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Histamine boosts inflammation, alters serotonin

Brain serotonin levels dropped within minutes of LPS injection, whereas they remained the same in control mice, demonstrating how quickly inflammatory responses in the body translate to the brain and affect serotonin. LPS is unable to cross the protective blood-brain barrier and could therefore not have caused this drop directly. On further examination they found that the histamine in the brain was triggered by the inflammatory response and directly inhibited the release of serotonin, by attaching to inhibitory receptors on the serotonin neurons. These inhibitory receptors are also present on human serotonin neurons, so this effect might translate to people.
#inflamation #serotonin #histamine - sciencedaily.com

Scientists find neurochemicals have unexpectedly profound roles in the human brain: Dopamine, serotonin involved in sub-second perception, cognition -- ScienceDaily

"An enormous number of people throughout the world are taking pharmaceutical compounds to perturb the dopamine and serotonin transmitter systems to change their behavior and mental health," said P. Read Montague, senior author of the study and a professor and director of the Center for Human Neuroscience Research and the Human Neuroimaging Laboratory at the Fralin Biomedical Research Institute at Virginia Tech Carilion. "For the first time, moment-to-moment activity in these systems has been measured and determined to be involved in perception and cognitive capacities. These neurotransmitters are simultaneously acting and integrating activity across vastly different time and space scales than anyone expected." Better understanding of the underlying actions of dopamine and serotonin during perception and decision-making could deliver important insight into psychiatric and neurological disorders, the researchers said. "Every choice that someone executes involves taking in information, interpreting that information, and making decisions about what they perceived," said Kenneth Kishida, a corresponding author of the study and an assistant professor of physiology and pharmacology, and neurosurgery, at Wake Forest School of Medicine. "There's a whole host of psychiatric conditions and neurological disorders where that process is altered in the patients, and dopamine and serotonin are prime suspects."
#medicalindustrialcomplex #synchronize #psychiatry #dopamine #serotonin - sciencedaily.com

Study shows how serotonin and a popular anti-depressant affect the gut's microbiota -- ScienceDaily

The team -- led by senior author Elaine Hsiao and lead author Thomas Fung, a postdoctoral fellow -- identified a specific gut bacterium that can detect and transport serotonin into bacterial cells. When mice were given the antidepressant fluoxetine, or Prozac, the biologists found this reduced the transport of serotonin into their cells. This bacterium, about which little is known, is called Turicibacter sanguinis. The study is published this week in the journal Nature Microbiology. "Our previous work showed that particular gut bacteria help the gut produce serotonin. In this study, we were interested in finding out why they might do so," said Hsiao, UCLA assistant professor of integrative biology and physiology, and of microbiology, immunology and molecular genetics in the UCLA College; and of digestive diseases in the David Geffen School of Medicine at UCLA. Hsiao and her research group reported in the journal Cell in 2015 that in mice, a specific mixture of bacteria, consisting mainly of Turicibacter sanguinis and Clostridia, produces molecules that signal to gut cells to increase production of serotonin. When Hsiao's team raised mice without the bacteria, more than 50% of their gut serotonin was missing. The researchers then added the bacteria mixture of mainly Turicibacter and Clostridia, and their serotonin increased to a normal level.
#microbiome #serotonin #turicibactor - sciencedaily.com

Whole grain can contribute to health by changing intestinal serotonin production - ScienceBlog.com

The consumption of wholegrain rye led to, among other things, significantly lower serotonin concentrations when compared to consumption of low-fibre wheat bread. The researchers also tested in mice whether the addition of cereal fibre to the diet changes serotonin production in the intestine. The diet of the mice was supplemented for nine weeks with rye bran, wheat bran or cellulose flour. The mice receiving rye or wheat bran had significantly lower serotonin in their colon. Serotonin is best known as a neurotransmitter in the brain. However, serotonin produced by the intestines remains separated from the brain, serving various peripheral functions including modulation of gut’s motility. Increased blood serotonin has also been associated with high blood glucose levels.
#serotonin #carbs #whole-grain - scienceblog.com

