depression

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Serotonin is a neurotransmitter produced in the brain known to influence the functioning of the cardiovascular, renal, immune, and gastrointestinal systems.Any disruption in the synthesis, metabolism or uptake of this neurotransmitter has been found to be partly responsible for certain manifestations of schizophrenia, depression, compulsive disorders and learning problems.Serotonin originates in neurons deep in the midline of the brainstem. Because these neurons profile diffusely throughout the...

SerotoninMind and Stomach

The brain and the gut have a lot in common, including the ways in which nerve cells talk with each other. Neurotransmitters are important chemicals that allow nerve cells to communicate. Serotonin is one of the most important neurotransmitters for that brain in your gut.

Serotonin is important for the functions of your brain and your mood, but it is crucial to the function of your digestive system. Your gut creates 95 percent of the serotonin in your body. Changes in your levels of serotonin and your sensitivity to serotonin signaling can change how your bowel works.

What Does Serotonin Do?Serotonin affects many aspects of your gut

function, including:

It changes the motility of your bowels (how fast food moves through your system).

It affects how much fluid, such as mucus, is secreted in your intestines.

It affects how sensitive your intestines are to sensations like pain and fullness.

Differences in serotonin levels between individuals also line up with the differences between people who suffer from IBS. For example, people with IBS who have

constipation often have lower-than-normal levels of serotonin. The muscles in their rectums are less reactive to serotonin, and they’re more likely to have hard or lumpy

stools. Others with IBS who have diarrhea have been shown to have higher-than-normal levels of serotonin. Their rectums are more reactive: more likely to empty too

early.

There are fourteen different kinds of receptors in your intestines that react in different ways to serotonin. Some receptors are responsible for sending messages to the brain that signal nausea, bloating, and pain. Other receptors change your sensitivity to or

intensity of how distended or full your intestines feel.

Serotonin levelOur body chemistry is complex; many different hormones, neurotransmitters, and other substances influence how we

feel. Serotonin is one chemical that has received a great deal of attention for its contribution to mood. It's a

neurotransmitter (a chemical involved in the transmission of nerve impulses between nerve cells) that's formed in the brain and primarily found in three parts of the body — the

brain, the lining of the digestive tract, and in blood platelets. In the brain, serotonin's main effects include

improving mood and giving you that "satisfied" feeling from food. It's also thought to help promote sleep and relaxation.

Carbohydrate-rich meals often increase serotonin levels. However, manipulating serotonin levels through food may be very difficult to achieve because serotonin's properties may have varying effects in different people. Some people may experience a temporary lift in mood after a carbohydrate-

rich meal, while others may become relaxed or sleepy. Certain foods that increase serotonin levels aren't the healthiest choices either. Believe it or not, candy and sweets, which are simple carbohydrates, have the greatest impact, but the effect will only last 1 to 2 hours. Complex carbohydrates (rice, potato, pasta) may increase serotonin levels, but not to the same extent because the

protein content of these foods might actually inhibit serotonin production.

Here's a brief explanation of the mechanism behind the effect of food on serotonin levels: after consumption of a carbohydrate-rich meal, the hormone insulin is

secreted. Insulin lowers the blood levels of most amino acids (the building blocks of protein), except for tryptophan (a precursor to serotonin). Amino acids compete for

transportation across the blood-brain barrier, and when there is a larger proportion of tryptophan, it enters the brain at a higher rate, thus boosting serotonin production. To

make matters more interesting, tryptophan is present in many protein-rich foods, which have been found to prevent serotonin production. So, you can see how intricate

and complex this system is.

Advice:If you're having trouble falling asleep, try a small snack of carbohydrate-rich food. Warm milk may work for the psychological comfort, but also because milk contains a moderate amount of carbohydrate in the form

of lactose (milk sugar).If you tend to have only carbohydrates (e.g., plain bagel or muffin)

before class, and you often fall asleep during class, try adding some protein by putting some hard cheese (cheddar, American, Swiss, etc.) or peanut butter on the bagel. Or, have a yogurt or cottage cheese instead.

