The Character Armor of Pattern Baldness: Anxiety, Depression, and Learned Helplessness

 
 

In 1950, Szasz et al. noticed something that anyone who has ever visited a baldness forum is well aware of: Men experiencing pattern baldness tend to have defensive attitudes.[1] While one only needs to venture to the Hair Loss Help forum thread entitled, "If you're bald you don't need to kill yourself, you're already dead" to view an example of the despair and hopelessness in the balding community,[2] Szasz et al. came to their conclusion after observing that "toothy smiles" and rigid facial expressions were common among balding males.

The group felt that these characteristics were a reflection of controversial psychologist Wilhelm Reich's concept of "character armor," or the psychological defenses of a neurotic personality, which serve as protection from feelings of insecurity and anxiety.[3] It might be said that this orientation stems from the negative cultural connotation of balding in a soulless culture obsessed with youth, however, I have a slightly different take.

 
Image: The Theory of The Pathogenesis of Ordinary Human Baldness (1950)

Image: The Theory of The Pathogenesis of Ordinary Human Baldness (1950)

 

I think the "balding personality" or "character armor" that Szasz et al. observed is the result of what pioneering physiologist, Hans Selye called stress. For Hans Selye, stress was an energy problem: an organism was challenged with a stressor (e.g., cold, low blood sugar, adrenaline, forced exercise, etc.) and based on the inherent amount of "adaptation energy" an organism either adapted positively or negatively. Depleting this organismic energy reserve caused the organism to adapt at its own expense traversing from an anabolic to a catabolic state. Perhaps most importantly, Selye found that adaptations were cumulative and tended to self-accelerate with age

I think the vicious cycle of stress and low metabolic energy is evident in those with pattern baldness. For example, a "significant elevation" of the classical stress hormone, cortisol, was discovered in both sexes experiencing pattern baldness.[4] Cortisol was a focal point of Hans Selye's research, and its main function is to provide an alternative source of glucose by breaking down the body's structures. In a study on post traumatic stress disorder (PTSD), the researchers found that cortisol increased as a result of an interference with cellular respiration,[5] which I have progressed as a more fitting explanation for pattern baldness than genetics or androgens.[6] 

If you’re bald you don’t need to kill yourself, you’re already dead.
— Hair Loss Help Forum Member Post (2013)

The prolonged exposure to cortisol might also help explain the defensive attitudes of balding men encountered by Szasz and his team. Cortisol is well-known to cause unpredictable changes in the mood ranging from euphoria to suicidal depression.[7,8]

In the complex biochemical web of signaling substances, there is a strong chemical romance between cortisol and serotonin. Serotonin increases cortisol in a dose dependent manner through the pituitary,[9] and acts indirectly on the adrenal glands by promoting the formation of estrogen,[10] prolactin,[11] and the prostaglandins.[12] Estrogen,[13] prolactin[14] and the prostaglandins[15] appear to be involved in baldness. Serotonin also increases the "salt retaining" hormone, aldosterone,[16] which is also associated with pattern hair loss.[17] 

It might surprise some, but like an excess of cortisol, elevated levels of serotonin are involved in unfavorable behavior. In fact, serotonin is responsible for one of the most serious stress states, learned helplessness

I: Learned Helplessness, Serotonin, and LSD

 
Image: "You're afraid to soar, afraid of heights and depths." Listen, Little Man! by Wilhelm Reich (1974)

Image: "You're afraid to soar, afraid of heights and depths." Listen, Little Man! by Wilhelm Reich (1974)

 

Learned helplessness is a behavior in which an organism is forced to endure aversive, painful or otherwise unpleasant stimuli, and becomes unable or unwilling to avoid subsequent encounters with those stimuli, even if they are escapable.

Learned helplessness can be induced by increasing levels of serotonin in animals.[18] Likewise, exposing animals to inescapable stress increases serotonin.[19] Active thyroid hormone, triiodothyronine or T3, reverses the phenomenon.[20] Moreover, low levels of serotonin are associated with playfulness,[21] while high levels are associated with aggression and anxiety.[22,23] 

Recently, the hardwired cultural idea that high levels of serotonin are associated with happiness and that low levels are involved in depression has been challenged.[24] In the 2015 paper, Is Serotonin an Upper or Downer? Andrews et al. suggested that serotonin re-uptake inhibitor drugs (SSRIs) weren't effective and that when they were effective, worked differently than advertised.