How to increase serotonin in the human brain without drugs

Relatively few generations ago, most of the world population was involved in agriculture and was outdoors for much of the day. This would have resulted in high levels of bright light exposure even in winter. Even on a cloudy day, the light outside can be greater than 1000 lux, a level never normally achieved indoors. In a recent study carried out at around latitude 45° N, daily exposure to light greater than 1000 lux averaged about 30 minutes in winter and only about 90 minutes in summer50 among people working at least 30 hours weekly; weekends were included. In this group, summer bright light exposure was probably considerably less than the winter exposure of our agricultural ancestors. We may be living in a bright light–deprived society. A large literature that is beyond the scope of this editorial exists on the beneficial effect of bright light exposure in healthy individuals. Lamps designed for the treatment of seasonal affective disorder, which provide more lux than is ever achieved by normal indoor lighting, are readily available, although incorporating their use into a daily routine may be a challenge for some. However, other strategies, both personal and institutional, exist. “Light cafes” pioneered in Scandinavia have come to the United Kingdom,51 and an Austrian village that receives no sunshine in the winter because of its surrounding mountains is building a series of giant mirrors to reflect sunlight into the valley.52 Better use of daylight in buildings is an issue that architects are increasingly aware of. Working indoors does not have to be associated with suboptimal exposure to bright light. A third strategy that may raise brain serotonin is exercise. A comprehensive review of the relation between exercise and mood concluded that antidepressant and anxiolytic effects have been clearly demonstrated.53 In the United Kingdom the National Institute for Health and Clinical Excellence, which works on behalf of the National Health Service and makes recommendations on treatments according to the best available evidence, has published a guide on the treatment of depression.54 The guide recommends treating mild clinical depression with various strategies, including exercise rather than antidepressants, because the risk–benefit ratio is poor for antidepressant use in patients with mild depression. Exercise improves mood in subclinical populations as well as in patients. The most consistent effect is seen when regular exercisers undertake aerobic exercise at a level with which they are familiar.53 However, some skepticism remains about the antidepressant effect of exercise, and the National Institute of Mental Health in the United States is currently funding a clinical trial of the antidepressant effect of exercise that is designed to overcome sources of potential bias and threats to internal and external validity that have limited previous research.55 Several lines of research suggest that exercise increases brain serotonin function in the human brain. Post and colleagues56 measured biogenic amine metabolites in cerebrospinal fluid (CSF) of patients with depression before and after they increased their physical activity to simulate mania. Physical activity increased 5-HIAA, but it is not clear that this was due to increased serotonin turnover or to mixing of CSF from higher regions, which contain higher levels of 5-HIAA, with lumbar CSF (or to a combination of both mechanisms). Nonetheless, this finding stimulated many animal studies on the effects of exercise. For example, Chaouloff and colleagues57 showed that exercise increased tryptophan and 5-HIAA in rat ventricles. More recent studies using intracerebral dialysis have shown that exercise increases extracellular serotonin and 5-HIAA in various brain areas, including the hippocampus and cortex (for example, see58–60). Two different mechanisms may be involved in this effect. As reviewed by Jacobs and Fornal,61 motor activity increases the firing rates of serotonin neurons, and this results in increased release and synthesis of serotonin.62 In addition, there is an increase in the brain of the serotonin precursor tryptophan that persists after exercise.63 The largest body of work in humans looking at the effect of exercise on tryptophan availability to the brain is concerned with the hypothesis that fatigue during exercise is associated with elevated brain tryptophan and serotonin synthesis. A large body of evidence supports the idea that exercise, including exercise to fatigue, is associated with an increase in plasma tryptophan and a decrease in the plasma level of the branched chain amino acids (BCAAs) leucine, isoleucine and valine (see64,65 for reviews). The BCAAs inhibit tryptophan transport into the brain.66 Because of the increase in plasma tryptophan and decrease in BCAA, there is a substantial increase in tryptophan availability to the brain. Tryptophan is an effective mild hypnotic,67 a fact that stimulated the hypothesis that it may be involved in fatigue. A full discussion of this topic is not within the scope of this editorial; however, it is notable that several clinical trials of BCAA investigated whether it was possible to counter fatigue by lowering brain tryptophan, with results that provided little support for the hypothesis. Further, exercise results in an increase in the plasma ratio of tryptophan to the BCAAs before the onset of fatigue.64,65 The conclusion of these studies is that, in humans, a rise in precursor availability should increase serotonin synthesis during and after exercise and that this is not related to fatigue, although it may be related to improved mood. Whether motor activity increases the firing rate of serotonin neurons in humans, as in animals, is not known. However, it is clear that aerobic exercise can improve mood.
#exercise #sunlight #serotonin - ncbi.nlm.nih.gov

