59. Clock genes at the heart of depression

24 October 2010 at 02:25 | Posted in Circadian rhythm | 8 Comments
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Which came first: the chicken or the egg?  The circadian rhythm dysregulation or the depression?

Traditionally, it has been claimed (assumed) that depression causes sleep problems including sleeping too early (the thinking in the 1980s) or too late (more recently).  We who have circadian rhythm disorders (CRDs) have always thought that depression and other mood disorders can be a result of circadian rhythm misalignment or disruption, rather than a cause.

Now a review* suggests that polymorphisms in some of the 18 clock genes may cause both depression and CRDs.

  • [T]reatment strategies or drugs aimed at restoring ‘normal’ circadian rhythmicity may be clinically useful.
  • [W]e may predict that new antidepressant drugs will emerge that (…) target and correct abnormalities in the circadian timing system. 


A recent careful study of patients with delayed sleep phase syndrome (DSPS) showed that

  • patients who also showed depressive symptoms had an even later peak in the 6-sulphatoxymelatonin rhythm than patients with no depression. 


Even research on rodents provides evidence

  • for a role of clock genes in behaviours that are relevant to mood disorders.


Much of the genetic info in this review goes way over my head, but this bit sounds reasonable:

  • The endogenous rythmicity within the master biological clock in the brain … is generated by interlinked positive and negative feedback loops of gene transcription and translation.  If there is to be a role of circadian rhythmicity in mood disorders then it almost certainly involves these genes….


Practical results?

I’m hoping that these ideas represent a turning point in circadian rhythm research.  I hope that, here on in, the researchers search for realistic and practical treatments, as well as useful diagnostic tests, for CRDs.


* Kennaway, David J. (2010) Review: Clock genes at the heart of depression.  Journal of Psychopharmacology Vol. 24 No. 5

The illustration is borrowed from a blogpost by Jeff Pruett.


Next post: 60. Charting the Course of N24



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  1. Greetings!

    First off, I’d like to thank you guys for this awesome blog with all the incredibly useful information.

    I myself am still undiagnosed, and have been examined for my extreme daily sleepiness for a long time now. I’ve gotten my hormones checked, my thyroid, I’ve done depression-tests, several blood tests, sleep apnea registration and the latest thing was an MSLT-test which basically told me that I suffer from mild hypersomnia – but no narcolepsy.

    I have trouble falling asleep at 11-12 (23-00) and when I finally do, I need to sleep at least 9 hours to be able to feel somewhat rested – and if nothing wakes me up, I can continue sleeping like a bear in hibernation mode. The sleep is rarely good and I am always tired the whole next day (which makes working impossible ’cause the lack of concentration).

    However, over the years, I’ve experimenting A LOT with exercises,
    different supplements and sleep cycles. So far I haven’t found anything that cures me. But lately, I’ve been testing out delayed regular circadian rhythms. I go to bed in the morning (4-6) and wake up 12-14, and the sleep is just magical. I sleep so good and so deep, it feels like I wake up on clouds every morning like a new person. It doesn’t eliminate the difficulties getting up after 8-9 hours “in the morning”, but at least I feel rested! Its still hard to concentrate, but nothing like earlier. And as you mentioned in a post, one can have more than one sleep disorder. I could easily have DSPS AND hypersomnia/ADD, its not easy for the doctors to tell I guess.

    As I mentioned earlier, I’m still undiagnosed and my psychiatrist is
    prescribing me different medicine that could help me – so far no success with any antidepressants or stimulants. So I’m eager to check if DSPS could be my demon or one of my demons. I have always been a night owl, and I enjoyed staying up late in my teenage years. Can these years have sabotaged my biological clock, or could it really be in the DNA from the beginning?

    Is there a page somwhere with a guide step by step how to test yourself with techniques, sleep charts e t c? If not, could you please write one? I must of course find a specialist on a sleep clinic, but it would speed up the process for me (and hopefully other people) if I already had data to bring.

