Sorry! We Meant To Say Lower Serotonin.
The oversimplistic and illogical idea that mental disorders, including depression and anxiety, are caused by insufficient serotonin levels in the brain, has never been properly demonstrated, and conflicts with a lot of basic physiology showing the role rising serotonin plays in stress, inflammation, and disease.
Regardless, extremely profitable drugs – like SSRI’s (Selective Serotonin Reuptake Inhibitors) and related so called anti-depressants – get prescribed with the intention of increasing levels of serotonin, and this is still a first line of defense for many doctors and psychiatrists. That’s despite the fact that benefits from ‘anti-depressants’ are inconsistent and unreliable, and the most popular ones, have been shown to be potentially very dangerous.
So why do so many people believe purposefully raising serotonin with ‘anti-depressants’, is an effective and safe approach to treating mental dysregulation issues? There are a number of ways to answer that question.
It’s important to remember that many people recover from depression and anxiety, without taking any serotonin raising pharmaceuticals. But there are also many who recover, whilst taking them. Are they getting better because of their medication? Or is it simply that it’s possible to recover, in spite of the reduction in biochemical function, and increase in stress, caused by an intentional greater exposure to serotonin.
Perhaps a better way to look at so called serotonin raising drugs, is to see them as something that has the potential to place an additional layer of biochemical interference and stress, onto preexisting health issues, that metabolic systems then have to attempt to deal with. Some are strong enough to deal with it, some get significantly worse.
“Our…claim…is that the direct pharmacological effects of SSRIs are not responsible for symptom reduction…SSRIs cause…a worsening of symptoms…symptom reduction is due to…the brain’s homeostatic mechanisms that attempt to restore energy homeostasis…which explains why symptoms fail to alleviate for several weeks after the initiation of SSRI treatment…” (Andrews PW, et al., 2015)
“The time differential between the onset of 5HT [serotonin] reuptake inhibition by SSRIs (minutes) and onset of their antidepressant efficacy (weeks to months), when considered with their overall poor therapeutic effectiveness, has cast some doubt on the role of 5HT in depression.” (Angoa-Pérez M, et al., 2014)
One of the problems with the official view, is the large amount of biological evidence, pointing to the conclusion, that rising (rather than insufficient) exposure to serotonin, is a central factor promoting learned helplessness-like metabolic symptoms (including anxiety and depression), and related inflammatory diseases. Although metabolic systems have ways of dealing with serotonin excess, it isn’t always easy.
Once you begin to view depression and anxiety, as possible side-effects of excessive and ongoing exposure to stress, and then when you examine the ways that biochemical stress can cause increases in systemic serotonin (and related stress substance) levels, the upside down nature of the ‘official’ doctrine becomes more apparent.
“While the literature on depressed patients is necessarily limited due to the methodological difficulties measuring serotonin…in the human brain, the most pertinent studies support the high serotonin hypothesis…that serotonin transmission is elevated in…depression.” (Andrews PW, et al., 2015)
“We demonstrate invariably increased serotonin synthesis and transporter availability in patients with SAD [social anxiety disorder] relative to healthy controls, which supports an overactive presynaptic serotonin system.” (Frick A, et al., 2015)
Anxiety and depression often go hand in hand, and evidence suggests that lowering exposure to serotonin (in the body and brain) promotes improvements in biological function, and vice versa, increasing protection against many inflammatory degenerative issues. Understanding how this works, can lead to a more effective approach to dealing with psychological disorders in general.
“Individuals with social phobia make too much serotonin. The more serotonin they produce, the more anxious they are in social situations…patients with social phobia produced too much serotonin in a part of the brain’s fear centre, the amygdala.” (Linda Koffmar, 2015)
It’s important to know that most serotonin found in the body, is produced in the intestines. A sub-optimal digestive system (due to excess stress, inflammation, and metabolic suppression) often results in an overgrowth of bacteria, increasing exposure to toxic bacterial byproducts, like endotoxin.
Endotoxin (LPS), which is directly inflammatory, has been shown to promote serotonin and other stress substances, including estrogen, nitric oxide and histamine. Estrogen and nitric oxide promote serotonin, and all three are involved with the progression of inflammatory disease, including mental disturbances.
“More than 90% of the body’s 5-HT is synthesized in the gut…gut microbiota plays a key role in promoting levels of colon and blood 5-HT…Interestingly, the indigenous microbiota also modulates hippocampal levels of 5-HT……revealing a role for the microbiota in regulating the brain serotonergic system.” (Yano JM, et al., 2015)
The stress related substances which rise alongside serotonin – and which can also be increased due to bacterial issues – play an important role in the promotion of systemic inflammation. Chronic inflammation has been shown to promote depression and anxiety, and this is one way to help explain the link between digestive distress and mental dysregulation.