For those who are active (athletes or exercisers), don't be fooled by carbohydrate's relaxing effects. You'll do best with a diet rich in

grains/starches, legumes (dried beans and peas), fruit, and vegetables in order to get carbohydrates for muscle energy. Don't skimp on protein either, which is necessary for muscle growth and repair. Additionally,

include some fat for satiety and healthy skin.

The carbohydrate/tryptophan/serotonin pathway

Since each of us is unique, in order to get a "desired effect" from food, you would need to experiment eating different foods and observing how your body reacts to each of them. You'll also need to take into consideration your other lifestyle choices — how

much sleep you get, whether or not you exercise regularly, the medications you take, your stress levels, etc. — when figuring out what affects your moods in what manners. If you have more questions about mood and food, consider scheduling an appointment

with a nutritionist at Health Services by calling x4-2284 or logging into Open Communicator. If you're not at Columbia, ask for a referral to one from your primary

health care provider.

Serotonin is known as the happy molecule. As consumers of health advice, we’re bombarded with top tips for boosting our serotonin levels – instant fixes for feeling

glum – based on the premise that low serotonin levels lead to feelings of sadness and depression. According to the internet, we should all be pounding on treadmills and

scoffing turkey sandwiches to make ourselves feel better. But while it’s true that turkey contains tryptophan – the essential amino acid that our bodies need to make

serotonin – the connection between serotonin and our state of mind is rather more complex.

Mechanism of action of serotonin

According to the present model of SERT function, the first step occurs when Na+ binds to the carrier protein. Serotonin, in its protonated form (5HT+), then binds

to the transporter followed by Cl-. Chloride ions are not required for 5HT+ binding to occur but are necessary for net transport to take place. The initial complex of serotonin, Na+, and Cl- creates a conformational change in the transporter protein. The protein, which began by facing the outside of the

neuron, moves to an inward position where the neurotransmitter and ions are released into the cytoplasm of the neuron. Intracellular K+ then binds to the SERT to promote reorientation of the carrier for another transport cycle. The

unoccupied binding site becomes, once again, exposed to the outside of the cell and the K+ is released outside the cell.

Chemistry of serotoninAlthough serotonin may be obtained from a variety of dietary

sources, endogenous 5-HT is synthesized in situ from tryptophan through the actions of the enzymes tryptophan hydroxylase and

aromatic L-amino acid decarboxylase. Both dietary and endogenous 5-HT are rapidly metabolized and inactivated by

monoamine oxidase and aldehyde dehydrogenase to the major metabolite, 5-hydroxyindoleacetic acid (5-HIAA).

Of the chemical neurotransmitter substances, serotonin is perhaps the most implicated in the etiology or treatment of various disorders, particularly those

of the central nervous system, including anxiety, depression, obsessive-compulsive disorder, schizophrenia, stroke, obesity, pain, hypertension,

vascular disorders, migraine, and nausea. A major factor in our understanding of the role of 5-HT in these disorders is the recent rapid advance made in

understanding the physiological role of various serotonin receptor subtypes. This review will summarize the physiological functions of serotonin--those

drugs currently available that act by mimicking or antagonizing the actions of serotonin--and the future development of serotonergic agents.

Serotonin was first isolated from blood in 1948 by Page and coworkers and was later identified in the central nervous system. As is the case for most

neurotransmitters, it has a relatively simple chemical structure but displays complex pharmacological properties. Based on the similarity of this structure

to the structures of norepinephrine and dopamine, it is not surprising that serotonin, like its catecholamine counterparts, possesses a diversity of

pharmacological effects, both centrally and peripherally. It is found in three main areas of the body: the intestinal wall (where it causes increased

gastrointestinal motility); blood vessels (where large vessels are constricted); and the central nervous system (CNS).

The most widely studied effects have been those on the CNS. The functions of serotonin are numerous and appear to involve control of appetite, sleep, memory and learning, temperature regulation, mood, behavior (including sexual and hallucinogenic behavior), cardiovascular function, muscle contraction, endocrine regulation, and depression. Peripherally, serotonin appears to play a major role in platelet homeostasis, motility of the GI tract, and carcinoid tumor secretion. This represents quite a broad spectrum of pharmacological and psychological effects, considering the fact that the average human adult possesses only about 10 mg of 5-HT. Subsequent to his discovery of serotonin, Page commented that no physiological substance known possesses such diverse actions in the body as does 5-HT.

