Thursday, September 1, 2011

Another Magical Mystery Cure

I enjoy hearing from visitors to my blog, so when Yale Landsberg, Executive Director of the GreenTyme Project sent me an email message after reading my Oughtism Blog, suggesting I comment on the possible role of circadian rhythm abnormalities in autism, I was pleased. 

After further thought and carefully reading his websites, I concluded it was worth writing about this idea because it’s bound to find its way onto the various parent autism listserves, with all kinds of people rushing out to try Chrono-Cognitive Therapy with their kids with autism. 

Yale Landsberg’s GreenTyme website says, here is what the largest funder of Autism research in the world says about Autistic time & timing: Time perception problems may explain autism symptoms. (Dr. Martine Delfos' book has more details!)”  The implication is that autism is caused by problems with autism time perception, or circadian rhythm.  The website is referring to a comment made by someone from the Simon Foundation, not NIH, which is actually the largest funder of autism research in the world.  What Dr. Delfos writes in her book is that placing a clock alongside the bed of a child with autism can be helpful…that’s all.  Nothing about circadian rhythm synchronization, chronobiology or anything else pertaining to Chrono-Cognitive Therapy.

Now lets be clear, the notion that there could be a link between autism and circadian rhythms is not without merit. We need to take a look at the evidence. I’ll get to the GreenTyme Project later, but first, what are circadian rhythms, and is there any evidence biorhythms are related to autism?

Circadian rhythms are internally driven roughly 24-hour cycles in biochemical, physiological, or behavioral processes. Circadian rhythms have been widely observed in plants, animals, fungi and even bacteria. The term circadian meaning "around" in Latin, and diem or dies, meaning "day".  The scientific study of biological temporal rhythms such as daily, tidal, weekly, seasonal, and annual rhythms is called chronobiology. Although circadian rhythms are built-in to the body, they are adjusted by external cues, the primary one of which is daylight.

I was an undergraduate student in 1956 at the University of Minnesota when Professor Franz Halberg, in the Biophysics program of the Physics Department, introduced the term circadian rhythm, so this isn’t entirely new to me. At that time Halberg was viewed as a visionary by some, but somewhat outlandish by many scientists. There is a great deal of scientific evidence that circadian rhythms exist and have profound effects on the human body including, physiological and biochemical functioning.  Anyone who has problems with jet lag when flying across several time zones, as I do, can attest to the fact that our circadian rhythms are formidable drivers of our internal world and can greatly influence how we function if they are out of whack. If you have ever awakened in the middle of the night and felt chilly, you might taken your temperature. You may be surprised to find that your body temperature is well below its normal daytime temperature.  An article in the British Medical Journal a few years ago summarized a good deal of this literature and is a good starting place.

The scientific world is divided into those who see chronobiology, and circadian rhythms in particular, as the root cause of virtually every disorder, disability or ailment under the sun, those who are highly skeptical that circadian rhythms actually cause any disorders, illnesses or disabilities, and the rest of us who are convinced they are important for some things, but their role in the causes of disorders has been greatly exaggerated and have to be considered carefully on a case by case basis.

  At Yale Landsberg’s suggestion I re-reviewed recent research on the possible link between autism and circadian rhythms.  The short answer is that there may be some link, but it isn’t clear there is, or whether it is part and parcel of autism or epiphenomenal.

Circadian Rhythms in Autism

There are two distinct autism problems that may be related to circadian rhythm dysfunction: sleep difficulties and problems with discrimination of elapsed time.  Most of the evidence available is about sleep problems.

