For the first time in humans, researchers have measured the release of a peptide that greatly increases when people are happy but decreases when they are sad.
Researchers at the University of California-Los Angeles say their findings suggest that boosting the peptide, a neurotransmitter called hypocretin, could elevate both mood and alertness in humans, laying the foundation for possible treatments of psychiatric disorders like depression.
The UCLA study also measured the release of another peptide, called melanin concentrating hormone (MCH). Researchers found that its release was minimal in waking but greatly increased during sleep.
“The current findings explain the sleepiness of narcolepsy, as well as the depression that frequently accompanies this disorder,” said senior author Jerome Siegel, M.D., a professor of psychiatry and director of the Center for Sleep Research at UCLA’s Semel Institute for Neuroscience and Human Behavior. “The findings also suggest that hypocretin deficiency may underlie depression from other causes.”
In 2000, Siegel’s research team published findings that showed that people suffering from narcolepsy, a neurological disorder characterized by uncontrollable periods of deep sleep, had 95 percent fewer hypocretin nerve cells in their brains than those without the illness. The study was the first to show a possible biological cause of the disorder, according to the researcher.
Since depression is strongly associated with narcolepsy, the researchers then began to explore hypocretin and its link to depression.
In the latest study, the researchers obtained their data on hypocretin and MCH directly from the brains of eight patients who were being treated at Ronald Reagan UCLA Medical Center for intractable epilepsy. The patients were implanted with intracranial depth electrodes to identify the area of the brain where seizures originate for potential surgical treatment.
With the patients’ consent, the researchers used the same electrodes to “piggyback” their research. A membrane similar to that used for kidney dialysis and a very sensitive radioimmunoassay procedure were used to measure the release of hypocretin and MCH.
The patients were recorded while they watched television, engaged in social interactions such as talking to physicians, nursing staff or family, ate, and experienced transitions between sleep and wakefulness. The researchers made notes of the patients’ activities every 15 minutes, which coincided with a 15-minute microdialysis sample collection by a researcher in the patients’ rooms.
The subjects also rated their moods and attitudes on a questionnaire, which was administered every hour during periods of wakefulness.
The researchers found that hypocretin levels were not linked to arousal in general, but were maximized during positive emotions, anger, social interactions and awakening. In contrast, MCH levels were highest during sleep onset and minimal during social interactions.
“These results suggest a previously unappreciated emotional specificity in the activation of arousal and sleep in humans,” Siegel said. “The findings suggest that abnormalities in the pattern of activation of these systems may contribute to a number of psychiatric disorders.”
Siegel noted that hypocretin antagonists are now being developed by several drug companies for use as sleeping pills. The current work suggests that these drugs will alter mood, as well as sleep patterns, he said.
Siegel’s research team had also previously reported that hypocretin is required for the “pursuit of pleasure” in rodents but plays no role in avoidance behavior.
“These results, in conjunction with the current findings, suggest that hypocretin administration will elevate both mood and alertness in humans,” Siegel said.
The study was published in the journal Nature Communications.