Human circadian rhythms Flashcards
What was found when measuring cortisol during the sleep/wake cycle?
Cortisol peaks during wakefulness, but was found to rise at the end of the night
Predicts that the body will wake
How are melatonin and core body temperature masked by behavioral/environmental cues?
Melatonin: maked by light (Light pulse during night causes abrupt cease in melatonin production)
CBT: masked by sleep (when testing 30 mins sleep: 60 mins wakefullness, CBT troughed during sleep but was found to be circadian overall
What are the two problems regarding the assesment of endogenous circadian rhythms in humans? What are the protocols to resolve these issues?
Masking: eg by sleep, activity, light, feeding, etc
Entrainment: eg by environmental cues
Protocols:
Constant routine protocol
- Sustained wakefulness
- Semi-recumbent posture, limited activity
- Dim light
- Hourly snacks
Removes many masking factors, allows phase evaluation, BUT cannot be extended beyond 40h (sleep deprivation, health hazard), cannot be used to measure FRP
Forced desynchrony protocol
- Subject forced to live on a T cycle outside range of entrainment (eg 20h or 28h)
- Circadian rhythms uncouple from sleep-wake cycles
THE gold standard to accurately measure FRP in humans, allows dissociation of circadian rhythms and sleep-wake/feeding cycles, and allows to compary effect of aligned/misaligned rhythms
BUT
Extremely expensive, time consuming, and personel demanding
Define the range of entrainment
What is the range of entrainment in humans?
The range of T cycles that a subject can entrain their circadian rhythm to
In humans, ~23h-25h
(humans will be unable to entrain to any T cycle longer/shorter than this range)
What was found when measuring response curves of human subjects to bright light stimuli?
Late day-late night: phase delays
late night-early day: phase advances
Light at ~5:00 subjective time causes a shift/delay of 12 hours
Light at ~17:00 causes no effect
How does the intensity of light affect the resetting of the human circadian clock?
Logarithmic ship
Lower intensities shift effect greatly, tapers off
What is a chronotype and how is this measured?
What was found when measuring CBT in different chronotypes?
“early bird” vs “night owl”
Phase of circadian rhythms
The lower the chronotype the more of an early bird you are
Tested with Horne-Ostberg chronotype questionnaire, or Munich chronotype questionnaire (MSF, mid sleep time on free days)
Measuring CBT: Early birds peaked earlier than night owls (difference of ~ 2 hours)
MSF of early birds is around 3, night owls is 6
How does chronotype vary with age? with gender? with geographic location? Why does the latter influence chornotype?
Males have a higher chronotype than females at younger ages
Peaks around 20s, then declines sharply (for both genders)
When plotting chronotype in germany, chronotype was proportional to longitude (people in the west are more night owly, people in easy are more early birdy)
Exposure to sunlight? This proportion is not seen in larger cities (light polution)
How does electrical light influence our circadian rhythm (compared to eg camping)?
How does chronotype influence Dim Light Melatonin Onset (DLMO) in both conditions?
Artificial life: not as much exposure to sunlight, artificial light prolonged wakefulness period
Camping: activity directly constrained by availability of sunlight (fall asleep/waking up more regularly)
DLMO during electrical lighting: steeper slope, more varied based on chronotype
DLMO during natural lighting: flatter slope, less dependent on chronotype and more dependent on sunset
How does using an E-book affect your circadian rhythms compared to a print book? Is this masking?
Shifts melatonin onset (but not peak) to the right (later)
However, after removing tablet shows persistence of delay (not just masking, possibly entrainment)
How many genes are implicated with morningness? How many of those are related to the circadian system?
15 morningness-associated loci, 7 of which related to circadian clockwork (PER2, VIP, PER3)
Describe ASPD, FASPD, and DSPD
Advanced sleep phase disorder
- Evening sleepiness
- sleep onset earlier than desired
- early morning awakenings
- Sleep recording generally normal, just shifted
- Prevalent in older individuals
Familial Advanced sleep phase disorder
- Mutation in Per2 and CK1delta (phosphorylates Per2)
- Leads to period AND phase mutations (similar phenotype to Tau mice)
Delayed Sleep Phase Disorder
- Difficulty falling asleep in evening
- Difficulty waking up spontaneously in morning
- Sleep onset ~3-6 AM, wake time ~11AM-3PM
- sleep recording normal, just out of phase
- More common than ASPD, more frequent in teens
- Genetic associaiton with Per3 (not causal)
Define Seasonal Affective Disorder and its possible cause
What is the main therapy for SAD?
No clear cause, but symptoms include sleep problems
Chronobiological hypothesis: phase delay caused by longer nights as basis for SAD?
Main therapy: light therapy (30 mins of bright light in early morning)
Has been associated with clock gene polymorphisms
Define shift work and its possible effects on the circadian system (and other symptoms)
How can shift work be dealt with?
Irregular ‘shifts’ of work
Causes desynchrony, 85% of shiftworkers unable to adapt
Circadian misalignment leads to various health problems such as sleep/mood disorders, cancer, metabolic syndrome etc)
Countermeasures include strategic napping, bright light exposure, pharmacological intervention
How do psychological disease affect the central clock?
Schizophrenic patients have random effects on the central clock, mostly random activity profiles independent of melatonin peaks
Patients with Alzheimer’s disease have decreased activity profiles as disease worsens
