Behavioural genetics. Worming out social secrets.
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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.
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In the wake of the recent announcements that the human genome has been mapped, efforts to identify the genetic loci underlying personality function will grow and intensify. Much research has already been done in this area, but it has for the most part been limited to classical biometrical approaches designed to determine if personality has a heritable basis. These so-called "heritability" studies estimate how much of the individual differences in personality are attributable to genetic differences among people. Molecular-genetic approaches, on the other hand, are designed to identify specific putative loci, but have yielded mixed results. The inconsistency in research findings can be attributed in part to the lack of sufficient numbers of genetic markers in the chromosomal regions of interest--a problem that the creation of a map of the human genome will help to rectify. This map and its inevitable refinements, however, can only advance the search for the genes for personality to a limited degree. Serious unresolved problems in the conceptualization and definition of personality and its dysfunction remain, which will hamper the search for personality genes.
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Although gender differences in the consumption and abuse of alcohol and drugs are frequently reported, the etiology of these differences has received limited attention. The present study applied biometric genetic analyses to determine whether self-report questionnaire items assessing problem alcohol and drug use are influenced by gender-specific genetic and environmental influences. The sample consisted of 693 volunteer general population twin pairs (209 monozygotic female, 138 monozygotic male, 170 dizygotic female, 82 dizygotic male, 94 dizygotic opposite-sex twin pairs). Heritability analyses showed that most aspects of drug and alcohol problems were differentially heritable by gender. Significant additive genetic effects were found only in males, whereas in females, most substance use problems were wholly determined by environmental factors. In both genders, non-shared environmental factors accounted for the largest proportion of the variance, and further gender-by-genotype analyses showed that these influences were not gender specific, but rather were common to males and females. Some preliminary evidence was also obtained that the use of illicit drugs may be etiologically distinct from the use of licit drugs in females and males.
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