Chemical neurotransmitters (CNTs) produce their effects as a consequence of interactions with appropriate receptors. As is the case with all the CNTs,

serotonin is synthesized in brain neurons and stored in vesicles. Upon a nerve impulse, it is released into the synaptic cleft, where it interacts with various

postsynaptic receptors.

The actions of 5-HT are terminated by three major mechanisms: diffusion; metabolism; and uptake back into the synaptic cleft through the actions of

specific amine membrane transporter systems. These events are summarized in Figure 1. Thus, the actions of 5-HT can be theoretically modulated by

agents that stimulate or inhibit its biosynthesis (step 1); agents that block its storage (step 2); agents that stimulate or inhibit its release (step 3); agents

that mimic or inhibit its actions at its various postsynaptic receptors (step 4); agents that inhibit its uptake back into the nerve terminal (step 5); agents

that affect its metabolism (step 6).

5-HTPby Debora-Dale Young

5-HTP (5-hydroxytryptophan) is an amino acid that is the active intermediate between L-Tryptophan and the important brain

chemical serotonin. Serotonin supports sleep, mood, appetite, temperature balance, sexual behaviour and pain sensation.

Lifestyle and dietary practices of many people today result in lowered levels of serotonin. As a result, many people are

overweight, crave sugar experience depression, headaches, and have muscle aches and pain.

- See more at: http://www.clinicians.co.nz/5-htp/#sthash.iplGBiPA.dpuf

The introduction of the antidepressant Prozac (fluoxetine) whose mode of action is to support ‘healthy serotonin’ levels, helped increase public

awareness regarding the role of serotonin as a ‘happy chemical’ for mood support. Serotonin has a number of actions in the body, it is also involved in sleep, eating, temperature regulation, movement and nervousness1 Natural

health practitioners on the other hand have used St. Johns wort and a substance called 5-HTP for the same reason. So what is 5-HTP or 5-

Hydroxytryptophan as it is otherwise known? It is a precursor or building block for the production of the neurotransmitter serotonin one of our ‘happy

chemicals.’ - See more at: http://www.clinicians.co.nz/5-htp/#sthash.iplGBiPA.dpuf

The brain is a chemical factory that works 24 hours a day to produce a range of neurotransmitters (mood messengers) and hormones involved in the regulation of

many body processes including the sleep/ wake cycle. To do this the brain and body utilizes vitamins, minerals and amino acids from protein that must all be obtained

from dietary sources. Poor digestion, excess or ongoing stress and poor dietary choices such as excess caffeine, alcohol and processed foods combined with insufficient

protein, rob the body of the building blocks and cofactors it requires for neurotransmitter production. This can lead to low mood and poor quality sleep.

Dietary levels of the amino acid tryptophan are directly related to the body’s ability to produce serotonin, which is also a precursor to the sleep hormone melatonin. The age old recommendation of a hot milk or chocolate drink at night to support sleep comes from milk and cocoa containing tryptophan. However 5-HTP which is commercially

obtained from the seeds of the Griffonia simplicifolia plant is a more efficient precursor to serotonin than Tryptophan and is often used in dietary supplements to support healthy sleep and mood, especially when combined with B-group vitamins

and magnesium as cofactors.2

- See more at: http://www.clinicians.co.nz/5-htp/#sthash.iplGBiPA.dpuf

Many individuals suffer from recurring migraine or tension headaches which can significantly impact on their quality of life. Nutrients such as magnesium

and B-group vitamins have been shown to be supportive in some people. There is also evidence from several studies in both children and adults that 5-HTP may be effective in reducing headache severity and frequency, including tension headaches and migraines. Fewer pain-relieving medications may be

needed when taken with 5-HTP. However, many of the available studies show that more proven pharmaceutical drugs may work better than 5-HTP for

headaches. Further research is needed. - See more at: http://www.clinicians.co.nz/5-htp/#sthash.iplGBiPA.dpuf

