Characterizing the ADHD phenotype for genetic studies (original) (raw)
Related papers
The genetics of ADHD: A literature review of 2005
Current Psychiatry Reports, 2006
Investigations into the genetic basis of attention-deficit/ hyperactivity disorder (ADHD) continue to yield compelling results as candidate gene studies reveal more information about this elusive disorder. Family, twin, and adoption studies further the notion that ADHD is a highly heritable disorder with direct genetic and environmental influence. The year 2005 saw many ADHD candidate gene studies, with most focused on the catecholaminergic candidates. Although many genes were studied in 2005, a large portion of findings has been supportive of the roles of dopaminergic genes’ relationship to clinical phenotypes and drug response. These studies often require replication. Clinical implications continue to be speculative, as larger sample sizes are needed to validate findings to the general population. Further understanding of endophenotypes and the impact of comorbidities also is necessary for proper clinical intervention. Forthwith, we provide a summary of ADHD genetic studies published in 2005.
Biochemical markers and genetic research of ADHD
2005
ADHD; candidate genes; biochemistry; correlations; comorbidity; research Abstract ADHD (attention hyperactivity disorder) is a polygenetic disorder with various candidate genes. At this time, more than thirty dopaminergic, noradrenergic, serotonergic and GABA-ergic genes are known. The research of only some can- didate genes (DRD4, DAT, DRD5, DBH, 5HTT, HTR1B and SNAP25) brought relatively consistent results confirming the heredity of ADHD syndromes.
Genetics of Attention Deficit Hyperactivity Disorder (ADHD): Recent Updates and Future Prospects
Attention deficit hyperactivity disorder (ADHD) is not only highly prevalent, persistent and impairing but also is one of the most heritable of all psychiatric disorders. As a result, ADHD has been the focus of considerable genetic research. The results of recent genetic studies are reviewed with a focus on the emerging picture and future trends. ADHD appears to be a complex disorder in which multiple genetic and environmental risks contribute to a quantitative trait. At the same time, there is growing evidence that in a proportion of cases, individually rare variants such as copy number variants may play an important causal role. The more genetic risks, both common and rare, the more extreme the trait. With increasing samples and advanced genetic methods, single nucleotide polymorphism (SNPs) and copy number variants (CNVs) conferring risk for ADHD are being identified. Further study will be required before we can understand the causal significance of these findings. Increased sample size is an urgent necessity if we are to discover potentially causal variants. Non-behavioral markers of genetic risk known as endophenotypes could also play a role in parsing the phenotypic and genetic heterogeneity of ADHD as they have in other complex disorders. Genetic studies in ADHD hold the potential for refined nosology, more precise diagnosis, and differential diagnosis, improved early identification leading to novel intervention strategies and identification of innovative targets for therapeutics based on a precise understanding of disease mechanism.
The IMAGE project: methodological issues for the molecular genetic analysis of ADHD
Behavioral and brain functions : BBF, 2006
The genetic mechanisms involved in attention deficit hyperactivity disorder (ADHD) are being studied with considerable success by several centres worldwide. These studies confirm prior hypotheses about the role of genetic variation within genes involved in the regulation of dopamine, norepinephrine and serotonin neurotransmission in susceptibility to ADHD. Despite the importance of these findings, uncertainties remain due to the very small effects sizes that are observed. We discuss possible reasons for why the true strength of the associations may have been underestimated in research to date, considering the effects of linkage disequilibrium, allelic heterogeneity, population differences and gene by environment interactions. With the identification of genes associated with ADHD, the goal of ADHD genetics is now shifting from gene discovery towards gene functionality--the study of intermediate phenotypes ('endophenotypes'). We discuss methodological issues relating to quanti...
Genetics of attention-deficit hyperactivity disorder (ADHD)
Attention-deficit hyperactivity disorder (ADHD) is a clinically and genetically heterogeneous syndrome which is comorbid with childhood conduct disorder, alcoholism, substance abuse, dis-social personality disorder, and affective disorders. A small but consistent overlap with autistic symptoms has also been established. Twin and family studies of ADHD show a substantial genetic heritability with little or no family environmental effect. Linkage and association studies have conclusively implicated the dopamine transporter gene (DAT1). DAT1 has also been confirmed as being associated with bipolar disorder. Remarkably, and for the first time in psychiatry, genetic markers at the DAT1 locus appear to be able to predict clinical heterogeneity because the non-conduct disordered subgroup of ADHD is associated with DAT1 whereas other subgroups do not appear to be associated. The second most well replicated susceptibility gene encodes the DRD4 dopamine receptor and many other dopamine related genes appear to be implicated. It is becoming increasingly clear that genes causing bipolar mania overlap with genes for a subtype of ADHD. The key to understanding the genetics of ADHD is to accept very considerable heterogeneity with different genes having effects in different families and in different individuals. It is too early to interpret the new wave of genome-wide association and copy number variant studies but preliminary data support the overlap with affective disorder genes and also with CNS connectivity genes likely to be involved in autism and affective disorders.
