Why boys are brats

The first Indian genetic study on a common behavioural disorder explores why inattentiveness and hyperactivity are more common in boys than in girls. G.S. Mudur reports .

Mothers who carry a ‘faulty’ version of the MAOA gene prefentially hand it down to their sons.

The exact biological basis for boys appearing naughtier than girls has long eluded scientists, but Calcutta-based geneticist Kanchan Mukhopadhyay has stumbled upon something that may at least partly explain why more boys than girls get into trouble in school and at home.

Mukhopadhyay has been looking for genes that might help unravel the complexity of attention deficit hyperactivity disorder (ADHD) — a behavioural disorder so common that psychiatrists expect two children in every class of 40 to have it. It’s a condition marked by inattentiveness, impulsive action and hyperactivity, and surfaces typically during early school years. Most children diagnosed with ADHD while in school continue to have the symptoms in adolescence and adulthood.

Now, in a study of a medium-sized gene on the human chromosome X — one of the two sex chromosomes — Mukhopadhyay and her colleagues have detected a possible mechanism that might explain why ADHD is four times more common in boys than in girls. The researchers at the Manovikas Biomedical Research and Diagnostic Centre, Calcutta, have discovered that mothers who carry a “faulty” version of the gene preferentially hand it down to their sons.

“This is an effort to understand better the biochemical changes in the brain that accompany ADHD,” said Swagata Sinha, a psychiatrist and a member of the research team. “When we treat patients with ADHD today — whether through behaviour therapy or medication — we find that some respond well, while others do not respond. A clearer picture of what’s going on inside the ADHD brain may help us improve therapy.”

In their study, the Manovikas Centre researchers analysed the genetic alphabets on a gene that makes an enzyme called monoamine oxidase (MAOA) in a group of 64 boys and nine girls with ADHD who were brought to their clinic as outpatients. They also examined the corresponding genes in both the parents of 67 children.

“We picked the MAOA gene because it has long been viewed as a candidate gene implicated in ADHD,” Mukhopadhyay told KnowHow.

Nearly a decade ago, researchers in the US had shown that mice that lack MAOA show aggressive behaviour. Several other studies have also pointed to a role for MAOA in human behaviour and brain physiology, perhaps through its action of altering the levels of various brain chemicals that neurons use to signal each other.

The study by the Manovikas Centre researchers has shown that one version of the gene that causes the MAOA enzyme to have lower-than-normal activity is associated with ADHD. Patients with ADHD are more likely to have this version of the gene than people without ADHD. Their findings were published in a recent issue of the American Journal of Medical Genetics: Neuropsychiatric Genetics.

The researchers caution that their findings need to be validated through larger samples of patients and that the presence of the variant of the gene that makes only low activity enzyme can at best only predispose people to ADHD. “Several genes are likely to be involved in ADHD — one gene alone cannot explain it,” said Mukhopadhyay.

Previous studies have suggested that environmental triggers may act on people who are already genetically predisposed to ADHD. And while ADHD had long been viewed as a problem emerging from a chemical imbalance in the brain, an imaging study three years ago revealed that there may also be subtle anatomical differences in areas of the brain that control behaviour changes observed in ADHD. In that study, US researchers had used a new brain mapping study to detect what they described as abnormal brain anatomy in a small set of children with ADHD.

The researchers at the North Shore Long Island Jewish Health System in New York found abnormalities in the circuitry in several regions of the brain such as frontal cortex, basal ganglia and the cerebellum.

“These areas are involved in the processes that regulate attention, impulsive behaviour and hyperactivity — the key symptoms of children with ADHD,” said Manzar Ashtari, associate professor of psychiatry and radiology at the clinic.

The evidence for the role of environmental triggers was bolstered by another study in the US last year which showed that genetic variations may determine how children respond to potential toxins in the environment. The study by researchers at the Cincinnati Children’s Hospital suggested that genes can predispose a child to negative effects of environmental exposure to lead.

The study found that only children with certain variations of a gene that helps control the levels of a brain chemical called dopamine appear specially vulnerable to the adverse effects of lead on attentiveness.

Increasing lead exposure tended to impair performance in boys more than in girls. Boys appear more vulnerable than girls. “This is consistent with the fact that boys have higher rates of ADHD than girls,” said Tanya Froehlich at the Cincinnati Children’s Hospital.

The Calcutta study has also revealed a possible additional mechanism to explain why boys have more ADHD than girls. The study has indicated that the version of the MAOA gene associated with low-activity enzyme is “preferentially transmitted” from mothers to boys with ADHD.

“It is still unclear why this variant of the gene is preferentially transmitted to boys,” Mukhopadhyay said. However, the researchers also point out that their study included only nine girls, and a larger study would be needed to ascertain that such transmission does not occur in girls.

The MAOA gene lies on the X chromosome which both boys and girls get from their mothers. In principle, this alone could explain why ADHD is less common in girls than in boys. The sex chromosome is XX in girls and XY in boys.

“Boys have only one copy of the X chromosome. If they get the low-activity version, they have nothing else to compensate for its low activity. But girls have two X chromosomes. In the event that one X has the low-activity enzyme, the other can compensate by producing normal levels,” said Mukhopadhyay.

Source:The Telegraph (Kolkata,India)

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