New Clues to Possible Genetic Basis for ADHD
10/04/10
MONDAY, Oct. 4 (HealthDay News) -- Children whose mothers are
likely to produce too little of the brain chemical serotonin
because of gene mutations may be at higher risk of developing
attention-deficit hyperactivity disorder (ADHD) later in life,
Norwegian researchers report.
Serotonin is involved in many physiological functions and plays
an important role during development, especially in the development
of nerve cells, the researchers say.
"An impaired maternal serotonin production may have profound long-term behavioral effects on [offspring], independent of the children's own genotypes," said lead researcher Dr. Jan Haavik, from the Department of Biomedicine at the University of Bergen.
"As technologies evolve, systematic gene sequencing can provide new insight into mechanisms of complex disorders like ADHD," he added.
The report is published in the October issue of the
Archives of General Psychiatry.
For the study, Haavik and colleagues took blood samples from 495
adults with ADHD and 97 of their family members as well as from 187
people without ADHD from across Norway. In addition, they collected
data on these individuals' psychiatric diagnoses and symptoms.
The researchers then sequenced the genes of 646 of the
participants and found nine mutations, eight of which were linked
to the two enzymes involved in the body's synthesis of
serotonin.
The researchers found that children of mothers who were
predisposed to impaired serotonin production were more likely to
have ADHD. Among 38 family members and 41 of the children, those
whose mother had one of the mutations had a 1.5 to 2.5 higher risk
of developing ADHD, compared with people or children who did not
have these mutations or children whose father had the
mutations.
The number and severity of ADHD symptoms varied widely, which
suggested that for children of mothers with these mutations, "the
clinical outcome probably depends on a sum of many different
genetic or environmental factors in addition to variations in
maternal serotonin levels," the Norwegian researchers noted.
They also stressed that further studies replicating the results,
"preferably in larger samples, will be required to corroborate this
relationship."
Dr. Stephan Zuchner, an associate professor and director of the
Center for Human Molecular Genomics at the University of Miami
Miller School of Medicine, said there is considerable debate of how
much of ADHD is genetically based.
"There is an extreme spectrum, from people who think it's not so much to people who think it's a lot," he said. "I think it's certainly significant -- the genetic contribution. There is little doubt that ADHD has a genetic component."
However, Zuchner thinks that developing ADHD is a result of both
genetics and environment. "It is rare to see that genetics alone
can cause ADHD," he said.
Zuchner also noted this is a small study, so it is premature to
try to identify the risk of developing ADHD based on these genetic
mutations. "I would be careful from this small study not to draw
any larger conclusions," he said.
At least one other study has found some evidence of a genetic
basis for ADHD.
A report in the Sept. 30 online edition of
The Lancet found that many who suffer from ADHD appear to
have a genetic abnormality that may predispose them to the
condition, British researchers report.
The U.K. team analyzed the genetic information of 366 children
with ADHD, comparing it to more than 1,000 unrelated but ethnically
matched individuals in a control group. Children with ADHD were
significantly more likely to have missing or duplicated segments of
DNA -- called copy number variations (CNVs) -- than were children
without ADHD, the researchers found. This type of genetic variation
is more common in those with brain disorders, they noted.
The findings were replicated in a study of 825 Icelandic
patients with ADHD and more than 35,000 Icelandic control group
members.
In background materials to the study, the British researchers
said they hoped their findings would help overcome the stigma
associated with ADHD -- which some people associate with parenting
problems or poor diet -- by suggesting that it has a genetic
basis.
Finally, a third study - this time a small case-control study of
about 250 children -- found that children with ADHD are more likely
to suffer from depression or attempt suicide as teens.
In fact, 16 to 37 percent of those with ADHD suffer from major
depressive disorder or a relatively mild form of depression known
as dysthymia, noted Andrea Chronis-Tuscano of the University of
Maryland and colleagues.
"These findings suggest that it is possible to identify children with ADHD at very young ages who are at very high risk for later depression and suicidal behavior," the authors wrote in the same issue of The Lancet. "Considered in light of what is already known about the antisocial outcomes of childhood ADHD and their risk for unintentional injury, it would not be premature to test early prevention programs designed to reduce both serious behavioral and affective [consequences] of ADHD in early childhood."
More information
For more information on ADHD, visit the
U.S. National Institute of Mental Health.
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