Sleep, Melatonin and Autism

The most consistent finding across studies that may be related to circadian rhythms is of sleep problems in ASD [Cortesi Sleep Med 7: 659-64]. For example it has been reported that there is commonly an irregular sleep-wake cycle appeared in early infantile autism in early childhood. This might occur as a result of complex interactions between biological, psychological, social/environmental, and family factors, including child-rearing practices that are not conducive to good sleep.  It has been suggested that circadian abnormalities in autism might be the result of genetic abnormalities related to melatonin synthesis and melatonin's role in modulating synaptic transmission, which appear to associated with androgen sensitivity [Hu (2009) Autism Res. 2: 78-97].  Several studies have reported that a gene required to synthesize melatonin, which plays an important role in sleep wake cycle is often deficient in autism. In one recent study it was found that these results indicate that a low melatonin level may be caused by a primary deficit in the gene required for melatonin synthesis [Melke (2008) Mol Psychiatry 13: 90-98].  One study included 14 children with classical infantile autism, who were investigated for the whole 24-hour circadian rhythm by collecting venous blood samples at 4-hour intervals. Serum levels of melatonin synthesis hormone were measured. The control group consisted of 20 age-matched children without known disabilities.  No autistic patient showed a normal melatonin synthesis circadian rhythm. However, autistic children showed significantly lower average concentrations of MLT, mainly during the dark phase of the day, with respect to the values observed in the controls [Kulman (2000) Neuro Endocrinol Lett 21:31-34].
A study with adults with Asperger syndrome showed lower-amplitude circadian rhythms that were less strongly linked to environmental synchronizers, like light dark cycle, but no evidence of significant desynchronization of circadian rhythm, though their overall sleep pattern was inefficient [Hare (2006) Autism. 10: 565-75].  Another study by the same group reported what appear to be conflicting results [Hare (2006) J. Intellec Diabil. Res. 50: (Pt. 10)701-10]. Data were collected from 31 participants with intellectual disabilities living in supported community-based residential provision aged between 20 and 58 years, of whom 14 had an ASD. Analysis indicated that there were no significant differences in sleep patterns and circadian rhythm function between those participants with an ASD and those without. The mean scores of the participants as a whole indicated abnormalities in the two key circadian rhythm parameters of inter-daily stability and intra-daily variability, but no differences related to autism.
Supporting the notion that endogenous melatonin abnormalities in autism are related to sleep problems are several studies that demonstrate oral melatonin is often helpful in regularizing sleep in autism, however a recent critical review of this literature concluded “As a whole, we found that the literature supports the existence of a beneficial effect of melatonin on sleep in individuals with ASD, with only few and minor side effects. However, considering the small number of studies and their methodological limits, these conclusions cannot yet be regarded as evidence-based. Randomized controlled trials and long-term follow-up data are still lacking to better assess efficacy and safety of exogenous melatonin for disordered sleep in individuals with ASD.” [Guenole Sleep Med Rev. 2011 Mar 8. [Epub ahead of print].  One very recent study not included in this review used a double blind, randomized, controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study. There were no significant differences between sleep measures at baseline. Melatonin significantly improved sleep latency (by an average of 47 min) and total sleep (by an average of 52 min) compared to placebo, but not number of night wakenings [Wright J Autism Dev Disord. 2011 Feb;41(2):175-84].

Sleep and Melatonin Summary:  There is some evidence of lower than normal levels of melatonin in individuals with autism and inefficient or fragmented sleep, which seems to be improved by oral treatment with melatonin.  There is no evidence melatonin is related to the cause of autism, though it has been speculated that it may be related to sensitivity to male sex hormones and sex ratio differences in autism.

Time Perception in Autism

Many parents, teachers and therapists who work with individuals with autism are aware that problems with estimating the time, and elapsed time, or the length of time until a future event is often impaired in autism.  There has been very limited scientific investigation of this phenomenon.

Allman, De Leon and Wearden [2011, Am. J. Intellect Dev Disabil. 116:165-78]  ) studied time perception of time, in the seconds to minutes range, as it was related to communication, social reciprocity, and other cognitive and behavioral functions. They used two versions of a temporal bisection procedure to study the perception of duration in individuals with autism and observed quantifiable differences and characteristic patterns in participants' timing functions.  Measures of timing performance were correlated with certain autism diagnostic and intelligence scores, and parents described individuals with autism as having a poor sense of time.  Martin, Poirier and Bowler [2010, J. Autism Dev Disord 40: 640-6]  tested a group of 20 high-functioning adults with ASD and 20 matched comparison participants on a temporal reproduction task. The ASD group reproduced time intervals that were significantly further from the base durations than did the comparison group. They were also more variable in their responses. Furthermore the ASD group showed particular difficulties as the base durations grew longer, tending to underestimate to a much greater degree than the comparison group. Janeslaat, Grandlund and Kottorp (2009) Disabil Health J. 2:15-19} investigated the hypothesized relation between children's time processing ability, daily time management, and self-rated independence. Participants were children aged 6 to 11 years with dysfunctions such as attention-deficit/hyperactivity disorder, autism, or physical or intellectual disabilities (N = 118). Time Processing Ability was measured with the instrument Kit for Multiprocessing Ability. They found a moderate significant relation between the parents' ratings of daily time management and time processing ability of the children, and between the self-rating of independence and time processing ability.  
Time Perception Summary: These studies lack proper controls matched for intellectual ability and chronological age as well as degree of disability, and other key variables that might effect time perception, so it is difficult to interpret the findings. The notion that children with ASDs have time processing problems is certainly credible in principle, but solid data are lacking.
Overall Scientific Evidence: 
1.     1. Children with autism often sleep poorly. You probably aleady knew that.  Some children with autism appear to have lower melatonin levels than comparison kids, and giving them oral melatonin increases the length of sleep and shortens the time to fall asleep. That’s great. Is there any objective evidence that it is possible to some how “synchronize” a child’s sleep so these sleep problems go away and their autism symptoms diminish or disappear by using a special clock? None, absolutely none, nada, ninguno, aucune, geen!
2. Children with autism seem to have problems estimating the length of time intervals and understanding when future events will happen. It isn’t entirely clear this is unique to kids with autism because the same thing occurs with most younger children and kids with various intellectual disabilities and ADHD.  Is there evidence that exposing them to a special clock that shows sun and moon phases will improve this ability to process time information?  None, absolutely none, keiner, nessuno, ingen!
Now About GreenTyme
The "GreenTyme" organization has made available free, they say, an online Circadian Meditation Optimizer, basically it’s an attractive clock fashioned after very old astrological clocks indicating sun and moon time. Their website describes the clock as providing Chrono-Cognitive Therapy.” The clock is accompanied by ethereal singing by "God's Cricket Chorus" [no kidding] which some people may find relaxing or possibly vaguely annoying. The website urges visitors to contact Dr. Oz to encourage him to include HourTyme in his television show [again, no kidding].  An article cited on the website in Newsweek by writer Christopher Dickey is titled, “Turning to ‘God’s’ Time,” which gives you a sense of how these devices are being promoted.  Whether any of this has anything to do with autism remains to be seen when an appropriate clinical trial of its use with matched groups of children with autism of known severity and another comparison group are tested with the Circa-Med clock.