Attention-Deficit/Hyperactivity Disorder Endophenotypes
Biological Psychiatry, 2005
Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable disorder with a multifactorial pattern of inheritance. For complex conditions such as this, biologically based phenotypes that lie in the pathway from genes to behavior may provide a more powerful target for molecular genetic studies than the disorder as a whole. Although their use in ADHD is relatively new, such "endophenotypes" have aided the clarification of the etiology and pathophysiology of several other conditions in medicine and psychiatry. In this article, we review existing data on potential endophenotypes for ADHD, emphasizing neuropsychological deficits because assessment tools are cost effective and relatively easy to implement. Neuropsychological impairments, as well as measures from neuroimaging and electrophysiological paradigms, show correlations with ADHD and evidence of heritability, but the familial or genetic overlap between these constructs and ADHD remains unclear. We conclude that these endophenotypes will not be a quick fix for the field but offer potential if careful consideration is given to issues of heterogeneity, measurement and statistical power.
A genetic study of ADHD and activity level in infancy
It is well known that there are strong genetic influences on attention-deficit hyperactivity disorder (ADHD), with genetic association studies providing good evidence for the involvement of the dopamine neurotransmitter system in its aetiology. Developmental origins of ADHD represent an interesting area of research to understand the genetics that underlie early appearing individual differences. However, understanding the molecular basis of ADHD requires accurate, unbiased, heritable measures that can be used for molecular genetic association analyses. We take two approaches to examine the genetics of ADHD behaviours in infancy. Using quantitative genetic techniques, we explore the relationship between objective measures of activity level (AL) in both home and laboratory environments as well as with parent ratings of ADHD symptoms in a population sample of 2-year-old twins. Molecular association analyses of these measures examine candidate genes previously associated with ADHD. We find that ADHD symptoms, AL in the home and AL in the lab represent heritable phenotypes in 2-year-old infants. AL measured in the home has a strong genetic correlation with symptoms of ADHD, whereas AL in the lab correlates only modestly with the same ADHD measure. Genetic correlations suggest that AL in the home is more comparable than AL in the lab to ADHD behaviour and support the separation of all three for molecular analyses. There was modest evidence for association between DAT1, NET1 and ADHD symptom scores, as well as between DAT1 and AL in the lab.
2013
The present thesis uses data collected from four studies. The research described in chapter 2 utilised data from the Twins' Early Development Study (TEDS); an ongoing general population cohort of twins headed by Professor Robert Plomin (funded by the UK Medical Research Council (MRC) grant G0901245 and G0500079 to Professor Robert Plomin). Chapters 3 to 5 were based on data collected from two studies. The first of these studies was the Study of Activity and Impulsivity Levels (SAIL) in children, headed by Dr Jonna Kuntsi (funded by a Wellcome Trust grant GR070345MF to Dr Jonna Kuntsi). The SAIL sample is a subsample recruited from TEDS. The second sample is an ADHD-proband sibling-pair sample (the London part of this project is funded by MRC grant G03001896 to Dr Jonna Kuntsi; the international collaboration with seven other teams from the International Multicentre ADHD Genetics Consortium (IMAGE) was funded, in part, by NIMH grant R01062873 to Professor Steve Faraone (London PI: Professor Philip Asherson)). I was not involved in the planning or collection of data for the above studies. The research described in chapter 6 is based on a selected sample of male adolescent twin pairs (NEurophysiology of Attention and Activity in Twins (NEATT); PI: Professor Robert Plomin and Dr Grainne McLoughlin), recruited from TEDS for consistently high/low parental ADHD ratings. Participants were invited to the research centre for cognitive-electroencephalography assessment and collection of salivary cortisol. I played a key role in the conception and design of the salivary cortisol component of the project, under the supervision of Dr Jonna Kuntsi and Professor Philip Asherson. I was involved in writing up the ethics application for the salivary cortisol component of the project, collecting salivary cortisol samples, collecting questionnaire data from both twin pairs and parents, and conducting expressed emotion tasks with parents
Mini-review on the Basic Genetic Aspects for the Attention Deficit Hyperactivity Disorder (ADHD)
Bulletin of Integrative Psychiatry
Attention deficit hyperactivity disorder (ADHD) is a common and generally inherited neuropsychiatric disorder that is present in children and adults, and it is considered a multifactorial disorder. Due to the limited effects of genes on the manifestation of the disorder, we wanted to analyze the impact of the genes SNAP25, BAIAP2, ANKK1, DAT1 on attention deficit hyperactivity disorder (ADHD) and to emphasize the importance of genetic architecture in the learning experience and the development of an individual since genes can negatively affect an individual's life. Another rationale for this study was the very well-known problem of accurately diagnosing ADHD because this is usually made through questionnaires or interviews with the patient suspected of having the disorder, which can lead to errors. The idea of genetic testing to identify the different polymorphisms of genes responsible for ADHD would make the diagnosis more accurate. As a result, we searched the databases for articles in which the authors reported the impact of the genes mentioned above. We identified a total of 12 relevant articles that were discussed throughout this article. We concluded that all the genes selected for this study were implicated in the manifestation of this disorder, only when a specific circumstance was met such as a specific ethnic group was tested, or a specific polymorphism was studied.