The Shadow of Your Smile

In 1813, it was a truth universally acknowledged that a single man in possession of a good fortune must be in want of a wife. In 2022, not so much. Unbalanced sexual endocrinology driven by the modern diet and the indiscriminate use of endocrine disrupting chemicals, solipsism enabled by social media and the fore-shadowing of the shades of the West, have conspired to produce an era of rampant sexual confusion.

Will Jane marry Bingley? Or will she prefer Charlotte? In any case, in our accelerated and technically disconnected age there will likely be heartbreak at the end of it. And from a health perspective, that is perhaps all that matters.

Roughly 50% of marriages fail (1), and the percentage of all relationships that fail is probably over 95% (2) These failures are generally stressful and depressing.

Stress and depression cause endocrine and immune system dysfunction resulting in chronic inflammation (3-5). Chronic inflammation is highly pathogenic. Failing and failed relationships therefore increase the risk of disease and death – as do bereavement, loss of employment and moving house (6, 7). Rack up too many of these ‘life events,’ and your risk of disease rockets (8).

Early life adversity (such as parental abuse) is another severe and long-term stressor which reliably induces raised levels of pro-inflammatory cytokines (9-11). It predicts severely reduced life expectancy in humans (12, 13), by as much as 20 years (14, 15) – or close to a third of our life-span. And it’s not just a people thing.

Baboons are long-lived, ground-living socially complex primates like us, but they are more sensitive souls. When exposed to early life adversity they lose fully half of their life expectancy (16); and so, alarmingly, do their offspring (17). Whether this inter-generational effect occurs in humans is not yet known but seems very possible. This has been hinted at in recent research of survivors of the Rwanda genocide (18), who were epigenetically reprogrammed by the extreme stresses they endured (19).

Another major stressor is social isolation, which kills baboons (20) and humans (21-23) alike. Isolation and loneliness shorten human life by up to 15 years (23), and given that 30 – 40% of people in the West feel themselves to be isolated (24-26), the negative effects of the plandemic will be with us for decades to come (6-8, 12, 13, 22, 23, 28).

Physical health, mental health and cognitive performance have been hammered by lockdowns, masking and social distancing. This government-imposed social isolation is now being associated with a 50% increased risk of dementia, and a 30% increased risk of heart disease and stroke (27-30).

Is the modern diet making us more vulnerable to these stressors, and the casual cruelty of our masters? Could we use dietary tools to reduce the health problems caused by loneliness, heartbreak and bad politics? A fascinating new paper in Nature Communications suggests that we can.

A multinational team in the USA, Canada, the UK and Singapore looked at the neurobiology of isolation (31), and found signatures for loneliness in a group of brain regions known as the ‘default mode network.’ Lonely subjects showed ‘stronger functional connections and greater microstructural integrity of the fornix pathway’. The researchers speculated that these circuits, which support mentalizing, reminiscence and imagination, were being up-regulated to fill the social void.

The default mode network is an assembly of higher association areas which overlaps with parts of the brain involved in sociability (32). It is involved in the internal construction (the imagined version) of social and other events (32), mental representations of oneself (33), the reconstruction of one’s personal past, and the simulation of events, places and people (32, 34). It is down-regulated when we interact with the external world, or when we meditate (35).

In short, the default network is where we recapitulate the past, imagine the future, and position and value ourselves in that matrix. If we are exposed to serious stresses (such as early life adversity), the resulting neuroinflammation skews the default network in a way that makes us focus on the negative aspects of our lives and experiences (36-41). And that in turn drives isolation, depression, anxiety and inflammation. It is a most vicious circle (42-44).

In a nutshell: social defeat (see Social Defeat post) triggers the Cell Danger Response, which drives inflammation, which skews the default system, which turn our inner gaze to the dark side, which makes us ill. Immune and cognitive / affective states are thus profoundly inter-connected. It is very certain that the pro-inflammatory nature of the modern, ultra-processed diet impacts negatively on these connections now – and in the future.

Excessive early life adversity builds the neuro-circuitry incorrectly. Loneliness and junk food give it a negative bias. Heartbreak knocks it off kilter and so too, we now learn, does the memory of heartbreak. The shadow, if you will, of your smile. (The soundtrack was the best thing in that tedious Taylor / Burton vehicle)

In a fascinating recent study (45), Israeli and US researchers used different insults to create chronic inflammation and accompanying pain in the colon and peritoneum of mice. This activated a specific group of neurones in the animal’s insular cortex, which connects to the default network. A month later, when these neurons were directly stimulated, inflammation reappeared in the original sites. Causality flowed in both directions!

This beautiful experiment opened two important doors. Firstly, it demonstrated a physical substrate for psychosomatic illness and a range of placebo effects. Secondly, and more specifically, it showed the ability of traumatic memory to cause physical trauma ranging from pain and chronic inflammation to disease.

This shows that we are not only connected internally and externally to the world, and everything in it, but also temporally, across years, decades and even generations. It is a profound reason for humans to be better, kinder, to love and care for those around us.

It is, I think, close to the core of unified field theories such as entanglement and Buddhism, a meditative faith shown to be able to knit up the raveled default network (35).

On a more prosaic note, it is yet another health warning to be attached to ultra-processed foods, and a call for better, anti-inflammatory nutrition. It may also be a warning of the dangers of the algorithms used to provide personalized content in social media (46), which are both isolating and associated with increased risk of depression and suicidal behaviour (47-49).

Finally, it is a reference to validated saffron extracts. These exert potent antidepressant and anxiolytic effects via the ventral tegmental area, which positively modulates the default mode network and enables us to turn like sunflowers towards the light (50), within hours.

Great artists have always understood the paradox of connection (51).

Next week: D-Day, Omaha Beach, ‘vitamin’ D and the art of staying alive.

References

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