Study: Evidence of Genetic Basis for ADHD

Attention-deficit/hyperactivity disorder is a neurodevelopmental disorder, rather than a purely social construct, according to British researchers who have found that a type of genetic variation associated with brain disorders such as schizophrenia and autism also occurs in excess in ADHD patients.

The findings provide the first direct evidence of a genetic basis for ADHD, Dr. Nigel Williams of Cardiff University, Wales, and his colleagues reported.

The investigators performed a genome-wide analysis of large, rare chromosomal deletions and duplications known as copy number variants (CNVs) in 366 children with ADHD and 1,047 controls. The genome-wide burden of CNVs was significantly greater in the ADHD patients, compared with that in the controls – rates of 0.156 and 0.075, respectively, they found (Lancet 2010 Sept. 30 [doi:10.1016/S0140–6736(10)61109-9]).

The CNVs identified in this study are similar to those found in patients with schizophrenia and autism, and are significantly enriched for loci that have previously been implicated in those disorders – with particular overlap at a region on chromosome 16 that spans a number of genes, including one that affects brain development.

Furthermore, although the rate of CNVs was significantly higher in children with ADHD with and without intellectual disability, compared with the general population, the rate was particularly high in those with intellectual disability, defined as those with an IQ of less than 70 (rates of 0.424 and 0.075, respectively).

The findings are noteworthy because despite evidence that ADHD might be a genetic condition – for example, it has an estimated heritability of 76% – there has been a great deal of debate over whether it is a result of bad parenting or other external factors, coauthor Dr. Anita Thapar said during a press conference.

"ADHD can be stigmatizing … and finding this direct genetic link to ADHD should help clear this misunderstanding and address this issue of stigma," said Dr. Thapar, professor of child and adolescent psychiatry at Cardiff University.

In addition to providing a window into the biology of the brain, the findings will also influence the way in which ADHD is classified and will improve communication between scientists and clinicians about “what we mean by ADHD,” she said. "This will be the start of a much more scientific venture because our findings are going to help us unravel the biologic basis of ADHD, and that's going to be really important in turn in the further future to help us develop new and much more effective treatments for affected individuals."

The subjects were recruited from community clinics and had met diagnostic criteria for ADHD or hyperkinetic disorder. They were aged 5–17 years (mean, 10.5 years), were of white U.K. origin, and had a mean IQ of 86. Controls were unrelated, ethnically matched children from the 1958 British Birth Cohort.

The finding that more than a third of ADHD children with intellectual disability carried a large, rare CNV – and the fact that none of these children had been assessed for this type of mutation by clinical services – suggest that routine referral to clinical geneticists and screening for such mutations could be helpful for children with ADHD who also have intellectual disability, they said.

Attention-deficit/hyperactivity disorder is a neurodevelopmental disorder, rather than a purely social construct, according to British researchers who have found that a type of genetic variation associated with brain disorders such as schizophrenia and autism also occurs in excess in ADHD patients.

The findings provide the first direct evidence of a genetic basis for ADHD, Dr. Nigel Williams of Cardiff University, Wales, and his colleagues reported.

The investigators performed a genome-wide analysis of large, rare chromosomal deletions and duplications known as copy number variants (CNVs) in 366 children with ADHD and 1,047 controls. The genome-wide burden of CNVs was significantly greater in the ADHD patients, compared with that in the controls – rates of 0.156 and 0.075, respectively, they found (Lancet 2010 Sept. 30 [doi:10.1016/S0140–6736(10)61109-9]).

The CNVs identified in this study are similar to those found in patients with schizophrenia and autism, and are significantly enriched for loci that have previously been implicated in those disorders – with particular overlap at a region on chromosome 16 that spans a number of genes, including one that affects brain development.

Furthermore, although the rate of CNVs was significantly higher in children with ADHD with and without intellectual disability, compared with the general population, the rate was particularly high in those with intellectual disability, defined as those with an IQ of less than 70 (rates of 0.424 and 0.075, respectively).

