The release of a specific peptide, a neurotransmitter called hypocretin, greatly increases when subjects are happy but decreases when they are sad, according to researchers at UCLA. 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 measurable abnormalities in brain chemistry.
The study also measured the release of another peptide 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 current findings explain the sleepiness of narcolepsy, as well as the depression that frequently accompanies this disorder," said senior author Jerome Siegel, 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."
Siegel's team has previously published findings showing that people suffering from narcolepsy had 95% fewer hypocretin nerve cells in their brains than those without the illness. They say the study was the first to show a possible biological cause of the disorder. Since depression is strongly associated with narcolepsy, Siegel's lab began to explore hypocretin and its possible link to depression.
In the current study, the researchers obtained their data on both hypocretin and MCH directly from the brains of eight patients who were being treated for intractable epilepsy. The patients had been implanted with intracranial depth electrodes to identify seizure foci for potential surgical treatment. The researchers used these same electrodes to piggyback their research. A membrane similar to that used for kidney dialysis and a sensitive radioimmunoassay procedure were used to measure the release of hypocretin and MCH from the patients' amygdalae.
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.
Hypocretin levels were not linked to arousal in general but were maximized during positive emotions, anger, social interactions, and awakening, the researchers found. In contrast, MCH levels were maximal during sleep onset and increased after eating, but were 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."
Hypocretin antagonists are now being developed by several drug companies for use as sleeping pills, Siegel noted, adding that the current work suggests that these drugs will alter mood as well sleep tendency.
The study is published in the March 5 online edition of the journal Nature Communications in a paper titled “Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction”.