What is the role of serotonin in the body?

The Role of Serotonin in the Body

Serotonin is a multifunctional neurotransmitter and hormone that regulates numerous critical physiological processes throughout the body, including mood, cognition, sleep, gastrointestinal function, cardiovascular regulation, and immune responses. 1

Central Nervous System Functions

Serotonin serves as a key neurotransmitter in the brain, where it:

• Regulates mood and emotional states - Plays a crucial role in depression, anxiety, and stress responses 2
• Controls sleep-wake cycles - Influences both sleep onset and maintenance 3
• Modulates cognitive functions - Affects learning, memory, and decision-making
• Regulates appetite and feeding behaviors - Influences satiety signals 2
• Mediates pain perception - Acts as a modulator in pain pathways

The serotonergic system in the brain involves neurons originating primarily in the raphe nuclei of the brainstem, with projections throughout the central nervous system. Serotonin exerts its effects through at least 15 different receptor subtypes, allowing for diverse and sometimes opposing physiological responses 4.

Peripheral Functions

Despite its well-known role in the brain, approximately 90% of the body's serotonin is produced in the periphery, primarily by enterochromaffin cells in the gastrointestinal tract 3. Peripheral serotonin:

• Regulates gastrointestinal motility and secretion - Controls peristalsis and fluid balance in the gut 5
• Modulates visceral sensitivity - Influences pain perception in the digestive system 5
• Affects cardiovascular function - Regulates blood pressure, heart rate, and platelet aggregation 1
• Influences immune and inflammatory responses - Modulates immune cell function and inflammatory pathways 5
• Contributes to metabolic regulation - Affects glucose homeostasis and adiposity 3

Molecular Mechanisms

Serotonin is synthesized from the essential amino acid tryptophan through a two-step process:

1. Conversion of tryptophan to 5-hydroxytryptophan (5-HTP) by the rate-limiting enzyme tryptophan hydroxylase (TPH)
2. Decarboxylation of 5-HTP to serotonin (5-HT) by aromatic L-amino acid decarboxylase

Two distinct isoforms of TPH exist:

• TPH1 - Primarily expressed in enterochromaffin cells and other peripheral tissues 3
• TPH2 - Expressed in neurons of the raphe nuclei and enteric nervous system 3

After release, serotonin's action is terminated by reuptake via the serotonin transporter (5-HTT), which removes serotonin from the synaptic cleft and determines the magnitude and duration of serotonergic signaling 6.

Role in Pathophysiology

Dysregulation of serotonergic signaling is implicated in numerous disorders:

• Psychiatric disorders - Depression, anxiety, OCD, and other mood disorders 6
• Gastrointestinal disorders - Irritable bowel syndrome, inflammatory bowel disease 5
• Cardiovascular conditions - Hypertension, heart disease 1
• Metabolic disorders - Obesity, diabetes 3

Serotonin in Psychiatric Disorders

In OCD, selective serotonin reuptake inhibitors (SSRIs) are first-line treatments, suggesting serotonergic dysfunction plays a role in the disorder. However, evidence for a primary serotonin deficit in OCD is surprisingly limited 6. Alterations in serotonin and its metabolites in cerebrospinal fluid have been reported in some studies, though findings are inconsistent 6.

Genetic studies have identified associations between variants in serotonergic genes (including the serotonin transporter) and OCD, and altered serotonin transporter binding in areas such as the midbrain has been observed in some studies 6.

Serotonin Syndrome

A potentially life-threatening condition called serotonin syndrome can occur when excessive serotonergic activity develops, typically due to medication interactions. Key features include:

• Neuromuscular abnormalities (clonus, hyperreflexia, rigidity)
• Autonomic instability (hyperthermia, tachycardia, diaphoresis)
• Mental status changes (agitation, confusion) 7

Treatment involves discontinuation of serotonergic agents, supportive care, and in moderate to severe cases, administration of serotonin antagonists like cyproheptadine 7.

Emerging Research

Recent research has revealed additional roles for serotonin:

• Gut-brain axis communication - Serotonin mediates bidirectional communication between the gut and brain 3
• Interaction with gut microbiota - Gut bacteria influence serotonin production and signaling 3
• Non-receptor mediated actions - Serotonin may regulate some processes through receptor-independent mechanisms, including transglutaminase-dependent covalent linkage to cellular proteins 1

Clinical Implications

Understanding serotonin's diverse roles has led to the development of numerous therapeutic agents targeting serotonergic systems:

• SSRIs - Used in depression, anxiety, OCD, and other psychiatric disorders 8
• Serotonin receptor agonists/antagonists - Used for various conditions including migraine, nausea, and irritable bowel syndrome 5

When prescribing serotonergic medications, clinicians must be vigilant about potential drug interactions that could lead to serotonin syndrome, particularly when combining multiple serotonergic agents 7, 8.