Is sleep the balm of hurt minds? It should be. Happily, sleep usually comes easily to me. There are some exceptions: the night before having to wake early for a long plane flight being one, but these events are few and far between.
Many people complain of insomnia, and this is a private disorder, in that it is rarely on public view. What could be more personal than to be stranded in wakeful isolation while the rest of the world is soundly asleep? However, if you have the great fortune to share a bed with someone else, you can sometimes judge whether the other person slept well, just by noting their regular breathing. You might even try a whispered “Are you awake?” to check whether you are judging their state of somnolence correctly. Then, if in the morning your partner claims not to have slept a wink, you can counter with your own observations about them having slept soundly for at least part of the night.
There are other methods to measure whether people are really awake for hours, or just exaggerating on the basis that any unwanted wakefulness at night can feel as if it lasted for ages. For example, having a bedside timer that has to be responded to every time a little light comes on is one such method used by sleep researchers. If you are wakeful you can do this monitoring task for a long while. Once you fall asleep you can no longer monitor the signals. To some extent, the perception of not having had a full night’s sleep can be measured objectively.
Be all this as it may, to rise from bed in the morning feeling you have not slept properly is a burden. What causes insomnia? A long list of foods and drinks usually follow, plus bad habits about getting too agitated prior to going to bed. “Sleep hygiene” is recommended by psychologists, and often works. You probably know the advice: prepare for sleep by following a sequence. Avoid bright lights and noise and troubling activities. Go through a ritual that calms you down and gently reminds you of comforting topics, and casts away troubling thoughts. If all that doesn’t work, get up and do some of the tasks that are worrying you, or at least write down a to-do list, and then go back to bed and try again.
Now Danielle Posthuma and colleagues have looked at the genetic angle. Are some people more prone to this disorder? So it would seem.
Genome-wide Analysis of Insomnia (N=1,331,010) Identifies Novel Loci and Functional Pathways
Philip R Jansen, Kyoko Watanabe, Sven Stringer, Nathan Skene, Julien Bryois, Anke R Hammerschlag, Chrstiaan A de Leeuw, Jeroen Benjamins, Ana B Munoz-Manchado, Mats Nagel, Jeanne E Savage, Henning Tiemeier, Tonya White, Joyce Y Tung, David A Hinds, Vladimir Vacic, Patrick F Sullivan, Sophie van der Sluis, Tinca JC Polderman, August B Smit, Jens Hjerling-Leffler, Eus JW van Someren, Danielle Posthuma
It is not often that one gets sent a paper with a 1.3 million sample size. I move in refined circles, it would seem.
Insomnia is the second-most prevalent mental disorder, with no sufficient treatment available. Despite a substantial role of genetic factors, only a handful of genes have been implicated and insight into the associated neurobiological pathways remains limited. Here, we use an unprecedented large genetic association sample (N=1,331,010) to allow detection of a substantial number of genetic variants and gain insight into biological functions, cell types and tissues involved in insomnia. We identify 202 genome-wide significant loci implicating 956 genes through positional, eQTL and chromatin interaction mapping. We show involvement of the axonal part of neurons, of specific cortical and subcortical tissues, and of two specific cell-types in insomnia: striatal medium spiny neurons and hypothalamic neurons. These cell-types have been implicated previously in the regulation of reward processing, sleep and arousal in animal studies, but have never been genetically linked to insomnia in humans. We found weak genetic correlations with other sleep-related traits, but strong genetic correlations with psychiatric and metabolic traits. Mendelian randomization identified causal effects of insomnia on specific psychiatric and metabolic traits. Our findings reveal key brain areas and cells implicated in the neurobiology of insomnia and its related disorders, and provide novel targets for treatment.
Well, at first glance these authors are on to something. These are brain areas one might have imagined would be implicated in sleep disorders. Also, the disorder picks up the nexus of psychiatric disorders, long suspected of having some biological roots. Let us read further.
Insomnia complaints were measured using questionnaire data, and the 36 specific questions were validated to be good proxies of insomnia disorder, using an independent sample (The Netherlands Sleep Register, NSR) in which we had access to 38 similar question data, as well as clinical interviews assessing insomnia disorder.
So, they seem to be measuring insomnia, which increases with age, and is more common among women. They pick up real genetic signals, not spurious associations.
We confirm previously reported genetic correlations between insomnia and neuropsychiatric and metabolic traits, and also identify several GWS SNPs for 249 insomnia that have previously been associated with these traits. The strongest correlations were with depressive symptoms (rg=0.64, SE=0.04 P=1.21×10-71 250 ), followed by anxiety disorder (rg=0.56, SE=0.11 P=1.40×10-7 251 ), subjective well-being (rg=−0.51, SE=0.03 P=4.93×10-52), major depression (rg=0.50, SE=0.07 P=8.08×10-12 252 ) and neuroticism (rg=0.48, SE=0.02 P=8.72×10-80 253 ).
Since a similar high reliability has been reported for both sleep and psychiatric phenotypes, the findings suggest that genetically insomnia more closely resembles neuropsychiatric traits than it resembles other sleep-related traits.
In addition, insomnia was bidirectionally associated with educational attainment, with a stronger effect from insomnia on educational attainment (bxy=−0.32, SE=0.02, P=1.68×10-77 265 ) (i.e. a higher risk for insomnia leads to lower educational attainment) than vice versa (bxy=−0.10, SE=0.01, P=2.27×10-23 266 ), the same pattern was observed for intelligence.
This is an extremely detailed paper, and I have only given you the very basic points. Yet, in another way, the results are very familiar. A pattern is beginning to emerge. If you take a behavioural problem, like being unable to get restful sleep, you find a genetic nexus of psychiatric disorders with deleterious effects on intellectual ability.
Dryden, whom I revere, intoned: Great wits are sure to madness near allied, and thin partitions do their bounds divide.
Far from that being the case, wit is diminished by mental disorders. When literary tradition collides with empiricism, woe to tradition.