The finding suggests that boosting hypocretin could elevate both mood and alertness in humans, thus laying the foundation for possible future treatments of psychiatric disorders like depression by targeting measureable abnormalities in brain chemistry. In addition, the study measured for the first time the release of another peptide, this one called melanin concentrating hormone, or MCH. Researchers found that its release was minimal in waking but greatly increased during sleep, suggesting a key role for this peptide in making humans sleepy.
“The work explains the sleepiness of narcolepsy, as well as the depression that frequently accompanies this disorder,” says Jerome Siegel, PhD, director of the Center for Sleep Research at UCLA’s Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA. “The findings also suggest that hypocretin deficiency may underlie depression from other causes.”
For the study, the researchers obtained their data on both 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 had been implanted with intracranial depth electrodes to identify seizure foci for potential surgical treatment. The location of electrodes was based solely on clinical criteria. The researchers, with the patients’ consent, used these 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; underwent various clinical manipulations; and experienced sleep-wake transitions. Notes of activities were made throughout the study every 15 minutes in synchrony with a 15-minute microdialysis sample collection by a researcher in the patients’ rooms.
The subjects rated their moods and attitudes on a questionnaire, which was administered every hour during waking. 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 maximal 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,” Dr. Siegel says. “The findings suggest that abnormalities in the pattern of activation of these systems may contribute to a number of psychiatric disorders.”
Dr. 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 tendency.
“Human Hypocretin and Melanin-concentrating Hormone Levels Are Linked to Emotion and Social Interaction,” Nature Communications, March 5, 2013