The beneficial effects from anti-depressants often come from a reduction in exposure to bacterial issues. This can be true in the case of drugs that are otherwise causing harm. There are a number of very safe and effective ways to lower bacterial endotoxin exposure, that do not increase systemic serotonin. Increasing serotonin, encourages circulation of endotoxin, and endotoxin directly promotes symptoms of depression and anxiety.
“LPS [endotoxin] administration in healthy male subjects induced a transient, dose-dependent inflammatory response characterized by increases in…cytokines, cortisol, and norepinephrine…we observed dose-dependent increases in negative mood and anxiety…” (Grigoleit JS, et al., 2011)
Excess stress tends to have an immediately noticeable effect upon intestinal function, and when high stress is ongoing, it can lead to significant changes in energy system production and overall metabolic performance. The more you understand how all of this works together, the more you will see how illogical it is to think of serotonin as something to purposefully raise.
“Regarding depression-related onset of diseases of the digestive system…experimental and clinical studies have demonstrated that acute and chronic stress have impacts on the gastrointestinal system, being permissive in the development of gut diseases.” (Marion Tegethoff, et al., 2016)
When stress goes up – and when the provision and availability of sugar is interfered with – cortisol and adrenaline tend to rise, and greater amounts of free fatty acids are released out of storage for fuel. When fat entering circulation is polyunsaturated, it can result in the creation of chronic inflammation, and long term interference with energy metabolism and thyroid function.
The inflammatory byproducts of the polyunsaturated fats (PUFAs), have been shown to be directly associated with the worsening of depression and anxiety, and it is no coincidence that serotonin, estrogen, nitric oxide and the break down products of the PUFAs, have a powerful synergistic relationship.
“…we assessed the effect of 4-hydroxy-2-nonenal (HNE), a component of oxidatively modified lipids…and its interaction with serotonin (5-hydroxytryptamine, 5-HT)…Our results suggest that HNE acts synergistically with 5-HT…” (Watanabe T, 2001)
PUFAs and their inflammatory byproducts, interfere with production of the protective (anti-depression and anti-anxiety) steroid hormones, like testosterone and progesterone, instead promoting substances which often rise during extended periods of high stress (like estrogen and cortisol), and which are closely involved in the progression of mental dysregulation. Serotonin is one of the stress substances, however all the stress substances have a tendency to promote each other.
“The potency of the unsaturated fatty acids paralleled to some degree the number of cis double bonds and carbon…The arachidonate inhibition was dose-dependent in the tissue steroid hormone receptors, except for dose-dependent potentiation of the brain cortical estrogen receptors.” (Kato J, 1989)
“When patients with depression were compared with healthy controls, depression was associated with higher oxidative stress MDA levels [malondialdehyde – resulting from lipid peroxidation of polyunsaturated fats]…suggest[ing] that oxidative stress plays a role in depression and that antidepressant activity may be mediated via improving oxidative stress/antioxidant function.” (Jiménez-Fernández S, et al., 2015)
“…we evaluated the association between…a biomarker of lipid peroxidation, and depressed mood in a large sample of community-dwelling older adults…A growing body of small clinical studies reported an association between oxidative damage markers and depression…Our study adds to this growing literature by showing evidence for this association in a large sample of older persons from the general population.” (Milaneschi Y, et al., 2013)
“Lipid peroxidation has been linked to a variety of neuropsychiatric disorders, including depression, schizophrenia, bipolar mood disorders, attention deficit hyperactivity disorder, and Alzheimer’s disease…results suggest that increased lipid peroxidation in children with anxiety disorders might be related to the disorder itself.” (Ceylan MF, et al., 2014)
The substances of stress in general promote psychological instability, and high cortisol (which is linked to high serotonin), is central to a number of mental disorders, in a seemingly causative manner.
The biological systems work in ways that make sense across the board, but only when serotonin is seen as a defensive stress substance, rising at times when thyroid energy metabolism is sub-optimal, and when stress is high. Serotonin is necessary, but not necessarily helpful beyond a certain point.
Even if serotonin does play a part in short term symptom reduction and defense against stress, that doesn’t mean that chronically high systemic serotonin exposure, works in the direction of metabolic energy system recovery. Conflating these two concepts can encourage treatments that are harmful, especially in the long term.
It doesn’t really make sense to argue that continuously high systemic serotonin exposure, causes a worsening of every metabolic illness, except for depression and anxiety and other mental dysregulation issues. That sounds less like science and more like science-fiction.
Why would minimizing serotonin be beneficial to health everywhere, except in the brain? That doesn’t seem very logical, and isn’t what the evidence shows. This is especially true in the context of the many other biochemical changes that go along with high serotonin, and that are also known to be involved in the progression of inflammatory disease and mental instability.
