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HD – melatonin levels changes affect sleep

Those of you who find yourself lying in bed with your mind on overdrive, desperate for sleep, will appreciate that it can be far less easy for those who suffer from Huntington’s disease according to new research.

It’s a well known fact that nearly 80% of Huntington’s disease sufferers experience sleep disturbances. These can include the length of time it takes to fall asleep, changes in what the brain is doing during sleep, and a lack of truly restful sleep. Currently, it’s not really understood why these disturbances occur in HD, but this new research indicates that changes in levels of melatonin (the chemical that regulates sleep and wakefulness in relation to the rising and setting of the sun) may be at play.

Our predisposition for sleep at night and activity during daylight is just one of many circadian rhythms, a term that refers to anything that changes within our bodies on a 24-hour cycle, and can be synchronised with what’s happening in our environment. Lots of human behaviours are rhythmic or change predictably over the course of a day. Not only sleep and alertness, but also digestion, body temperature, and the immune system change depending on what time it is.

Since Huntington’s disease patients have problems regulating the normal sleeping/waking cycle, a group of researchers led by Professor Tom Warner wanted to ask whether the rise and fall of melatonin levels in HD patients is abnormal compared to unaffected individuals. Previous studies had measured patients’ melatonin at a single time point, early in the morning, but Professor Warner’s group wanted to monitor melatonin levels throughout the 24-hour cycle to get a better sense of how the rhythm of melatonin production is affected in HD.

Mature man waking up for daily job

They recruited 13 patients with moderate to advanced HD, and 15 people who did not have the HD gene. They also included 14 people who carry the HD gene, but had not yet shown disease symptoms. Each person involved in the study spent a day and night in a private room, under supervision. They could walk around and do what they liked during the day, but they weren’t allowed to nap, and the lights were out between 10 pm and 6 am. The researchers inserted an IV line so that they could collect a small amount of blood every hour, even in the middle of the night, with minimal interruption of the volunteers’ sleep.

Using a sensitive type of chemical analysis, the researchers determined the amount of melatonin in each person’s blood, then compared the three groups with one another using a variety of statistical methods.

They found that the HD patients had much lower levels of melatonin in their blood than those without HD – around 85% lower on average. Presymptomatic carriers of the HD gene also had slightly lower melatonin levels than normal.

Another finding was that HD patients and gene carriers showed more variation in the time of day that their melatonin levels began to rise. Most of the volunteers without HD had a surge of melatonin around bedtime, while HD-affected individuals’ melatonin levels rose at different times – some in the afternoon, some in the middle of the night.

By consistently monitoring blood levels of melatonin for a full 24 hours in Huntington’s disease patients, presymptomatic HD carriers, and unaffected control participants, this study showed that melatonin levels are indeed altered in HD, a finding which may help to explain why patients experience disrupted sleep.

There hasn’t been a clinical trial of melatonin as a therapy for Huntington’s disease patients with sleep disturbances, but this study provides good evidence of HD-related changes in melatonin levels, and suggests that a clinical trial might be warranted. Melatonin is already an approved supplement that many people buy over-the-counter or get on prescription, to adjust their sleep patterns. Some patients appear more responsive than others to melatonin and other sleep aids; perhaps this could be explained by the variable timing of melatonin production that this study found in HD patients.

Finally, these results don’t provide any explanation for why changes in melatonin occur in HD. We can speculate that the SCN or its communication with the pineal gland may be disrupted, but the reasons for that are unclear. It’s also fairly clear that changes in melatonin are only one of several things that can cause sleep disruption in Huntington’s disease, and no one is saying that every HD patient should take melatonin. However, these results make a solid case for a clinical trial, and importantly, the study provides one explanation for why many HD patients find sleep so elusive.


Extracts from an article on HDA.org.uk by Leora Fox; edited by Dr Ed Wild

About Marcia Garcia