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By Aalok Mehta
December 24, 2008
Scientists have identified the first known brain chemical abnormality associated with insomnia: a substantial reduction in levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
Otherwise healthy people with insomnia have, on average, 25 to 30 percent less GABA in their brains than do normal sleepers, according to the new study, which appeared in the Nov. 1 issue of the journal Sleep.
Scientists have long suspected a link between GABA and insomnia. The neurotransmitter is known to help brain regions shut down by reducing electrical activity, and several common sleeping pills work by helping nerve receptors link to the chemical more efficiently. But the new study is the first to quantify GABA levels in the brains of insomniacs.
Because the GABA measurements were made during the day, the findings also lend further credence to the theory that insomnia is a “state of hyperarousal” extending throughout the waking hours rather than just a nighttime disease, the study authors wrote.
“The results suggest that insomnia is not just a sleep problem,” says principal investigator John Winkelman, a physician at Brigham and Women's Hospital, which is an affiliate of Harvard Medical School. “It’s a 24-hour-a-day problem.”
Mysterious disease
In many ways, insomnia remains largely a mystery to the medical community. “It’s the most common sleep disorder but the most poorly understood,” says Jerome Siegel, a psychiatry professor at the University of California, Los Angeles.
Part of the difficulty is that most people with insomnia also have other medical or psychiatric conditions, making it difficult to isolate the exact effects and possible causes of each one.
To get around this problem, Winkelman and his colleagues looked at 16 people with primary insomnia—that is, people free from any other known medical or sleeping conditions. About one-quarter of chronic insomniacs fall into this category.
Researchers collected data on the sleeping habits of the study participants using electroencephalography (EEG) and other monitoring devices. To measure GABA levels noninvasively, the scientists used a novel form of magnetic resonance spectroscopy, which uses magnetic resonance imaging to investigate brain tissue as well as structure. The team averaged GABA signals from the basal ganglia, thalamus and parts of the parietal, temporal and occipital lobes.
In addition to finding lower levels of GABA overall, Winkelman says, “one of the things that encouraged us we were on the right track was that in each of these sleep studies, the amount of wake time during the night was inversely correlated—highly—with GABA levels.”
Despite the promising results from those tests, Winkelman says much work remains to clarify the link between GABA levels and insomnia. “It could be that insomnia produces low GABA, or low GABA produces insomnia, or hyperarousal causes both,” he says. “We just don’t know.”
More details needed
Siegel, who has studied GABA release during sleep but was not involved with this study, echoed Winkelman’s caveat but was impressed by the findings and techniques used.
“This is sophisticated, elegant, cutting-edge work,” he says. “It’s one of the first, if not the first, to use this technique. I expect to see a lot more people using the technique they’re using.
“People with insomnia are not sleepy all the time,” he says. “People with chronic insomnia are more awake all the time. This may be what they are seeing with GABA levels.”
More work also is needed to identify the exact areas affected by these GABA levels. The neurotransmitter is one of the most common in the brain and can have opposing effects in different brain regions, including stimulating some areas that promote wakefulness.
Winkelman agrees. “We’re now trying to find out the specific areas of the brain that are active in insomniacs,” he says.
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