Wake therapy, a specific application of intentional sleep deprivation, encompasses many sleep-restricting paradigms that aim to address mood disorders with a form of non-pharmacological therapy.
Wake therapy was first popularized in 1966 and 1971 following articles by Schulte and by Pflug and Tölle describing striking symptom relief in individuals who had depression after 1 night of total sleep deprivation. Wake therapy can involve partial sleep deprivation, which usually consists of restricting sleep to 4-6 hours, or total sleep deprivation, in which an individual stays up for more than 24 consecutive hours. During total sleep deprivation, an individual typically stays up about 36 hours, spanning a normal awakening time until the evening after the deprivation. It can also involve shifting the sleep schedule to be later or earlier than a typical schedule (eg. going to bed at 5 am), which is called Sleep Phase Advancement. Older studies involved the repetition of sleep deprivation in the treatment of depression, either until the person showed a response to the treatment or until the person had reached a threshold for the possible number of sleep deprivation treatments.
Sleep deprivation is a quick and efficient way to treat depression. It works 60 to 70 percent of the time—far better than existing drugs—but the mood boost usually lasts only until the patient falls asleep. As an ongoing treatment, sleep deprivation is impractical, but researchers have been studying the phenomenon in an effort to uncover the cellular mechanisms behind depression and remission.
The researchers previously found that astrocytes, a star-shaped type of glial cell, regulate the brain chemicals involved in sleepiness. During our waking hours, astrocytes continuously release the neurotransmitter adenosine, which builds up in the brain and causes “sleep pressure,” the feeling of sleepiness and its related memory and attention impairments. The neurotransmitter causes this pressure by binding to adenosine receptors on the outside of neurons like a key fitting into a lock. As more adenosine builds up, more receptors are triggered, and the urge to sleep gets stronger.
The scientists investigated whether this process is responsible for the antidepressant effects of sleep deprivation. Mice with depressivelike symptoms were administered three doses of a compound that triggers adenosine receptors, thus mimicking sleep deprivation. Although the mice continued to sleep normally, after 12 hours they showed a rapid improvement in mood and behavior, which lasted for 48 hours.
The results confirm that the adenosine buildup is responsible for the antidepressant effects of a lack of sleep. This finding points to a promising target for new drug development because it suggests that mimicking sleep deprivation chemically may offer the antidepressant benefits without the unwanted side effects of actually skipping sleep. Such an intervention could offer immediate relief from depression, in stark contrast with traditional antidepressants, which take six to eight weeks to kick in.
There are lots of signs that point toward the involvement of the neurotransmitter dopamine in wakefulness. Drugs that increase levels of dopamine in brain (including, but not limited to, drugs like cocaine, amphetamine, meth, and Ritalin) also increase feelings of wakefulness. Increasing dopamine in the brain via genetic alterations, like getting rid of the dopamine transporter in a mouse, stopping dopamine from getting recycled, produces a mouse that sleeps less. Diseases that are characterized by low dopamine levels, like Parkinsons, also have daytime sleepiness.
But a neurotransmitter is only as good as its receptor. Dopamine has two main types of receptors, and the current hypothesis is that the wakefulness promoting effects of dopamine may be controlled partially by the D2 type receptor. Antipsychotics, which block D2 type receptors, make people sleepy, and previous studies showed decreased D2 binding in the brains of sleep deprived people. But the question is: what is causing the decreases in D2 when people are sleep deprived? The authors of this study hypothesized that this was due to increased dopamine release, which would cause decreases in D2 receptors (this is a basic idea in pharmacology, when a group of receptors is overstimulated, some receptors will leave the membrane, making the membrane less sensitive to stimulation).
To test this hypothesis, they took a bunch of human volunteers, and either sleep deprived them overnight (they kept them in a facility with a nurse bugging them to keep their eyes open if they got drowsy), or kept them in the facility to get a good night's rest (all participants underwent both conditions). In the morning, they looked at the D2 receptors in the striatum of the brain, an area with loads of dopamine and associated with things like arousal and reward. To do this, they used positron emission tomography (PET), which uses a radioactive tracer (C-raclopride), which binds to D2 type receptors, allowing you to see how many are present.
