by Dr Greg Brown
Intersecting with this discussion of inflammation, the gut, and psychosocial stress is the other half of my theme — sleep and circadian rhythms.
Inadequate sleep is endemic, and dealing with sleep problems is a noticeably increasing part of my practice. Both acute and chronic sleep deprivation cause issues with the functioning of the immune system and raise, you guessed it, cytokine levels, particularly interleukin-6, which seems to be most implicated in depression. It should be said that there is some evidence that reducing the amount of sleep from eight to six hours a night is enough to trigger noticeable elevations in these cytokines, so it really doesn’t take much.
Circadian rhythms are physiological, cellular, and behavioural cycles lasting approximately 24 hours. The sleep-wake cycle is the obvious one, but there are also cycles of hormonal patterns, body temperature, and cell-cycle regulation, to name a few.
Circadian regulation is capable of adapting to major changes in its operating environment like seasonal changes of day length, and even sudden changes in daily light schedule like air travel or shift work. These are recent, novel stressors in evolutionary terms, and yet we have this ability to adapt.
In term of how circadian regulation occurs, it’s all down to the control of a master clock, a region of the hypothalamus known as the Suprachiasmatic Nucleus (SCN). This master clock sits just above the optic nerves, and is hard wired into the retina. It therefore has a direct line to the outside world, receiving signals from the daily cycle of environmental light. The master clock is a literal “body clock” which exerts central control over a hierarchical network of clock cells, down to elementary clocks in individual cells. It’s likely that most, if not all, cells are capable of generating circadian rhythms. One of the ways the master clock communicates with the periphery, synchronising the oscillations of peripheral and central clocks, is through release of the hormone melatonin, from the adjacent pineal gland. Melatonin release, then, is tied to environmental light signals via the retina and the master clock.
In addition, there are significant potential epigenetic implications arising from the fact that the genes and proteins comprising the core molecular clock regulate the timing of the expression of about 10% of all transcripts, RNA copies of DNA, produced in any given tissue or organ. Still think you haven’t got time to prioritise sleep?
Still think you haven’t got time to prioritise sleep?
Why am I going on about circadian rhythms, clocks and melatonin? Well, a hallmark feature of mood disorders is disrupted circadian and sleep patterns, and this is almost universal.
One could legitimately ask, however, which comes first? Is it the insomniac chicken or the scrambled egg? Animal studies have shown some interesting links in this regard, for example in one study mice with a particular mutation of the clock gene showed sleep disturbance, as one might expect, but also manic-like behaviour which reversed with lithium (a anti-mania drug).
Another mouse study, published this year in PlosOne, showed that circadian rhythm disruption impacts the intestinal microbiota, and this was particularly the case with a “high (unsaturated) fat, high sugar” diet.
The same team, who clearly have a thing for studying restless rodents, showed in another paper last year that repeated phase shifts, circadian disorganisation, increases intestinal permeability (yep, it’s that leaky gut again). This particularly occurs in the presence of an injuring agent, which in this study happened to be alcohol.
It turns out that clock dysfunction is very much intertwined with mood disorders, and we do have some studies which show that insomnia symptoms are correlated with subsequent, with future, mood disorders. So to quote again from the “nutritional psychiatry” review paper referenced earlier,
Circadian rhythm disruption appears to be a distinct biological stressor that interacts with Westernized dietary patterns in the promotion of intestinal permeability and the loss of normal intestinal microbiota.
Most people living the modern, predominantly urban, lifestyle experience multiple circadian rhythm disruptors day after day, principally from incongruent light signals (including late night short wavelength light exposure). Mental resiliency slowly erodes.
The recurring theme of mismatch, this concept that our ancient genes and the modern environment may not be interacting too harmoniously, is highly relevant in an Ancestral approach to psychiatry, and has great explanatory power as to why we might be seeing this general increase in mood disorders. To summarise, we have a model where an individual is predisposed by a high inflammatory load from the standard Western diet high in sugar, grains and seed oils, from resultant bacterial translocation, from childhood trauma, chronic stress, and inadequate sleep (which itself causes inflammation, exacerbates leaky gut, and alters the microbiome). Resiliency is impaired. Then we have an added stressor and/or a learned behavioural response from previous trauma. This proverbial “last straw” tips the inflammatory balance over the edge and we have a mood disorder.
we have a model where an individual is predisposed by a high inflammatory load from the standard Western diet… from resultant bacterial translocation, from childhood trauma, chronic stress, and inadequate sleep… Resiliency is impaired. Then we have an added stressor and/or a learned behavioural response from previous trauma. This proverbial “last straw” tips the inflammatory balance over the edge and we have a mood disorder.
Your mental resiliency and mental health would appear to be highly dependent, at least in part, on the inputs you give your brain. Ancestral Health principles provide some real insights into this most complex and emotive area of medicine, and give some practical avenues of help. We are not passive victims of neurotransmitter misfiring and “nothing buttery”.