In summary, we propose that depressed states are high serotonin phenomena, which challenges the prominent role the low serotonin hypothesis continues to have in depression research. We also propose that the direct serotonin-enhancing effects of antidepressants disturb energy homeostasis and worsen symptoms. We argue that symptom reduction, which only occurs over chronic treatment, is attributable to the compensatory responses of the brain attempting to restore energy homeostasis.
— Is serotonin an upper or a downer? (2015)

Serotonin is often considered a brain chemical, however, 95% of it is produced in the intestine.[25] Chronic bowel disorders are associated with the so-called "type D personality" ('D' stands for distressed), and elevated levels of serotonin are seen in inflammatory gut diseases such as irritable bowel syndrome (IBS), celiac, and Crohn's.[26] Serotonin causes inflammation in the intestine,[27] and elevated levels of serotonin are a marker for appendicitis.[28] Unsurprisingly, bacterial endotoxin, a constant source of stress in the intestine, increases the release of serotonin.[29]

The antiserotonin drug ondansetron is helpful for inflammatory bowel problems, and can relieve "some of the most intrusive symptoms of IBS."[30] Another antiserotonin drug, cyproheptadine, protects against endotoxin and is probably useful for bowel inflammation.[31]

Similar to ondansetron and cyproheptadine, LSD appears to antagonize serotonin,[32] and might help explain the stereotypical "child-like" playfulness associated with taking the drug. In the 1950s, "acid therapy" was effective in the "wholesale revamping" of one's value system.[33]

Oftentimes those who underwent psychedelic therapy reported dramatic personality changes involving not only the relief of neurotic symptoms but a wholesale revamping of value systems, religious and philosophical beliefs, and basic life-style.
— Acid Dreams (1985)

Raymond Peat, PhD was the first person to bring the role of serotonin in inflammation, pain, and depression to my attention. Seemingly light years ahead of the current batch of nutritional personalities, Dr. Peat's research details simple yet effective therapies for reducing serotonin and thus increasing the rate of metabolism, generation of carbon dioxide, and the ability to retain a sunny disposition.  

II: Taming Serotonin

 Finding Good Information & Self-Experimentation

In 1957, Dr. Curt P. Richter demonstrated the effects of learned helplessness with experiments on rats enduring highly stressful swim tests. Dropping a rat into a clear cylinder of water frequently caused the animal to drown in despair very quickly. However, when two rats were dropped into a clear cylinder of water, and the doctor 'saved' one rat, the other rat swam in hope for three days before drowning in exhaustion.[34]

One of the reasons I spend so much time deconstructing the "genetic-androgen" hypothesis of baldness is that I think it progresses a hopeless view of life for the individual. Pattern baldness usually takes a few decades to manifest, and for some, I think the powerlessness arising from the day-to-day repeated trauma of hair loss, leads to a distorted view of themselves, sometimes extending into a state of learned helplessness. Finding the best available information, and engaging in repeated experimentation, I think, is an important aspect of maintaining a sense of "agency," or coherence when dealing with a sometimes confusing and frustrating problem like pattern baldness.

 Thyroid Hormone

 
Image: Cynomel (T3)

Image: Cynomel (T3)

 

By increasing carbon dioxide, thyroid supplementation helps lower serotonin,[35,36] and is well-known to increase the ability to withstand stress and maintain a positive outlook.[37] Active thyroid hormone, triiodothyronine or T3, shows efficacy in ameliorating depression, and in one study, those with very low levels of the pituitary hormone, TSH, faired better than those with a so-called "normal" levels of TSH.[38] When one suspects low thyroid function, I think it's important to record the rhythmic changes in the resting pulse and temperature in the morning, noon, and before bed, for about a week. Coupled with simple lab tests like total cholesterol, TSH, carbon dioxide, prolactin, albumin, and vitamin D, the pulse and temperature can be free and easy metrics for making evidence-based decisions about one's own health.