Serotonin can regulate gene expression inside neurons -- ScienceDaily

The study revolves around DNA and how it works to form each person's individual biological map. Each cell in the body contains two meters of DNA, the blueprint for all functions of all cells in the body. This DNA is wound around spools of histone proteins (proteins that package DNA in the nucleus of cells, and are heavily prone to chemical modifications that aid in the regulation of gene expression) into structures referred to as nucleosomes. When DNA encoding a specific gene is wound tightly within the spool, that gene is less likely to be expressed. When the gene is not wound as tightly, it is more likely to be expressed. This can affect many functions of a given cell. Serotonin is a chemical that can transmit signals between neurons in the brain and is involved in the regulation of mood. Selective serotonin reuptake inhibitors, known as SSRIs, alter the amounts of serotonin in the brain, which enables mood changes. When small packages of serotonin are released from a neuron, the resulting signals set up a chain reaction of communication between different parts of the brain. The research team discovered that a protein called tissue transglutaminase 2 can directly attach serotonin molecules to histone proteins (a process called histone serotonylation), which in turn loosens the spool to enable more robust gene expression. Specifically, they found that in developing rodent brains and human neurons, genes near the part of the spool loosened by the serotonin are more likely to be expressed. They also showed that a specific binding complex enables this process.
#depression #neurons #DNA #serotonin #methylation - sciencedaily.com

Tolerance must occur?

Specifically, not the serotonin receptors that LSD binds to in the claustrum region of the brain. “Once LSD gets in the receptor, you can think of it as a hole in the ground. LSD jumps into it and then pulls a lid down over the top,” says study co-author Bryan Roth, a pharmacologist at the University of North Carolina at Chapel Hill School of Medicine. “Basically, from the structure we could tell that once LSD gets in there it can't get out. That's why it lasts so long.” We’re talking 12, 18, maybe 24 hours, by the way. Still, that lid will move around, so some LSD molecules will escape as the high wears off.
#serotonin #psychotropics - wired.com

Painting a Nuanced Picture of Brain System Regulation Moods and Movements - Neuroscience News

What’s more, the group found that the serotonin neurons themselves were more complex than originally thought. Rather than just transmitting messages with serotonin, the cortical-projecting neurons also released a chemical messenger called glutamate – making them one of the few known examples of neurons in the brain that release two different chemicals. “It raises the question of whether we should even be calling these serotonin neurons because neurons are named after the neurotransmitters they release,” Ren said. Taken together, these findings indicate that the brain’s serotonin system is not made up of a homogenous population of neurons but rather many subpopulations acting in concert. Luo’s team has identified two groups, but there could be many others. In fact, Robert Malenka, a professor and associate chair of psychiatry and behavioral sciences at Stanford’s School of Medicine, and his team recently discovered a group of serotonin neurons in the dorsal raphe that project to the nucleus accumbens, the part of the brain that promotes social behaviors.
#depression #pharma #serotonin #SSRI - neurosciencenews.com

