Insomnia and sleep deprivation are often conflated. The health risks of sleep deprivation, those people who simply do not allow themselves to sleep enough, are well documented – mortality, weight gain, high blood pressure, diabetes . . . the list goes on and on. And so it is natural for people with insomnia to worry about these issues. Surely decades of poor sleep would give rise to the same damaging consequences on health? However, sleep deprivation and insomnia are quite different. If you study someone who is sleep-deprived in the sleep lab, they doze off very quickly, and while they are awake they perform poorly in tests of vigilance. In stark contrast, insomniacs with short sleep will take much longer to drop off to sleep, and are much more vigilant while awake.
But here, the distinction between the different types of insomnia – with short sleep duration and normal sleep duration – is of fundamental importance. Both types of insomnia are associated with the brain being more active than normal. Using imaging techniques and monitoring brainwaves, both groups of insomniacs are found to have increased brain activity in sleep, which may explain why patients with sleep state misperception or a normal-ish sleep duration experience sleep as wakefulness or have sleep that is not refreshing. But it is only those with a short sleep duration who have this heightened activity in the whole body, as demonstrated by chemical and physiological markers like heart rate. While the effects on brain activity are important in terms of the subjective experience of sleep, many of the health problems related to insomnia seem limited to those with a short sleep duration and the physiological hyperarousal affecting the whole body, rather than just the brain. Studies of cognitive performance in people who say they have insomnia do not show major differences when compared to normal sleepers, but when you separate those with normal amounts of sleep, even poor-quality and broken sleep, from those with objectively measured short sleep, it is the insomniacs with short sleep duration who have significant cognitive problems. In contrast, people without insomnia who are sleep-deprived do not exhibit features of activation of these hormones, neurotransmitters and cardiovascular markers of hyperarousal, nor do they show cognitive problems to the same extent.
Similarly, when the risk of conditions like high blood pressure and diabetes are analysed in people with insomnia, those with properly measured short sleep have higher rates of these conditions, while those sleeping six hours or more have no increased risk at all. Insomniacs with short sleep have even been shown to have slightly increased mortality. But how this might occur seems to be different from people who are simply sleep-deprived. We know that sleep deprivation is associated with weight gain, so could it simply be that insomniacs sleeping very few hours gain weight, which then predisposes them to diabetes, high blood pressure and all the associated ills? Well, actually, chronic insomniacs with short sleep duration do not seem to gain weight any more than normal sleepers. In fact, if anything, these patients are less likely to become obese than normal individuals. Instead, it is likely that the chemical and physiological effects of hyperarousal directly contribute.
Cortisol, a natural steroid, is associated with increases in blood pressure and diabetes. We see this all the time in patients on steroids to suppress their immune system if they have an autoimmune neurological disorder. The increased activity of the sympathetic nervous system and related chemicals like adrenaline directly influence the heart and blood vessels, leading to the loss of the usual drop in blood pressure expected at night.
To summarise, the physical effects of insomnia with very curtailed sleep seem to be a marker for these physical changes in one’s hormone and cardiovascular state, and look to be responsible for some of the risks to health that insomnia entails. For people with insomnia with a reasonable sleep duration, there is evidence of abnormal brain activation, but from a physical perspective, this group of insomniacs shares more with people with normal sleep.
So what drives this hyperarousal state seen in people with severe insomnia, those who sleep very little? Is hyperarousal caused by the short sleep of these insomniacs, or is the insomnia generated by this hyperarousal state? The answer is not entirely clear, but the lower levels of activation of these chemical and neurological systems in those with sleep state misperception – those people who have subjective poor sleep but have a normal total sleep duration – and those people without insomnia but who are sleep-deprived would certainly suggest that it is the hyperarousal state itself that causes these more severe forms of insomnia.
