Human circadian rhythms Flashcards

1
Q

What was found when measuring cortisol during the sleep/wake cycle?

A

Cortisol peaks during wakefulness, but was found to rise at the end of the night

Predicts that the body will wake

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2
Q

How are melatonin and core body temperature masked by behavioral/environmental cues?

A

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

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3
Q

What are the two problems regarding the assesment of endogenous circadian rhythms in humans? What are the protocols to resolve these issues?

A

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

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4
Q

Define the range of entrainment

What is the range of entrainment in humans?

A

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)

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5
Q

What was found when measuring response curves of human subjects to bright light stimuli?

A

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

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6
Q

How does the intensity of light affect the resetting of the human circadian clock?

A

Logarithmic ship

Lower intensities shift effect greatly, tapers off

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7
Q

What is a chronotype and how is this measured?

What was found when measuring CBT in different chronotypes?

A

“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

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8
Q

How does chronotype vary with age? with gender? with geographic location? Why does the latter influence chornotype?

A

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)

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9
Q

How does electrical light influence our circadian rhythm (compared to eg camping)?

How does chronotype influence Dim Light Melatonin Onset (DLMO) in both conditions?

A

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

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10
Q

How does using an E-book affect your circadian rhythms compared to a print book? Is this masking?

A

Shifts melatonin onset (but not peak) to the right (later)

However, after removing tablet shows persistence of delay (not just masking, possibly entrainment)

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11
Q

How many genes are implicated with morningness? How many of those are related to the circadian system?

A

15 morningness-associated loci, 7 of which related to circadian clockwork (PER2, VIP, PER3)

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12
Q

Describe ASPD, FASPD, and DSPD

A

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)
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13
Q

Define Seasonal Affective Disorder and its possible cause

What is the main therapy for SAD?

A

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

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14
Q

Define shift work and its possible effects on the circadian system (and other symptoms)

How can shift work be dealt with?

A

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

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15
Q

How do psychological disease affect the central clock?

A

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

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16
Q

How can we monitor the function of human central/peripheral clocks?

A

Central: CBT, melatonin

Peripheral: White blood cells, skin cells, oral mucosa, bone marrow, etc

17
Q

How do the central/peripheral clocks adjust to a night shift schedule?

A

Central clock doesn’t adjust (peaks decrease but phase is the same)

Peripheral clocks don’t adjust either (maybe per1 and per2)

18
Q

What is Cortef and how does it affect the central/peripheral clocks?

What are the limitations of assessing clock gene expression in PBMCs?

A

Synthetic hydrocortisone

Does not affect SCN (recall lack of GC receptor)

Does not affect PBMC Per1, but resets Per2/3 and bmal1

*per3 is bimodal, presumably receives signals from SCN too

Limitations: variability, invasiveness, time-consuming, expensive

19
Q

How does clock gene expression in hair root cells change during a schedule advancement of 4 hours?

A

Gene expression advances

20
Q

How was clock gene expression in different brain regions of Alzheimer’s Disease patients measured? What did they find?

A

Cadavers who died at different times used as individual data points (mRNA doesn’t change after death)

PER2, BNST, BMAL were all perfectly out of phase