“…depression has been associated with disturbances in the hypothalamic–pituitary–adrenal axis (HPA) in humans…depressed patients have enhanced levels of adrenal hormones and corticotropin-releasing factor (CRF) in the blood…it is clear that serotonin and adrenal hormones may contribute to the symptoms of depression.” (Shors TJ, Leuner B. 2003)
“There is now a growing consensus that serotonin acts at multiple sites to contribute to stress-induced HPA axis activation…Depression has long been linked to dysregulated HPA axis function, and depressed men exhibit higher levels of salivary cortisol across the day compared to healthy men…” (Brummett BH, et al., 2012)
Although it is claimed that SSRI’s (and other so called serotonin increasing ‘antidepressants’) improve mental stability by boosting serotonin levels in the brain, the positive effects which sometimes coincide with their use, can be explained in a variety of other ways. Many of the ‘serotonin raising’ drugs, have a wide range of effects (including a potential benefit from dopamine increase), and whenever there are positive results, it often gets incorrectly assumed that increasing serotonin is the explanation.
Positive changes can sometimes occur as a result of the damage caused by SSRIs and related drugs, similar to the ‘benefits’ that arise from iron supplementation. But long term, promoting biochemical stress as a form of therapy, harms metabolism and increases inflammation, and very often leads to a worsening of the same symptoms being treated.
“…we propose that the brain is attempting to restore energy homeostasis rather than serotonin homeostasis…the upward trajectory in serotonin during initial ADM [antidepressant medication] treatment is often associated with a worsening of symptoms…the downward trajectory…with symptom reduction.” (Andrews PW, et al., 2015)
The results of studies showing the impact of inactivation of the serotonin transporter, keeping serotonin outside platelets (leading to an increase in exposure to the harmful effects of serotonin), regularly get misinterpreted as evidence of low serotonin (instead of high serotonin) exposure, as the cause of worsening mental instability issues.
“…the effects of…inactivation of the 5-HTT [serotonin transporter or SERT] on anxiety-like behavior in mice are robust and provide an independent line of evidence supporting a link between the low-expressing 5-HTT…with anxiety in humans.” (Hariri AR, Holmes A. 2006)
There are also a number of drugs, which have been shown to be very effective in the treatment of depression and anxiety, which are known to work specifically by protecting against, or reducing serotonin. Tissue levels of serotonin, like estrogen, can be much higher than blood levels.
Serotonin and estrogen both promote prolactin, and prolactin has been connected to mental dysregulation, including bipolar disorder, depression and anxiety. Blood levels of prolactin are considered an accurate measure of whole body serotonin and estrogen levels, and high prolactin levels are seen in numerous other inflammatory diseases including cancer, MS, cardiovascular disease, and IBS. High prolactin has been shown to be involved with blood sugar instability, including insulin resistance, which adds to the weight of the argument that depression and anxiety are low energy, high serotonin symptoms. Interference with dopamine production promotes serotonin as well as prolactin.
When stress is high and resources are limited, one way of understanding the role of serotonin (in relation to depression), is to see it as part of an attempt by the body to survive on less, shutting down whatever is unnecessary in the short term. Although from an immediate survival perspective this can be helpful, there are often serious metabolic consequences when this continues for too long.
Many people now understand depression to be one of the results of a hypo-metabolic state, and the relationship between serotonin, the PUFAs and animal hibernation (in some ways similar to human depression) is not unexplainable.
Sub-optimal body temperature is a symptom of a hypo-metabolic state, and the factors which promote stress and inflammation – including rising systemic levels of endotoxin, serotonin, nitric oxide, cortisol and estrogen – can all suppress thyroid energy system function, and have all been implicated in the pathophysiology of mental dysregulation.
“T3 deficiency is responsible for the clinical and biochemical manifestations of hypothyroidism…The decrease in energy metabolism and heat production is reflected in the low basal metabolic rate, decreased appetite, cold intolerance, and slightly low basal body temperature.” (Kostoglou-Athanassiou I, Ntalles K. 2010)
Just raising body temperature can alone be enough to treat depression. Many of the things which help to lower the substances of stress and improve indicators of proper thyroid metabolism (pulse and temperature changes are a good measure) – like sufficient intake of sugar and animal protein – can be used to improve symptoms of anxiety and depression.
“Participants…received heating…until their core body temperature reached 38.5°C…the current study found that WBH [whole-body hyperthermia] was associated with a substantial reduction in depressive symptoms…WBH holds promise as a safe, rapid-acting, antidepressant modality with a prolonged therapeutic benefit.” (Clemens W. Janssen, PhD, 2016)
Serotonin exposure has been shown to go up as a result of a hypometabolic, hypothyroid stress state. A suppressed metabolism promotes the release of polyunsaturated free fatty acids. Because PUFAs are known to suppress digestion and interfere with liver function, they have the effect of further encouraging bacterial overgrowth, increasing exposure to the damaging effects of endotoxin and serotonin. All of these factors then promote the circulation through the system of serotonin and estrogen, dramatically increasing levels of stress, and the potential to suffer from mood dysregulation issues.
