- circadian rhythms and mental illness

• seasonal a ective disorder

- SAD

- a mood disorder characterized by depression that occurs at the same time every year.
typically winter. this is thought to be because the lack of light during winter (particularly
while waking up) does not properly induce wakefulness, leading to unusual circadian
rhythm’s

• depression

- night shift workers (sleep-wake cycle opposite normal circadian rhythms) are as much
as 40% more likely to be diagnosed with depression

• anxiety

- Shift work (not consistently working at night, but going back and forth) results in
increased anxiety diagnosis. Also e ects the ability to fall asleep and stay awake. Jet
lag results in increased anxiety levels.

- Treatments for Misalignment of Circadian Rhythms

• These are all a result of misalignment of circadian rhythms with behavior. That is, you're
supposed to be awake/working when your body wants you to sleep

• Bright light - use a bright light early in the morning to wake up

• Interpersonal and Social Rhythm Therapy - rst used to treat bipolar disorder. The
therapist works with the patient to maintain their schedules and times for things, to
maintain circadian rhythms

- can we use other cues to help enforce circadian rhythms?

• establishing a bed time routine has been shown to help people fall asleep faster and wake
less frequently

• this could be due to helping establish sleep cues (ie i’m going to bed to sleep now)

• this could also be due to prevention of poor sleep habits

- SCN

• suprachiasmatic nucleus

• part of the hypothalamus: master clock

- sleep, temperature

• circadian rhythms driven by light

- zeitgerber : “time-giver”

• light -> specialized retinal cell (RCG) in retina -> SCN

- retinohypothalamic tract

• SCN -> pineal gland

- melatonin, light inhibits

- Clock genes

• clock genes & their protein products

- in neurons of SCN

- made and degrade in a 24hr period ->

- activity of SCN neurons cycles every 24 hours ->

- physiological & behavioral circadian rhythms

• how do we know SCN is important for circadian rhythms?

- destroy SCN -> abolish rhythms (arrythmatic)

- replace SCN -> reestablish rhythms

• how do we know clock genes are important?

- mutations & polymorphisms -> dysregulation of circadian rhythm (shorter or longer)

- clock and cycle genes

• clock and cycle bind to form a diner -> promotes transcription of period (per) and
cryptochrome (cry) during sleep

• per and cry bind, inhibit clock+cycle

• decrease in per and cry production

• breakdown of per and cry results in transcription of clock and cycle

• ~24 hours, light activates production of per via glutamate in SCN

- lesioning/ transplanting SCN

• lesioning the SCN in a hamster: rhythms disappear

• transplanting with an SCN from a hamster with a 20 hour cycle

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 - recipient also has 20 hour cycle

- sleep stages

• EEG records electrical activity in the brain

• voltage increase and frequency decreases as you go through stage 1 to 2 to 3 to 4

• delta waves appear in stages 3 and 4

- synchronous activity of neurons : brief period of low ring

- important for memory consolidation

- REM - rapid eye movement

• also paradoxical sleep

• high activity, musicale tone low, increased facial twitch and irregular breathing

- nightmares vs. night terrors

• de ned by when they occur during your sleep cycle

• nightmares

- long, bad dreams that occur during REM

• night terrors

- sudden arousals from stage 3 SWS, marked by fear and autonomic activity

- sleep stages

• a full cycle through all stages take ~90 minutes

• throughout the night, REM takes longer, deep sleep shorter/disappears

- naps

• power nap

- 10-20 minutes

- stay in SWS1/2, easy to wake up, won’t feel groggy. gives you a break and boosts
energy and alertness

• 30 minutes

- bad

- start SW3/4, but cannot complete, leaving you feeling tired and groggy

• 60 minutes

- nish SW3/4, but not REM. helps with memory performance, but you may not be fully
alert upon waking up

• 90 minute nap

- one full sleep cycle. pass through all stages of SWS and REM

- why do we sleep?

• brain development

• energy conservation

- evolutionary adaptation to reduce metabolic demands

• predators

• memory consolidation

- REM for procedural

- SWS (mainly 3 & 4) for declarative

• restoration

- break down adenosine, clear out amyloid beta

- sleep and memory consolidation

• sleep also helps consolidate memory

• one theory for how this works is called the hippocampal indexing theory

• during experience, you have all of this activation in various cortical areas processing your
experience

• during sleep, the cortical areas “replay” these same activity patterns (what happens when
these cells all re together?)

• this hippocampus tags, or indexes, each of these various areas with the time and place of
the memory, so that all of these aspects of the memory are played together

- adenosine and sleep

• result of ATP breakdown (energy use)

• in postsynaptic cell

• binds to receptors on presynaptic cell to inhibit

• ca eine: adenosine receptor antagonist (inhibits receptor signaling)

- maintains alertness by keeping neurons active

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 - a ects circadian rhythms: phase delay or advance

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