Author Topic: Serotonin and other molecules involved in depression  (Read 103 times)

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Serotonin and other molecules involved in depression
« on: July 07, 2019, 12:06:42 PM »
source: https://thebrain.mcgill.ca/flash/d/d_08/d_08_m/d_08_m_dep/d_08_m_dep.html and it's links

Note: the source has many links so if you are interested then I suggest a visit to it.

SEROTONIN AND OTHER MOLECULES INVOLVED IN DEPRESSION



Serotonin is a chemical messenger in the central nervous system and is involved in many physiological functions, including sleep, aggression, eating, sexual behaviour, and depression.

Serotonin is produced by a particular type of neurons, named accordingly: the serotonergic neurons. The cell bodies of these neurons are grouped in several nuclei in the brainstemWiki.

A decline in the activity of these neurons is believed to be associated with various forms of depression, in particular those that lead to suicide.

\

Serotonin is a molecule composed of 10 carbon atoms (black), 12 hydrogen atoms (white), 2 nitrogen atoms (blue), and 1 oxygen atom (red).

But scientists have been able to measure the decline in serotonin levels in the bloodstreams of depressed people only indirectly.

After serotonin is released from the nerve ending of a neuron, it is either reabsorbed by that neuron or broken down into another molecule, known as a serotonin degradation by-product.

Thus, the more serotonin there is in someone's brain, the more serotonin degradation by-product there will be in that person's blood. In the blood of depressed people, the levels of this by-product have often been found to be abnormally low, which suggests that their serotonin levels are abnormally low as well.

There are specific receptors for serotonin on neurons in several different parts of the brain. Depending on the type of serotonin receptor, serotonin will either excite or inhibit the activity of the neuron on which this receptor is located. Thus it is the differences in the types of serotonin receptors that explain why the same molecule can have a variety of effects.

ANTIDEPRESSANTS
   
Depression has been linked to imbalances in certain chemical messengers in the body, such as serotonin, norepinephrine, and dopamine. Antidepressants—medications that effectively relieve the symptoms of depression—act directly on these neurotransmitters, which represents strong evidence that these chemical messengers are involved in this disorder.

Starting in the mid-20th century, as scientists began to suspect that there were some biochemical bases for depression, they developed several hypotheses that attributed a key role to neurotransmitters: chemical messengers such as serotonin, norepinephrine, and dopamine. The discovery of antidepressant medications-molecules that could effectively calm the symptoms of depression-lent support to these hypotheses, because these molecules acted specifically on these neurotransmitters.

It should be remembered, however, that the primary purpose of neurotransmitters is to let neurons communicate with one another. Thus these diseases must be regarded as the result of disturbances in the communications between neurons.

Such disturbances can occur at any of the steps in the transmission of neurotransmitters across synapses and are also the source of the effects that drugs have on the brain.

Some of the street drugs that people take to get high—such as ecstasy—exert their effects through mechanisms similar to those of antidepressants.

SEROTONIN AND OTHER MOLECULES INVOLVED IN DEPRESSION   
      
Two of the nine serotonergic nuclei in the brainstem, the dorsal and medial raphe nuclei, are composed of neurons whose fibres terminate in many different areas of the brain, such as the forebrain and the limbic system. The fibres arising from the dorsal and medial raphe nuclei represent almost the only source of serotonin in the anterior portions of the central nervous system.

There are 15 known types of serotonin receptors (also known as 5-HT receptors, after the chemical name for serotonin, 5-hydroxytryptamine). These 15 types can be grouped into 3 major families according to their mode of operation.

Serotonin is clearly not the only neurotransmitter involved in depression. For example, there are known, close linkages between the serotonergic system and the norepinephrinergic system in the central nervous system. Thus norepinephrine, which is affected by several antidepressants, also is involved in depression.

Many studies have also shown that the activation of the body's stress axis has a significant effect on depression. Depressed or suicidal patients show signs of hypersecretion of stress hormones, in particular glucocorticoids from the adrenal glands, which affects their serotonergic systems.

source: https://thebrain.mcgill.ca/flash/a/a_08/a_08_m/a_08_m_dep/a_08_m_dep.html#2

SEROTONIN AND OTHER MOLECULES INVOLVED IN DEPRESSION

Excerpts only:



When someone experiences a stressful event, the level of glucocorticoids in their blood rises. Stress activates the hypothalamus, which then secretes corticotropin-releasing hormone (CRH). The CRH in turn causes the pituitary gland to release adrenocorticotropic hormone (ACTH) into the bloodstream, from which it enters the adrenal glands and causes them to secrete cortisol.

This process creates a negative feedback loop in which the excess cortisol activates the brain's glucocorticoid receptors and suppresses the production of CRH. In depressed patients, however, this loop no longer works, resulting in excess production of CRH and hence of cortisol
.

In rats, chronic stress and/or a high level of glucocorticoidsWiki alters certain serotonergic receptors (increases the 5-HT2A receptors in the cerebral cortex and reduces the 5-HT1A receptors in the hippocampus). These same changes have been observed in humans who have committed suicide or suffered from diseases that cause hypersecretion of glucocorticoids.

The continued administration of antidepressants causes changes in the serotonergic receptors that are the opposite of the changes produced by chronic stress. It also reverses the hypersecretion of stress hormones.

Not incidentally, in humans, many glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) (see sidebar) are located in the hypothalamus and the hippocampus, two structures involved in mood control and the ability to experience pleasure. These receptors are sensitive both to the levels of the various corticosteroids in the body and to the length of time that they are active, so their activation mechanisms will have direct impacts on the behavioural response chosen to a given stimulus.

For example, when corticosteroidsWiki circulate at low levels they facilitate, via the MR receptors, the reactions associated with fear (momentary paralysis and turning toward the frightening stimulus). But when corticosteroids circulate at high levels (for example, when the organism is exposed to chronic stress), they instead potentiate inhibition of action, via the GR receptors .

Prolonged chronic stress also seems to alter the response of the MR and GR receptors and to have very harmful effects on people's mental equilibrium, especially when social or family supports are absent. Under these conditions, the glucocorticoid response, which was originally highly adaptive, becomes clearly maladaptive.

Many seriously depressed patients have high blood levels of cortisol, caused by chronic stress.

Over 90% of all computer problems can be traced back to the interface between the keyboard and the chair !

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