Life Intertwined
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Someone has said that character is the willingness to accept responsibility for ones own life. People with self respect have the courage of their mistakes (Joan Didion, 1967).

Parsing the influence of the ebb and flow of major brain/body chemicals can increase your choices to develop life patterns that intentionally optimize emotional contentment and health. An expanding knowledge base has enabled us to progress in our ability to deliberately sway our underlying genes and chemistry. Research is beginning to unravel the cadence of chemical components in your body’s sleep/wake life concerto.The synchronization of our rhythms of daily living to day/night earthly cycles turns out to be intrinsically important to the balance of our underlying chemistry and genetic well being.

Only this year the Nobel Prize was awarded to scientists who isolated a gene that controls the rhythm of daily life of all living organisms and some plants. They found that this gene encoded a protein that accumulates in the cells at night and degrades during the day. This inner genetic biochemical clock system adapts our physiology to day night intervals. It strongly influences our behavior, hormones, sleep, body temperature, and metabolism. This kind of information empowers us to intentionally calibrate habits of living that decisively setup an optimal tempo to our life path.

Awake and Sleep

It is believed that the two states, wake and sleep, have evolved in the historic evolution of life at discrete times. Awake and sleep are triggered to switch from one to the other through a confluence of environmental and internal factors such as underlying chemical changes related to genetic cycles, experienced light/ dark, and fatigue.The consolidation of sleep and wake periods has always been essential for successful participation in productive human activity and survival. It is important to be awake in the daylight and to have restorative sleep at night. We cannot do this readily without synchronizing our own genetic circadian clock system to the light/dark earthly rhythm.

Our waking sets the stage for our sleep and our sleep determines the energy and quality of awakened life. Both states are characteristic of all living beings and involve complexities and cyclical variance. Sleep and wake are so profoundly vital that they could not only be left to 1 or 2 biochemical systems. There are redundant, underlying chemical circuitries associated with the cycles of wake and sleep. These circuits are collaborative, with different systems serving varying functions at distinct times. All of the major chemicals multitask, interface, and are on a circadian tempo set up by a convergence of genes and environment. Everything seems to interface with almost everything in a very precise and timed manner.

The stimulating “wake” brain chemical systems that we are happy to have in morning crescendo must be dampened in sleep. Throughout the waking day the activating chemicals are depleted, while they are replenished during rest at night. In juxtaposition, the sleep promoting chemicals and cellular waste build up during the waking day and are cleared at night. Many of the primary brain chemicals target one area during awake and another during sleep. We know, for example, that histamine (HA) is an activating chemical that is released in circadian fashion, higher in the morning and mostly off line at night. Adenosine, a metabolic byproduct of cellular firing, accrues in the day time to help push us into sleep where it gradually falls to a lower level in the morning. Melatonin rises at night but is low in the morning.

While each underlying circuitry is associated with certain survival states and tasks, it is not just chemical levels that matter. The sensitivity of targeted receptor systems during different time periods and experienced life circumstances is crucial. Sometimes the rise or fall of body/brain chemicals have complex and nuanced effect. For instance, independent populations of Acetylcholine (Ach) cells fire at different times of our day and night. One population fires during REM sleep, while another fires only in waking states.

Major Awake Chemicals

The primary wake activating chemicals include the so called Monoamines. These are familiar neurotransmitters such as Serotonin(5-HT), Neuropinephrine (NE), Dopamine (DA), Histamine(HA), Acetylcholine(ACh), as well as the very prolific Glutamate(Glu). There are also more minor chemical players that rouse us for daytime activity. For instance, the gut neurohormones like Ghrelin-feeding promoting, and Neuropeptide Y(NPY), which also appears activating and related to feeding, circadian regulation, and pain. A newly discovered incentivizing circuit, the Orexin system, seems to galvanize a chorus of other energizing daytime chemicals that work to stabilize wakefulness and keep sleep, particularly REM (rapid eye movement-dream sleep) at bay. It goes without saying that successful survival would be compromised if sleep impinged upon waking activities. It is during our arousal, waking state that we take care of our necessary life needs. It is crucial for survival to have these activating chemicals preeminent during the awake times. We have clear evidence that serotonin (5-HT, the stuff of most antidepressants) is primarily related to awake ventures and, if it continues to be at high levels at night, it reduces REM sleep. Elevated NE helps us to energize and focus during the day, but at night researchers describe NE as an “off button” for REM sleep.