 Salt To Taste

 
Image: Morton's Canning & Pickling Salt

Image: Morton's Canning & Pickling Salt

 

One of the ways low thyroid function stimulates serotonin production is through the loss of sodium. Thyroid hormone allows the cell to retain magnesium and potassium inside the cell and helps keep an excess of calcium and sodium outside the cell. When a cell is de-energized, and isn't getting everything it needs, it takes up an excess of sodium and calcium, leading to an "excitotoxic" overstimulated state. At the same time that an excess of sodium is moving inside the cell, the surrounding tissue becomes sodium deficient, increasing the release of substances like serotonin,[39] prolactin, and aldosterone to compensate. Prolactin powerfully suppresses thyroid function,[40] and both prolactin and aldosterone are associated with depression.[41,42] 

 Ray Peat's Famous Carrot Salad

 
 

The intestine has been a large focus for many in the nutritional and health field for the last decade, however, rarely is the deleterious nature of serotonin mentioned as a factor in bowel problems. Bacterial endotoxin can increase levels of serotonin, and antibiotics (with vitamin K), like penicillin VK, can be used to suppress endotoxin. Dr. Peat's famous carrot salad recipe has a mild antibiotic-like effect and is probably a safer option to use every day.[43,44] In my experience, a few courses of penicillin VK (with vitamin K) have been worthwhile. One specific takeaway was the reemergence of positive sensations in my chest that I was previously unaware of, similar to the first time I took LSD.