“Ovarian hormones have also been shown to affect numerous factors regulating serotonin synthesis and serotonin levels…ovarian hormones promote…tryptophan hydroxylase, the rate-limiting enzyme in the synthesis of serotonin, and reduce serotonin reuptake transporter…expression…numerous serotonergic receptor subtypes are reportedly regulated by ovarian steroids, as well as implicated in depression…” (Shors TJ, Leuner B. 2003)
Estrogen interferes with the anti-stress, anti-inflammatory neurotransmitter, GABA (γ-aminobutyric acid), and GABA has been shown to protect against depression and anxiety, and also helps keep serotonin levels down. Estrogen promotes the excitatory neurotransmitter, glutamate, which is a driver of mental dysregulation and which interacts closely with serotonin, and is promoted by systemic inflammation. Good thyroid energy system function, protects against glutamate toxicity, and promotes the anti-stress impact of GABA.
“Control of serotonin release and synthesis by amino acid neurotransmitters was investigated…GABA reduced 5-HT metabolism…This effect was totally antagonized…by…a GABAA receptor antagonist…a GABAB receptor agonist, induced a decrease of 5-HT release…L-glutamate stimulated 5-HT metabolism…” (Becquet D, et al., 1993)
Stress and thyroid suppression causes cortisol levels to go up. As cortisol continues to rise, more muscle tissue is broken down, causing an increase in the release of the inflammatory amino acids, in particular tryptophan. Tryptophan is the precursor to serotonin.
Stress and cortisol promotes glutamate, and excess serotonin and glutamate can icreasese nitric oxide. High nitric oxide interferes with the protective anti-stress effects of GABA, and these biochemical changes interact with exposure to the break down of PUFAs, and are involved in the progression of PTSD and Alzheimer’s.
Chronic PTSD can sometimes lead to a condition where even cortisol production is low, often in the presence of increasing catecholamines, such as noradrenaline and serotonin. Attempting to increase cortisol, rather than lowering stress and inflammation by improving thyroid energy system function, is probably not a good idea.
“Stress increases glutamate and 5HT [serotonin] release in the hippocampus…The result is the genesis of an anxiety state as well as…adversely affect neuronal function and integrity, such that the biobehavioral and neurodegenerative changes that occur in PTSD are mediated by glutamate but driven by excessive 5HT…iNOS-activity is increased over a sustained period post stress…thus producing increased levels of NO…culminating in local neuronal damage and hippocampal shrinkage, as observed in patients with PTSD.” (Oosthuizen F, et al., 2005)
Chronic exposure to rising levels of stress and the associated interaction between greater amounts of tryptophan and PUFAs throughout the system, can set in motion a self-fueling inflammatory hypo-metabolic stress state, encouraging increasingly harmful levels of serotonin in the body and the brain. Preventing stress induced muscle tissue breakdown, is one way to significantly decrease tryptophan levels, limiting serotonin production.
“The administration of amino acid…mixtures that are selectively deficient…in tryptophan…can decrease serotonin…synthesis…Neuroimaging, cerebrospinal fluid, microdialysis and postmortem tissue punch studies indicate that this magnitude of decline decreases brain 5-HT” (Leyton M, et al., 2003)
Estrogen, serotonin and endotoxin (as well as other inflammatory substances released in the body under stress), interact powerfully with the polyunsaturated fats, suppressing thyroid energy metabolism, potentially worsening many of the symptoms of depression and anxiety.
Bacterial overgrowth and suppression of metabolic function, promote nitric oxide (NO), which further interferes with energy metabolism, and has been closely associated with mood and stress issues. Reducing bacterial issues reduces exposure to NO and promotes thyroid function, protecting against anxiety and depression. Serotonin can cause NO to increase and vice versa.
“…studies have also noted that glutamate and nitric oxide (NO) play a causal role in anxiety-related behaviors….nitrergic pathways may have an important role in stress-related hippocampal degenerative pathology and cognitive deficits seen in patients with PTSD.” (Oosthuizen F, et al., 2005)
Suppressed thyroid energy system function, promotes hyperventilation and the loss of CO2, and the low CO2, high lactate state causes an increase in serotonin (and related substances of stress), and also encourages mental dysregulation. Bag breathing is known to be an antidote for hyperventilation, increasing CO2, lowering lactate, stress and anxiety, protecting against serotonin. Increased serotonin and nitric oxide also promote the low CO2, reduced body temperature, hyperventilation state, potentially causing a vicious circle of hypometabolism and stress promotion.
