In what a press release from Sweden’s Uppsala University called a “major leap forward” in understanding of mental disorders, a study in JAMA Psychiatry reported that, “Individuals with social phobia make too much serotonin. The more serotonin they produce, the more anxious they are in social situations.”
“Previous studies have led researchers to believe that individuals with social anxiety disorder/social phobia have too low levels of the neurotransmitter serotonin,” explained the press release about the significance of this new study. Indeed, some psychiatric researchers are today trying to distance themselves from older, unproven claims that anxiety and depression were linked to low levels of the neurotransmitter serotonin in the brain; however, the Uppsala researchers said that they’ve discovered that the real problem is that people with social anxiety disorders (SAD) produce too much serotonin.
According to the press release, the Uppsala University study involved using “a so-called PET camera and a special tracer to measure chemical signal transmission by serotonin in the brain.” The study itself explained that the researchers actually measured proxies; namely, “The influx rate of [11C]5-HTP as a measure of serotonin synthesis rate capacity and [11C]DASB binding potential as an index of serotonin transporter availability.”
The researchers then determined the mean of each of the groups, and based on that stated that they identified increased levels of “serotonin synthesis” in the people who’d been diagnosed with social anxiety disorder compared to healthy controls, as exhibited in the accompanying figure below.
“Serotonin can increase anxiety and not decrease it as was previously often assumed,” said lead author Andreas Frick. The press release did not mention that all of the brain scans were done while the participants were in resting states and were not reported to have been actively experiencing any anxiety.
The examination of serotonin synthesis rate capacity involved 18 people with SAD and 18 controls. The examination of serotonin transporter availability involved 26 people with SAD and the same control group. There was no mention by the authors in their limitations section that the small sample size might limit the strength of their conclusions. And though the study excluded participants with current use or previous histories of “long-term” use of Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants, presumably because SSRIs can fundamentally alter the brain’s serotonin-related functions, the study’s limitations did not mention that about 16% of the participants with SAD had previously taken SSRIs. However, the authors did note that their measurements may not have actually reflected serotonin levels in people’s brains. “Among the study limitations, we could not correlate [11C]5-HTP and [11C]DASB PET measures in a meaningful way because these tracers were collected in different SAD cohorts. This lack of correlation limits the inferences that can be made of the interaction between serotonin synthesis and reuptake. Moreover, some issues regarding the capacity of [11C]5-HTP to measure the serotonin synthesis rate have been raised. For example, since the decarboxylation of 5-HTP to serotonin involves the enzyme amino acid decarboxylase, which is found not only in serotonergic but also in dopaminergic and noradrenergic neurons, the [11C]5-HTP tracer trapping may reflect amino acid decarboxylase activity.”
And while lead author Andreas Frick, a doctoral psychology student, was quoted in the press release stating that the study had discovered that, “Serotonin can increase anxiety,” in the study itself the authors stated that any potential “causal” relationships between serotonin and anxiety were not actually examined and were a matter about which they could only “speculate.”
Frick A, Åhs F, Engman J, and et al. “Serotonin Synthesis and Reuptake in Social Anxiety Disorder: A Positron Emission Tomography Study.” JAMA Psychiatry, June 17, 2015. doi:10.1001/jamapsychiatry.2015.0125. (Full text)
Individuals with social phobia have too much serotonin — not too little (Uppsala University press release on ScienceDaily, June 17, 2015)