Serotonin is an important neurotransmitter that is involved in regulating many functions in the brain including mood, sleep, appetite, and cognition. An imbalance in serotonin levels has been implicated in several different mental illnesses. Specifically, having too little serotonin in the brain is thought to play a role in depression.
What is Serotonin?
Serotonin is a chemical messenger in the brain known as a neurotransmitter. It is synthesized from the amino acid tryptophan and acts to transmit signals between nerve cells or neurons. Serotonin is primarily produced in the raphe nuclei of the brainstem and releases serotonin to other areas of the brain via axons.
When serotonin is released into the synaptic cleft between neurons, it binds to specific serotonin receptors on the post-synaptic neuron. This binding causes changes in the receiving neuron and allows communication between the neurons. After serotonin signaling is completed, the serotonin is taken back up into the pre-synaptic neuron by serotonin transporters. This reuptake removes serotonin from the synapse and allows the signaling process to start again.
Functions of Serotonin
Serotonin is involved in regulating many important bodily functions:
– Mood – Serotonin influences mood and emotions. Higher levels are associated with increased happiness.
– Sleep – Serotonin promotes healthy sleep cycles and patterns.
– Appetite – Serotonin suppresses appetite signals to the brain.
– Learning and memory – Serotonin modulates memory formation and storage.
– Behavioral inhibition – Serotonin signaling facilitates impulse control.
– Body temperature regulation – Serotonin helps maintain normal body temperature.
– Nausea – Serotonin receptors mediate nausea and vomiting signals.
– Sexual function – Serotonin affects libido and sexual arousal.
– Cardiovascular function – Serotonin regulates vasoconstriction and heart rate.
– Muscle contraction – Serotonin stimulates muscle contractions.
– Endocrine system – Serotonin interacts with the pituitary gland and hormones.
Serotonin and Mental Illness
Given its widespread influence on neurological functions, improper serotonin signaling is thought contribute to several different mental illnesses including:
– Depression
– Anxiety disorders
– Obsessive compulsive disorder
– Bipolar disorder
– Schizophrenia
– Eating disorders
– Chronic fatigue syndrome
– Fibromyalgia
– Insomnia
– Migraines
Of these conditions, depression has the strongest established link with low serotonin levels.
The Serotonin Theory of Depression
The serotonin theory of depression posits that one underlying cause of major depressive disorder is insufficient serotonin neurotransmission in the brain. This theory is based on several key pieces of evidence:
– Drugs like selective serotonin reuptake inhibitors (SSRIs) that increase serotonin levels are effective antidepressants.
– Depleted tryptophan levels, which leads to lower serotonin synthesis, can cause depressive symptoms.
– PET imaging studies show reduced 5-HT1A receptor binding potential in patients with major depression, indicating fewer functioning serotonin receptors.
– Post-mortem analyses demonstrate fewer serotonin transporter sites in the brains of some depressed individuals.
– Cerebrospinal fluid levels of a serotonin metabolite are reduced in some people with depression.
Together this data provides strong support for the idea that inadequate serotonin signaling underlies at least some cases of major depression. However, other factors like genetics, environmental stressors, and neuronal plasticity are also likely involved.
Symptoms of Low Serotonin Depression
Some symptoms and signs that are particularly associated with low serotonin levels in depression include:
– Loss of interest in activities or hobbies
– Fatigue and low energy
– Difficulty feeling pleasure (anhedonia)
– Social isolation or withdrawal
– Feelings of worthlessness or guilt
– Suicidal thoughts
– Insomnia or hypersomnia
– Anxiety
– Irritability and anger
– Reduced appetite and weight loss
– Cognitive dysfunction and poor concentration
– Physical pains like headaches, cramps or digestive issues
Causes of Low Serotonin in Depression
There are several potential causes contributing to inadequate serotonin signaling in major depression:
– Decreased serotonin synthesis – This could be due to reduced tryptophan availability or impaired enzyme function involved in serotonin synthesis like tryptophan hydroxylase.
– Fewer serotonin receptors – Lower expression of serotonin receptors, like the 5-HT1A and 5-HT2A receptors, reduces signaling capacity.
– Excess serotonin transporters – Higher density of serotonin transporters enhances reuptake and lowers serotonin levels in synapses.
– Dysfunctional serotonin receptors – Errors in serotonin receptor structure can prevent signaling even when serotonin is released.
– Increased monoamine oxidase levels – Higher activity of this enzyme enhances serotonin breakdown.
– Problems with serotonin release – Disruptions in neuron firing patterns or vesicle release can lead to less serotonin release.
– Chronic inflammation – Inflammatory cytokines may impair serotonin synthesis.
– Genetic factors – Variations in genes impacting serotonin signaling, like SLC6A4, HTR1A, and TPH2, can increase depression risk.
Treatment for Low Serotonin Depression
Boosting inadequate serotonin neurotransmission is a key goal in the treatment of major depressive disorder. Common medical treatments targeting the serotonin system include:
Selective serotonin reuptake inhibitors (SSRIs)
SSRIs like fluoxetine (Prozac), sertraline (Zoloft), citalopram (Celexa), and escitalopram (Lexapro) block the serotonin transporter which normally reuptakes serotonin. This leaves more serotonin available in the synaptic cleft to bind receptors and prolongs the serotonin signaling effects. SSRIs can raise serotonin levels by up to 50-150%.
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
SNRIs like venlafaxine (Effexor) and duloxetine (Cymbalta) block both serotonin and norepinephrine transporters. This boosts signaling of both neurotransmitters. They may be preferable when depression involves pain or fatigue symptoms.
Tricyclic antidepressants (TCAs)
TCAs like imipramine and amitriptyline prevent serotonin and norepinephrine reuptake, similar to SNRIs. However, they generally have more side effects.
Monoamine oxidase inhibitors (MAOIs)
MAOIs like phenelzine (Nardil) and tranylcypromine (Parnate) block monoamine oxidase enzymes from breaking down serotonin, norepinephrine, and dopamine. This indirectly increases neurotransmitter levels.
Other medications
– Tryptophan supplements to increase serotonin synthesis.
– 5-HT1A receptor agonists like buspirone directly activate serotonin receptors.
– Mirtazapine enhances serotonin and norepinephrine release.
– Lithium may boost serotonin neurotransmission.
– Ketamine promotes synapse formation and improves signaling.
Psychotherapy
Talk therapy techniques like cognitive behavioral therapy (CBT) help manage negative thought patterns and behaviors that contribute to low serotonin depression.
Light Therapy
Daily exposure to bright artificial light can help stabilize serotonin levels and supplement low sunlight exposure in winter months.
Exercise
Regular aerobic exercise elevates tryptophan levels and stimulates serotonin synthesis and release.
Healthy Diet
Eating foods high in tryptophan like turkey, eggs, cheese and nuts supports serotonin production. A balanced diet also provides vitamins and minerals important for neurotransmitter synthesis.
Conclusion
In summary, major depression with low serotonin neurotransmission tends to involve symptoms like loss of pleasure, low energy, and feelings of worthlessness. Contributing factors can include impaired serotonin production, release, receptor binding, and excess transporter reuptake activity. Treatment focuses on boosting serotonin signaling through medications like SSRIs, psychotherapy, light therapy, exercise, and nutrition. While low serotonin plays a significant role, depression is a complex and multifactorial condition. Ongoing research continues to uncover new mechanisms and possibilities for more effective treatment.