References

  1. Szasz, T.S., and Robertson, A.M. A theory of the pathogenesis of ordinary human baldness. Arch Derm Syphilol. 1950 Jan;61(1):34-48, illust. ““In many [pattern baldness patients], we encountered various types of ‘fixed smiles,’ and in a few, a rather striking, characteristic expression best described as a ‘toothy smile.’ Such rigid facial patterns are thought to reflect, psychologically speaking, defensive attitudes. Wilhelm Reich in his book, ‘Character Analysis,’ pointed out what he called ‘muscular armor’ as a frequently observed somatic reflection of ‘character armor.’ ‘Character armor’ refers to the psychologic defenses of a neurotic personality which serve as protection from feelings of insecurity and anxiety.”
  2. http://bit.ly/1IGdab5
  3. Reich, W. Character Analysis. 1945.
  4. Schmidt, J.B. Hormonal basis of male and female androgenic alopecia: clinical relevance. Skin Pharmacol. 1994;7(1-2):61-6. “Our findings showed a significant elevation of cortisol in both male and female AH patients compared to controls, pointing to the suprarenes as a contributing factor in AH. This is confirmed by the observation of exacerbated AH in periods of increased stress.”
  5. Zhang, L., et al. Stress-induced change of mitochondria membrane potential regulated by genomic and non-genomic GR signaling: A possible mechanism for hippocampus atrophy in PTSD
  6. Roddy, D. Hair Like A Fox: A Bioenergetic View of Pattern Hair Loss. 2013.
  7. Selye, H. The Story of Adaptation Syndrome. 1952. “Adaptive hormones can cause mental changes in man. Many patients who take ACTH or COL first develop a sense of extraordinary wellbeing and buoyancy, with excitement and insomnia; this is sometimes followed by a depression which may go so far as to create suicidal tendencies.”
  8. Martin, C. Endocrine Physiology. 1985. “Glucocorticoids exert early influences on the brain that tend to elevate mood and increase the sense of ‘well-being.’ Larger amounts can bring on temporary euphoria. However, the secondary effects include psychic depression. Patients with chronically elevated levels tend to have mood swings. They have been known to display bizarre behavior and to suffer hallucinations.”
  9. Lefebvre, H., et al. Serotonin-induced stimulation of cortisol secretion from human adrenocortical tissue is mediated through activation of a serotonin receptor subtype. Neuroscience. 1992;47(4):999-1007. Serotonin (5-HT) plays a pivotal role in the regulation of the hypothalamo-pituitary-adrenal axis. In the central nervous system,5-HT stimulates corticotropin-releasing factor (CRF) release from hypothalamic neurons.15 In the pituitary gland, 5-HT triggers adrenocorticotropin (ACTH) release from corticotroph cells.” “Graded doses of serotonin (from 10(-8) M to 3 x 10(-7) M) increased cortisol production in a dose-dependent manner. Prolonged exposure of adrenal fragments to serotonin (10(-7) M) induced a biphasic response, i.e. a rapid and transient increase in cortisol secretion followed by a plateau phase, suggesting the existence of a desensitization phenomenon.” “Taken together, these data suggest that serotonin, locally released by intra-adrenal mast-like cells, may act as a paracrine factor to stimulate cortisol secretion in man.”
  10. Bethea, C.L., et al. Steroid regulation of tryptophan hydroxylase protein in the dorsal raphe of macaques. Biol Psychiatry. 2000 Mar 15;47(6):562-76. “Tryptophan hydroxylase (TPH) is the rate-limiting enzyme for the synthesis of serotonin…” “E treatment for 28 days increased TPH protein mass four to six fold over ovariectomized controls.” “The stimulatory effect of E and P on TPH protein in the dorsal raphe of macaques correlates with the previously observed effect at the level of mRNA expression.” “Tamoxifen acted as a potent anti estrogen on TPH protein expression. If TPH protein mass influences serotonin synthesis, then these steroids will impact many autonomic systems that are regulated by serotonin.” 
  11. Martin C. Endocrine Physiology. 1985;352 “The amine [serotonin] plays important roles in the regulation of pituitary hormone secretion. It is implicated in promoting prolactin release in response to suckling stimulus, and it affects the secretions of growth hormone, ACTH, TSH, and the gonadotrophins.” 
  12. Sharma, H.S., et al. Prostaglandins modulate alterations of microvascular permeability, blood flow, edema and serotonin levels following spinal cord injury: an experimental study in the rat. Neuroscience. 1993 Nov;57(2):443-9. “Since indomethacin is a potential inhibitor of prostaglandins synthesis our observations indicate: (i) that prostaglandins participate in many microvascular responses (permeability changes, edema, blood flow) occurring after a trauma to the spinal cord; (ii) that these effects of the drug seem to be dose dependent, and (iii) that the prostaglandins may influence the serotonin metabolism following trauma to the spinal cord.” 
  13. Montagna, W. The Biology of Hair Growth. 1958. “It is agreed that estrogenic hormones inhibit hair growth.”