There are undoubtedly genetic factors at play. Insomnia often runs in families, and studies of twins have suggested that 57 per cent of insomnia can be explained by genes. A recent study has identified seven genes that contribute to insomnia, so a genetic predisposition to this hyperarousal state is certainly possible. It is quite normal for people under stress, due to a new job, a relationship issue, a death in the family, to have a period of insomnia, and a period of hyperarousal. But it may be that if you have the right genes, in the context of such a stressor, you are at higher risk of that state of increased excitability, mentally and biologically, persisting beyond the presence of that stressor. And that state of increased vigilance or arousal drives the insomnia to become chronic.
There are clearly also psychological factors in the mix. As I’ve already said, roughly half of patients with chronic insomnia have underlying psychiatric disorders, especially anxiety – and hyperarousal is a strong feature of anxiety. So the anxiety itself may be driving the insomnia. But what about those without anxiety, the other 50 per cent who do not have any psychiatric disorder?
For many of the people I see in clinic, they do not have panic attacks, are not worriers during the day. But many tell a common tale. They report feeling fine during the day, but at the point of going up to bed they start to worry, specifically about the process of going to sleep. They become anxious that they will not drift off to sleep, that they will struggle throughout the night. They live in dread of the night ahead. When their head hits the pillow, rather than associating their comfortable bed with the delights of drifting into blissful sleep, they see their bedroom as a place of torment, an instrument of torture. ‘I feel exhausted as I get into bed, but as soon as the lights go off, my mind races and I feel wide awake,’ is the common refrain. It is at that moment that they become hyperaroused, their brain feels ‘wired’, and sleep suddenly becomes out of reach. Like Sisyphus rolling his stone almost to the top of the hill before it slips out of his hands and rolls all the way down again, they are tantalisingly close to sleep when it is suddenly snatched away from them. The longer this persists, the worse their relationship with sleep becomes.
There is, however, another aspect to this state of heightened psychological and physical stress response. It makes people feel awful. Alongside the poor sleep, sufferers of insomnia can feel like they are on the verge of dying, and unless it is immediately obvious to you that there is a significant element of anxiety, it can contribute even more to the insomnia, because then you begin to worry that you have something seriously wrong with you. Claire says, ‘I used to go online and google insomnia problems. I convinced myself I had certain syndromes.’ I ask her if she was worried about any syndrome in particular, fully knowing the answer, having heard it many times: ‘Fatal familial insomnia. I convinced myself I was going to die within six months.’
Fatal familial insomnia is a prion disorder related to Creutzfeldt–Jakob disease, or ‘mad cow disease’. Caused by a faulty gene, passed down through generations, it is a relentlessly progressive neurological disorder, invariably fatal after an average of eighteen months. Patients present with insomnia that gradually worsens. As the disease progresses, there are changes to the autonomic nervous system, an inability to maintain blood pressure with marked fluctuations, high and low, sweating, and constipation. Delirium ensues with hallucinations and behavioural change, and in the latter stages sufferers drift constantly in a limbo between wake and sleep. This condition is, however, unbelievably rare, affecting only forty known families in the entire w
orld. Perhaps it is indicative of the level of anxiety with which people with insomnia can be afflicted that they occasionally quickly jump to this diagnosis, convincing themselves of the other symptoms of this disease.
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When I first meet Claire, she recognises certain personality traits in herself that might have led her to this point. Moreover, when we discuss her sleep prior to her current problems, she tells me that her sleep would always be somewhat affected by other things going on in her life. The trigger for her hyperarousal state is evident to both her and me: ‘I just think the stress of work, the stress I put on myself for work, was self-inflicted,’ she tells me. ‘Because of this need to prove myself as an older woman, going back into the workplace. Somebody else might have reacted very differently to what was going on. But it’s just in my nature to want to do a good job and I’m quite sensitive to any kind of criticism. So I would come home and agonise over them [criticisms] and replay them in my mind.’ She also recognises this hyperarousal state in herself. ‘I just basically got to the point where I was not able to fall asleep. That switch that sends people to sleep stopped working for me. So whether it’s a nap during the day or going to bed at night, it didn’t work.’ She describes that very typical difficulty in sleeping during the day and the increased vigilance of the hyperarousal state. ‘My brain was trying so hard to function that it had to produce so much adrenaline that it was just permanently on alert. It wouldn’t go to that place of rest.’