    Thanks a bunch so far!

    PS: I apologize for my slightly deficient english, its not my mother language =)

  2. Welcome Niklas. We’ll think about writing a guide, but I think the best one can do is to sleep freely with no obligations to school, job, family etc. for 2-3 weeks or more, keeping a detailed diary about when you fall asleep and wake spontaneously and when you’re most tired/ most alert. Additional helpful information can be when you eat, take medications or drink alcohol. The first week or more may not be so helpful, as you’re probably catching up. A person with DSPS goes to sleep naturally at least 2 hours after midnight and awakens 8 or 9 hours later.
    We don’t really think that bad habits in one’s teens lead to circadian rhythm disorders (DRDs), but no one knows for sure. I’ve had DSPS since I was little and I’m not alone in that.
    The next steps are finding a doctor who knows enough about CRDs, and then finding a job that allows you to sleep when your body dictates. Unfortunately such doctors are still rare. Good luck.

  3. That is very interesting about depression and DSPS. My father was bi-polar and toward the end of his life never slept, just napped.

    I have been trying to get to the root of my problem for decades. I am not bi-polar but have experienced two extreme “specific” anxiety disorders in the past.

    Obviously this sleep disorder is genetic and closely linked with other chemical imbalances in the brain. But does lack of sleep cause the imbalance or does the imbalance cause the lack of sleep? Back to the chicken and egg.

  4. Thanks for commenting, dsps2. Lack of sleep does not cause DSPS, nor does DSPS cause lack of sleep when a person sleeps 4 AM to noon or whichever schedule the individual’s body dictates.

  5. This topic is very interesting for me. I have what looks like N24 and major depressive order. I believe both started at the same time, when i was 13. The sleep disorder started as DSPS and got very severe in University. Both illnesses appear to have multiple subtypes, and both are likely to be triggered, in certain cases by the same underlying pathology.I believe the “clock” gene has been implicated in both disorders (at least certain subtypes). And I am sure there are cases where N24 and DSPS are the cause. In my case I am now convinced that the return of my originally, successfully treated depression was triggered by the stress from trying to force myself to live a normal life over a 30 year period. I was able to function fairly well with a younger body, but the fight took its toll, until eventually I lost what seems like everything. But my recent discovery of this disorder gives me new hope that I might be able to deal with both disorders and live the rest of my life in a much healthier, if not wealthier, manner. Thanks for this wonderful site, and all of the dedication it entails. BM

  6. Thanks for the good words, Brian. Since learning what DSPS is, I’ve assumed it causes my depression(s). The concept that both may have the same cause is new and exciting. Now if the research community would please get on it and come up with some more definitive answers!

  7. i was diagnosed with bipolar in my mid 20’s and am now 57.DSPS is the closest explanation to my disorder that i can find and my doctor agrees with me,even though i’ve not been tested//dsps explains me to a tee//it’s not unusual for me to sleep around the clock so to speak.i going to bed later everyday,until i wind up going to bed at the same time i was going to bed two weeks prior(that’s the best way i can explain it)..ie,for example,start on monday going to bed at 6am,the next day 8am,next day 10am,etc,until i’m going to bed at 6am again in a week or two).this has been my lifestyle most of the time for nearly 31 years.i’m currently taking effexer for depression and lunesta and 100mg trazedone to sleep,(plus earplugs)which works rather well for me.it’s mandatory that i sleep each day until i’m rested,like a spring is unwinding in my body (uninterupted sleep) elsewise i can’t function properly and feel totally stressed/

  8. Hi and thanks for commenting. What you’ve clearly described is Non-24 rather than DSPS. DSPS people can go to sleep at the same time each night and wake at the same time of day each day; it’s all just much later than the norm. Non-24 hour people do not adjust to a 24-hour day. They sleep later and later each day. It would be interesting to hear at what age this started for you. It’s possible that you HAD DSPS first and it developed into Non-24.

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