Mood disorders are a manifestation of impaired neuronal pathways and disruption in the synthesis and release of neurotransmitters. Alterations in the limbic system of the brain are involved in the onset of mood disorders. The brainstem of the central nervous system contains serotonergic neurons present in the raphe nuclei. The serotonergic neurons send synaptic fibers to the brain and spinal cord of the central nervous system. Serotonergic fibers innervate almost every neuron in the brain and mediate a number of functions. Antidepressants or selective serotonin reuptake inhibitors (SSRIs) are usually prescribed for individuals suffering from mood disorders and work by increasing serotonin concentrations.
Neural Pathways Of Mood
The limbic system of the brain, including the amygdala, hippocampus, and prefrontal cortex, is associated with the emotions and mood of an individual. Alterations in the limbic system may lead to the occurrence of mood disorders. The limbic system in mood disorders demonstrates a reduction in the number of GABAergic neurons and a decrease in the size of pyramidal neurons. Brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and insulin-like growth factor 1 (IGF1) are important neurotrophic or growth factors that are implicated in mood disorders including depression.
What Is The Source of Serotonin In the Body?
Antidepressant medications are primarily selective serotonin reuptake inhibitors (SSRIs) that promote serotonin neurotransmission. This implies the importance of serotonin in the pathogenesis of mood disorders. Serotonin is produced and released by the raphe nuclei that are found in the midline of the brainstem. The rostral, dorsal, and medial groups of raphe nuclei innervate the brain whereas the caudal group innervates the spinal cord. The serotonergic fibers innervate almost every brain cell.
What Happens When Serotonin Is Deficient In the Body?
Serotonin deficiency or dysfunction has a significant association with behavioral disorders that include anxiety disorders, posttraumatic stress disorder, and attention deficit hyperactivity disorder. Serotonin deficiency may occur due to dietary deficiency of tryptophan or due to enzyme dysfunction that is involved in the synthesis of serotonin.
Natural Sources of 5-HTP
5-HTP or 5-hydroxytryptophan, also called oxitriptan, is a chemical precursor for the synthesis of serotonin. 5-HTP forms the natural component of dietary supplements for the treatment of mood disorders. The natural food sources of 5-HTP include Caesalpinaceae and Griffonia simplicifolia Baill. Commercial preparations of 5-HTP supplements are derived from the extracts of these plant sources. However, 5-HTP is not usually derived from edible and natural food sources. The body converts tryptophan, a dietary amino acid precursor molecule, to 5-HTP which is then used for the synthesis of serotonin. This is an essential amino acid that can be obtained from meats, seeds, fruits, and dairy products.
How Does Body Synthesize 5-HTP From Food?
The essential amino acid tryptophan is converted to 5-HTP, an immediate precursor of the neurotransmitter serotonin, via a rate-limiting enzyme called tryptophan hydroxylase. This enzyme is also called L-tryptophan-5-monooxygenase. The enzyme is present only in those cells that synthesize serotonin. Tryptophan hydroxylase is produced in serotonergic cell bodies that are found in raphe nuclei of the brainstem. Exercise and dietary supplements including omega-3 fatty acids promote the gene expression of tryptophan hydroxylase and enhance the formation of 5-HTP and subsequent production of serotonin in the body.
Serotonin Synthesis From 5-HTP
The conversion of 5-HTP to serotonin is catalyzed by the enzyme known as aromatic L-amino acid decarboxylase (AADC) which is a pyridoxal-5-phosphate-dependent enzyme. Pyridoxine supplementation promotes the rate of production of this enzyme. AADC is only found in serotonergic and catecholaminergic neurons. In catecholaminergic neurons, AADC catalyzes the production of dopamine from DOPA. The enzyme carboxylates DOPA and 5-HTP for the synthesis of dopamine and serotonin respectively. 5-HTP is rapidly decarboxylated to serotonin, hence, only trace amounts of 5-HT are found in the brain tissue.
The serotonergic neurons attribute to the phenomenon of neuroplasticity. This enables the serotonergic neurons to increase the rate of production and release of the neurotransmitter serotonin in response to increased activity of the brain. The production and release of serotonin are proportional to the electric stimulation of these neurons as well as the concentration of calcium ions in the extracellular matrix. Calcium-dependent phosphorylation of tryptophan hydroxylase and changes in the kinetic properties of this enzyme results in increased production of 5-HTP and ultimately serotonin.
How Does Serotonin Improve Mood?
Serotonin plays a significant role in the modulation of mood and cognition. Serotonin receptors are located in the cortex, amygdala, and hippocampus of the brain that are actively involved in memory and learning. Serotonin binds to these receptors and modulates cognitive functions. Serotonin has positive effects on mood regulation, hence, serotonin deficiencies manifest as mood disorders. Tryptophan and subsequently serotonin also have positive effects related to sleep. Tryptophan and serotonin lead to increased subjective sleep and reduces total wakefulness, improving the overall quality of sleep. This eventually leads to improved attention, alertness, and cognition.
Individuals suffering from mood disorders often experience anhedonia, characterized by the failure to feel pleasure and experience the feeling of reward. The subcortical and cortical reward areas of the brain are extensively innervated by the serotonergic neurons that are located in the raphe nuclei of the brainstem. The serotonergic system is involved in both consummatory pleasure and reward anticipation. The involvement of serotonergic reward mechanisms in mood disorders justifies the use of serotonergic drugs in the treatment of these disorders. Serotonin holds significant importance in terms of reward processing as other neurotransmitters including dopamine.
The human body synthesizes 5-HTP and serotonin by consuming a diet rich in an essential amino acid tryptophan. Tryptophan hydroxylase catalyzes the conversion of tryptophan to 5-HTP which is an immediate precursor of serotonin. 5-HTP undergoes carboxylation catalyzed by AADC. These enzymes are found in serotonergic neurons of raphe nuclei in the brainstem. Different areas of the brain that control reward mechanisms, cognition, and emotions express serotonin receptors and are influenced by the fluctuating levels of serotonin. Consuming adequate amounts of tryptophan in diet replenishes the levels of serotonin and modulates the mood, emotions, cognition, and sleep quality of an individual.