  14. Foitzik, K., et al. Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression. Am J Pathol. 2006 Mar;168(3):748-56. “PRL has also been implicated in the pathogenesis of androgenetic alopecia by modulation of androgens, and hyperprolactemia is associated with an androgenetic alopecia-type hair loss pattern, along with hirsutism (in females).”
  15. Garza, L.A., et al. Prostaglandin d2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. Sci Transl Med. 2012 Mar 21;4(126):126ra34. “Given the androgens are aromatized into estrogens, these results may be relevant to hair growth and alopecia in both men and women. Thus, these or similar pathways might be conserved in the skin and suggest that sex hormone regulation of Ptgds may contribute to the pathogenesis of AGA.” “…demonstrates elevated levels of PGD2 in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD2 as an inhibitor of hair growth in AGA and suggest the PGD2-GPR44 pathway as a potential target for treatment.”
  16. Shenker, Y. et al. Central serotonergic stimulation of aldosterone secretion. J Clin Invest. 1985 Oct;76(4):1485-90. “We conclude that central serotonergic pathways are involved in the stimulation of aldosterone induced by administration of 5HTP. This mechanism may be an important etiologic factor in the hyper secretion of aldosterone that occurs in patients with idiopathic aldosteronism.”
  17. Arias-Santiago, S., et al. Br J Dermatol. 2009 Nov;161(5):1196-8. Elevated aldosterone levels in patients with androgenetic alopecia. “Patients with AGA showed significantly higher systolic blood pressure values (136.23 vs. 124.10 mmHg, P = 0.01) and aldosterone levels (197.35 vs. 133.71 pg mL(-1), P = 0.007) vs. controls.” “The elevated aldosterone values in these patients may contribute, together with other mechanisms, to the development of AGA and may also explain the higher prevalence of hypertension. Blood pressure screening of patients with AGA will permit earlier diagnosis of an unknown hypertension and initiation of appropriate treatment.”
  18. Petty, F., et al. Does learned helplessness induction by haloperidol involve serotonin mediation? Pharmacol Biochem Behav. 1994 Jul;48(3):671-6. “Learned helplessness (LH) is a behavioral depression following inescapable stress. Helpless behavior was induced in naive rats by the dopamine D2 receptor blocker haloperidol (HDL) in a dose-dependent manner, with the greatest effects seen at 20 mg/kg (IP).” “Haloperidol (IP) increased release of serotonin (5-HT) in medial prefrontal cortex (MPC) as measured by in vivo micro dialysis.”
  19. Maswood, S., et al. Exposure to inescapable but not escapable shock increases extracellular levels of 5-HT in the dorsal raphe nucleus of the rat. Brain Res. 1998 Feb 2;783(1):115-20. “The effects of escapable and yoked inescapable electric tailshocks on extracellular levels of serotonin (5-HT) in the dorsal raphe nucleus were measured by in vivo micro dialysis. In comparison to either control rats or to their own preshock baseline, rats exposed to inescapable shock showed an increase in extracellular 5-HT within 25 min of shock initiation, and 5-HT levels continued to rise during the remainder of the shock session. Rats that were exposed to comparable shock treatment, but that were given the opportunity to escape, did not show an increase in 5-HT. Rats that were restrained but not shocked also did not show an increase in 5-HT. These results add further support to suggestions that serotonergic changes occur in the dorsal raphe nucleus during inescapable shock and that such changes may contribute to the behavioral effects of inescapable shock.”
  20. Martin, P., et al. Triiodothyronine-induced reversal of learned helplessness in rats. Biol Psychiatry. 1985 Sep;20(9):1023-5. “This study shows that rats preexposed to inescapable electric foot-shocks and treated with triiodothyronine (T3) for 4 consecutive days did not exhibit escape and avoidance deficits when tested in the shuttle-box paradigm. This protective antidepressant-like effect seemed to affect deficit rather specifically, as T3 neither caused intertrial shuttling nor did it facilitate shuttle-box responses in animals not trained for learned helplessness. These findings extend to the thyroid axis the neuroendocrine systems that can be affected by exposure to uncontrollable stressors.” “In conclusion, our findings are consonant with clinical observations suggesting a deficient thyroid function in depressed patients. Numerous investigations have reported a blunted thyroid- stimulating hormone response to thyroid-releasing hormone, the normalization of which correlated positively with sustained clinical improvement.”
  21. Popova, N.K., and Bertogaeva, V.D. [Participation of the serotonin-reactive brain structure in certain forms of behavior in golden hamsters]. Farmakol Toksikol. 1975 Mar-Apr;38(2):148-51. “A viviacious play of young hamsters is shown to be accompanied by a drop of the serotonin level in the brain stem and the subsequent slumber - by its rise, while the corticosteroids content of the peripheral blood with the playful behavior experiences no changes. Iprazid and 5-oxytryptophan inhibit the playful activity, while dioxyphenylalanina (DOPA) does not influence it. A similar depression of the serotonin level in the brain stem was also noted in an aggressive behavior and stress conditions arising when adult male-hamsters are grouped together. A conclusion is drawn to the effect that changes in the content of serotonin in the brain stem are not associated with the emotional colouration of the condition, but rather reflect the transition from the somnolence to a highly active behavior.”