They showed that D2 type receptor binding was definitely lower in sleep deprived people. But what does this mean? Does it mean that there's more dopamine release when you're tired, decreasing the D2 type receptors? Or do the D2 type receptors decrease for some other reason? To look at this, the authors of the study treated the participants with methylphenidate (Ritalin), which increased the amounts of dopamine. They hypothesized that if sleep deprivation produced more dopamine release, the methylphenidate should produce larger increases in dopamine than in well rested patients.
This means that the decrease in D2 type receptors that the authors see with sleep deprivation is NOT due to increases in DA release during sleep deprivation. They confirmed this with studies in rats, and showed that the sleep deprived rats showed no increases in dopamine, but showed similar D2 type receptor changes.
So what is going on? Unfortunately, the authors didn't go after that question, though they talk about a "different physiological mechanism". They do hypothesize that adenosine might have something to do with it. Adenosine is a neurochemical which you know best from your morning cup of coffee. Caffeine increases wakefulness by antagonizing adenosine receptors, and adenosine itself promotes sleepiness. Not only that, one of the areas involved in this effect appears to be the striatum, the dopamine-rich area the authors were looking at in this study. Caffeine can increase D2 type receptor levels in this area. So it seems like the next thing to look at would be how adenosine and dopamine might be interacting following sleep deprivation (though unfortunately, they didn't look at it here).
So what does this mean? Well, the changes in D2 type receptors could help explain some of the other changes in behavior that come with sleep deprivation, changes like increases in risk taking behavior, impulsivity, and drug relapse. These are all things which increase when people are sleep deprived. So the changes seen in D2 type receptors could help explain show these behavioral changes occur. But while we see changes in receptors, we still don't know why, and the proposed mechanism still needs to be tested.
Wake therapy was first popularized in 1966 and 1971 following articles by Schulte and by Pflug and Tölle describing striking symptom relief in individuals who had depression after 1 night of total sleep deprivation. Wake therapy can involve partial sleep deprivation, which usually consists of restricting sleep to 4-6 hours, or total sleep deprivation, in which an individual stays up for more than 24 consecutive hours. During total sleep deprivation, an individual typically stays up about 36 hours, spanning a normal awakening time until the evening after the deprivation. It can also involve shifting the sleep schedule to be later or earlier than a typical schedule (eg. going to bed at 5 am), which is called Sleep Phase Advancement. Older studies involved the repetition of sleep deprivation in the treatment of depression, either until the person showed a response to the treatment or until the person had reached a threshold for the possible number of sleep deprivation treatments.
Wake therapy - Wikipedia
en.wikipedia.org
Sleep deprivation is a quick and efficient way to treat depression. It works 60 to 70 percent of the time—far better than existing drugs—but the mood boost usually lasts only until the patient falls asleep. As an ongoing treatment, sleep deprivation is impractical, but researchers have been studying the phenomenon in an effort to uncover the cellular mechanisms behind depression and remission.
The researchers previously found that astrocytes, a star-shaped type of glial cell, regulate the brain chemicals involved in sleepiness. During our waking hours, astrocytes continuously release the neurotransmitter adenosine, which builds up in the brain and causes “sleep pressure,” the feeling of sleepiness and its related memory and attention impairments. The neurotransmitter causes this pressure by binding to adenosine receptors on the outside of neurons like a key fitting into a lock. As more adenosine builds up, more receptors are triggered, and the urge to sleep gets stronger.
The scientists investigated whether this process is responsible for the antidepressant effects of sleep deprivation. Mice with depressivelike symptoms were administered three doses of a compound that triggers adenosine receptors, thus mimicking sleep deprivation. Although the mice continued to sleep normally, after 12 hours they showed a rapid improvement in mood and behavior, which lasted for 48 hours.
