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Gene variation may flag risk for early-onset depression.

BARCELONA -- Patients with childhood-onset depression who have a variant in the gene that codes for brain-derived neurotrophic factor also show unique variations in their electroencephalograms, opening the door to a possible screening tool for children deemed at risk for these psychiatric disorders.

Although the evidence is preliminary, "We're getting pretty good data showing that people who are at risk of early-onset depression can be identified by a combination of EEG and genetic information," Dr. James Kennedy said at the annual congress of the European College of Neuropsychopharmacology.

"The gene that codes for brain-derived neurotrophic factor (BDNF) has been studied for about 15 years," Dr. Kennedy said. "Emerging evidence indicates that this protein, which is reduced in depression, rises in the bloodstream after treatment with antidepressants or electroconvulsive therapy." Postmortem studies of suicide completers have shown that the protein is significantly decreased, compared with controls, he said.

As head of psychiatric neurogenetics at the Centre for Addiction and Mental Health, Toronto, Dr. Kennedy has been one of the key players in proving a link between the genetic variant and early-onset depression. Working with Maria Kovacs, Ph.D., of the University of Pittsburgh, Dr. Kennedy has confirmed this link in two large data sets--a group of 191 patients (children and adults) in the United States, with up to 25 years of follow-up, and a cohort of 258 child patients in Hungary.

Three variants are possible, Dr. Kennedy said: The gene can be homozygous for valine, homozygous for methionine, or contain both proteins. In both the Pittsburgh and Hungarian cohorts, the valine/methionine combination was significantly more common among cases than controls.

"In the Hungarian sample, we also looked at how the variants were transmitted from parents to children," Dr. Kennedy said. "The valine version was transmitted 100 times in the families of depressed children, while the methionine version as transmitted only 59 times. This is a highly significant indication that the valine version is creating a higher risk for childhood-onset depression."

His most recent study looked at EEG patterns in 187 adults with a history of childhood-onset depression and 93 healthy controls. Dr. Kennedy expected to find changes in the leads recording hippocampal activity, because BDNF is highly expressed in that area. Instead, he found changes in the theta waves. The changes were not seen in controls and occurred significantly more often in cases with the valine/methionine polymorphism.

"This suggests that that the functional BDNF variant affects EEG symmetry in the parietal brain regions in individuals with childhood-onset major depression," Dr. Kennedy and his colleagues wrote in the study (Neuromuscular Medicine 2008; doi:10.1007/sl2017-008-8038-x).


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Title Annotation:Child/Adolescent Psychiatry
Author:Sullivan, Michele G.
Publication:Clinical Psychiatry News
Date:Oct 1, 2008
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