Sometimes, I read a paper, and I'm just suddenly struck by the sheer interconnectedness of the brain. This is one of those papers. Not because of the paper itself, but because when you see the association between one change in the brain (ADHD) and another (circadian rhythm), you can start to intuit other changes that might result from the two systems. Soon, you're just overwhelmed by the idea that it's all a vast web, a pull in one direction changes something in another, different systems adapting to tiny changes elsewhere to maintain homeostasis. The brain is a marvelous thing.
And today's paper concerns an association between two brain "systems" that you might think very different: attention, and circadian clock.
Baird et al "Adult attention-deficit hyperactivity disorder is associated with alterations in circadian rhythms at the behavioural, endocrine and molecular levels" Molecular Psychiatry, 2012.
ADHD (attention deficit hyperactivity disorder) is usually thought of as a disorder of attention, associated with behavioral and social difficulties. Scientists are very interested in associations between ADHD and increased likelihood of drug abuse, and of course they are interested in addressing how to relieve the social difficulties that people with ADHD often face. But there are other features of ADHD which tend to be less studied. In particular, people with ADHD often complain of...problems sleeping. Up to 83% of adults with ADHD report sleep problems, and children with ADHD also show differences in sleep patterns.
What kind of sleep difficulties? Pretty much all kinds, trouble falling asleep, increased nighttime movement, decreased REM sleep, you name it. And all of these things are connected with the circadian clock, which generates your biological rhythms. Everything from being hungry to pooping is modulated by the biological rhythm produced by your body. The center for this rhythm is thought to be in the hypothalamus, in a little area called the suprachiasmatic nucleus.
Our biological clock runs on a roughly 24 hour schedule, mediated by the presence of light during the day, and with other oscillations that are somewhat independent. As the day goes on, the biological clock controls the transcription of genes and the making of proteins in a specific, 24 hour pattern. Messing with this pattern messes with the rhythm and with your ability to do things like sleep at night and remain alert during the day.
So is there a connection between ADHD and sleep? To look at this, the authors of this study recruited people with ADHD (13 of them), and controls (19 of them, low numbers, but human studies often suffer from this, especially as they had to exclude a lot of other factors, like working night shifts and comorbid psychiatric disorders). They had them wear actigraphs to look at when they were active and awake, and took samples of their saliva and mouth mucosa, to look at the expression of clock related genes and hormones associated with circadian rhythm, in this case cortisol and melatonin.
They found that ADHD patients were overall more active than controls (well it IS hyperactivity disorder after all), but they also showed differences in rhythm. ADHD people tended to be much more active at night (they call this a shift toward "eveningness"), and they also had much more trouble falling asleep, on average taking an hour after going to bed to get some z's, while no controls complained of this.
But when they looked at the clock genes BMAL1 and PER2, they saw something particularly interesting:
What you can see here are the rhythms for controls (the two left graphs), and ADHD (the two right graphs). You can see for BMAL1 (top), and PER2 (bottom), the controls show a nice rhythm, with a peak in the middle of the day and lower at night. In contrast, the ADHD patients showed no discernable rhythm. Not a shift in rhythm, but no rhythm at all.
The hormone studies showed something else interesting:
The controls are still on the left, the ADHD patients are on the right. On the top is melatonin, a hormone which helps control circadian rhythm, and on the bottom is cortisol, which varies with circadian rhythm.
You can see that the melatonin had a very large and obvious rhythm in the controls, but that this was dampened in the ADHD group, they just didn't have as strong a rhythm. With cortisol, while both the controls and the ADHD patients showed a rhythm, in the ADHD patients it was shifted, to 3 hours after the time when they usually woke up. No wonder they complained of feeling sluggish in the morning.
And here we come to another aspect of the inter-relatedness of it all. One of the hormones they looked at was cortisol, which varies on a diurnal schedule. The rhythm was different in people with ADHD. But cortisol is not just a circadian hormone, it's a chemical signal strongly associated with stress response. Is there a link to altered stress response here as well? And stress response alterations are often associated with changes in depressive behaviors and addictive behaviors. How deep does the rabbit hole go? And where do we begin to correct it all?
Clearly, this study does not provide proof that ADHD and insomnia always go together. But it does show an association between ADHD and a disregulated circadian rhythm. Of course, here we have a chicken and egg problem, does the ADHD cause the circadian issues? Do the circadian issues result in ADHD? It's a new angle for ADHD research, and one that might be interesting in the long run. If one thing changes, something else changes too, and it may take a deep understanding of how many different systems work together to figure what puts a brain in balance.
Baird AL, Coogan AN, Siddiqui A, Donev RM, & Thome J (2012). Adult attention-deficit hyperactivity disorder is associated with alterations in circadian rhythms at the behavioural, endocrine and molecular levels. Molecular psychiatry, 17 (10), 988-95 PMID: 22105622