Serotonin And Depression

Overview

Serotonin has a crucial effect on human mood. As a result, the media always encourages eating foods that are rich in them. These serotonin-rich foods, such as avocados and bananas, are really useful for their nutritive value. However, obtaining the benefits of serotonin does not seem to be as simple. This owes to its side effects, toxicity such as the serotonin syndrome, and its interaction with other factors such as medications or nutrition may lead to different psychiatric conditions due to the alteration in serotonin levels as shown in the image below.

About serotonin

Serotonin, also known as 5` hydroxytryptamine,  is a chemical derivative of tryptophan amino acid. It is formed in the body by specific types of gut cells and can cause the coming together of platelets and narrowing of the blood vessel.¹ It is worth noting that serotonin carries different regulatory functions in the brain. One of which is the balance between hunger and food intake according to energy consumption. Consequently, the disturbance in serotonin in brain cells may be accompanied by weight gain.² Serotonin is broken down into end metabolites by mono-amine oxidases in addition to its ability to form melatonin that controls sleep rhythm.

Foods rich in serotonin

Serotonin can be easily taken through several types of food such as

• Dairy products³
  • Milk contains alpha-lactalbumin which has a high level of the amino acid tryptophan amino acid which can raise serotonin as one of its derivatives
  • Poultry meat such as chicken and turkey, especially cage-free, have high serotonin levels due to the variable exposure to daylight⁴

• Some cultivated seeds such as chickpeas, however, corn seeds may have an enhanced tryptophan and serotonin content on boiling with alkali.
• Salmon, which includes omega-3 fatty acids, raises the level of serotonin in the body.
• High glycaemic foods may increase the availability of tryptophan due to a shift in the body's dependence on energy expenditure on carbohydrates.⁵
• Compounds with polyphenols, such as honey, may antagonize inflammatory conditions, enhancing the action of serotonin.Bananas are believed to be a good source of tryptophan and serotonin, whereas eating three bananas per day may enhance the body's serotonin level.⁶

Diseases related to Serotonin

Since the receptors of serotonin are distributed in areas such as the brain or GIT, Serotonin is related to the pathology of several diseases across different body systems, either due to local or distant action, as follows:

• Mental disorders such as obsessive compulsion, anxiety, phobias, panic attacks, aggression and depression⁷
• Gastrointestinal disturbances such as inflammatory bowel disorders, acid reflux,  and chronic constipation⁸
• Respiratory disorders such as chronic obstructive pulmonary disease (COPD) and sleep apnea show a relation to serotonin levels in the human body⁹
• Serotonin shows an impact on the deterioration of kidney functions, as a part of the urinary system¹⁰
• Serotonin may cause heart diseases, especially in the valves¹¹
• Disturbed serotonin metabolism may negatively affect skeletal muscle diseases such as fibromyalgia¹²

About depression

Depression is the most common presenting psychiatric illness, affecting more than 264 million persons worldwide. It is characterized by a lack of interest in daily life activities¹³ Although sadness is a common association, low mood is not usually the case. Depression has a high recurrence rate and commonly accompanies chronic health problems such as diabetes mellitus and hypertension. Depression is highly linked to suicidal thoughts, even under regular medical supervision. This arises from the feeling of low-self worthing¹⁴

 According to the NHS website, depression has several types as follows:¹⁵

1. Clinical depression, which varies from mild to severe, may have the following symptoms:
   • Sensation of unhappiness
   • Desire of self-execution or harm
   • Less sleep
   • Fatigue.
   • Pain and body aches
   • Fearful ideas

2. Psychotic depression may have similar symptoms to clinical depression in addition to the  following psychosis symptoms:
   • Delusions
   • Hallucinations

3. Pregnancy-related depression 
   • It affects the biological mother of the child
   • It occurs either during pregnancy or within the first year after labour
   • It affects one in every 10 persons
   • It is characterized by tearful, sad or anxious characteristics

4. Depression of young people and children
   • It can be caused by bullying, family difficulties, or sexual/physical abuse
   • It is characterized by an irritable personality
   • It can be accompanied by a lack of confidence
   • Social isolation can be observed in such cases
   • Malnourishment is a sign in addition to any of the common depressive symptoms

5. Major depressive illness is characterized by the following:¹⁶

6. Bipolar disorders¹⁸ 
   • It includes a swinging mood between depression and mania, however, depression seems to be longer-lasting than Mania. Depression in bipolar disorders is more related to type II than type I, unlike mania. This is seen in the overlap of the genetic factors between major depressive illness and type II bipolar disorders
   • Consequently, antidepressants constitute a part of its treatment, besides the antipsychotics, despite their short-term effect in proportion to the course of the depressive component of the disease

Serotonin and depression: the link in between

Serotonin was believed to have a link to depression within the context of some single-caused theories. As a derivative of tryptophan, serotonin has recently been associated with depression in people with tryptophan deficiency. However, this involved healthy people with a positive family and past history rather than other healthy populations.¹⁹

Several studies at University College London(UCL)  tried to diminish the role of serotonin levels alone in the progression of depression, while other factors play a role in such disorders. Moreover, several biomarker-based studies suggest tryptophan deficiency to be a potential risk factor for depression in case of a preceding inflammatory condition within the human body²⁰.  This may owe to the additional tryptophan catabolism in case of cytokine release within chronic inflammatory disorders, suggesting that not only serotonin but also the antioxidants in food would antagonize depression²¹. This effect is evident in severe cases of depression, explaining the rapid response of these cases to the therapy with selective serotonin reuptake inhibitors (SSRIs).¹⁹

Serotonin is believed to show its role in depression through two receptors, receptor 1A and 2A. On one hand, the mechanism of activation for receptor 2A reveals a tolerance to stress in a passive pattern, once bound to serotonin. On the other hand, the mechanism of receptor 2A stimulation suggests an active role in encountering stress through neuronal plasticity.