The results confirm that the adenosine buildup is responsible for the antidepressant effects of a lack of sleep. This finding points to a promising target for new drug development because it suggests that mimicking sleep deprivation chemically may offer the antidepressant benefits without the unwanted side effects of actually skipping sleep. Such an intervention could offer immediate relief from depression, in stark contrast with traditional antidepressants, which take six to eight weeks to kick in.
Why Sleep Deprivation Eases Depression
Glial activity reveals how sleep deprivation elevates mood
www.scientificamerican.com
There are lots of signs that point toward the involvement of the neurotransmitter dopamine in wakefulness. Drugs that increase levels of dopamine in brain (including, but not limited to, drugs like cocaine, amphetamine, meth, and Ritalin) also increase feelings of wakefulness. Increasing dopamine in the brain via genetic alterations, like getting rid of the dopamine transporter in a mouse, stopping dopamine from getting recycled, produces a mouse that sleeps less. Diseases that are characterized by low dopamine levels, like Parkinsons, also have daytime sleepiness.
But a neurotransmitter is only as good as its receptor. Dopamine has two main types of receptors, and the current hypothesis is that the wakefulness promoting effects of dopamine may be controlled partially by the D2 type receptor. Antipsychotics, which block D2 type receptors, make people sleepy, and previous studies showed decreased D2 binding in the brains of sleep deprived people. But the question is: what is causing the decreases in D2 when people are sleep deprived? The authors of this study hypothesized that this was due to increased dopamine release, which would cause decreases in D2 receptors (this is a basic idea in pharmacology, when a group of receptors is overstimulated, some receptors will leave the membrane, making the membrane less sensitive to stimulation).
To test this hypothesis, they took a bunch of human volunteers, and either sleep deprived them overnight (they kept them in a facility with a nurse bugging them to keep their eyes open if they got drowsy), or kept them in the facility to get a good night's rest (all participants underwent both conditions). In the morning, they looked at the D2 receptors in the striatum of the brain, an area with loads of dopamine and associated with things like arousal and reward. To do this, they used positron emission tomography (PET), which uses a radioactive tracer (C-raclopride), which binds to D2 type receptors, allowing you to see how many are present.
They showed that D2 type receptor binding was definitely lower in sleep deprived people. But what does this mean? Does it mean that there's more dopamine release when you're tired, decreasing the D2 type receptors? Or do the D2 type receptors decrease for some other reason? To look at this, the authors of the study treated the participants with methylphenidate (Ritalin), which increased the amounts of dopamine. They hypothesized that if sleep deprivation produced more dopamine release, the methylphenidate should produce larger increases in dopamine than in well rested patients.
This means that the decrease in D2 type receptors that the authors see with sleep deprivation is NOT due to increases in DA release during sleep deprivation. They confirmed this with studies in rats, and showed that the sleep deprived rats showed no increases in dopamine, but showed similar D2 type receptor changes.
So what is going on? Unfortunately, the authors didn't go after that question, though they talk about a "different physiological mechanism". They do hypothesize that adenosine might have something to do with it. Adenosine is a neurochemical which you know best from your morning cup of coffee. Caffeine increases wakefulness by antagonizing adenosine receptors, and adenosine itself promotes sleepiness. Not only that, one of the areas involved in this effect appears to be the striatum, the dopamine-rich area the authors were looking at in this study. Caffeine can increase D2 type receptor levels in this area. So it seems like the next thing to look at would be how adenosine and dopamine might be interacting following sleep deprivation (though unfortunately, they didn't look at it here).
So what does this mean? Well, the changes in D2 type receptors could help explain some of the other changes in behavior that come with sleep deprivation, changes like increases in risk taking behavior, impulsivity, and drug relapse. These are all things which increase when people are sleep deprived. So the changes seen in D2 type receptors could help explain show these behavioral changes occur. But while we see changes in receptors, we still don't know why, and the proposed mechanism still needs to be tested.
Sleep Deprived? Mind your dopamine.
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