Painting a Nuanced Picture of Brain System Regulation Moods and Movements - Neuroscience News

In a series of behavioral tests, the scientists also showed that serotonin neurons from the two groups can respond differently to stimuli. For example, neurons in both groups fired in response to mice receiving rewards like sips of sugar water but they showed opposite responses to punishments like mild foot shocks. “We now understand why some scientists thought serotonin neurons are activated by punishment, while others thought it was inhibited by punishment. Both are correct – it just depends on which subtype you’re looking at,” Luo said.
#paleotherapy #pharma #anxiety #antidepressants #serotonin #SSRI - neurosciencenews.com

Traumatic brain injury causes intestinal damage, study shows: Two-way brain-gut interactions may worsen outcome after TBI -- ScienceDaily

This is the first study to find that TBI in mice can trigger delayed, long-term changes in the colon and that subsequent bacterial infections in the gastrointestinal system can increase posttraumatic brain inflammation and associated tissue loss. The findings were published recently in the journal Brain, Behavior, and Immunity. "These results indicate strong two-way interactions between the brain and the gut that may help explain the increased incidence of systemic infections after brain trauma and allow new treatment approaches," said the lead researcher, Alan Faden, MD, the David S. Brown Professor in Trauma in the Departments of Anesthesiology, Anatomy & Neurobiology, Psychiatry, Neurology, and Neurosurgery at UMSOM, and director of the UMSOM Shock, Trauma and Anesthesiology Research Center.
#concussions #serotonin #gut - sciencedaily.com

Serotonin receptors in depression: from A to B

Despite the relative success in treating depression by increasing extracellular serotonin, there is a lack of strong evidence supporting a direct correlation between low serotonin signaling and depression. While some studies report an association between levels of platelet serotonin and depression, this has not been a consistent finding in large sample sets, and it is also unclear how platelet levels are related to brain levels of serotonin 10, 11. Additionally, few studies report direct correlations between cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, and depression 12, 13. Low levels of tryptophan have been consistently linked to depression; however, these effects could be independent of serotonin 14, 15. The lack of consistent clear-cut abnormalities in global measures of serotonin signaling isn’t surprising if one considers the complexity of the receptors at which serotonin binds, the intricate neuroanatomical circuitry of the serotonin system, and the developmental role serotonin plays as a neurotrophic factor 16– 18. Many recent studies have focused on understanding the mechanisms through which serotonin affects depression by studying the impact of 5-HTT and the 15 known receptors through gene-association studies, human brain imaging, and pharmacological and genetic mouse models 19.
#medicalindustrialcomplex #serotonin #SSRI - ncbi.nlm.nih.gov

Antidepressants associated with significantly elevated risk of death, researchers find

Antidepressants block the absorption of serotonin in these organs as well, and the researchers warn that antidepressants could increase the risk of death by preventing multiple organs from functioning properly. The researchers reviewed studies involving hundreds of thousands of people and found that antidepressant users had a 33% higher chance of death than non-users. Antidepressant users also had a 14% higher risk of cardiovascular events, such as strokes and heart attacks. The findings were published today in the journal Psychotherapy and Psychosomatics.
#depression #serotonin - medicalxpress.com

Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration

Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.
#medicalindustrialcomplex #depression #serotonin #SSRI - journals.plos.org

Mice Genetically Depleted of Brain Serotonin Do Not Display a Depression-like Behavioral Phenotype - ACS Chemical Neuroscience (ACS Publications)

