Tentacles of Love

No, this is not a reference to obscure Hentai. And before you ask, I only know about that because I stumbled into it when researching Hokusai’s Dream of the Fisherman’s Wife; not as famous as his Great Wave but to me, as a child who grew up in a home decorated with original Hokusai prints (my beloved grandmother was an avid and catholic collector of art in the 1920’s, when Hokusai was hardly known in the West), just as familiar.

Katsushika Hokusai had no idea that his wonderful and erotic art would become Ground Zero for tentacle porn. But I love his work, and I also love what little I know of him. The beautiful 2015 anime Miss Hokusai, which focuses on Katsushika’s artist daughter O-Ei, shows her father as a painter who strove obsessively and constantly to improve his art.  Aged 89 and on his death-bed he said ‘If only Heaven will give me … Just another five more years, I could become a real painter.” I sometimes think that if I had another 25 years, I might become a real scientist; an aspiration that a few of my colleagues have poured cold water on, for reasons that I fully understand and appreciate.

Back, then, to octopi and love. 

Only love can break your heart (𝄢). Well of course that’s not true. Atheromatous disease will do the trick, if it involves the coronary arteries, and so will a number of other diseases including viral myocarditis, uncontrolled hypertension, cardiomyopathy, heart valve failure and ventricular fibrillation.

The heart is a complex thing, with multiple vulnerabilities. But it turns out that love can break your heart too, so Neil Young wasn’t completely wrong.

‘Broken heart syndrome’ is a temporary but life-threatening heart condition typically triggered by stress, such as the painful dissolution of a relationship or the death of a spouse. The adrenals and other tissues pump out stress hormones, and a toxic mixture of glucocorticoids, catecholamines, growth hormone and prolactin start to attack the heart, the immune system, the brain and the autonomic nervous system.

Glucocorticoids such as cortisol drive the immuno-suppression that increases the risk of infections and cancer in the chronically stressed individual. They enhance the memory of emotionally intense events (such as the break-up you are so desperately trying to forget), while damaging your memory for other, non-emotionally charged facts and events, making daily life more difficult (2, 3). If the stress is protracted, elevated levels of cortisol may eventually start to degrade memory and attention, a condition known to medics who dose their asthmatics with steroids as ‘steroid dementia’ (4).

But it is the catecholamines adrenaline and noradrenaline that damage the heart, causing it to contort into the shape of the Japanese octopus trap known as a taksubo (5). Because the syndrome was first discovered in Japan, the broken heart syndrome is also known as takotsubo heart, or takotsubo cardiomyopathy.

The taksubo trap has convex, bulging sides and a concave base. This shape is excellent for trapping octopi but terrible for pumping blood; it typically leaves the victim weak, with chest pains and shortness of breath, a combination of symptoms easily mis-diagnosed as a heart attack, and can cut cardiac output by as much as 80%, causing symptoms of heart failure. There are no hard and fast figures as to how many people are affected by the condition, but clinicians estimate that about 1-2% of patients reported with heart attacks may in fact have a broken heart; which would amount to millions of cases every year.

Broken heart syndrome may be caused by the end of an affair, but different people respond to different stressors.

The jeweler who developed takotsubo after being robbed is a darkly tragi-comic figure (6). Other recorded triggers include a patient’s dog caught in a raccoon trap, losing a large amount of money in a casino, getting lost while driving in an unsafe neighborhood at night and feeling overwhelmed by new computer software (7). Adverse drug reactions, surgery and even alcohol withdrawal can also precipitate the condition; as can pheochromocytoma, a cancer of the adrenals that produces large amounts of catecholamines (8, 9).

If takotsubo heart is caused by catecholamine flooding, beta blockers would theoretically be the drugs of choice to treat the condition. But they may not be enough to counter the effects of extreme emotional stress; as many as 20% of patients presenting with takotsubo are already taking these drugs for pre-existing reasons, and the beta blockers they were taking manifestly did not protect them.

What interests me is the possibility that octopus trap heart may be on the increase, because it is not just about the heart. The brain is involved too. 

That might seem obvious, given that the condition is usually precipitated by emotional distress, but it is only very recently that scientists have found autonomic dysregulation at the central level in takotsubo patients. There is evidence of re-wiring in the hippocampus, parahippocampus and limbic system, and changes in the cortical and sub-cortical networks that feed to the these structures (10, 11); changes that were presumably initiated by the emotional trigger(s) that started the whole thing.

Not everybody subjected to emotional extremes develops takotsubo heart, so clearly some people are more susceptible and some less so. In other words, it is another of those bi-cameral nature / nurture models, where the amount of stress (environmental) and the resistance to stress (genetic, nutritional) interact. And as I see it, two out of those three components are deteriorating.

