Neuropsychiatric Genetics Research
Group Attention-Deficit/Hyperactivity Disorder
Attention Deficit Hyperactivity Disorder (ADHD) affects approximately 3-6 % of all children. Onset is prior to seven years of age and generally persists throughout childhood but often beyond into adolescence and adulthood. It is a biological, brain-based condition which results in two primary areas of impairment - attention and impulsive-hyperactive. These in turn cause educational, family and social problems.
We have found evidence that genetic variation at the Dopamine transporter gene possibly contributes in a small way to the cause of ADHD. We have also found evidence that two further genes may be involved. These genes are known as Dopamine beta hydroxylase, which is a gene coding for a naturally occurring enzyme, which is necessary to break down the neurotransmitter dopamine in the brain after its use. The second gene we have identified as potentially playing some role, is the Dopamine 5 receptor (the fifth subtype in a family of five Dopamine receptors). Our studies suggest that subtle DNA sequence difference (inherited differences) at these genes may contribute to risk, in addition to risk caused by the Dopamine transporter. Over the past two years we have taken advantage of significant advances in genetic technology platforms. In one of our studies (the IMAGE project) this has enabled “whole genome” analysis of common variation in our DNA sequence. Our strategy examines how DNA is passed on from parents to their child with ADHD. We have recently completed a study, as part of the GAIN Initiative to examine over 600,000 DNA markers in nearly 1000 mothers, fathers and their children who have ADHD. Many biologically plausible novel genes and pathways have been identified from these studies that can be further examined in individuals with ADHD.
The finding that several genes are possibly involved is very much what we expected given that ADHD is quite common and yet does not follow a clear inheritance pattern.
This pattern is also seen for many other conditions such as asthma, diabetes and many other common disorders, which are at least partially inherited. It indicates that it is likely that many genes of small effect combine to contribute to risk, but in any individual case, it may be impossible to determine which genes are involved.
This research will involve a member of the research team carrying out a clinical interview with a parent of each child with ADHD. The interview is confidential and will take approximately an hour, or alternatively, it could be divided into two sessions. We will also need to obtain a small blood sample from the child and from both mother and father.
There are a number of studies into ADHD on-going in the group at the moment:
- On-going ADHD Genetics Study with Dr Ziarah Hawi and Dr Naomi Lowe
- Deficits in attention and executive function in relation to genotype Study with Prof. Michael Gill and Prof. Ian Robertson
- International Multi-center ADHD Genetics Project (IMAGE) with Dr. Aisling Mulligan and Louise Butler
- STAR Study - A prospective study of the clinical genetics of methylphenidate response in children with ADHD with Drs. Aiveen Kirley, Edwina Barry, Marie Cox
For more information
Biofeedback-attentional Training Study
In the Trinity College Institute of Neuroscience, they are conducting a study to examine the effects of a biofeedback-attentional training on adult ADHD patients. They are looking for adult, aged 18-50 years, who have been diagnosed with ADHD, to participate in this study. If you would like to participate or would like further information, please contact: Simona Salomone T: +353 1 896 8403, firstname.lastname@example.org or Sophia Kilcullen T: +353 1 896 8403, email@example.com.
Information on Study
The study involves attending the Institute of Neuroscience for 3 sessions for cognitive as well as EEG/fMRI assessment. Other 2 or 3 additional training sessions will be needed. Before starting the study, patients will be fully informed about EEG/fMRI procedures. Moreover, subjects who agree to participate will be randomly assigned to a biofeedback training called Self-Alert Training (SAT) group and a standard attentional training group.
Participants in both groups will receive in the first session a baseline cognitive, psychological and EEG/fMRI assessment.
The self-alert training group will attend two/three training sessions providing psychoeducation regarding arousal and attention, demonstration of external control over attention using skin conductance response, and self-initiated control over the arousal response. They will identify goals for the application of this strategy to key situations in everyday life. Participants will then practice self-alerting over a 2 week period at home using a home Electrodermal Activity (EDA) device that includes a remote monitoring system. The participant will be contacted twice a week during this period and their progress reviewed. There will be a final top-up training session.
The standard attentional training group will attend for the same number of training sessions and be contacted by the research team but will carry out Nintendo DS ‘brain training exercises’ rather than self-alert training.
