Chromosome glitch tied to separation anxiety

WASHINGTON — Separation anxiety in some children may be due to extra doses of a particular gene.

The gene, GTF2I, is located on human chromosome 7. People missing part of the chromosome that contains GTF2I have a condition called Williams syndrome and are generally extra social. On the other hand, people who have extra copies of that part of chromosome 7 may have social and other types of anxiety: About 26 percent of children with an extra copy the region containing GTF2I have been diagnosed by a doctor as having separation anxiety, human geneticist Lucy Osborne of the University of Toronto said November 15 at a press conference at the Society for Neuroscience’s annual meeting.

Osborne and colleagues genetically engineered mice to have a duplicate copy or two of GTF2I, or to be missing one copy of the gene, then tested the effect of the gene dosage on separation anxiety with a squeak test. Week-old baby mice separated from their mothers send out ultrasonic distress calls. “It’s a ‘come get me’ signal,” Osborne said.

Baby mice with a normal two copies of GTF2I squeaked an average of 192 times over four minutes when removed briefly from their nests. Mice with three or four copies squeaked nearly twice as much, indicating greater anxiety at being separated from their mothers. Mice missing one copy of the gene were a little bit less vocal.

Previous studies have linked missing or duplicated genes to schizophrenia (SN: 4/25/09, p. 16), autism (SN: 7/3/10, p. 12) and attention deficit hyperactivity disorder (SN: 9/10/11, p. 12), but this is the first study to show that some forms of anxiety may be linked to added or subtracted genes. The researchers don’t yet know how the gene leads to anxiety, but GTF2I regulates the activity of other genes and helps control levels of calcium, which brain cells use to communicate with each other.

The mouse experiments make the observation of greater separation anxiety of children with extra copies of GTF2I much more believable than a mere association of a genetic change with a certain human disease, says Klaus Miczek of Tufts University in Boston, who was not involved in the work.

Even though the researchers have shown that duplications of the gene may be involved in some cases of separation anxiety, the gene is probably not involved in all types of anxiety, Osborne said. And not every child with separation anxiety will have extra copies of GTF2I.