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February 12, 2015
Digest

Schizophrenia’s Strongest Known Genetic Risk Deconstructed

Versions of a gene linked to schizophrenia may trigger runaway pruning of the teenage brain’s still-maturing communications infrastructure, NIH-funded researchers have discovered. People with the illness show fewer such connections between neurons, or synapses. The gene switched on more in people with the suspect versions, who faced a higher risk of developing the disorder, characterized by hallucinations, delusions and impaired thinking and emotions.

“Normally, pruning gets rid of excess connections we no longer need, streamlining our brain for optimal performance, but too much pruning can impair mental function,” said Dr. Thomas Lehner, director of the Office of Genomics Research Coordination at NIMH, which co-funded the study along with the Stanley Center for Psychiatric Research at the Broad Institute and other NIH components. “It could help explain schizophrenia’s delayed age-of-onset of symptoms in late adolescence/early adulthood and shrinkage of the brain’s working tissue. Interventions that put the brakes on this pruning process-gone-awry could prove transformative.”

The gene, called C4 (complement component 4), sits in by far the tallest tower on schizophrenia’s genomic “skyline” of more than 100 chromosomal sites harboring known genetic risk for the disorder. Affecting about 1 percent of the population, schizophrenia is known to be as much as 90 percent heritable, yet discovering how specific genes work to confer risk has proven elusive, until now.

A team of scientists led by Dr. Steve McCarroll of the Broad Institute and Harvard Medical School leveraged the statistical power conferred by analyzing the genomes of 65,000 people, 700 postmortem brains and the precision of mouse genetic engineering to discover the secrets of schizophrenia’s strongest known genetic risk. C4’s role represents the most compelling evidence, to date, linking specific gene versions to a biological process that could cause at least some cases of the illness. The results were published Jan. 27 in Nature.

“Since schizophrenia was first described over a century ago, its underlying biology has been a black box, in part because it has been virtually impossible to model the disorder in cells or animals,” said McCarroll. “The human genome is providing a powerful new way [of prying] into this disease. Understanding these genetic effects on risk is a way of prying open that black box, peering inside and starting to see actual biological mechanisms.”

More Than 1 in 20 U.S. Children Have Dizziness, Balance Problems

More than 1 in 20 (nearly 3.3 million) children between the ages of 3 and 17 have a dizziness or balance problem, according to an analysis of the first large-scale, nationally representative survey of these problems in U.S. children. Prevalence increases with age, with 7.5 percent of children ages 15-17 and 6 percent of children ages 12-14 having any dizziness or balance problem, compared with 3.6 percent of children ages 6-8 and 4.1 percent of children ages 3-5. The research was led by investigators at NIDCD.

Researchers found that girls have a higher prevalence of dizziness and balance problems compared to boys, 5.7 percent and 5 percent, respectively. In addition, non-Hispanic white children have an increased prevalence of dizziness and balance problems (6.1 percent) compared with Hispanic (4.6 percent) and non-Hispanic black (4.3 percent) children. The findings were published online Jan. 27 in the Journal of Pediatrics.

“These findings suggest that dizziness and balance problems are fairly common among children, and parents and providers should be aware of the impact these problems can have on our children,” said Dr. James F. Battey, Jr., director of NIDCD and a pediatrician. “Parents who notice dizziness and balance problems in their children should consult a health care provider to rule out a serious underlying condition.”

Previous estimates of dizziness and balance problems in children have ranged from 5 to 18 percent and have been based on limited, foreign, population-based studies.

Uncorrected Farsightedness Linked to Literacy Deficits in Preschoolers

A study funded by NEI has shown that uncorrected farsightedness (hyperopia) in preschool children is associated with significantly worse performance on a test of early literacy.

Moderate hyperopia, if not treated, may affect reading ability and grade school readiness among preschoolers.
Moderate hyperopia, if not treated, may affect reading ability and grade school readiness among preschoolers.

PHOTO: JOE BALINTFY

The results of the Vision in Preschoolers-Hyperopia in Preschoolers study, which compared 4- and 5-year-old children with uncorrected hyperopia to children with normal vision, found that children with moderate hyperopia did significantly worse on the Test of Preschool Early Literacy than their normal-vision peers.

“This study suggests that an untreated vision problem in preschool, in this case one that makes it harder for children to see things up-close, can create literacy deficits that affect grade school readiness,” said Dr. Maryann Redford, a program director in collaborative clinical research at NEI.

In most children with hyperopia, the condition is mild and has little impact on vision. A small number of preschool children have high hyperopia that is corrected with eyeglasses. It’s estimated that 4-14 percent have moderate hyperopia, which often goes undiagnosed and untreated.

“Prior studies have linked uncorrected hyperopia and reading ability in school-age children,” said Dr. Marjean Taylor Kulp, distinguished professor in the College of Optometry at Ohio State University and lead author of the study. “But large-scale investigations looking at reading readiness skills hadn’t been conducted in preschool children. This study was necessary to determine whether or not, at this age, there was a link between the two.”

The results were published Jan. 27 in Ophthalmology.

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