Both groups will be reassessed after 5 weeks (session 2) and 17 weeks (session 3) using the cognitive, psychological, EEG and fMRI measures.
The study aims to evaluate the effectiveness of attentional training for adult with ADHD aged form 18 y.o. to 50 y.o. on cognitive and mental abilities as well as how it impacts on daily life.
This study is the result of a collaboration between Trinity's research team, led by Professor Ian Robertson, in the Trinity College Institute of Neuroscience, and dott. Jessica Braham from San Patrick Hospital.
There is strong evidence that ADHD is in part caused by something that is inherited within families. It is thought that many genes contribute to these disorders, each having a small effect. The study we are conducting aims to identify the genes involved, which will increase our understanding of these disorders. This is important, and may eventually lead to better treatment or even prevention of these common disorders.
What is involved?
You will be visited at home or invited to attend an appointment with a member of the research team at a time that is convenient for you. You will:
- Be asked a series of questions about your child with ADHD.
- Complete brief questionnaires about your child's symptoms and also about yourself.
- Be asked if your child with ADHD and both biological parents can each give a blood sample.
This study is strictly confidential and no one else will have access to your personal details. No individual results will be generated by this study, but by being involved you are helping researchers understand the causes of ADHD.
Inclusion Exclusion Criteria
To be suitable to take part in the study, we recommend:
- The child has been diagnosed with ADHD by a health professional
- The child is not adopted and will be able to give a small blood sample
- There are two biological parents available to give a blood sample each
- The child does not have the following conditions: Epilepsy, Fragile X Syndrome, Autism, Asperger's Syndrome, Tourette Disorder, Moderate Learning Disability (IQ below 70).
For more information:
E: Aiveen Kirley: firstname.lastname@example.org
Deficits in Attention and Executive function in relation to ADHD genotype
We have previously identified three genes (DAT1, DBH and DRD5) contributing to ADHD in Irish families in a study funded by the Health Research Board. Each of these may influence the liability of the clinical diagnosis of ADHD to a small degree.
However, it is most unlikely that genes map directly to the clinical phenotype of ADHD. It is more likely that individual genes influence individual neuropsychological systems, which in certain combinations, result in the clinical diagnosis. The genetic architecture underlying these 'traits' is likely to be less complicated than for the ADHD clinical diagnosis.
Clear abnormalities in specific neuropsychological measures of attention and executive function are known to exist in ADHD and one of our researchers has been influential in developing new measures of attention that build on recent theoretical advances in understanding the differing attention systems of the brain.
The aim of this study is to measure patterns of attentional and executive dysfunction in a large sample of children diagnosed as suffering from ADHD. This will establish neuropsychological phenotypes to be used as quantitative traits in a genetic association study of gene polymorphisms.
For more information contact:
Many families with a child with ADHD have met with researchers from Trinity College Dublin and contributed to research into ADHD. The IMAGE study has been run in 11 centres in Europe, as well the Department of Psychiatry, TCD. It is funded by the National Institute of Mental Health in the USA. The aim is to collect blood samples from 1400 families where there is a child with ADHD. Blood samples are sent to the USA, where they are preserved for research into ADHD and genetics. At Trinity College Dublin, we have taken an active role in the analysis of both the clinical and genetics data coming from this collaboration.
From a clinical perspective, at Trinity College Dublin we have focused on examining the clinical co-morbidity in ADHD, including the presence of conduct, oppositional disorders and autism-traits (Mulligan, Anney, et al., 2008). These data and others are being examined within the various genetic resources that have been generated on this cohort.