Yale Landsberg says he got the idea for the clock when he was recovering, or actually not recovering in an ICU from quadruple by-pass heart surgery, which is bound to get anyone’s attention.  He says he experienced an  “ICU Psychosis.”  There seems to be a “New Age” quality to Yale Landsberg’s HourTyme websites, with references to Buckminster Fuller, and other visionaries intermixed with testimonials about the marvelous things his clocks are alleged to do.  I was unable to find anything about legitimate controlled clinical evidence.

Here’s a list of conditions that Yale Landsberg implies on his website that may profit from his Synclecron on his website: Arthritis, Asthma, Autism, AIDS/HIV, Bipolar Depression, Breast Cancer, Cardiovascular/High Blood Pressure, Cluster and Migraine Headaches, Chronic Fatigue Syndrome, Drug Addiction, Diabetes, Epilepsy, Fibromyalgia, Huntington's, Insomnia, Multiple Sclerosis, Obesity, Parkinson's, Prostate Cancer, Schizophrenia, Sundown Syndrome in Alzheimer's patients, Tourette's Syndrome, and many other diseases -- and even "Senior Moments." He doesn't promise they definitely WILL profit, but he suggests they probably will. 

Oh, one other thing.  Everything you read on most of the website states that the “therapy” clocks are free, that is until you reach the page that mentions donations and buying the clocks… for money, using your credit card, which it appears, in the last analysis, is what it may be all about.


  1. Travis, several medical doctors who think I MIGHT be onto something which still gets no attention from Autism and other experts (my hypothesis that the consequences of having biological clocks which are chronically under-informed may be the same or similar to the consequences biological clocks other-wise disrupted) have suggested I refer you to this study for your feedback.

    BTW, please note per my continued requests that users buy TrueTyme: Its SunTyme version remains free on the web and is now also on some mobile phones, whereas a user's ability to make contributions for use of MoodTyme and MoodTyme after the end of a trial is now being put into place. More information on everything we are doing is now found on our somewhat upgraded and BetterTymes4.Us sites .

    As usual, I would love to get your comments and suggestions here on your blog and elsewhere.


  2. Travis, much thanks for publishing my above esponse. You are a gentleman as well as a scholar.

    Warmest regards, Yale

  3. Hello, Travis. Hope all is well with you and yours.

    That said, it has been several years I last saw your comments about what we are doing and why. So I thought it time to, with more than a bit of trepidation, tell you you that per your...

    "Oh, one other thing. Everything you read on most of the website states that the “therapy” clocks are free, that is until you reach the page that mentions donations and buying the clocks… for money, using your credit card, which it appears, in the last analysis, is what it may be all about"

    if you visit our much revised site, you will see that in addition to a free one week trial and a $4.21 "full features forever one", we also make available that full feature forever version for free, upon request in order to encourage both professional and citizen-scientist chrono-cognitive research.

    As you have been helpful in the past, please fire away if you feel the need to do so!!! :-)

    Be well and warmest regards, Yale

    P.S. Whatever you think about what we are doing -- and why, you might find of some interest my pamphlet about time as a Mobius strip, as found at .