene studies of ADHD: a meta-analytic review.

http://hawley_montgomery-downs.psychology.wvu.edu/r/download/139791

Use of actigraphy for assessment in pediatric sleep research

The idea that some phenotypes bear a closer relationship to the biological processes that give rise to psychiatric illness than diagnostic categories has attracted considerable interest. Much effort has been devoted to finding such endophenotypes, partly because it is believed that the genetic basis of endophenotypes will be easier to analyse than that of psychiatric disease. This belief depends in part on the assumption that the effect sizes of genetic loci contributing to endophenotypes are larger than those contributing to disease susceptibility, hence increasing the chance that genetic linkage and association tests will detect them. We examine this assumption by applying meta-analytical techniques to genetic association studies of endophenotypes. We find that the genetic effect sizes of the loci examined to date are no larger than those reported for other phenotypes. A review of the genetic architecture of traits in model organisms also provides no support for the view that the effect sizes of loci contributing to phenotypes closer to the biological basis of disease is any larger than those contributing to disease itself. While endophenotype measures may afford greater reliability, it should not be assumed that they will also demonstrate simpler genetic architecture.

/pdf/the-endophenotype-concept-in-psychiatric-genetics-212mgiikfz.pdf

The endophenotype concept in psychiatric genetics

http://www.people.vcu.edu/~mreimers/SysNeuro/Barnett%20-%20meta-analysis%20of%20COMT%20Val-Met.pdf

Meta-Analysis of the Cognitive Effects of the Catechol-O-Methyltransferase Gene Val158/108Met Polymorphism

Objectives: Genetic and nonshared environmental factors (experienced by 1 family member to the exclusion of the others) have been strongly implicated in the causes of attention-deficit hyperactivity disorder (ADHD). Pregnancy, labour/delivery and neonatal complications (PLDNC) have often been associated with ADHD; however, no investigations aimed at delineating the shared or nonshared nature of these factors have been reported. We aimed to identify those elements of the PLDNC that are more likely to be of a nonshared nature. Methods: We used an intrafamily study design, comparing the history of PLDNC between children diagnosed with ADHD, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders , fourth edition (DSM-IV), and their unaffected siblings. Children with ADHD were recruited from the outpatient, day-treatment program of the Child Psychiatry Department, Douglas Hospital, Montreal. The unaffected sibling closest in age to the child with ADHD was used as a control. The history of PLDNC was assessed using the Kinney Medical and Gynecological Questionnaire and the McNeil–Sjostrom Scale for both children with ADHD and their siblings. Seventy children with ADHD along with 50 of their unaffected siblings agreed to participate in the study. Child Behavior Checklist (CBCL), Continuous Performance Test (CPT) and Restricted Academic Situation Scale (RASS) scores were also used as measures of ADHD symptoms in children with ADHD. Results: The children with ADHD had significantly higher rates of neonatal complications compared with their unaffected siblings (F4,196 = 3.67, p < 0.006). Furthermore, neonatal complications in the children with ADHD were associated with worse CBCL total and externalizing scores and with poorer performance on the CPT. Conclusions: These results suggest that neonatal complications are probably a nonshared environmental risk factor that may be pathogenic in children with ADHD.

/pdf/perinatal-complications-in-children-with-attention-deficit-3nctac8i8x.pdf

Perinatal complications in children with attention-deficit hyperactivity disorder and their unaffected siblings

Objective Sleep disturbances appear as a comorbid condition in children with attention-deficit/hyperactivity disorder. The aim of this study was to investigate the relationship of activity levels during sleep and therapeutic response to methylphenidate (MPH). Method Nightly sleep actigraphic recordings during a double-blind, placebo-controlled, crossover clinical study (1-week of 0.5 mg/kg MPH; 1-week of placebo) were obtained on 44 children, 6 to 12 years old, diagnosed with attention-deficit/hyperactivity disorder ( DSM-IV ). Results Significant ( p Conclusions MPH, given twice daily, induces a slight but significant sleep disturbance. Motor activity levels during sleep did not differentiate children who responded to MPH from those who did not respond. This suggests that responders to MPH treatment do not experience greater sleep disturbances than nonresponders, at least at the dose studied.

Actigraphic monitoring during sleep of children with ADHD on methylphenidate and placebo.

Background
An association has been observed between the catechol-O-methyltransferase (COMT) gene, the predominant means of catecholamine catabolism within the prefrontal cortex (PFC), and neuropsychological task performance in healthy and schizophrenic adults Since several of the cognitive functions typically deficient in children with Attention Deficit Hyperactivity Disorder (ADHD) are mediated by prefrontal dopamine (DA) mechanisms, we investigated the relationship between a functional polymorphism of the COMT gene and neuropsychological task performance in these children

/pdf/catechol-o-methyltransferase-comt-val-108-158-met-4kwhaj05o4.pdf

Catechol-O-Methyltransferase (COMT) Val 108/158 Met polymorphism does not modulate executive function in children with ADHD

OBJECTIVE: To assess which measurements best predict improvement on ADHD symptomatology after medication is given. METHODS: 147 children aged 6 to 12 years, diagnosed with ADHD, participated in a double-blind placebo controlled twoweek crossover trial of methylphenidate. RESULTS: There were statistically significant differences on all measures between placebo and medication. Effect size for the overall group was 0.33 (CGI-P), 0.80 (CGI-T), 1.33 (CGI), 0.56 (CPT), 0.82 (RASS). CONCLUSIONS: Acute behavioural response measures, where children are observed by clinicians (RASS and CGI), were overall more reliable than parent reports in detecting improvement on ADHD symptomatology. Teacher reports were also very important, especially in the 9 to 12 year old group.

Sensitivity of Tests to Assess Improvement In ADHD Symptomatology

Background: To study the factor structure of the Restricted Academic Situation Scale (RASS), a psychometric tool used to assess behavior in children with ADHD, 117 boys and 21 girls meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria for ADHD and aged between 6 and 12 years were recruited. Assessments were carried out before and 65 min after the administration of either a placebo or 0.25 mg/kg of methylphenidate. Placebo and methylphenidate were each administered according to a double-blind placebo-controlled crossover design. Results: Principal component analysis, followed by a confirmatory maximum likelihood factor analysis, revealed two main factors for the RASS, task disengagement (TD) and motor activation (MA). Only TD was inversely correlated with age, indicating that TD and MA may be differentially modulated during development. Conclusions: MA and TD are distinct traits of ADHD. It may be important to consider them separately when conducting studies on ADHD. (J....

Chantal Baron

Papers

Perinatal complications in children with attention-deficit hyperactivity disorder and their unaffected siblings

Actigraphic monitoring during sleep of children with ADHD on methylphenidate and placebo.

Catechol-O-Methyltransferase (COMT) Val 108/158 Met polymorphism does not modulate executive function in children with ADHD

Sensitivity of Tests to Assess Improvement In ADHD Symptomatology

Factor structure of the restricted academic situation scale: implications for ADHD.