Foods known to be high in Tryptophan include; spirulina, oat or wheat bran, wheat germ, brewer’s yeast, dairy products, soy beans and soy protein. Other sources include

meats such as beef, chicken, turkey and pork and seafood such as crab and tuna, pumpkin and pumpkin seeds, chocolate and cocoa powder and a range of nuts and

seeds.1 - See more at: http://www.clinicians.co.nz/5-htp/#sthash.iplGBiPA.dpuf

There is no substitute for a healthy diet, eating a wide variety of fresh seasonal coloured fruits and vegetables along with lean meat and good

quality protein is important. Likewise avoiding or minimizing processed or white foods such as cakes, biscuits, pasta and high calorie snack foods is a

good idea. These foods tend to be high in calories but deficient in the many essential vitamins and mineral that the body needs for its many metabolic

processes. In fact these foods can often rob the body of essential nutrients.

The first approach to improve health should always be to improve your diet and optimize digestion, reduce stress where possible, get sufficient sleep (7-8 hours per night) and exercise regularly. We all lead busy stressful lives and do

not always eat drink or sleep as we should. Taking a daily multivitamin and some omega-3 fish oil or krill oil helps to provide nutritional insurance of a daily basis to keep us on top of our game. Consult a health professional to

address any other health issues to ensure you choose the correct supplements for your needs or for a referral to an appropriate health

professional.

- See more at: http://www.clinicians.co.nz/5-htp/#sthash.iplGBiPA.dpuf

MAO-inhibitorMonoamine oxidase inhibitors (MAOIs) are chemicals which inhibit the activity of the

monoamine oxidase enzyme family. They have a long history of use as medications prescribed for the treatment of depression. They are particularly effective in treating

atypical depression.[1] They are also used in the treatment of Parkinson's Disease and several other disorders.

MAOIs have been found to be effective in the treatment of panic disorder with agoraphobia,[6] social phobia,[7][8][9] atypical depression[10][11] or mixed anxiety and depression, bulimia,[12][13][14][15] and post-traumatic stress disorder,[16] as

well as borderline personality disorder.[17] MAOIs appear to be particularly effective in the management of bipolar depression according to a recent retrospective-analysis.

[18] There are reports of MAOI efficacy in obsessive-compulsive disorder (OCD), trichotillomania, dysmorphophobia, and avoidant personality disorder, but these

reports are from uncontrolled case reports.[5]

MAOIs can also be used in the treatment of Parkinson's disease by targeting MAO-B in particular (therefore affecting dopaminergic neurons), as well as providing an alternative for migraine prophylaxis. Inhibition of both MAO-A

and MAO-B is used in the treatment of clinical depression and anxiety.

MAOIs appear to be particularly indicated for outpatients with "neurotic depression" complicated by panic disorder or hysteroid dysphoria, which

involves repeated episodes of depressed mood in response to feeling rejected.

MAOIs act by inhibiting the activity of monoamine oxidase, thus preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability. There are two isoforms of monoamine oxidase, MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin, epinephrine, and

norepinephrine. MAO-B preferentially deaminates phenylethylamine and trace amines. Dopamine is equally deaminated by both types.

MAO-A inhibition reduces the breakdown of primarily serotonin, norepinephrine, and dopamine; selective inhibition of MAO-A allows for

tyramine to be metabolised via MAO-B.[21] Agents that act on serotonin if taken with another serotonin-enhancing agent may result in a potentially

fatal interaction called serotonin syndrome or with irreversible and unselective inhibitors (such as older MAOIs), of MAO a hypertensive crisis as a

result of tyramine food interactions is particularly problematic with older MAOIs. Tyramine is broken down by MAO-A and MAO-B, therefore inhibiting this action may result in its excessive build-up, so diet must be monitored for

tyramine intake.

