It’s great to be happy and many factors influence one’s happiness. Now, a new UCLA study has found that a specific peptide, a neurotransmitter called hypocretin, is greatly increased when an individual is happy but decreased when he or she is sad. The findings may need to new therapies for psychiatric disorders, particularly those which have a depression component. They published their findings online on March 5 in the journal Nature Communications.
The researchers note that neurochemical changes underlying human emotions and social behavior are largely unknown. However, the new study has revealed that hypocretin levels are involved. The finding suggests that boosting the level of this peptide could elevate both mood and alertness in humans; thus, providing a foundation for possible future treatments of psychiatric disorders such as depression by targeting measureable abnormalities in brain chemistry.
The study also measured for the first time the release of another peptide, melanin concentrating hormone (MCH). The researchers found that its release was minimal in waking but greatly increased during sleep; thus, 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,” explained 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. He added, “The findings also suggest that hypocretin deficiency may underlie depression from other causes.” In 2000, Dr. Siegel and his colleagues published findings showing that individuals suffering from narcolepsy, a neurological disorder characterized by uncontrollable periods of deep sleep, had 95% 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.
Dr. Siegel noted that depression is the leading cause of psychiatric disability in the nation. More than 6% of the population is affected each year, with lifetime prevalence exceeding 15%. However, the use of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), has not been based on evidence of a deficiency, or excess, of any neurotransmitter. Several recent studies have questioned whether SSRIs, as well as other depression-fighting drugs, are any more effective than placebos.
Since depression is strongly associated with narcolepsy, the researchers began to explore hypocretin and its possible link to depression. They 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 by Dr. Itzhak Fried, a UCLA professor of neurosurgery and psychiatry and a co-author of the study, 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 during the following activities: 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 coinciding 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 investigators 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. Dr. Siegel explained, “These results suggest a previously unappreciated emotional specificity in the activation of arousal and sleep in humans. 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 (substances that lower hypocretin levels) 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 sleep tendency.
In a previous study, the researchers 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,” Dr. Siegel said.
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