While I love my work at NeuroScience, I also love a three day weekend, especially for that additional bit of sleep I gain before getting back to the fast pace of the work week. Did you know that sleep disorders affect an estimated 10-40% of American adults, and according to the CDC, 25-39% of us get less than 7 hours a night of sleep, including yours truly? Chronic sleep disturbances can lead to impaired concentration, cognition, memory, and coordination, as well as a host of chronic health issues.
Frustratingly, there is no “magic bullet” that brings relief to all sufferers. If you think about the neurocircuitry of sleep, this shouldn’t be a surprise – there are many points in this circuitry when things can go out of balance. Here’s a quick review.
During wakefulness, the brain is kept active and alert by the actions of neurotransmitters that include acetylcholine, norepinephrine, serotonin, dopamine, and histamine. Norepinephrine contributes to elevated energy, mood, and vigilance. Histamine promotes wakefulness and arousal. In the absence of light, the brain’s wake-promoting centers are inhibited when sleep-promoting regions of the brain release gamma amino-butyric acid (GABA) as well as melatonin, resulting in a sleep-state.
Sleep is characterized by stages of non-rapid eye movement (NREM) and rapid eye movement (REM). Here too, neurotransmitters play a role in the transition between these stages; particularly the reciprocal actions of norepinephrine and serotonin (enhancing NREM sleep) and acetylcholine (which is involved in inducing REM sleep).
In recent years, researchers have made great strides toward understanding the neurocircuitry that controls sleep-wake states. As we’ve discussed previously in this space, neurocircuitry has helped us understand some of the possible causes of sleep difficulties, for example:
- Excess release of norepinephrine and histamine results in a state of wakefulness .
- Perturbations in neurotransmitter signaling can interfere with REM/NREM oscillations, leading to impaired sleep.
Understanding the neurocircuitry of sleep has allowed researchers to identify biomarkers that can be measured for example in urine. These biomarkers can help characterize patients’ individual biochemical imbalances, as well as help healthcare practitioners select and monitor therapeutic interventions. Several correlations between central brain activity and peripheral biomarkers have been reported, such as:
- Overactivity of certain wake centers in the brain can trigger the release of norepinephrine which is reflected in urinary norepinephrine levels. Therapeutic strategies that successfully regulate norepinephrine output may help promote sleep.
- Exercise-induced increase in epinephrine correlates with a delay in REM sleep onset (Netzer, 2001), and total REM sleep is lower following exercise. Accordingly, exercise has been shown to stimulate an increase in urinary epinephrine.
Data suggests that neurotransmitter imbalances that have been associated with neuropsychological disorders, such as insufficient serotonin and elevated glutamate, norepinephrine, dopamine, and epinephrine may also contribute to sleep disturbances. Depression has been reported to be one of the strongest risk factors for current insomnia, but it has also been suggested that current insomnia is a risk factor for future depression. Interestingly, certain therapeutic interventions that target neuropsychological disorders have also been shown to improve sleep. For example, 5-hydroxytryptophan (5-HTP), the amino acid precursor to serotonin, has been reported to promote sleep quality in patients with insomnia.
Analysis of peripheral biomarkers may also help predict who will respond to various sleep medications and/or supplements, thereby simplifying the therapeutic protocol. For example, in a study of a sleep-inducing benzodiazepine, patients who had a favorable antidepressant response had significantly higher pretreatment urinary epinephrine and norepinephrine levels than control subjects, while no such difference was found among nonresponders.
Overall, it’s become clear that individuals with sleep disorders may exhibit a spectrum of different biochemical imbalances. Using neurocircuitry to define clinically relevant peripheral neurotransmitter and hormone biomarkers, we are beginning to characterize individual patients’ imbalances, thus customizing sleep aids for better likelihood of efficacy.