Reductions in function within the serotonin (5HT) neuronal system have long been proposed as etiological factors in depression. Selective serotonin reuptake inhibitors (SSRIs) are the most common treatment for depression, and their therapeutic effect is generally attributed to their ability to increase the synaptic levels of 5HT. Tryptophan hydroxylase 2 (TPH2) is the initial and rate-limiting enzyme in the biosynthetic pathway of 5HT in the CNS, and losses in its catalytic activity lead to reductions in 5HT production and release. The time differential between the onset of 5HT 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. Mice lacking the gene for TPH2 are genetically depleted of brain 5HT and were tested for a depression-like behavioral phenotype using a battery of valid tests for affective-like disorders in animals. The behavior of TPH2–/– mice on the sucrose preference test, tail suspension test, and forced swim test and their responses in the unpredictable chronic mild stress and learned helplessness paradigms was the same as wild-type controls. While TPH2–/– mice as a group were not responsive to SSRIs, a subset responded to treatment with SSRIs in the same manner as wild-type controls with significant reductions in immobility time on the tail suspension test, indicative of antidepressant drug effects. The behavioral phenotype of the TPH2–/– mouse questions the role of 5HT in depression. Furthermore, the TPH2–/– mouse may serve as a useful model in the search for new medications that have therapeutic targets for depression that are outside of the 5HT neuronal system.
#medicalindustrialcomplex #depression #serotonin #SSRI - pubs.acs.org

Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response - ScienceDirect

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.
#medicalindustrialcomplex #serotonin #SSRI - sciencedirect.com

Is the dark really making me sad? | Ars Technica

the leading theory is the ‘phase-shift hypothesis’: the idea that shortened days cause the timing of our circadian rhythms to fall out of sync with the actual time of day, because of a delay in the release of melatonin. Levels of this hormone usually rise at night in response to darkness, helping us to feel sleepy, and are suppressed by the bright light of morning. “If someone’s biological clock is running slow and that melatonin rhythm hasn’t fallen, then their clock is telling them to keep on sleeping even though their alarm may be going off and life is demanding that they wake up,” says Kelly Rohan, a professor of psychology at the University of Vermont. Precisely why this should trigger feelings of depression is still unclear. One idea is that this tiredness could then have unhealthy knock-on effects. If you’re having negative thoughts about how tired you are, this could trigger a sad mood, loss of interest in food, and other symptoms that could cascade on top of that. However, recent insights into how birds and small mammals respond to changes in day length have prompted an alternative explanation. According to Daniel Kripke, an emeritus professor of psychiatry at the University of California, San Diego, when melatonin strikes a region of the brain called the hypothalamus, this alters the synthesis of another hormone—active thyroid hormone—that regulates all sorts of behaviours and bodily processes. When dawn comes later in the winter, the end of melatonin secretion drifts later, says Kripke. From animal studies, it appears that high melatonin levels just after the time an animal wakes up strongly suppress the making of active thyroid hormone—and lowering thyroid levels in the brain can cause changes in mood, appetite, and energy. For instance, thyroid hormone is known to influence serotonin, a neurotransmitter that regulates mood. Several studies have shown that levels of brain serotonin in humans are at their lowest in the winter and highest in the summer. In 2016, scientists in Canada discovered that people with severe SAD show greater seasonal changes in a protein that terminates the action of serotonin than others with no or less severe symptoms, suggesting that the condition and the neurotransmitter are linked.
#depression #paleotherapy #sunlight #serotonin #bipolar #sad #thyroid - arstechnica.com

Exercise boosts tryptophan, a mild hypnotic and serotonin precursor

The largest body of work in humans looking at the effect of exercise on tryptophan availability to the brain is concerned with the hypothesis that fatigue during exercise is associated with elevated brain tryptophan and serotonin synthesis. A large body of evidence supports the idea that exercise, including exercise to fatigue, is associated with an increase in plasma tryptophan and a decrease in the plasma level of the branched chain amino acids (BCAAs) leucine, isoleucine and valine (see64,65 for reviews). The BCAAs inhibit tryptophan transport into the brain.66 Because of the increase in plasma tryptophan and decrease in BCAA, there is a substantial increase in tryptophan availability to the brain. Tryptophan is an effective mild hypnotic,67 a fact that stimulated the hypothesis that it may be involved in fatigue. A full discussion of this topic is not within the scope of this editorial; however, it is notable that several clinical trials of BCAA investigated whether it was possible to counter fatigue by lowering brain tryptophan, with results that provided little support for the hypothesis. Further, exercise results in an increase in the plasma ratio of tryptophan to the BCAAs before the onset of fatigue.64,65
#exercise #paleopsychiatry #serotonin #hypnosis #mantras - ncbi.nlm.nih.gov