  22. Malick, J.B., and Barnett, A. The role of serotonergic pathways in isolation-induced aggression in mice. Pharmacol Biochem Behav. 1976 Jul;5(1):55-61. “Male mice that became aggressive following four weeks of social isolation were treated with seven known serotonin receptor antagonists. All of the antiserotonergic drugs selectively antagonized the fighting behavior of the isolated mice; the anti aggressive activity was selective since, at anti fighting doses, none of the drugs either significantly altered spontaneous motor activity or impaired inclined-screen performance. Antagonism of 5-HTP-induced head-twitch was used as an in vivo measure of antiserotonergic activity and a statistically significant correlation existed between potency as an antiserotonergic and potency as an anti aggressive. PCPA, a serotonin depletor, also significantly antagonized isolation-induced aggression for at least 24 hr post drug administration.”
  23. McMillen, B.A., et al. Effects of gepirone, an aryl-piperazine anxiolytic drug, on aggressive behavior and brain monoaminergic neurotransmission. Naunyn Schmiedebergs Arch Pharmacol. 1987 Apr;335(4):454-64. “In support of this conclusion was the observed potentiation of anti aggressive effects by blocking 5HT receptors wit small doses of methiothepin or methysergide, which would exacerbate the decreased release of 5HT caused by gepirone. These results are in harmony with reports that decreased serotonergic activity has anxiolytic-like effects in animal models of anxiety.”
  24. Andrews, P.W., et al. Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response. Neurosci Biobehav Rev. 2015 Apr;51:164-88. “The role of serotonin in depression and antidepressant treatment remains unresolved despite decades of research. In this paper, we make three major claims. First, serotonin transmission is elevated in multiple depressive phenotypes, including melancholia, a subtype associated with sustained cognition. The primary challenge to this first claim is that the direct pharmacological effect of most symptom-reducing medications, such as the selective serotonin reuptake inhibitors (SSRIs), is to increase synaptic serotonin. The second claim, which is crucial to resolving this paradox, is that the serotonergic system evolved to regulate energy. By increasing extracellular serotonin, SSRIs disrupt energy homeostasis and often worsen symptoms during acute treatment. Our third claim is that symptom reduction is not achieved by the direct pharmacological properties of SSRIs, but by the brain’s compensatory responses that attempt to restore energy homeostasis. These responses take several weeks to develop, which explains why SSRIs have a therapeutic delay. We demonstrate the utility of our claims by examining what happens in animal models of melancholia and during acute and chronic SSRI treatment.” “In summary, we propose that depressed states are high serotonin phenomena, which challenges the prominent role the low serotonin hypothesis continues to have in depression research. We also propose that the direct serotonin-enhancing effects of antidepressants disturb energy homeostasis and worsen symptoms. We argue that symptom reduction, which only occurs over chronic treatment, is attributable to the compensatory responses of the brain attempting to restore energy homeostasis. Understanding the true relationship between serotonin and depressed states will be important in understanding the etiology of those states and developing effective treatments.”
  25. Martin C. Endocrine Physiology. 1985;333. “Approximately 98% of total serotonin is found outside of the central nervous system. The blood platelets and gastrointestinal tract account for around 95% and serotonin is a component of both central and peripheral mast cells.”
  26. Spiller R. Serotonin, inflammation, and IBS: fitting the jigsaw together? J Pediatr Gastroenterol Nutr. 2007 Dec;45 Suppl 2:S115-9. “…Clinical conditions with an inflammatory basis, such as coeliac and Crohn disease, also are characterised by excess postprandial serotonin release. Several studies report evidence of low-grade inflammation in IBS with diarrhoea. However, reliable markers of low-grade inflammation that may predict response to serotonin antagonists or other anti-inflammatory agents remain a goal for future research.”