MAO-B inhibition reduces the breakdown mainly of dopamine and phenethylamine so there are no dietary restrictions

associated with this. MAO-B would also metabolize tyramine, as the only differences between dopamine, phenethylamine, and

tyramine are two phenylhydroxyl groups on carbons 3 and 4. The 4-OH would not be a steric hindrance to MAO-B on tyramine.[22] Two MAO-Bi drugs, selegiline and rasagiline have been approved

by the FDA without dietary restrictions, except in high-dosage treatment, wherein they lose their selectivity

Catechol-O-methyltransferase (COMT; EC 2.1.1.6) is one of several enzymes that degrade catecholamines such as dopamine, epinephrine, and

norepinephrine. In humans, catechol-O-methyltransferase protein is encoded by the COMT gene.[2] As the regulation of catecholamines is impaired in a

number of medical conditions, several pharmaceutical drugs target COMT to alter its activity and therefore the availability of catecholamines.[3] COMT

was first discovered by the biochemist Julius Axelrod in 1957.[4]

Specific reactions catalyzed by COMT include:

Dopamine → 3-MethoxytyramineDOPAC → HVA (homovanillic acid)

Norepinephrine → NormetanephrineEpinephrine → Metanephrine

Dihydroxyphenylethylene glycol (DOPEG) → Methoxyhydroxyphenylglycol (MOPEG)

3,4-Dihydroxymandelic acid (DOMA) → Vanillylmandelic acid (VMA)

In the brain, COMT-dependent dopamine degradation is of particular importance in brain regions with low expression of the presynaptic dopamine

transporter (DAT), such as the prefrontal cortex.[5][6] This process is supposed to take place in postsynaptic neurons, as, in general, COMT is

located intracellularly in the CNS.

Catechol-O-methyltransferase is involved in the inactivation of the catecholamine neurotransmitters (dopamine, epinephrine, and norepinephrine). The enzyme introduces a methyl group to the

catecholamine, which is donated by S-adenosyl methionine (SAM). Any compound having a catechol structure, like catecholestrogens and catechol-

containing flavonoids, are substrates of COMT.

Levodopa, a precursor of catecholamines, is an important substrate of COMT. COMT inhibitors, like entacapone, save levodopa from COMT and prolong the

action of levodopa. Entacapone is a widely used adjunct drug of levodopa therapy. When given with an inhibitor of dopa decarboxylase (carbidopa or

benserazide), levodopa is optimally saved. This "triple therapy" is becoming a standard in the treatment of Parkinson's disease.

Chocolate Consumption and Effects on Serotonin Synthesis

The ingestion of carbohydrates stimulates the release of insulin which, along with its anabolic effects, promotes amino acids in the blood to enter muscle cells, except for tryptophan.2 This will cause a relative increase of tryptophan over other amino acids, which compete for passing the blood-brain barrier. As a consequence, more tryptophan enters the brain, and there is an increase in the synthesis of serotonin,3 a neurotransmitter postulated to have a major role in mood disorders and a target of many psychopharmaceuticals.

Chocolate: Good for the Mind, Body & Spirit

Chocolate may also make a person feel better by directly interacting with the brain. One of the ingredients in chocolate is tryptophan, an essential amino

acid needed by the brain to produce serotonin. Serotonin is a mood-modulating neurotransmitter, the brain's "happy chemical." High levels of

serotonin can give rise to feelings of happiness .

Chocolate contains another neurotransmitter, anandamide. Anadamine targets the same brain structure as THC (tetrahydrocannabinol), the active ingredient in cannabis. Chocolate also contains two chemicals that slow the

normal breakdown of anandamide and prolong the action of this natural stimulant in the brain. The BBC's Hot Topic article on Chocolate provides an excellent Flash animation demonstrating how chocolate might prolong the

effects of anadamine. (1) However, one must note that experts estimate the levels of these substances are so low in most chocolate, that a person would need to eat several pounds of chocolate in order to substantially impact the

brain's own normal anandamide levels.

Many people consume chocolate during moments of emotional distress, for its comforting properties, ability to improve mood and restore a sense of well being. The comforting, mood-elevating properties are most likely caused by

the release of endorphins resulting from chocolate consumption

not all types of chocolate are healthy. When choosing chocolate for the health benefits consider the type of

cocoa bean, the processing method used and what other ingredients have been added to the chocolate .