Rising levels of serotonin (and estrogen and nitric oxide) have been shown to be important factors in the progression of many kinds of degeneration and inflammatory disease, including cancer. This makes sense, and is all relevant to a discussion with regards to the impact of ongoing exposure to a hypometabolic/hypothyroid state of stress, and how this is a factor in mental dysregulation issues.
“…this report makes…a parallel between induced tumorigenicity by expression of the 5-HT2B receptor in nontransformed fibroblasts and its expression by spontaneous tumors…” (Jean-Marie Launay, et al., 1996)
“…hypothyroidism increases cadiomyocyte inducible NOS (iNOS) expression, which plays an important role in hypothyroidism-induced depression of cardiomyocyte contractile properties…Up-regulation of cadiomyocyte iNOS may promote progressive cardiac dysfunction in hypothyroidism…” (Qun Shao, et al., 2016)
It is common for IBS [Irritable Bowel Syndrome] to occur together with symptoms of depression and anxiety, and IBS and other related inflammatory intestinal conditions, have been shown to be promoted by chronic stress and increased exposure to bacterial endotoxin, serotonin and nitric oxide.
“In case of IBS patients with predominant diarrhea subtype, there is increased serotonin production leading to increase in secretions…in patients with constipation predominant IBS there occurs an increased serotonin concentration…studies show that among patients who seek medical attention for IBS, around 70% have psychiatric comorbidity.” (Padhy SK, et al., 2015)
The high stress inflammatory state – where thyroid is under active and tryptophan and cortisol are rising – is known to encourage an increase in serotonin circulation throughout the body, and in the brain. Based on this alone, it doesn’t make sense to suggest that mental dysregulation is the result of a lack of serotonin. It is far more logical to assume that the mainstream understanding of serotonin is confused.
A diet removing the polyunsaturated fats and limiting intake of difficult to digest starches and fibers, whilst providing sufficient protein from milk, cheese and gelatin, and plenty of sugar from sweet ripe juicy fruits, fruit juice, honey, and white sugar, is one possible way to help limit serotonin, and protect against depression and anxiety.
Maintaining blood sugar stability has been shown to help by reducing stress and limiting the release of polyunsaturated free fatty acids into the blood. This protects against interference with energy metabolism and inflammation, and can go a long way towards improving mood stability.
Regular snacks throughout the day – made up of a combination of some of the above sources of protein and carbohydrate, in varying ratios depending on individual metabolic needs – has been shown to help to achieve this.
I’m not a doctor, scientist or nutritionist, and I know that the relationship between mood and serotonin, is not always entirely black and white. But if it makes sense that protection from the disorders of the mind, is brought about by improvements in the functioning of overall thyroid metabolism, and from an increase in the provision of metabolic energy and reduction in systemic inflammation, then it also makes sense that mental stability will be enhanced by less (not more) exposure to serotonin.
Some things which can also help protect against serotonin, and generally lower stress and improve metabolism (and which have been successful in the treatment of mood related issues), include cyproheptadine, methylene blue, thyroid hormone, pregnenolone, progesterone, aspirin, glycine, theanine, caffeine and coffee, salt and sugar, niacinamide, and others pro-metabolic things.
“…cyprohepradine is effective in prevention of depression, anxiety, hallucination, aggressive behaviors, emotional withdrawal, poor rapport, poor impulse control, active social avoidance, suicidal ideation, and improved sleep quality…” (Dabaghzadeh F, et al., 2013)
What do doctors really understand about the role of serotonin in relation to depression and anxiety, and how would a greater awareness of the available science, influence treatment approaches recommended by them?
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JAMA Psychiatry. 2015 Aug;72(8):794-802. Serotonin Synthesis and Reuptake in Social Anxiety Disorder. Frick A, Åhs F, Engman J, Jonasson M, Alaie I, Björkstrand J, Frans Ö, Faria V, Linnman C, Appel L, Wahlstedt K, Lubberink M, Fredrikson M, Furmark T.
Nature. 2016 Sep 1;537(7618):97-101. Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. Marcinkiewcz CA, Mazzone CM, D’Agostino G, Halladay LR, Hardaway JA, DiBerto JF, Navarro M, Burnham N, Cristiano C, Dorrier CE, Tipton GJ, Ramakrishnan C, Kozicz T, Deisseroth K, Thiele TE, McElligott ZA, Holmes A, Heisler LK, Kash TL.
Neurosci Biobehav Rev. 2015 Apr;51:164-88. Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response. Andrews PW, Bharwani A, Lee KR, Fox M, Thomson JA Jr.
ACS Chem Neurosci. 2014 Oct 15;5(10):908-19. Mice Genetically Depleted of Brain Serotonin Do Not Display a Depression-like Behavioral Phenotype. Angoa-Pérez M, Kane MJ, Briggs DI, Herrera-Mundo N, Sykes CE, Francescutti DM, Kuhn DM.