Overview of exercise and serotonin

A third strategy that may raise brain serotonin is exercise. A comprehensive review of the relation between exercise and mood concluded that antidepressant and anxiolytic effects have been clearly demonstrated.53 In the United Kingdom the National Institute for Health and Clinical Excellence, which works on behalf of the National Health Service and makes recommendations on treatments according to the best available evidence, has published a guide on the treatment of depression.54 The guide recommends treating mild clinical depression with various strategies, including exercise rather than antidepressants, because the risk–benefit ratio is poor for antidepressant use in patients with mild depression. Exercise improves mood in subclinical populations as well as in patients. The most consistent effect is seen when regular exercisers undertake aerobic exercise at a level with which they are familiar.53 However, some skepticism remains about the antidepressant effect of exercise, and the National Institute of Mental Health in the United States is currently funding a clinical trial of the antidepressant effect of exercise that is designed to overcome sources of potential bias and threats to internal and external validity that have limited previous research.55
#exercise #paleopsychiatry #serotonin - ncbi.nlm.nih.gov

Light boosts serotonin

Exposure to bright light is a second possible approach to increasing serotonin without drugs. Bright light is, of course, a standard treatment for seasonal depression, but a few studies also suggest that it is an effective treatment for nonseasonal depression38 and also reduces depressed mood in women with premenstrual dysphoric disorder39 and in pregnant women suffering from depression.40 The evidence relating these effects to serotonin is indirect. In human postmortem brain, serotonin levels are higher in those who died in summer than in those who died in winter.41 A similar conclusion came from a study on healthy volunteers, in which serotonin synthesis was assessed by measurements of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the venous outflow from the brain.42 There was also a positive correlation between serotonin synthesis and the hours of sunlight on the day the measurements were made, independent of season. In rats, serotonin is highest during the light part of the light–dark cycle, and this state is driven by the photic cycle rather than the circadian rhythm.43,44 The existence of a retinoraphe tract may help explain why, in experimental animals, neuronal firing rates, c-fos expression and the serotonin content in the raphe nuclei are responsive to retinal light exposure.44–48 In humans, there is certainly an interaction between bright light and the serotonin system. The mood-lowering effect of acute tryptophan depletion in healthy women is completely blocked by carrying out the study in bright light (3000 lux) instead of dim light.49
#depression #sunlight #paleopsychiatry #serotonin #sad - ncbi.nlm.nih.gov

The Serotonin Surprise | DiscoverMagazine.com

Glenmullen has long suspected that drugs that alter serotonin metabolism cause profound changes in the brain. He bases his suspicion on a body of research during the last 20 years by scientists investigating another class of drugs that includes MDMA (Ecstasy) as well as fenfluramine, the diet drug recently removed from the market because of its association with heart valve problems. These drugs do more than just block serotonin reuptake; they primarily stimulate the release of large quantities of serotonin from nerve endings into the brain. The resulting flood is thought to cause the mind-altering effects of MDMA. And that flood, some scientists argue, leaves brain damage in its wake. When monkeys and rats are given high doses of serotonin releasers--up to 40 times the dose that people generally take--the microscopic architecture of their brains looks different from normal brains. The nerve fibers (axons) that carry serotonin to the target cells seem to change their shape and diminish in number--effects some scientists claim are properly understood as brain damage.
#depression #neurons #psychiatry #serotonin - discovermagazine.com