The findings are noteworthy because despite evidence that ADHD might be a genetic condition – for example, it has an estimated heritability of 76% – there has been a great deal of debate over whether it is a result of bad parenting or other external factors, coauthor Dr. Anita Thapar said during a press conference.

"ADHD can be stigmatizing … and finding this direct genetic link to ADHD should help clear this misunderstanding and address this issue of stigma," said Dr. Thapar, professor of child and adolescent psychiatry at Cardiff University.

In addition to providing a window into the biology of the brain, the findings will also influence the way in which ADHD is classified and will improve communication between scientists and clinicians about “what we mean by ADHD,” she said. "This will be the start of a much more scientific venture because our findings are going to help us unravel the biologic basis of ADHD, and that's going to be really important in turn in the further future to help us develop new and much more effective treatments for affected individuals."

The subjects were recruited from community clinics and had met diagnostic criteria for ADHD or hyperkinetic disorder. They were aged 5–17 years (mean, 10.5 years), were of white U.K. origin, and had a mean IQ of 86. Controls were unrelated, ethnically matched children from the 1958 British Birth Cohort.

The finding that more than a third of ADHD children with intellectual disability carried a large, rare CNV – and the fact that none of these children had been assessed for this type of mutation by clinical services – suggest that routine referral to clinical geneticists and screening for such mutations could be helpful for children with ADHD who also have intellectual disability, they said.

Attention-deficit/hyperactivity disorder is a neurodevelopmental disorder, rather than a purely social construct, according to British researchers who have found that a type of genetic variation associated with brain disorders such as schizophrenia and autism also occurs in excess in ADHD patients.

The findings provide the first direct evidence of a genetic basis for ADHD, Dr. Nigel Williams of Cardiff University, Wales, and his colleagues reported.

The investigators performed a genome-wide analysis of large, rare chromosomal deletions and duplications known as copy number variants (CNVs) in 366 children with ADHD and 1,047 controls. The genome-wide burden of CNVs was significantly greater in the ADHD patients, compared with that in the controls – rates of 0.156 and 0.075, respectively, they found (Lancet 2010 Sept. 30 [doi:10.1016/S0140–6736(10)61109-9]).

The CNVs identified in this study are similar to those found in patients with schizophrenia and autism, and are significantly enriched for loci that have previously been implicated in those disorders – with particular overlap at a region on chromosome 16 that spans a number of genes, including one that affects brain development.

Furthermore, although the rate of CNVs was significantly higher in children with ADHD with and without intellectual disability, compared with the general population, the rate was particularly high in those with intellectual disability, defined as those with an IQ of less than 70 (rates of 0.424 and 0.075, respectively).

The findings are noteworthy because despite evidence that ADHD might be a genetic condition – for example, it has an estimated heritability of 76% – there has been a great deal of debate over whether it is a result of bad parenting or other external factors, coauthor Dr. Anita Thapar said during a press conference.

"ADHD can be stigmatizing … and finding this direct genetic link to ADHD should help clear this misunderstanding and address this issue of stigma," said Dr. Thapar, professor of child and adolescent psychiatry at Cardiff University.

In addition to providing a window into the biology of the brain, the findings will also influence the way in which ADHD is classified and will improve communication between scientists and clinicians about “what we mean by ADHD,” she said. "This will be the start of a much more scientific venture because our findings are going to help us unravel the biologic basis of ADHD, and that's going to be really important in turn in the further future to help us develop new and much more effective treatments for affected individuals."

The subjects were recruited from community clinics and had met diagnostic criteria for ADHD or hyperkinetic disorder. They were aged 5–17 years (mean, 10.5 years), were of white U.K. origin, and had a mean IQ of 86. Controls were unrelated, ethnically matched children from the 1958 British Birth Cohort.

The finding that more than a third of ADHD children with intellectual disability carried a large, rare CNV – and the fact that none of these children had been assessed for this type of mutation by clinical services – suggest that routine referral to clinical geneticists and screening for such mutations could be helpful for children with ADHD who also have intellectual disability, they said.