Okay, now we're going to move to talk a little bit about some of the consequences of insomnia. And how sleep loss, in the case of its association with this particular disorder, can impact a variety of issues related to individuals' activities of daily living, their mood, their performance at the workplace, and their mental health. So first of all, certainly one of the consequences of insomnia has to do with sleep loss. And that sleep loss can impact learning, it can impact safety in a variety of ways such as increasing risk for accidents. And it can also impact physical health as well as quality of life in terms of family relationships. So we're going to talk about some of those issues now. First, when we look at sleep deprivation related to insomnia, it certainly can have an impact on brain functioning. This is actually a study which was done with normal individuals who were sleep-deprived for one full night. And as we can see here, metabolism, particularly in the frontal areas of the brain, related to things like planning and multi-tasking, the executive areas of the brain, have a reduced amount of metabolism as we can see here, as shown in blue. Also the thalamus and some other areas, particularly in the cortical areas, have a reduction of activity. But in the case of individuals with insomnia, not only is there reduced metabolic activity in the brain in terms of the cortex, but there's actually elevated activity in the subcortical area. So, for example, as we can see on this left panel, there's actually activation that occurs in subcortical areas of the brain. These are areas that are robustly related to things like emotion. So this is the limbic system being activated. The interior singular cortex, the ascending reticular activating system is also activated, more so than in individuals without insomnia. So we can really think of this disorder as having a double whammy, both activated brain areas that normally shouldn't be activated at night, and also on the right panel, deactivated areas. Now here, shown in red, there's reduced metabolism in the prefrontal cortex. So we have impairments associated with sleep loss that we would normally see in individuals who deprive themselves or restrict themselves of sleep, but we also see evidence of hyperarousal in individuals with insomnia. So again, these kinds of brain differences can lead to behavioral differences as well. What we see with insomniacs is a reduction in health-related quality of life. And in some cases when we look at the degree of reduction, particularly in severe insomniacs, we see the level of impairment is similar to or even more, in some cases, than what we see in more chronic health conditions such as congestive heart failure, or in the case of depression. So insomnia does have a significant impact on quality of life. It also expresses itself in terms of morbidity, with regard to absenteeism. So this is data showing that in insomniacs, compared to good sleepers, there's a much greater duration of absenteeism over the course of two years. This is an effect which is very strong, in fact, about double the rate of absenteeism overall. But it's an effect which occurs across a variety of different white collar and blue collar workers, also in terms of gender. A very similar distribution as well in managers. So clearly, there is a functional impairment in terms of work. There's also a functional impairment in terms of actual objectively measured performance deficits. So not only absenteeism, but presenteeism effects occur as well. So, for example, what we can see from this data is, in red, primary insomniacs have impairments on reaction time relative to normal sleepers, they have a longer time to react to stimuli. And because of that increased reaction time, it can impair a variety of different tasks. What's important to understand is that on the left panel, what we see are no differences. These are very simple reaction time measures. So individuals with insomnia can respond to a single reaction time, or a continuous performance test, but when we add some cognitive complexity to those responses where we ask individuals to switch their attention back and forth from one side of the screen to the other, we begin to see those impairments. So that increasing cognitive load begins to impair an ability for the insomniacs to keep up and maintain attentional capacity relative to normal sleepers. And we also see at the bottom panel that there's a greater degree of variability. These are standard deviations of the amount of time it takes. So what this just simply shows is that individuals with insomnia have a much more variable response pattern than do normal sleepers. In addition, as you may well know, sleep has an effect to improve our ability to consolidate memories during the night. That's an effect we have seen in a number of studies. We see that here in this particular study, which is a measure of learning correct word pairs. And we can see in the evening to the morning, there's an improvement in performance, again, having to do with consolidation of, in this case, declarative memories in control participants. But we don't see that improvement in ability to remember, a morning retrieval of those words that you memorized the night previous, in patients with insomnia. So it does impair our ability to consolidate memories during the night. We also see, in conjunction with some of these impairments, an overall increase in accident rates in persons with insomnia. And we can see about 9% accident rate, in this particular study, in insomniacs relative to individuals without chronic insomnia or high distress. And that's a very important aspect to think about. And here we can see, for example, the outside of an insomnia-related or sleepiness-related crash. But what we also can see are the inside effects of what's going on when someone's driving and is having a sleepiness-related crash. Or in this case, in the case of insomnia, it may not be sleepiness-related but attentional-related impairments. There's also data suggesting an increased risk for nursing home placement in male patients with insomnia. In this case we can see the risk factors on the left panel include sleep disturbance, and that sleep disturbance increases the risk by about 500% for an individual being placed in a nursing home. We can see that risk is much higher than most of the other risks associated with nursing home placement. And in fact, when we compare the risk of disturbed sleep to that of mental impairment, in fact, insomnia or sleep disturbance is actually a greater risk. One of the reasons to think about why this might be the case is that individuals who are older and waking up frequently during the night may be ambulating during a time of increased, what we call sleep inertia. Which may be in fact much greater in the middle of the night than during the daytime after, say, for example, a nap. So individuals with insomnia who are not treated may be at greater risk for other kinds of morbidities associated with nocturnal awakenings, for example, falls. And those risks may be important factors in determining whether someone should be sent into a nursing home or assisted living facility. So, for example, this is a study of nursing home residents, predominately women in this case. 34,000 individuals between 65 and older with 150 to 210 days of follow up. And what we find is the relationship between insomnia, hypnotic use, falls, and hip fractures is particularly important. So, for example, insomnia did predict future falls. Individuals in nursing homes and elsewhere are much more likely to have a fall if they're ambulating and waking up in the middle of night more frequently. Whereas hypnotic use was not a predictor of falls. And in fact, if we can treat insomnia, there is the possibility that we may be able to determine a reduction in risk for falls. But those studies are ongoing at the present time. Now, there are also a number of morbidities related to insomnia that have to do with psychiatric conditions. And there's in fact a circular relationship between insomnia and psychiatric disorders. So we're all very familiar with the risk for sleep disturbance in individuals with a psychiatric disorder, say, for example, depression or anxiety. But, in fact, there are a lot of data now suggesting there is also a relationship, a predictive relationship, in terms of insomnia increasing the risk for the future development of depression or another psychiatric disorder. There are a number of studies to draw on to look at some of this data. But this happens to be one of the longer studies with about a 40 year duration follow-up. And what we see is about a three times risk for depression over the course of the 40 year follow up for individuals who had insomnia at the beginning of this particular study. Now this is a very important potential risk factor for developing depression and it's been studied in a number of other investigations. And, in fact, there are now over 14 studies which show, in most cases, that insomnia is a prospective risk factor for the development of major depression. The odds ratios range from two times an increased risk to six times the risk for developing depression, relative to individuals without insomnia. There is also some dissociation between insomnia and depression. So, for example, if individuals with depression are successfully treated with an antidepressant, in this case fluoxetine, or prozac, what we see is the number one and two residual symptoms In these treated individuals are sleep disturbance and fatigue. So even in treated depressed patients, there is a common reason for addressing sleep disturbance and fatigue. In addition, there are a number of studies which suggest an increased risk for relapse in patients who are successfully treated, depressed patients if there is insomnia present or other kinds of refractory symptoms. So it's very important to address these issues. Well, we're going to talk now a little bit about some of the causes of insomnia and the pathophysiology of this particular disorder.