AIDS Patient Care STDS. 2013 Mar;27(3):146-54. Cyproheptadine for prevention of neuropsychiatric adverse effects of efavirenz: a randomized clinical trial. Dabaghzadeh F, Ghaeli P, Khalili H, Alimadadi A, Jafari S, Akhondzadeh S, Khazaeipour Z.
PLoS One. 2013 Jun 11;8(6):e65406. Lipid Peroxidation and Depressed Mood in Community-Dwelling Older Men and Women. Milaneschi Y, Cesari M, Simonsick EM, Vogelzangs N, Kanaya AM, Yaffe K, Patrignani P, Metti A, Kritchevsky SB, Pahor M, Ferrucci L, Penninx BW; Health ABC study.
J Neurosci Res. 2008 Nov 1;86(14):3117-25. Thyroid hormone increases astrocytic glutamate uptake and protects astrocytes and neurons against glutamate toxicity. Mendes-de-Aguiar CB, Alchini R, Decker H, Alvarez-Silva M, Tasca CI, Trentin AG.
Cell. 2015 Apr 9;161(2):264-76. Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis. Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Mazmanian SK, Hsiao EY.
Atherosclerosis. 2001 Mar;155(1):37-44. Lipid peroxidation product 4-hydroxy-2-nonenal acts synergistically with serotonin in inducing vascular smooth muscle cell proliferation. Watanabe T, Pakala R, Katagiri T, Benedict CR.
J Med Microbiol. 2003 May;52(Pt 5):409-15. Aspirin inhibits Chlamydia pneumoniae-induced NF-kappa B activation, cyclo-oxygenase-2 expression and prostaglandin E2 synthesis and attenuates chlamydial growth. Yoneda H, Miura K, Matsushima H, Sugi K, Murakami T, Ouchi K, Yamashita K, Itoh H, Nakazawa T, Suzuki M, Shirai M.
J Neurosci. 2016 Jun 1;36(22):6041-9. Maternal Inflammation Disrupts Fetal Neurodevelopment via Increased Placental Output of Serotonin to the Fetal Brain. Goeden N, Velasquez J, Arnold KA, Chan Y, Lund BT, Anderson GM, Bonnin A.
Neurochem Int. 1993 Sep;23(3):269-83. Glutamate, GABA, glycine and taurine modulate serotonin synthesis and release in rostral and caudal rhombencephalic raphe cells in primary cultures. Becquet D, Hery M, Francois-Bellan AM, Giraud P, Deprez P, Faudon M, Fache MP, Hery F.
Neuron. 2008 May 22;58(4):584-98. Estradiol induces dendritic spines by enhancing glutamate release independent of transcription: A mechanism for organizational sex differences. Schwarz JM, Liang SL, Thompson SM, McCarthy MM.
Biol Psychiatry. 1995 Feb 1;37(3):161-9. Brain hypometabolism of glucose in anorexia nervosa: A PET scan study. Delvenne V, Lotstra F, Goldman S, Biver F, De Maertelaer V, Appelboom-Fondu J, Schoutens A, Bidaut LM, Luxen A, Mendelwicz J.
Endocrinology, Volume 148, Issue 12, 1 December 2007, Pages 5746–5751. Influence of Thyroid Hormone and Thyroid Hormone Receptors in the Generation of Cerebellar γ-Aminobutyric Acid-Ergic Interneurons from Precursor Cells. Jimena Manzano, Maria Cuadrado, Beatriz Morte, Juan Bernal.
Nat Med. 2014 Jul;20(7):764-8. miR-1202: A Primate Specific and Brain Enriched miRNA Involved in Major Depression and Antidepressant Treatment. Lopez JP, Lim R, Cruceanu C, Crapper L, Fasano C, Labonte B, Maussion G, Yang JP, Yerko V, Vigneault E, El Mestikawy S, Mechawar N, Pavlidis P, Turecki G.
Mol Psychiatry. 2016 Nov;21(11):1599-1607. Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features. Heidari M, Johnstone DM, Bassett B, Graham RM, Chua AC, House MJ, Collingwood JF, Bettencourt C, Houlden H, Ryten M, Olynyk JK, Trinder D, Milward EA.
Biol Psychol. 2012 Jan;89(1):94-8. Cortisol responses to emotional stress in men: Association with a functional polymorphism in the 5HTR2C Gene. Brummett BH, Kuhn CM, Boyle SH, Babyak MA, Siegler IC, Williams RB.