After a couple of years of terrible sleep, however, Claire hit a wall.
That was when I asked for my pay rise. There were some hard negotiations which I just found too much. I spiralled downwards basically. And with the lack of sleep, combined with my reaction to those events, I went into a place of deep depression really, and I didn’t know how to get out of that. And then the depression led to more insomnia and the insomnia made the depression worse. And my hair started falling out by the handful. I lost about half of my hair. But I don’t think I recognised it for what it was for quite a long time.
By the time I meet Claire, she has already been diagnosed with anxiety and depression. She has been seeing someone for her psychiatric issues and, after cycling through various drugs, has finally been commenced on an antidepressant that has helped her a lot. ‘I think about the fourth drug we tried suddenly worked really well. Within a few weeks I felt so much better. The sleep didn’t automatically get better, it’s just my mood changed so much. And it was like this cloud lifted. It made me realise that I think I’ve had depression to some degree since my children were born twenty years ago. Because it [the medication] changed everything.’
Despite the medication, there are ongoing issues with her anxiety and depression – and her sleep is still terrible. She has been trialled on several medications specifically for sleep, and some of these worked briefly before wearing off. Others have triggered a worsening of what was previously mild restless legs syndrome, an unfortunate complicating factor in Claire’s case. She has also tried a psychological therapy called acceptance and commitment therapy, which focuses on teaching people to accept or embrace their insomnia, and thus aims to reduce the feelings of stress associated with their lack of sleep, but for Claire it has done nothing.
Her insomnia persists a year after her breakdown. At the moment, she gets into bed at 10 p.m., feeling exhausted, but at the point of getting into bed, she describes that familiar alerting response, that loss of the switch into sleep. Like a carrot on a stick, when she approaches the point of sleep, it constantly moves away from her. She lies in bed for three or four hours, seeking sleep, before finally giving up and going downstairs. By 3 or 4 a.m., the sheer exhaustion of having been awake for twenty-odd hours eventually overrides the adrenaline and cortisol pumping through her veins and brain. She finally drifts off to sleep, only to wake up without an alarm between six and seven in the morning.
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The relationship between insomnia and psychological or psychiatric problems is complex. As I have already said, anxiety in some shape or form may underlie the hyperarousal state that is common to more severe forms of insomnia. Insomniacs with short sleep often have a particular psychological profile, with low mood, fatigue, and anxieties about health. Those people with sleep state misperception have a degree of overlap, with low mood and anxiety, but have a tendency to spend time ruminating, thinking about things over and over, as well as intrusive thoughts. These subtle differences in psychological picture, and the associated physical derangement of hormones and cardiovascular measures, have led some researchers to propose that these two types of insomnia are fundamentally different. Those insomniacs with normal sleep duration, i.e. sleep state misperception, do not have the bodily features of hyperarousal, and therefore few long-term consequences, and seem to be more responsive to treatment. Those short sleepers with physical hyperarousal – the amplified chemical and biological systems that mediate the ‘fright-fight-flight’ response – have a different psychological profile, are at increased risk of health problems related to their insomnia, and are more likely to be difficult to treat.
So, psychiatric problems can certainly give rise to insomnia. Ninety per cent of people with clinical depression have insomnia. Even as a medical student I was taught that early-morning waking is a hallmark of depression, but other types of insomnia – such as difficulty getting off to sleep and staying asleep – are also common. Patients with schizophrenia will often have terrible insomnia, and frequently the slipping into a psychotic episode will be heralded by increasing difficulty with sleep. But the relationship between sleep and psychiatric disorders also goes in the opposite direction. Insomnia itself is a risk factor in developing psychiatric disorders or can make these disorders more difficult to treat. The presence of insomnia, entirely independent of all other factors, significantly increases the risk of developing depression subsequently, and this is especially the case for those people with insomnia and a short sleep duration. And for those people with depression already, insomnia is a marker for increased suicidal thinking and increased risk of relapse back into depression. Patients with depression are more refractory to treatment when insomnia complicates matters.