Neuropinephrine (NE) is one of the primary neurotransmitter associated with anxiety. Elevations of NE rise along with increases in our primary stress neurohormone and place us in a focused fight or flight condition of high arousal. In the past this facilitated a quick reactive response circuit that likely helped to save us throughout our foraging history and in war. Anxiety related REM sleep fragmentation is thought to be essentially caused by the sustained elevation of our “anxious arousal neurochemical” NE.

Too Much Activation

Fascinating new research points to genetic stress predisposition, trauma history, and early childhood adversity as precursors of high lifetime stress reactivity and REM fragmentation. We are now able to track REM sleep and to see on a sleep graph when it is not fully consolidated. Fragmented REM sleep promotes the feeling that the night is spent in thought, often worrisome thought, rather than in dreams. Upset events are cooled in REM sleep so that what may feel as a terrific worry one day, after a good night’s sleep may seem quite manageable. This quieting of emotional upset primarily happens during REM sleep. If it is fragmented the person often awakens, still vigilant and upset. If REM fragmentation continues, the result is a more and more agitated person.

Many psychiatric antidepressant drugs inhibit REM sleep, so this is troublesome. Alcohol also inhibits REM sleep as do Benzodiazepine medications like Valium and Klonopin type drugs. Chronic REM sleep deprivation leaves one less able to think clearly and increasingly stress reactivity and impulsive. We have had some success treating insomnia related elevations of NE which are usually manifested in nightmares and anxious night time rumination. Small amounts of anti-hypertensive medications that lower NE blood levels, like Clonidine and Prazosin, can be helpful. The veterans administration has used these NE lowering medications effectively for a number of years with Post Traumatic Stress REM related sleep disorders of traumatized veterans.

Sleep Restoration Chemistry

Interestingly, the wake promoting neurons inhibit the sleep promoting neurons. The GABA (gamma-aminobutyric acid) neurons are the most important and prolific inhibitory neuronal system in the brain. These sleep promoting GABA neurons inhibit the wake promoting neurons. This is another wonderful example of our genetic/environment synchrony. The GABA system is a critical chemical constituent that signals the more stimulating daytime brain chemicals to subside. Melatonin and Adenosine, and several other minor players, link with the GABA system to start the sleep section of our daily life concerto. All of the stimulating brain chemicals are lowered during sleep, excepting ACh which increases somewhat during REM sleep. It is fascinating that ACh and Glu, which play a crucial parts in learning and memory, are the primary “REM On” chemicals. REM sleep, remember, is a period when we are unable to move but the brain itself is quite active. On a sleep graph it looks a bit like an awake brain. It is thought that memory, cognitive integration, creativity, and emotional calibration emerge from REM sleep.

Almost all emotional dysregulation may be a stress reactive circuitry problem with circadian components. For some people activating chemicals are chronically elevated, inhibiting sleep nurturing chemicals. There is speculation that certain genetic groups may have a mammalian brain bias that is quick to threat rejoinder. The thinking is that historically those mammals that responded with this predilection would be able to rouse the foraging community to survive to pass along their genes. Unfortunately for today’s “uptight folks” a state of vigilance, fostered either by genetics or environmental experience, is antithetical to restorative rest.

Finding Balanced Chemical Integration and Peace

Neuroscientists point to underlying dysregulated body chemistry as having a negative impact on health and emotion. Habitual thoughts, focus, and patterns of living become automatic pathways that are our default circuits, reinforcing or modulating genetic predispositions. Consciously establishing healthy, balanced habits that become automatic with repetition is essential for living our better selves. If one is highly stress reactive, it helps to know it. Using that anxious stress reactivity to advantage may be important. Interestingly, in the monkey research the “uptight” babies that are fostered by “laid back” mothers are the leaders.

As our knowledge in genetics and body chemistry increases, we have more understanding of the underlying physical substrates and circadian rhythms that dovetail with health and emotional wellbeing. Incorporating this into regular patterns of living, including habits of thinking, wake/sleep, exercise, social interaction, and nutrition may be an evolving hope for a more actualized life. It is clear that these regular, deliberate templates of living can nurture our better selves and increase our potential for a life well spent.

- Dr. Linda Klaitz, Medical Psychologist

“Neurochemistry of Sleep and Wakefulness” Edited: Jaime M. Monti, S.R. Pandi-Perumal, and Chrisstopher M. Sinton- Cambridge University Press.
American Academy Sleep Medicine -2017.


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