EBioMedicine. 2018 Apr;30:283-294. GABA Regulates Release of Inflammatory Cytokines From Peripheral Blood Mononuclear Cells and CD4+ T Cells and Is Immunosuppressive in Type 1 Diabetes. Bhandage AK, Jin Z, Korol SV, Shen Q, Pei Y, Deng Q, Espes D, Carlsson PO, Kamali-Moghaddam M, Birnir B.
J Clin Psychiatry. 2015 Dec;76(12):1658-67. Oxidative Stress and Antioxidant Parameters in Patients With Major Depressive Disorder Compared to Healthy Controls Before and After Antidepressant Treatment: Results From a Meta-Analysis. Jiménez-Fernández S, Gurpegui M, Díaz-Atienza F, Pérez-Costillas L, Gerstenberg M, Correll CU.
Elevated morning cortisol is a stratified population-level biomarker for major depression in boys only with high depressive symptoms. Matthew Owens, Joe Herbert, Peter B. Jones, Barbara J. Sahakian, Paul O. Wilkinson, Valerie J. Dunn, Timothy J. Croudace, and Ian M. Goodyer.
Zhonghua Yu Fang Yi Xue Za Zhi. 2012 Jul;46(7):635-9. Chinese. [Effects of theanine on monoamine neurotransmitters and related genes in cerebral ischemia-reperfusion injury rats]. Yao J, Shen XN, Shen H, Wu M.
Cell Mol Neurobiol. 1993 Jun;13(3):247-61. Chronic Caffeine Alters the Density of Adenosine, Adrenergic, Cholinergic, GABA, and Serotonin Receptors and Calcium Channels in Mouse Brain. Shi D, Nikodijević O, Jacobson KA, Daly JW.
J Consult Clin Psychol. 2010 Oct;78(5):691-704. Respiratory and Cognitive Mediators of Treatment Change in Panic Disorder: Evidence for Intervention Specificity. Meuret AE, Rosenfield D, Seidel A, Bhaskara L, Hofmann SG.
Clin Endocrinol (Oxf). 2006 Apr;64(4):366-70. The influences of hyperprolactinemia and obesity on cardiovascular risk markers: effects of cabergoline therapy. Serri O, Li L, Mamputu JC, Beauchamp MC, Maingrette F, Renier G.
Mol Psychiatry. 2017 Feb;22(2):209-214. An epigenetic mechanism links socioeconomic status to changes in depression-related brain function in high-risk adolescents. Swartz JR, Hariri AR, Williamson DE.
PLoS One. 2017 Apr 6;12(4):e0175204. Association between serum prolactin levels and insulin resistance in non-diabetic men. Daimon M, Kamba A, Murakami H, Mizushiri S, Osonoi S, Yamaichi M, Matsuki K, Sato E, Tanabe J, Takayasu S, Matsuhashi Y, Yanagimachi M, Terui K, Kageyama K, Tokuda I, Takahashi I, Nakaji S.
PLoS One. 2016 Oct 21;11(10):e0165196. Chronology of Onset of Mental Disorders and Physical Diseases in Mental-Physical Comorbidity – A National Representative Survey of Adolescents. Tegethoff M, Stalujanis E, Belardi A, Meinlschmidt G.
JAMA Psychiatry. 2016 Aug 1;73(8):789-95. Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder. Janssen CW, Lowry CA, Mehl MR, Allen JJ, Kelly KL, Gartner DE, Medrano A, Begay TK, Rentscher K, White JJ, Fridman A, Roberts LJ, Robbins ML, Hanusch KU, Cole SP, Raison CL.
Neurosci Lett. 2001 May 25;304(3):194-8. The role of dopamine in methylene blue-mediated inhibition of estradiol benzoate-induced anterior pituitary hyperplasia in rats. Nedvídková J, Pacák K, Haluzík M, Nedvídek J, Schreiber V.
Int J Cardiol. 2016 Feb 1;204:229-41. Overexpression myocardial inducible nitric oxide synthase exacerbates cardiac dysfunction and beta-adrenergic desensitization in experimental hypothyroidism. Shao Q, Cheng HJ, Callahan MF, Kitzman DW, Li WM, Cheng CP.
Biol Psychiatry. 2006 Aug 1;60(3):288-95. Estrogen selectively increases tryptophan hydroxylase-2 mRNA expression in distinct subregions of rat midbrain raphe nucleus: association between gene expression and anxiety behavior in the open field. Hiroi R, McDevitt RA, Neumaier JF.
Pharmacol Rep. 2010 Nov-Dec;62(6):1030-40. Effects of neurosteroids on the human corticotropin-releasing hormone gene. Budziszewska B, Zając A, Basta-Kaim A, Leśkiewicz M, Steczkowska M, Lasoń W, Kaciński M.
Front Physiol. 2015 May 11;6:139. Role of nitric oxide and related molecules in schizophrenia pathogenesis: biochemical, genetic and clinical aspects. Nasyrova RF, Ivashchenko DV, Ivanov MV, Neznanov NG.