  27. Bischoff, S.C, et al. Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice. Am J Physiol Gastrointest Liver Physiol. 2009 Mar;296(3):G685-95. “Serotonin (5-HT) regulates peristaltic and secretory reflexes in the gut. The serotonin reuptake transporter (SERT; SLC6A4), which inactivates 5-HT, is expressed in the intestinal mucosa and the enteric nervous system. Stool water content is increased and colonic motility is irregular in mice with a targeted deletion of SERT. We tested the hypotheses that 5-HT plays a role in regulating intestinal inflammation and that the potentiation of serotonergic signaling that results from SERT deletion is proinflammatory. Rectal installation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to induce an immune-mediated colitis, which was compared in SERT knockout mice and littermate controls. Intestinal myeloperoxidase and histamine levels were significantly increased, whereas the survival rate and state of health were significantly decreased in TNBS-treated mice that lacked SERT. Deletion of SERT thus increases the severity of TNBS colitis. These data suggest that 5-HT and its SERT-mediated termination play roles in intestinal immune/inflammatory responses in mice.”
  28. Kalra, U., et al. Evaluation of plasma serotonin concentration in acute appendicitis. Indian J Gastroenterol. 1997 Jan;16(1):18-9. “The levels in patients with acute appendicitis were significantly higher (p < 0.001) than in the other groups, giving 93.8% sensitivity and 95.7% specificity to the test. Plasma serotonin level is a reliable marker of acute appendicitis, especially in the first 48 hours.”
  29. Davis, R.B, et al. Serotonin release by bacterial endotoxin. Proc Soc Exp Biol Med. 1961.
  30. Garsed, K. A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea. Gut. 2014 Oct;63(10):1617-25. “Ondansetron relieves some of the most intrusive symptoms of IBS-D, namely loose stools, frequency and urgency.”
  31. Wang, L., et al. Anti-endotoxic shock effects of cyproheptadine in rats. Chin Med J (Engl). 2002 Mar;115(3):443-5. “Cyp 5 mg/kg injected immediately after i.v. LPS raised the mean arterial blood pressure (MABP) of shocked rats and improved their 24 h survival rate.” “Cyp exerts an anti-endotoxic shock effect by inhibiting TNF(alpha) gene expression, enhancing SOD activity, reducing lipid peroxidation, and preventing [Ca(2+)] overload.”
  32. Gaddum, J.H., et al. The Distribution of Substance P and 5-Hydroxytryptamine in The Central Nervous System of The Dog. J. Physiol. (I954) I26, 596-6I8. “Attention has already been drawn to the possibility that there may be some connection between the two known powerful actions of lysergic acid diethyl amide, which seriously affects the brain in a dose of 1 [kg/kg (Stoll, 1947) and antagonizes some of the actions of HT on isolated organs in a concentration of 1 Ktg/l. The evidence for the presence of HT in certain parts of the brain may be used to support the theory that the mental effects of lysergic acid diethyl amide are due to interference with the normal action of this HT.”
  33. Lee, M.A, and Shlaine, B. Acid Dreams. 1985. “Originally tested on alcoholics in Canada with remarkable results, high-dose therapy was subsequently applied to a wide range of diagnostic categories: juvenile delinquency, narcotics addiction, severe character neurosis, and the like. This approach was particularly effective in treating people who were emotionally blocked; they were able to cut through a lot of psychological red tape, so to speak, and get right to the heart of the matter. Oftentimes those who underwent psychedelic therapy reported dramatic personality changes involving not only the relief of neurotic symptoms but a wholesale revamping of value systems, religious and philosophical beliefs, and basic life-style. Numerous patients claimed that a few LSD trips proved more fruitful than years of psychoanalysis—at considerably less expense. In some cases spectacular success was achieved with only one dose of the drug. LSD was the talk of the town in Hollywood and Beverly Hills in the late 1950s as various movie stars were dosed on the psychiatrist’s couch. Participants in such sessions included several of the glamour elite, each capable of generating a flash of publicity. Cary Grant first took LSD under the guidance of Dr. Mortimer Hartmann and then with Dr. Oscar Janiger. His therapy was such a success that he became a zealous missionary for LSD. ‘All my life,’ Grant stated, ‘I’ve been searching for peace of mind. I’d explored yoga and hypnotism and made several attempts at mysticism. Nothing really seemed to give me what I wanted until this treatment.’ People from all walks of life echoed Grant’s plaudits for the drug, and psychiatrists who practiced LSD therapy were inundated with inquiries.”
  34. Richter, C.P. On the phenomenon of sudden death in animals and man. Psychosom Med. 1957 May-Jun;19(3):191-8.
  35. Henley, W.N., and Koehnle, T.J. Thyroid hormones and the treatment of depression: an examination of basic hormonal actions in the mature mammalian brain. Synapse 1997 Sep;27(1):36-44.”In spite of a large clinical literature, little is known about the mechanism by which thyroid hormones elevate mood. The lack of mechanistic insight reflects, in large part, a longstanding bias that the mature mammalian central nervous system is not an important target site for thyroid hormones.” “This paper offers the hypothesis that the thyroid hormones influence affective state via post receptor mechanisms that facilitate signal transduction pathways in the adult mammalian brain. This influence is generalizable to widely recognized targets of antidepressant therapies such as noradrenergic and serotonergic neurotransmission.” 
