Living the Scientific Life (Scientist, Interrupted)

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“Starry Night” (1889) is an oil painting by Dutch post-impressionist artist Vincent van Gogh. It was added to the permanent collection of the Museum of Modern Art (MoMA) in New York City in 1941. [wallpaper size].

ResearchBlogging.org

According to a “NewsFocus” article that appeared in last Friday’s Science, there is a move afoot to use light therapy and sleep deprivation to help the body’s circadian clock reset and maintain itself in those people who suffer from bipolar disorder. This treatment option has already been used with people who suffer from depression, especially depression that occurs in the autumn and winter months, when daylength is growing shorter. This form of depression is known as “Seasonal Affective Disorder” or SAD.


How is SAD mediated in the body? It is well-documented that the body’s master clock resides in the suprachiasmatic nucleus of the brain. This biological clock regulates changing concentrations of numerous hormones and proteins in the body over an approximately 24-hour cycle. Additionally, the concentrations of many of these neurochemicals change during the course of the day, particularly that of melatonin, which is secreted in the highest concentrations by the pineal gland when it is dark, and also that of serotonin, whose levels are boosted as the result of exposure to sunlight. Serotonin is a neurotransmitter that is associated with the feeling of well-being.

Basically, humans begin secreting melatonin in the evening to prepare the body for sleep. Previous studies had shown that people with SAD who were exposed to bright morning light showed improvement while those who experienced bright evening light did not. Additionally, people with SAD whose circadian rhythyms lagged behind a normal 24-hour sleep-wake cycle that took melatonin in the late afternoon experienced improvement in their mood while those who received melatonin in the mornings did not. On the other hand, this same treatment regimen had the opposite effect in those people whose sleep-wake cycle was advanced from normal (see figure, below).

According to the article, recent research has shown that people who suffer from mood disorders other than depression, and from thought disorders such as schizophrenia, may also be experiencing disruptions to their circadian clocks. For example, a study by Vishwajit Nimgaonkar that was published two years ago in Chronobiology International proposed that people with bipolar disorder had disturbed biological clocks, based on survey information that probed their activity and sleep patterns.

But most convincing to me are the genetic studies that appear to support these circadian rhythym survey data. In a series of elegant experiments, Colleen McClung and her colleagues at the University of Texas Southwestern Medical Center in Dallas created mice that were missing the Clock gene. This gene encodes a key protein that is an integral part of the circadian system. Clockless mice became hyperactive and were more likely to take risks — manic behavior. Further, the researchers found that expressing the CLOCK protein in the animals’ midbrains rescued these mutant mice, effectively restoring their behavior to normal, as they reported in their paper published in the Proceedings of the National Academy of Sciences on 10 April 2007 (read more about this).

Interestingly, an ongoing study led by Anna Wirz-Justice of the Centre for Chronobiology at the Psychiatric University Clinic in Basel, Switzerland, seems to show that patients with schizophrenic disorder and borderline personality disorder also experience abnormal circadian rhythyms. Also, psychiatrist Namni Goel of the University of Pennsylvania recently presented her data at the meeting for biological clocks and rhythms at Cold Spring Harbor Laboratory in New York state showing that many 24-hour hormonal rhythms in patients with night eating syndrome were either advanced or delayed with respect to a normal sleep-wake cycle.

Light therapy has traditionally been viewed with suspicion. According to the article, even a few years ago, “people looked at us as if we were some kind of strange witch healers,” says Benedetti, who began combining light therapy with sleep deprivation in the 1980s.

But the psychiatric community is starting to come around to the potential benefits of light therapy. For example, in 2005, a group led by Robert Golden of the American Psychiatric Association examined the efficacy of light therapy by conducting a meta-analysis of published literature. They concluded that light treatment significantly reduced the depressive symptoms of SAD, as well as those of other mood disorders.

But funding for light research has not been forthcoming, mainly because the community sees antidepressants as being effective. However, antidepressants are not always effective or even recommended for everyone, especially for pregnant or nursing women.

Unfortunately, based on my own experience, altering the body’s circadian clock is not necessarily always effective. My own body clock is apparently not affected by light therapy, even though I did use it (in the mornings only) for nearly one year when in graduate school. At that time, I did not experience any change in mood, although I did end up getting a lot of reading done. Curiously, my own episodes of mania and depression appear to only vaguely track daylength changes (but I also experience “rapid mood cycling” which makes for a more complicated picture overall).

On one hand, perhaps I am like those poor Clockless mutant mice, and thus, unable to respond to light manipulation? But on the other hand, and based on what I read in this article, it is also possible that my own circadian clock cycles with a longer rhythym than 24 hours, which the article’s author says is relatively unusual. Although, considering that my moods cycle rapidly, I am not convinced that I have a longer circadian cycle than 24 hours. Because it is known that exposure to bright lights in the evening can reset a slow cycling circadian clock, it is possible that this might effectively reset my own biological clock (unfortunately, I no longer possess that light box, nor any bright lights, so I cannot test this hypothesis now).

However, despite my own reservations about light therapy, I still think that it is worth investigating, especially for those of you who know that you experience seasonally-related changes in your mood. Further, many people suffering from a mood disorder tend to resist using medications for a variety of valid reasons, particularly due to the side-effects — and light does not have any known side-effects, except potentially, an elevation in mood and perhaps an increased amount of reading.

Source

“Is Internal Timing Key to Mental Health?” By Ryudhijit Bhattacharjee. Science 31:1488-1490 (14 September 2007)

Comments

  1. #1 Bob O'H
    September 17, 2007

    Hmm, interesting. I’ve used bright lights in the autumn and winter and found it helps, and it’s relatively common in Finland (less so, I would guess in South Africa, for example).

    Where does the sleep deprivation fit into this?