Hallucinogens (vasoactive psychotics)  enhance the latter mechanism through serotonin 2A receptor stimulation, while SSRIs potentiate the former mechanism of serotonin through its 2A receptors in the treatment of depression.²²

What does serotonin do

Molecular psychiatric studies have been focusing on the serotonin activity in the brain centres of emotion such as the amygdala and hippocampus.²³ Subsequently, the use of SSRIs would enhance a positive shift of the emotional initiatives in the memory centre, meaning that the serotonin level would be more greatly produced after SSRI intake, combined with any positive emotional stimulation. Thus, serotonin is indirectly linked to mood through emotional affection, where emotions are short-term and mood is long-term.

The memory centres store the repetitively positive shift of the emotional initiatives after the usage of SSRIs. Later these centres integrate these positive emotions into a mood effect. The studies show the resulting improvement in mood in either healthy or depressed persons.²⁴ The computational studies consider this positive mood modification as a re-learning process. This may be explained by the effect of serotonin on restoring the cell function and integrity in a process called neuroplasticity.²⁵

Medications that interfere with serotonin metabolism

Serotonin levels and activity have been widely affected by interactions with some other medications. Among those are antidepressant drugs and non-antidepressant ones as following:²⁶

Psychiatric medications including antidepressants

• Selective serotonin reuptake inhibitors (SSRIs), such as Celexa (citalopram), Lexapro(escitalopram), Luvox(fluvoxamine), Paxil(paroxetine), Prozac (fluoxetine), Trintellix (vortioxetine), Viibryd (vilazodone) and Zoloft (sertraline), inhibit the reuptake of serotonin for more availability of a longer action

• Monoamine oxidase inhibitors, such as Nardil (phenelzine), Parnate (tranylcypromine), Marplan (isocarboxazid) and Emsam (selegiline), also increase the level of serotonin by inhibiting degradation. However, they may exacerbate the action of serotonin on taking food or drugs that affect serotonin levels. Consequently, they are not the first choice for depression therapy

• Tricyclic antidepressants, such as Elavil(amitriptyline), Tofranil (imipramine), Sinequan (doxepin), and Anafranil (clomipramine), increase the serotonin levels on usage in the treatment of depression

• Triptans, such as Amerge(naratriptan), Axert(almotriptan), Frova(frovatriptan), Imitrex (sumatriptan), Relpax (eletriptan), Maxalt and Maxalt-MLT (rizatriptan), Zomig and Zomig ZMT (zolmitriptan), act on serotonin receptors, altering the actions of serotonin

• Some psychotic drugs, such as buspirone and lithium, may affect the level of neurotransmitters like serotonin

Non-psychiatric medications

• Analgesics, such as codeine, fentanyl and tramadol, can interfere with body levels of serotonin.
• Recreational addictive drugs, such as Amphetamine, cocaine and LCD, can interfere with the serotonin levels in the body

• Antibiotics, such as Zyvox (linezolid) and Ranvir (ritonavir), are interacting with serotonin in the human body

What is serotonin syndrome?

Serotonin syndrome is a result of too much available serotonin in the body. Due to this, there is a change in the mental state of an individual due to the over-excitation of peripheral nerves. It can result from tumour secretions, an overdose of SSRIs,  the use of 2 SSRIs together, or the start of one SSRI after an already established serotonin-level preserving drugs.

Serotonin syndrome may cause the following:²⁷

1. Excitation of the brain centres, resulting in
   • Anxiety
   • Agitation
   • Confusion

2. Excitation of the neuromuscular receptors, causing
   • Repeated muscle twitching
   • Exaggerated reflex actions
   • Rigid muscle
   • Tremors ( shivering)

3. Excitation of the involuntary nervous system, resulting in
   • Increase in heart rate
   • Increased sweating
   • Increased blood pressure
   • Raised body temperature
   • Vomiting and diarrhoea
   • Difficulty in respiration

Serotonin syndrome is managed primarily by close monitoring and follow-up of the concentration of the serotonin-level preserving medications in the body to avoid these disastrous consequences. In addition, life support for the symptoms can help as oxygen therapy, giving sedatives such as benzodiazepines or even the usage of serotonin antagonists such as cyproheptadine.²⁸

Summary

Serotonin is similar to any chemical substance, having satisfactory benefits as well as potential risks. While different generic categories of serotonin-preserving medications are released, their role in depression is getting clearer towards management. However, more concerns arise about how far its pharmacology would contribute to other disorders. It would be better to promote serotonin level elevation in the body, naturally rather than chemically. This would need more awareness campaigns about the importance of a healthy lifestyle by either mass media or communities.