Br J Psychiatry. 2017 Jan;210(1):54-60. Methylene blue treatment for residual symptoms of bipolar disorder: randomised crossover study. Alda M, McKinnon M, Blagdon R, Garnham J, MacLellan S, O’Donovan C, Hajek T, Nair C, Dursun S, MacQueen G.
Psychopharmacology (Berl). 2002 Apr;160(4):353-61. Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Bymaster FP, Zhang W, Carter PA, Shaw J, Chernet E, Phebus L, Wong DT, Perry KW.
Pharmacol Biochem Behav. 2014 Sep;124:361-6. Effects of aspirin on immobile behavior and endocrine and immune changes in the forced swimming test: comparison to fluoxetine and imipramine. Guan XT, Shao F, Xie X, Chen L, Wang W.
Neuropharmacology. 2012 Jan;62(1):485-91. Inhibition of iNOS induces antidepressant-like effects in mice: pharmacological and genetic evidence. Montezuma K, Biojone C, Lisboa SF, Cunha FQ, Guimarães FS, Joca SR.
Elife. 2015 Dec 1;4:e08833. Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality. Rangaraju S, Solis GM, Thompson RC, Gomez-Amaro RL, Kurian L, Encalada SE, Niculescu AB 3rd, Salomon DR, Petrascheck M.
Pharmacol Biochem Behav. 2014 Sep;124:361-6. Effects of aspirin on immobile behavior and endocrine and immune changes in the forced swimming test: comparison to fluoxetine and imipramine. Guan XT, Shao F, Xie X, Chen L, Wang W.
Behav Brain Res. 2017 Mar 30;322(Pt A):70-82. Inhibition of iNOS alleviates cognitive deficits and depression in diabetic mice through downregulating the NO/sGC/cGMP/PKG signal pathway. Zhou XY, Zhang F, Ying CJ, Chen J, Chen L, Dong J, Shi Y, Tang M, Hu XT, Pan ZH, Xu NN, Zheng KY, Tang RX, Song YJ.
Clin Exp Pharmacol Physiol. 2016 Dec;43(12):1208-1215. Beneficial effect of aspirin against interferon-α-2b-induced depressive behavior in Sprague Dawley rats. Bhatt S, Pundarikakshudu K, Patel P, Patel N, Panchal A, Shah G, Goswami S.
Atherosclerosis. 2016 Mar;246:157-60. Serotonin in peripheral blood reflects oxidative stress and plays a crucial role in atherosclerosis: Novel insights toward holistic anti-atherothrombotic strategy. Sugiura T, Dohi Y, Yamashita S, Hirowatari Y, Fujii S, Ohte N.
Gen Pharmacol. 1994 Oct;25(6):1257-62. Serotonin-induced decrease in brain ATP, stimulation of brain anaerobic glycolysis and elevation of plasma hemoglobin; the protective action of calmodulin antagonists. Koren-Schwartzer N, Chen-Zion M, Ben-Porat H, Beitner R.
PLoS One. 2011;6(12):e28330. Dose-Dependent Effects of Endotoxin on Neurobehavioral Functions in Humans. Grigoleit JS, Kullmann JS, Wolf OT, Hammes F, Wegner A, Jablonowski S, Engler H, Gizewski E, Oberbeck R, Schedlowski M.
Redox Rep. 2014 Mar;19(2):92-6. Lipid peroxidation markers in children with anxiety disorders and their diagnostic implications. Ceylan MF, Guney E, Alisik M, Ergin M, Dinc GS, Goker Z, Eker S, Kizilgun M, Erel O.
J Neurogastroenterol Motil. 2017 Jul 30;23(3):349-362. The Increased Level of Depression and Anxiety in Irritable Bowel Syndrome Patients Compared with Healthy Controls: Systematic Review and Meta-analysis. Lee C, Doo E, Choi JM, Jang SH, Ryu HS, Lee JY, Oh JH, Park JH, Kim YS;
J Clin Psychopharmacol. 2017 Feb;37(1):40-45. Increased Brain Lactate during Depressive Episodes and Reversal Effects by Lithium Monotherapy in Drug-Naive Bipolar Disorder: A 3T 1H-MRS Study. Machado-Vieira R, Zanetti MV, Otaduy MC, De Sousa RT, Soeiro-de-Souza MG, Costa AC, Carvalho AF, Leite CC, Busatto GF, Zarate CA Jr, Gattaz WF.
Am J Physiol Endocrinol Metab. 2018 Mar 1;314(3):E206-E213. Endotoxin-initiated inflammation reduces testosterone production in men of reproductive age. Tremellen K, McPhee N, Pearce K, Benson S, Schedlowski M, Engler H.
Artist: walmazan: “Serotonin & the Dopamines”