No evidence of association of two 5HT transporter gene polymorphisms and attention deficit hyperactivity disorder.

OBJECTIVES: Three studies to date have found evidence (or a trend for evidence) of linkage and association between the long allele of the 44 base pair repeat insertion/deletion 5-HTT functional polymorphism (5-HTTLPR) and attention deficit hyperactivity disorder (ADHD). In an attempt to replicate these findings, we examined this polymorphism and a variable number tandem repeat in the second intron of 5-HTT for association with ADHD. METHODS: One hundred and fifty children who met diagnostic criteria for ADHD and their parents (where available) were genotyped for these polymorphisms. Analysis was undertaken using the transmission disequilibrium test and haplotype analysis, as well as case-control comparisons using a control group of 121 individuals. RESULTS: No association between either the 5-HTTLPR or the variable number tandem repeat (VNTR) in ADHD was found (extended transmission disequilibrium test; P=0.37 and P=0.62, respectively). Haplotype analysis was also non-significant. Further analysis revealed no evidence of association in the subgroups of those without conduct disorder and in medication non-responders. CONCLUSIONS: Failure to replicate findings from previous studies may be due to a lack of statistical power. However, given recent findings by Kent et al. (2002) of association with another polymorphism in the 5HTT gene, we hypothesise that previous positive findings may have arisen by the LPR and VNTR being in linkage disequilibrium with the true susceptibility polymorphism.

Analysis of compositional data in communication disorders research.

UNLABELLED: The study of communication and its disorders often involves coding several behaviors and examining the proportions with which individual behaviors are produced within data sets. Problems are encountered when studying multiple behaviors between data sets, because of the interdependence of the proportions: as one coded behavior increases, at least one other must decrease. The interdependence of data means that traditional statistical techniques can be used to analyse differences in the proportion of only one behavior over time or between clinical groups. We describe a statistical technique, previously used in geological and biomedical research, which can be used to analyse all behaviors in compositional data sets, and give examples of its use with interaction data. The technique allows, for the first time, full comparison of entire patterns of multiple communication behaviors, both over time and between clinical groups. The technique will aid both basic and applied communication research. LEARNING OUTCOMES: Readers will understand the advantages and limitations of frequency counts and proportions for the analysis of multiple behaviors. Readers will be able to analyze change in proportions of multiple behaviors within a data set between groups and across time.

The Child Attention-Deficit Hyperactivity Disorder Teacher Telephone Interview (CHATTI): reliability and validity.

BACKGROUND: The ICD-10 and DSM-IV diagnostic criteria for hyperkinetic disorder and attention-deficit hyperactivity disorder (ADHD) require symptoms or impairment in two or more settings. Thus, information on children's symptoms in school is usually required. This paper presents the Child ADHD Teacher Telephone Interview (CHATTI), an instrument aimed at systematically obtaining this information. AIMS: To examine the stability, test-retest reliability and criterion validity of the CHATTI for children referred with a suspected diagnosis of ADHD. METHOD: Data were obtained from 79 teachers, of whom 36 were interviewed on two occasions. RESULTS: Overall, the CHATTI shows good stability, test-retest reliability and criterion validity for symptom scores. Test-retest reliability for some individual items was low. Reliability for the operationalised criteria of 'pervasiveness' (i.e. symptoms at school and home) and 'school impairment' was excellent (kappa=1). CONCLUSIONS: The CHATTI appears to be a promising tool for assessing ADHD symptoms in a school setting and could be useful in clinical as well as research settings.

Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder. Although the causes of ADHD are unknown, dopaminergic, serotonergic and nor-adrenergic pathways have been strongly implicated. Monoamine Oxidase A (MAOA) is involved in the degradation of all three of these neurotransmitters and therefore has been suggested as a strong candidate gene for ADHD. Animal and human studies have implicated MAOA and 5-HT in impulsive and aggressive behavior. We therefore additionally postulated that MAOA might be associated with a subtype of ADHD where aggressive and impulsive features are especially prominent. We have tested this hypothesis by genotyping two polymorphisms (the 30-bp VNTR in the promoter and the Fnu4HI 941T-->G) in MAOA that are associated with altered MAOA function. Our sample consisted of 171 British Caucasian children 6-16 years of age fulfilling DSM-III R, DSM-IV or ICD-10 criteria for ADHD/Hyperkinetic Disorder. Using case control analysis and then the TDT, no association was found between these two MAOA polymorphisms and ADHD. Case control analysis of the VNTR showed an association with a subgroup of children with comorbid conduct problems (OR = 2.0, 95% CI = 1.09, 3.5), and TDT analysis indicated a statistical trend toward association. Our findings highlight the importance of phenotype definition and the need for the MAOA VNTR to be further examined.