Sleep is regulated by the brain. So it makes sense to look inside the brain to find out what might be hampering insomniacs’ ability to fall and stay asleep. Is there some substance under- or overrepresented in our brains? Something that keeps us conscious when our brains should be turned off?
A study published in PLoS One last month suggests a role for two important neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate. Here’s a bit of background and what the new research tells us about the neurobiology of insomnia.
GABA, Hypnotist of the Brain
GABA is the most important inhibitory neurotransmitter of the central nervous system. Found throughout the brain, GABA-producing neurons help us fall and stay asleep. When the GABA neurons start firing, we get sleepier and sleepier and suddenly the lights go out. Most sleeping pills today—zolpidem (Ambien), eszopiclone (Lunesta), zaleplon (Sonata), and temazepam (Restoril)—work by enhancing the GABA system.
A deficiency of GABA might cause symptoms of insomnia. Two studies, published in 2008 and 2012, respectively, found lower levels of GABA in insomniacs’ brains than in the brains of normal sleepers. Both studies were conducted using magnetic resonance spectroscopy (MRS). MRS is similar to MRI but different in that it can determine the concentration of various neurotransmitters in the brain.
Results of the first study showed that insomniacs’ average brain GABA levels were lower by nearly 30 percent. Results of the second study were confirmatory, showing that insomniacs had significantly less GABA in two areas of the cerebral cortex. But in a third study, also published in 2012, insomniacs were shown to have higher levels of GABA in the occipital cortex than normal sleepers.
Current Study: Evidence for GABA’s Role Is Mixed
One difference between the studies showing reduced and increased brain GABA was the time when data were gathered. In the first two studies, the brain scans were administered in the morning. In the third, participants’ brains were scanned a few hours before bedtime.
So for the current PLoS One study, investigators scanned the brains of their subjects (20 insomnia patients and 20 good sleepers) twice: after they got up in the morning and in the evening before they went to bed. Prior to the scans, participants were screened with sleep-related questionnaires and spent two nights in a sleep lab. There, they underwent polysomnography to determine, objectively, how long and how solidly they slept.
On both nights in the lab, the insomniacs slept significantly less than the good sleepers. The first night, it took them longer to fall asleep and they awakened more frequently. On the second, they spent a significantly lower percent of the night in deep sleep. In short, their sleep was disrupted in all the ways insomniacs’ sleep typically is.
But the brains of the insomnia patients did not have any more or any less GABA than the brains of the normal sleepers. The one correlation that did emerge was between GABA in an area called the anterior cingulate cortex and objectively short sleep. Investigators concluded that reduced GABA levels may be a trait marker of objective sleep problems.
A Role for Glutamate
Glutamate plays a role opposite GABA. It’s the major excitatory neurotransmitter in the brain, found in abundance everywhere. When glutamate-producing neurons are firing, we’re alert and thinking and taking in the world around us.
Investigators in the current study compared the amount of brain glutamate in insomnia patients and controls in the morning and in the evening. Here, they found a significant difference: glutamate levels in the insomnia patients increased from morning to evening but did not increase in the normal sleepers. So higher levels of glutamate in the evening may reflect the hyperarousal many insomniacs experience at bedtime.
I wouldn’t bet the farm on it, though. The problem with these and other MRS studies is that they’re small (and very costly) and the results may or may not be confirmed in the next study down the line. Insomnia symptoms (or short sleep) may have something to do with reduced levels of GABA and increased glutamate at bedtime—and that’s all we can say for now.