There are a number of unanswered questions, however. This is a scientific field in its infancy, and we do not yet fully understand either the intricacies of the relationship between sleep and mental health or what underlies it. Both insomnia and psychiatric disorders result in changes to both brain circuitry and brain biochemistry, and so it is not surprising that changes in sleep or mental health may have knock-on consequences on one another. They are both the chicken and the egg. But it may also be that there are shared genetic factors that predispose both to insomnia and psychiatric issues, to add an additional layer of complexity to this area of research. Whatever the true nature of this relationship, it highlights the need for psychiatrists and sleep physicians to think holistically, to not simply focus on the problem that they are most familiar with, to approach these patients without the blinkers of having been trained in one particular specialty.
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Strategies for the treatment of insomnia have historically focused on medication. Benzodiazepines hit the market in the early 1960s, and rapidly became the staple of treatment for insomnia and anxiety, popped in vast amounts. So mainstream were these drugs that the Rolling Stones, not known for their reluctance to indulge in recreational chemicals, wrote an ode to Valium entitled ‘Mother’s Little Helper’. Over the past few decades, however, the dangers of benzodiazepines and related drugs like zolpidem and zopiclone have become apparent: risks of morning sedation, road traffic accidents, falls and hip fractures; the triggering of sleepwalking and other non-REM parasomnias; and, importantly, withdrawal effects and dependence, with ever-increasing doses required to get the same effect on sleep.
As a result, there has been a shift away from these types of drugs to other agents such as melatonin, antihistamines and sedating antidepressants. They all have their problems, dif
ferent side effects and a wearing-off effect, but used in the right way they can make a big difference.
Most alarmingly, there is growing evidence that points to hypnotic drugs, particularly benzodiazepines and related drugs, increasing the risk of subsequent dementia. However, as with many questions in sleep, this is a complex area. We have already discussed the glymphatic system, a network of channels in the brain responsible for clearing waste products, akin to the lymphatic system in the rest of the body. In deep sleep, these channels open up by up to 60 per cent, allowing the carriage of potentially toxic substances like beta-amyloid, the protein implicated in the process that underlies Alzheimer’s, away from the brain. Deep sleep facilitates housekeeping of the brain, and if you are sleep-deprived, due to insomnia or otherwise, this process of brain cleansing is affected. Sleep deprivation results in increased levels of beta-amyloid in the fluid within these channels, implying reduced clearance of this protein and other toxins into the cerebrospinal fluid, the liquid that bathes the brain and spinal cord. So sleep deprivation, and insomnia with a short sleep duration, could well in itself carry an increased risk for Alzheimer’s disease.
There is yet another possible explanation, though. Many degenerative disorders of the brain result in subtle changes years or even decades before symptoms become more obvious. Consider John and his dream-enactment behaviour, often a precursor to Parkinson’s disease by many years, and the association of anxiety with this condition. It may be that, in Alzheimer’s disease, early changes to the biochemical pathways in the brain years before memory deteriorates result in worsening sleep or anxiety. It may be that the insomnia is not the cause of Alzheimer’s, but the result of the very early stages of the disease.
The reality of this association between poor sleep and Alzheimer’s disease is yet to be fully unravelled, but whatever its nature, concerns regarding this and the other side effects of drug-based treatments has led to a sea change in how we treat insomnia. Specifically, there has been a massive shift towards non-drug-based treatments. The most widely studied and used of these is a treatment called cognitive behavioural therapy for insomnia, or CBTi. This treatment uses behavioural techniques to essentially reprogramme the brains of people with insomnia.
The Nocturnal Brain Page 28