Chronobiological theories of mood disorders
Another comprehensive review article: Chronobiological theories of mood disorders (Zaki et al., 2017)

Here is my summary and opinions about it.

Tl;dr: the authors cautiously explored the bidirectional and/or causal effect of sleep & circadian disorders vs. mood disorders. I appreciated their caution but a lot of the evidence presented suggested circadian arrhythmia as a causal agent.

Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) don't address underlying circadian and seasonal rhythm dysfunctions, so patients are usually prescribed these meds indefinitely.

In the future, they see light therapy and melatonin receptor agonists as better treatments. I'd say an outdoor walk sunlight exposure after breakfast in the morning, blue blockers or nix artificial light at night, and instead of melatonin agonists, consider serine.

"The master clock controlling chronophysiological rhythms of theand body organs is located in the SCN..." VIP and AVP are abundant in the SCN!
I knew it! LOL

"Humans' endogenous rhythmic activity has a period slightly longer than 24 hours, hence, it needs daily entrainment to 24 hours with zeitgebers."


Evidence favoring circadian and sleep disorders as causal agents in mood disorders:

Single nucleotide polymorphisms (SNPs) in BMAL1, Period3, and Timeless have all been linked to major depressive disorder and bipolar disorder.

"A SNP in CLOCK correlates with sleep profiles, rest/activity rhythms, and relapse of depressive disorders." If it's genetic, that suggests causal. Maybe it doesn't always manifest, but it still suggests causation.

"There are roughly 10 million SNPs in the human genome." Most of them are meaningless.

3 interesting SNPs in Period3: one influences a patient's response to SSRIs, another is associated with a morning chronotype, and the third associated with an evening chronotype and delayed sleep phase disorder.

Prozac may actually work by inducing a circadian phase advance! In other words, Prozac doesn't work for a lot of people; maybe it only works when there's an underlying circadian disorder. Same goes for lithium: it inhibits GSK-3b which directly targets PER2 (another circadian enzyme).

Insomnia is formally recognized as a predisposing factor in depression.

I liked this part: the authors considered circadian may independently predispose to sleep disorders and mood disorders whereas previously it was thought more linearly: circadian disorder -> sleep disorder -> mood disorder. I don't know, but it's food for thought.

More evidence for circadian disorder -> mood disorder: 1) diurnality (a subgroup of depressed patients are worse in the morning); 2) seasonality ("winter depression"); and efficacy of light therapy, blue blockers, and melatonin.

"Patients with major depression also often show lower blood concentrations of melatonin with pronounced circadian phase advances in melatonin secretion." Sometimes.

Cool figure (focus on lower right):

Emphasis on "Increase zeitgeber strength; eg, light."

Chronobiological models of mood disorders

  1. depression is more common among shift workers than the general population and onset of symptoms occurs after shift work began.
  2. mismatched sleep and circadian phases. Some MAOi's and lithium correct bring the circadian component back in line with the sleep phase. Also evidenced by efficacy of light therapy and melatonin in "winter depression."
  3. and what might be the most (or least?) controversial: the "you did it to yourself" model. Chronic exposure to artificial light at night and skipping breakfast fully de-entrains central and peripheral circadian clocks and are fully modifiable behaviors.
  4. pregnancy -> sleep & circadian disruption -> postpartum depression

Conclusion:  Breakfast, sunlight, and a good walk in the morning ... ... darkness or blue blockers at night. Might be a role for SR9009 (morning) or serine (evening), but I'd go for the lower-hanging fruits first.

 That's all for now!

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