There are five major genetic datasets based on the IMAGE consortia collections;
- Study 1: Candidate Gene Study on approximately (~1000 DNA Markers)
- Study 2: CIDR Linkage Study (~6000 Markers)
- Study 3: CIDR Linkage Study Follow-Up (~6000 Markers)
- Study 4: GAIN Perlegen Genome-Wide Association Study (GWAS) (~600,000 Markers [Perlegen Array])
- Study 5: IMAGE-II GWAS Follow-Up (~500,000 Markers [Affymetrix Array]) – (complete mid-2009)
The IMAGE consortium initially examined individuals from this study with a selection of hypothesis-defined DNA markers in 51 candidate genes (Study 1) implicated in ADHD (Brookes, Xu, Chen et al., 2006). This was followed by specific follow-up of interesting findings around the dopamine transporter gene (SLC6A3) (Brookes, Xu, Anney.,et al 2008), and the inheritance of risk DNA from mothers and fathers (Anney, Hawi, Sheehan, et al., 2008).. We continued this analysis using the hypothesis-free linkage approach, identifying regions of interest on chromosome 1, 9 and 16 (Zhou, Asherson, Sham., et al 2008; Asherson, Zhou, Anney., et al 2008).
In 2007, we were awarded a GAIN project, which enabled this sample to be examined using a new technology that looks at many hundreds of thousands of DNA markers across the genome. This study is important as so many families and so many markers can be studied together in one group. This will ultimately enable us to better identify genes and variation that offer risk or protection against developing ADHD or aspects of ADHD.
Study 4, the GAIN GWAS was the first published GWAS of ADHD (Neale, Lasky-Su, Anney et al., 2008). Additional research manuscripts have followed from this data looking at symptom severity (Lasky-Su, Neale, Franke, et al., 2008), age-of-onset (Lasky-Su, Anney, Neale, et al., 2008), and co-morbid disorders such as conduct disorder and autism-traits (Anney, Lasky-Su, O'Dúshláine, et al., 2008).
We are entering Study 5, where we can further examine the association signals identified through our previous research in large independent samples including the IMAGE-II project. Moreover, we have joined the ADHD component of the Psychiatric Genetics Consortium – the largest single global collaboration of psychiatric geneticists. The PGC is set with the task to bring together data from 47 studies, including whole genome data of over 500,000 markers on over 80,000 individuals. These data will undergo sophisticated statistical analysis to understand within and across disorder genetic risk.
Many thanks to all the families who have given samples the IMAGE study, without whose contribution this work could not take place. Your time and effort are much appreciated. We have been invited to present aspects of these data at many prestigious local and international meetings on genetics and psychiatry including the World Congress on Psychiatric Genetics, the American Society of Human Genetics, the ADHD Genetics Network, the Irish Society of Human Genetics and the Irish College of Psychiatrists.
For further information
Dr Aisling Mulligan
We would like to invite you to take part in this project that is designed to find out about the genetic causes determining response to stimulants i.e. Ritalin, Concerta, Dexedrine in children with Attention Deficit Hyperactivity Disorder.
There is strong evidence that ADHD tends to run in families. Research has shown the importance of genetic influences in the development of ADHD, although this does not mean that the behaviour is caused by genetic factors alone. The genetic predisposition is modified in turn by environmental factors that are also unclear. The STAR Study is designed to look for genes and clinical factors influencing response to stimulant medication in ADHD. The study will use molecular genetic techniques and match the genes to detailed clinical examination findings.
The STAR Study is funded by the Health Research Board of Ireland. This is a government body which funds medical research. The study is a joint Trinity College Dublin and UCD project and the research team office is in St. James Hospital. The study is currently waiting to be examined by the ethics committee in your health board area and has already been approved by three other ethics committees. This ensures that patient interests have been protected.
The STAR Study is currently recruiting children aged 5 to 15 years who have been diagnosed with ADHD and are due to start taking stimulant medication for the first time. The study involves the researchers Dr. Edwina Barry and Marie Cox meeting families before the child starts on medication and three times during the following year to assess the child's response. Dr. Barry will interview the parent about the child's behaviour while the psychologist Marie Cox will ask the child to complete a series of tasks to assess attention, general intelligence, language development and reading ability. The parent and child's teacher will be asked to complete a number of brief questionnaires about the child's symptoms. We also need to obtain a small blood sample from the child and the biological parent(s).
Participation in this study is voluntary and you have the right to withdraw at any time without your child's treatment being affected. Participation is confidential and your medical information and DNA will be stored using a code. Feedback is given to your child's doctor from the psychological assessments and rating sale measures of response.
If you have any questions about the study please feel free to contact the researchers at:
T: +353 1 8962464 or email:
Dr Edwina Barry: email@example.com
Ms Marie Cox