  36. Scwhark, W.S. and Keesey, R.R. Thyroid hormone control of serotonin in developing rat brain. Res Commun Chem Pathol Pharmacol. 1975 Jan;10(1):37-50. “Experimental cretinism, induced by daily propylthiouracil treatment starting at birth, caused increased serotonin levels in all brain regions studied.” “The data suggest that thyroid hormone may exert an important regulatory influence on serotonin metabolism in the developing brain.”
  37. The Merck Manual Seventh Edition. 1940. “Hypothyroidism. Gradual onset of apathy, gain in weight, and development of nonpittng edema, especially of hands, feet and face. Skin dry and scaly. Hair becomes brittle and thin, nails rough, striated and break easily. There are lassitude, fatiguability, drowsiness, imperfect cerebration, even psychosis; poor appetite and constipation; pulse slow, blood pressure low, temperature subnormal; menstruation irregular; may cease or become excessive. Anemia in majority of cases.” “Causes: A disease in middle life, 6 times more common in women than in men, especially liable to occur with menstrual disturbances. Diagnoses: Gradual onset of apathy, gain in weight, and development of nonpitting edema, especially of hands, feet and face (“full moon-like” face and coarse features). Skin dry and scaly (scales best seen in stockings. Hair becomes brittle and thin, nails rough, striated and break easily. There are lassitude, fatiguability, drowsiness, imperfect cerebration, even psychosis; poor appetite and constipation; pulse slow, blood pressure low, temperature subnormal; menstruation irregular; may cease or become excessive. Anemia in majority of cases. Tests: Basal metabolism low, hypercholesteremia, alimentary tolerance for dextrose greatly increased, diminished sensitivity to epinephrine and pilocarpine. Therapy: The administration of desiccated thyroid which may have to be continued throughout life is best divided into two periods: 1. Initial Dose: One usually may commence with 1 grain of thyroid 3 times a day; and increased dose by 1 grain a week until 3 grains is taken three times a day or until there is feeling of warmth, increased pulse rate, quicker mental reaction. These symptoms are followed by elevation of temperature, sharp loss of body weight, sweating and increased metabolic rate… Exercise should be very constricted until improvement is well advanced.”
  38. Rosenthal, L.J., et al. T3 Augmentation in Major Depressive Disorder: Safety Considerations. The American Journal of Psychiatry, VOL. 168, No. 10. “After 8 weeks of T3 supplementation, the mean TSH level fell significantly from 1.70 μIU/ml at baseline to 0.28 μIU/ml in responders, whereas non responders had mean pre- and post treatment levels of 1.88 μIU/ml and 0.76 μIU/ml, respectively; responsiveness to treatment was significantly correlated (p=0.01) with the change in TSH level, suggesting that the therapeutic benefit could have been due to changes in the thyroid axis in this population.”
  39. Sharma, A.M., et al. Effect of dietary salt restriction on urinary serotonin and 5-hydroxyindoleacetic acid excretion in man. J Hypertens. 1993 Dec;11(12):1381-6.During the low-salt diet, 24-h urinary excretion of serotonin increased by 42%, accompanied by a 52% rise in the excretion of 5-HIAA. Salt restriction also increased noradrenaline excretion by 77% and VMA excretion by 40%. Regression analysis revealed a strong positive relationship between the excretion of serotonin and of noradrenaline (r = 0.84, P < 0.001) and between that of 5-HIAA and of VMA (r = 0.74, P < 0.001). Salt restriction stimulates the serotonergic system in man."
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  41. Kellner, R. et al. Hyperprolactinemia, distress, and hostility. Am J Psychiatry. 1984 Jun;141(6):759-63. “Hyperprolactinemic patients were significantly more hostile, depressed, and anxious and had more feelings of inadequacy than family practice patients and non patient employees. The authors recommend measuring the serum prolactin levels of women with depression, hostility, anxiety, and symptoms or signs suggestive of hyperprolactinemia.”
  42. Emanuele, E., et al. Increased plasma aldosterone in patients with clinical depression. Arch Med Res. 2005 Sep-Oct;36(5):544-8. ‘Our present findings support the hypothesis that hyperaldosteronism could be a common feature among depressed patients, thereby suggesting that increased aldosterone levels may act as a mediator in the pathway linking depression to unfavorable vascular events.”
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  44. Babic, I., et al. Antimicrobial activity of shredded carrot extracts on food-borne bacteria and yeast. J Appl Bacteriol. 1994 Feb;76(2):135-41. “Purified ethanolic extracts of peeled and shredded carrots showed an antimicrobial effect against a range of food-borne micro-organisms.”