Biomedical subjects

Philippe Lageix

Publications and source records attributed to Philippe Lageix.

4 recordsLinked to original sources

PubMed2006

Dopamine transporter 3'-UTR VNTR genotype and ADHD: a pharmaco-behavioural genetic study with methylphenidate.

We sought to test the hypothesis that the variable number of tandem repeat (VNTR) polymorphism in the 3'-untranslated region (3'-UTR) of the SLC6A3 gene modulates behavior in children with ADHD and/or behavioral response to methylphenidate (MPH). One hundred and fifty-nine children with AHDH (6-12 years) were assessed with regard to the Conners' Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) and the response of these behaviors to MPH (0.5 mg/kg/day) using a 2-week prospective within-subject (crossover) trial. Based on CGI-Parents, the profile of behavioral response to MPH as compared to placebo was not parallel in the three groups of children separated according to their genotype in the 3'-UTR VNTR polymorphism of SLC6A3, as indicated by a significant (p=0.017) genotype by treatment two-way interaction. Individuals having the 9/10 and 10/10 genotypes displayed a significant positive response to MPH as opposed to those homozygous for the 9-repeat allele. No genotype or genotype by treatment interaction was observed for CGI-Teachers. These findings support a role for the DAT gene 3'-UTR VNTR polymorphism in modulating the response of some behavioral dimensions to MPH in children with ADHD. They also suggest the presence of genetic heterogeneity that could be indexed by the quality of behavioral response to MPH.

3' Untranslated Regions↗

PubMed2005

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

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.

Adult↗

PubMed2004

Catechol-O-methyltransferase (COMT) Val108/158 Met polymorphism does not modulate executive function in children with ADHD.

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. METHODS: The Val108/158 Met polymorphism of the COMT gene was genotyped in 118 children with ADHD (DSM-IV). The Wisconsin Card Sorting Test (WCST), Tower of London (TOL), and Self-Ordered Pointing Task (SOPT) were employed to evaluate executive functions. Neuropsychological task performance was compared across genotype groups using analysis of variance. RESULTS: ADHD children with the Val/Val, Val/Met and Met/Met genotypes were similar with regard to demographic and clinical characteristics. No genotype effects were observed for WCST standardized perseverative error scores [F2,97 = 0.67; p > 0.05], TOL standardized scores [F2,99 = 0.97; p > 0.05], and SOPT error scores [F2,108 = 0.62; p > 0.05]. CONCLUSIONS: Contrary to the observed association between WCST performance and the Val108/158 Met polymorphism of the COMT gene in both healthy and schizophrenic adults, this polymorphism does not appear to modulate executive functions in children with ADHD.

Amino Acid Substitution↗

PubMed2004

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

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 <.005) differences between the conditions were found in several software-computed parameters: sleep onset latency (MPH, 39.3 minutes; placebo, 28.2 minutes), sleep efficiency (MPH, 78.0%; placebo, 80.4%), total sleep time (MPH, 7 hours; 57 minutes; placebo, 8 hours, 16 minutes). No significant differences on any of these measures were found among the 26 subjects who showed a moderate or large global improvement on MPH over placebo compared with 18 subjects who showed mild or no clinical improvement. 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.

Attention Deficit Disorder with Hyperactivity↗