The three main forms of chocolate available are: (4, 21-23)

Dark, Semisweet ChocolateUnsweetened chocolate combined with added sweeteners and cocoa

butter which contain at least 35% chocolate liquor.; the fat content averages 27%. Dark chocolate has two to four times (or more) the

amount of flavonoids than milk chocolate.

Milk Chocolate-Unsweetened chocolate with added cocoa butter, milk, sweeteners

and flavorings. All milk chocolate made in the U.S. contains at least 10 % cocoa mass and 12 % whole milk.

White Chocolate

Contains cocoa butter but no nonfat cocoa solids. It is the term used to describe products made from cocoa butter, milk solids and nutritive carbohydrate sweeteners. White chocolate contains no cocoa solids or

chocolate liquor, so it provides none of the health benefits from flavanoids

Recommendations for Choosing a Life with Chocolate

For many people chocolate remains a favorite food and beverage. Results show both positive and negative aspects about consuming chocolate. It is

important to consider the various components of chocolate and the complex interplay of both nutrition and health before making a decision to include

chocolate as part of a diet plan( .

Food and Mood

One theory is that carbohydrates stimulate serotonin production and thus eating them is an attempt to self-medicate depression.

Studies focused on this link do seem to back this up. High carbohydrate meals raise serotonin1 while fatty or protein rich

meals tend to lower it .

The type of carbohydrate chosen seems to be based upon it's glycemic index, or how high it causes blood sugar levels to peak.

The higher glycemic index carbohydrates like sugar have a greater effect2 on serotonin than starchy, lower glycemic index

foods like potatoes

Certain alkaloids3 have been isolated in chocolate that may raise brain serotonin levels. Scientists now speculate that

"chocoholism" may actually have a real biological basis4 with a serotonin deficiency being one factor. Another mechanism5 that

has been proposed for why chocolate has such a powerful influence on mood is that chocolate has 'drug-like' constituents

including anandamines, caffeine, and phenylethylamine.

If you slip, don't beat yourself up over it. You're a work in progress. Mistakes will happen. Dust yourself off and keep trying.Don't completely deprive yourself. Find healthier substitutes for what you're craving. Try eating a sugar free chocolate pudding instead of that large chocolate bar. Or allow yourself a small

portion of the dessert that you are coveting so much. No food is totally bad. It's all in how much you eat of it.

Be mindful of what you are consuming rather than grazing all day. A food journal can be very helpful.

Strangely, eating chocolate also causes an increased activation of the motor cortex – the area of the brain which controls voluntary

movement. This may not mean however that after eating chocolate people can move better or faster – even just reading a verb which relates to the arm, face or leg will increase activation

of the motor cortex.

The brain functions by producing chemicals called neurotransmitters which transmit messages from one part of the

brain to another. Increased brain activity is due to increased levels of these neurotransmitters. Three major neurotransmitters are called dopamine, serotonin, and opioids – all are commonly affected by drugs and both have been found to be affected by

chocolate.

serotonin has many roles in the brain, including regulating sleep, appetite and mood. There has been evidence that chocolate increases serotonin levels of

people who are deficient, including people with seasonal affective disorder or non-typical depression. This increase in serotonin is through an indirect

mechanism using the carbohydrates in chocolate (such as sugar); however this effect is counteracted by protein and fat. There is a limit at how much protein or fat a food can contain before it stops this increase of serotonin, and, sadly, chocolate has too much of both, suggesting thatchocolate does

not in fact increase serotonin at all.

When activated, opioids cause the release in the brain of endorphins, a chemical which causes a pleasurable feeling. Opioids can be released in the

brain in response to sweet foods, including chocolate, and this opioid release caused by sweet foods can lead to an analgesic feeling from endorphin

release.

Depression strikes some 35 million people worldwide, according to the World Health Organization,

contributing to lowered quality of life as well as an increased risk of heart disease and suicide. Treatments

typically include psychotherapy, support groups and education as well as psychiatric medications. SSRIs, or selective serotonin reuptake inhibitors, currently are

the most commonly prescribed category of antidepressant drugs in the U.S., and have become a

household name in treating depression.

thanks

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