At the population level, the frequency of those genes that predispose to takotsubo are unlikely to be changing. However, our world is becoming a good deal more stressful, as we tack painfully into the Fourth Turning. At the same time, the phytonutrient and other factors that support resilience by optimizing the function of brain structures such the ventral tegmental area (12 – 16) are being removed from our diet, making us less able to deal with stress. As a history of depression is an exacerbating factor (17), we have to add progressive depletion of omega 3 HUFA’s to the mix also.

This is a rather toxic brew, and I think we will see many more broken hearts in the near future.

References

𝄢. Young N. After the Goldrush, 1970. Track 3

2. Lupien SJ, Maheu F, Tu M, Fiocco A, Schramek TE. “The effects of stress and stress hormones on human cognition: Implications for the field of brain and cognition”. Brain and Cognition 2007. 65 (3): 209–37.

3. de Quervain DJ, Roozendaal B, McGaugh JL. “Stress and glucocorticoids impair retrieval of long-term spatial memory”. Nature 1988. 394 (6695): 787–90.

4. Varney NR, Alexander B, MacIndoe JH. “Reversible steroid dementia in patients without steroid psychosis”. Am J Psychiatry. 1984,141 (3): 369–72.

5. Coupez E, Eschalier R, Pereira B, Pierrard R, Souteyrand G, Clerfond G, Citron B, Lusson JR, Mansencal N, Motreff P. A single pathophysiological pathway in Takotsubo cardiomyopathy: Catecholaminergic stress. Arch Cardiovasc Dis. 2014 Apr; 107(4):245-52.

6. Savall F, Dedouit F, Telmon N, Rougé D.J Takotsubo cardiomyopathy in a jeweler following a hold-up: forensic considerations. Forensic Sci. 2013 Nov; 58(6):1648-50.

7. Sharkey SW, Windenburg DC, Lesser JR, Maron MS, Hauser RG, Lesser JN, Haas TS, Hodges JS, Maron BJ. Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy. J Am Coll Cardiol. 2010 Jan 26;55(4):333-41.

8. Kim S, Yu A, Filippone LA, Kolansky DM, Raina A. Inverted-Takotsubo pattern cardiomyopathy secondary to pheochromocytoma: a clinical case and literature review. Clin Cardiol. 2010 Apr;33(4):200-5.

9. Rossi AP, Bing-You RG, Thomas LR. . Recurrent takotsubo cardiomyopathy associated with pheochromocytoma. Endocr Pract. 2009 Sep-Oct;15(6):560-2.

10. Silva AR, Magalhães R, Arantes C, Moreira PS, Rodrigues M, Marques P, Marques J, Sousa N, Pereira VH. Brain functional connectivity is altered in patients with Takotsubo Syndrome. Sci Rep. 2019 Mar 12;9(1):4187.

11. Templin C, Hänggi J, Klein C, Topka MS, Hiestand T, Levinson RA, Jurisic S, Lüscher TF, Ghadri JR, Jäncke L. Altered limbic and autonomic processing supports brain-heart axis in Takotsubo syndrome. Eur Heart J. 2019 Apr 14;40(15):1183-1187.

12. Aubry AV, Khandaker H, Ravenelle R, Grunfeld IS, Bonnefil V, Chan KL, Cathomas F, Liu J, Schafe GE, Burghardt NS. A diet enriched with curcumin promotes resilience to chronic social defeat stress. Neuropsychopharmacology. 2019 Mar;44(4):733-742. 

13. Yang X, Chen X, Fu Y, Luo Q, Du L, Qiu H, Qiu T, Zhang L, Meng H. Comparative efficacy and safety of Crocus sativus L. for treating mild to moderate major depressive disorder in adults: a meta-analysis of randomized controlled trials. Neuropsychiatr Dis Treat. 2018; 14: 1297–1305.

14. Asrari N, Yazdian-Robati R, Abnous K, Razavi BM, Rashednia M, Hasani FV, Hosseinzadeh H. Antidepressant effects of aqueous extract of saffron and its effects on CREB, P-CREB, BDNF, and VGF proteins in rat cerebellum. J Pharmacopuncture. 2018 Mar; 21(1): 35–40.

15. Darcey VL, McQuaid GA, Fishbein DH, VanMeter JW. Dietary Long-Chain Omega-3 Fatty Acids Are Related to Impulse Control and Anterior Cingulate Function in Adolescents. Front Neurosci. 2019 Jan 9;12:1012.

16. Treadway M, Cooper JA, Miller AH. Can’t or won’t? Immunometabolic constraints on dopaminergic drive. Trends in Cognitive Sciences 2019, May 1, 435-448 (Review)

17. Kim H, Senecal C, Lewis B, Prasad A, Rajiv G, Lerman LO, Lerman A. Natural history and predictors of mortality of patients with Takotsubo syndrome. Int J Cardiol. 2018 Sep 15;267:22-27.