Serotonin States and Social Anxiety.

This Neuroscience and Psychiatry article published in JAMA Psychiatry online on June 17, 2015 discusses the role in social anxiety of a novel disrupted regulatory sequence in serotonin neurochemistry resulting from overactive serotonin signaling.

Following factors have motivated interest in identifying a serotonergic basis for social anxiety disorder:
1. Some patients with social anxiety disorder respond exceptionally well to SSRIs.
2. Social anxiety disorder is a frequent precursor to major depressive episodes.
3. Social anxiety disorder is the most common comorbid disorder in patients with anxious depression.

Serotonin synthesis is highly regulated at many levels. Check the figure below demonstrating the role of enzymes, transporters, receptors, oxygen, pteridine cofactor and intracellular calcium in serotonin pathway regulation.





Patient with Social Anxiety Disorder (PET study findings):
- Increased Serotonin Synthesis, and
- Greater number of plasma membrane SERT was found.

So “an overactive presynaptic serotonin system, with increased serotonin synthesis and transporter availability.”

In mice with genetically engineered reductions in SERT resulted in a phenotype characterized by increased anxiety-related (conflict and avoidance) behavior and stress sensitivity, as well as decreased fear extinction and social behavior:
- Increased extracellular serotonin concentrations
- Desensitize 5HT1A autoreceptor function
- Reduced intracellular (recycled) serotonin
- Compensatory increases in serotonin synthesis


Q: HOW TO EXPLAIN THESE TWO FINDINGS NOW?

ANS: Focus on the extracellular serotonin signaling levels.

This article reports that Social Phobia is linked to high levels of Serotonin.