Neuroscientists at Maynooth are uncovering how working with circadian rhythm can aid recovery from illness​

Each of us has a biological clock ticking away inside us. It runs a 24-hour schedule and keeps this up no matter what crazy schedule we live. Fighting against the natural rhythm of your clock is unhealthy, however, and many of us are guilty of this.
 

Social Jetlag
“About two-thirds of people say they need an alarm clock to wake up on a workday,” says neuroscientist Dr Andrew Coogan, director of the Chronobiology and Sleep Research Laboratory and Head of Psychology at Maynooth University. “Social and work schedules are competing against our internal clock.”  On a free morning at the weekend most people sleep in an extra 90 minutes compared with work days; this difference has been termed ‘social jetlag’ and is a symptom of our modern society.

Going against your biological clock is no trivial matter, Dr Coogan’s research shows. One study underway with colleagues at Connolly Hospital is examining if social jetlag may, in part, explain why some patients with type II diabetes have less good control over their disease than others. "This is an important link and suggests that it may be possible to give patients practical advice regarding sleep and social schedules which could help with their disease." 

Another aspect of Dr Coogan's work examines the interaction of the circadian clock and attention deficit hyperactivity disorder (ADHD). His group have recently been examining how social jetlag may contribute to symptoms of impulsiveness and lack of attention, as occur in ADHD. "This may help us understand the link we have previously described between the circadian clock and ADHD," Coogan explains.

Understanding the circadian clock
Scientists figured out how the body clock ticks in recent years. Fifteen clock genes form a cycle, turning on and off over a 24-hour period. A study last year suggested that over 40% of our genes track to our circadian rhythm, so a large chunk of our genome is under its sway. This is why so many of our functions follow a daily path; it is why eating late at night is not so good for us – our digestive system and liver are not prepared.

There are important positives to understanding the circadian clock. Getting to know the nuts and bolts of our clock is allowing researchers better treat some patients and know when to give or not give therapies to increase their effectiveness and decrease side effects.

Co-ordinating drug administration with the body clock
Symptoms of many common and important illnesses also follow a daily rhythm.  Dr Coogan and colleagues this year described the benefits of giving therapy for rheumatoid arthritis just before bedtime, as the inflammatory cytokines involved in this autoimmune disorder spike during the night.  “Taking steroids just before bedtime and during the night,” he explains, “targets the rise in inflammatory mediators and you get less joint stiffness and less pain than if the same drug is taken during the day.”

Many old drugs, which never made it into pharmacies, could even be revived if more attention was paid to timing.  “There is very often no mention of dosing times in clinical trials, and this is a major omission,” says Dr Coogan. Indeed Dr Coogan believes that paying more attention to our biological clocks may lead to fewer side effects in other drugs, including cancer treatments.

Behavioural-based therapies
There are significant other potential benefits too from understanding the clock. “It is very common for conditions such as major depression, ADHD and bipolar disorder to be associated with high levels of sleep disturbance,” Dr Coogan notes.  “Sleep and circadian rhythm disruption may be an important part of these disorders, and there are indications that these changes may precede the onset of other symptoms".  Here again, knowledge of how the clock functions allows for the development of new behavioural-based therapies that alter the clock.

"There are studies showing you can relieve symptoms of depression by a combination of light therapy and melatonin [a nocturnal hormone] to alter the time of the body clock,” Dr Coogan explains. "Such approaches may have the capacity to address a large clinical need, for example in the treatment of depression in people for whom other treatments have failed."

Links between illness and shift work
Ignoring messages from our biological clock is also bad for our physical health. This is proven by large studies which revealed links between heart disease and cancer and shift work.  “The elevation in cancer risk described for shift work is two or three time higher than for processed meat,” says Dr Coogan, referring to the recent controversy over World Health Organisation guidelines, though this is a very moderate increase. 

This fits with the big picture. Obeying your biological clock is a healthy option.  A study this year suggested that the body’s work crews that fix DNA damage can be slowed when our biological clock is disrupted. This might help explain why cancer is slightly higher in shift workers. “As a rule of thumb, if you don’t have to do shift work, then don’t. Although lots of people need to do it of course,” notes Dr Coogan. Even in the 19th century factories had to operate from dusk to dawn, whereas these days electric lighting allows for around-the-clock work. But this is not necessarily a healthy development. “In modern society our working day has changed so much, but our biological clocks evolved over millions of years and are not going to snap back just because we invented the light bulb,” adds Dr Coogan.

Electronic devices
Another issue is the light from electronic devices like phones and tablets and especially their use at night. We use rods and cones for our vision, but a photopigment called melanopsin detects light and cues us to dusk and dawn. “We know this is most sensitive to blue light, so we are talking to industry to design lights and products less enriched at the blue end of the spectrum,” says Dr Coogan.  “This would be less likely to upset our circadian rhythm.” Street lighting is moving from the old yellow sodium lights to new LEDs, but these are much richer in blue light and so more disruptive to our biological clocks.  Simple changes can be made to roll with our clocks, rather than fight a biological mechanism put there over millions of years of evolution.

There are other areas of our lives, in which application of knowledge of the circadian clock may lead to benefits. Teenagers notoriously are not early risers, given a choice, but this can be pinned on their biological clocks too, says Dr Coogan. "Adolescence is associated with eveningness, reflected by later wake times and later sleep times". Given this, there may be a logic in considering later school starts for such adolescents.

“My teenage son starts at 8:20 in the morning. Yet teenagers are the naturally least-suited group of people for such early starts. By aligning school start times with the biological clock, there may be benefits in terms of academic performance, school attendance and behaviour” he adds. "This is an example of how we might exploit fundamental knowledge to effect societal change for the better, which in the end is what science is all about."