    Bob

  2. #2 Dave Dragon
    September 17, 2007

    I have been under pharmacological treatment for Bipolar Disorder and PTSD for some time now.

    I’m just glad that researchers are still at work attempting to understand this condition.

    Thanks for the posts!

    Dave Dragon
    Ride it like you stole it

  3. #3 Hank Roberts
    September 17, 2007

    Dark therapy for rapid cycling (using amber lights/lenses might also work rather than complete darkness):
    http://www.psycheducation.org/depression/darkrx.htm

  4. #4 carrie
    September 17, 2007

    Thanks for your report on this. I suffer from depression and I find that light really helps my mood, as well as getting less sleep. The biggest problem with this is that I find it really hard to alter my sleep schedule!

  5. #5 "GrrlScientist"
    September 17, 2007

    bob; according to the article, sleep deprivation works best for people who are depressed. by keeping depressed people awake all night, they report that their mood has significantly improved the next day. of course, this is a one-day effect, so light therapy must follow to help the depressed person maintain this diminished depression.

    hank; that’s interesting to know. i will see if i can locate some amber sunglasses and try this out. i do know that i don’t tend to sleep very well, or very long, especially when i am manic, although, oddly, i can sleep during the day when depressed.

    carrie; is there some way you can put your lights on a timer so they gradually brighten over a period of say, half an hour, and reach their brightest shortly before you should be getting out of bed? you know, sort of like a morning sunrise?

  6. #6 Sandra Kiume
    September 17, 2007

    Harry, and Grrl, there’s a terrific article by Jim Phelps on that very topic.

    Dark therapy for bipolar disorder using amber lenses for blue light blockade. James Phelps, Medical Hypotheses 2007 epub ahead of print

    Abstract:

    “Dark Therapy”, in which complete darkness is used as a mood stabilizer in bipolar disorder, roughly the converse of light therapy for depression, has support in several preliminary studies. Although data are limited, darkness itself appears to organize and stabilize circadian rhythms. Yet insuring complete darkness from 6 p.m. to 8 a.m. the following morning, as used in several studies thus far, is highly impractical and not accepted by patients. However, recent data on the physiology of human circadian rhythm suggests that “virtual darkness” may be achievable by blocking blue wavelengths of light. A recently discovered retinal photoreceptor, whose fibers connect only to the biological clock region of the hypothalamus, has been shown to respond only to a narrow band of wavelengths around 450 nm. Amber-tinted safety glasses, which block transmission of these wavelengths, have already been shown to preserve normal nocturnal melatonin levels in a light environment which otherwise completely suppresses melatonin production. Therefore it may be possible to influence human circadian rhythms by using these lenses at night to blunt the impact of electrical light, particularly the blue light of ubiquitous television screens, by creating a “virtual darkness”. One way to investigate this would be to provide the lenses to patients with severe sleep disturbance of probable circadian origin. A preliminary case series herein demonstrates that some patients with bipolar disorder experience reduced sleep-onset latency with this approach, suggesting a circadian effect. If amber lenses can effectively simulate darkness, a broad range of conditions might respond to this inexpensive therapeutic tool: common forms of insomnia; sleep deprivation in nursing mothers; circadian rhythm disruption in shift workers; and perhaps even rapid cycling bipolar disorder, a difficult- to -treat variation of a common illness.

    doi:10.1016/j.mehy.2007.05.026

    Carrie, and Grrl, there are dawn simulator devices available commercially, with timed lights that gradually increase lux. You can even get one that wakes you with bright light and your favourite aromatherapy scent.

  7. #7 Lost Clown
    September 18, 2007

    That’s just another reason to use my sunrise/sunset simulator. I am very intrigued by dark therapy as I am bipolar much more then I am affected by SAD.

  8. #8 Sandra
    September 18, 2007

    D’oh! Sorry Hank, I know your name is not Harry. A little slip. :)

  9. #9 Dan
    September 18, 2007

    Several researchers (Anna Wirtz-Justice included) who have investigated sleep deprivation with light therapy prefer to call it ‘wake therapy,’ because they discovered that it is only necessary to awaken early, say 1 or 2 am, instead of staying awake all night (You can email me for references). The reasoning for this may be that it is only necessary to be awake when the body clock is most sensitive. However, because of potential manic reactions to light therapy, one should always consult his/her physician.

    I may have misread the commentary about delayed and advance body clocks. Most people have slightly delayed body clocks, and thus benefit by morning light which speeds the body clock up. Conversely evening light will slow the body clock down. One can usually tell whether he or she has a body clock problem by their natural, habitual sleep/wake cycle (I can send you a phase response curve illustration if you like). If it is difficult to fall asleep and easy to sleep in, one likely has a delayed body clock. If on the other hand, one awakens early and usually falls asleep easily, he or she likely has an advanced body clock. Our body clocks respond to light (speed up or slow down) based on when we receive light in relation to our body temperature minimum (BTM), BTM usually occurs 2-3 hours before natural awakening. This is very important because someone with a severely delayed body clock may use bright light in the morning at 7:00 am, when his/her BTM may be occurring at 9:00 am–causing the opposite effect and making his symptoms worse.

  10. #10 Sylvie
    December 20, 2007

    Great article! Thanks for the info. My brother is manic depressive and schizophrenic. He tends to sleep all day and stay up all night. It’s pretty easy to believe that a circadian rhythm disorder is a part of his other problems.

    Being related, I don’t have the manic or schizophrenic issues, but have always struggled with the phase delayed syndrome and seasonal depression. Before learning about light therapy I had no idea you could actually change your body clock. It is pretty amazing!

  11. #11 Dave Dragon
    September 9, 2008

    I read somewhere that there is now a Blood Test for Bipolarisim.

    Anyone seen or used such?

    Ride it like you stole it