Those with social anxiety disorder are reported to suffer from debilitating, uncontrollable anxiety in social situations. This condition, also known as “social phobia” can lead to an intense fear of public speaking, forming friendships, maintaining social bonds, and even getting a job. Individuals living with social anxiety often isolate themselves, suffer from low self-esteem, and feel out of place in society.
Since the inception of antidepressants in the 1950s, it was thought that low serotonin was the root cause of social anxiety disorder. Researchers speculated that suboptimal production of serotonin was involved in causing social anxiety due to the fact that those treated with SSRIs (selective-serotonin reuptake inhibitors) reported increased levels of relaxation. In double-blind, placebo-controlled studies, many SSRIs have been proven effective for treating social anxiety disorder.
However, just because a drug is effective for treating a psychological disorder doesn’t automatically mean that it’s targeting the root cause. A recent study suggests that not only are SSRIs unlikely to be targeting the root cause of social anxiety, but they may actually be making it worse. The new finding from this study suggests that social anxiety is actually caused by too much serotonin – not too little.
Too Much Serotonin Causes Social Anxiety Disorder
Most research suggests that people with social anxiety disorder have brains that aren’t able to produce enough serotonin. A study conducted by Uppsala University analyzed serotonin synthesis and reuptake in the brains of people with social anxiety. Results from the study were published in JAMA Psychiatry.
Basis for the research
The researchers noted that social anxiety disorder reduces quality of life for those with the condition and is a major societal burden. They noted that the neural correlates associated with social anxiety were not fully understood, but serotonin (5-HT) likely played a role. They highlighted the fact that only a few studies have taken advantage of using molecular neuroimaging to examine serotonin dysfunction in social anxiety disorder.
In the past, various PET scans noted increased numbers of serotonin transporters in the thalamus among those with social anxiety, whereas those without social anxiety didn’t have this increase. Other PET scans have demonstrated that those with social anxiety have a notable reduction in 5-HT1A receptor binding. Other brain scans have documented increased amygdala reactivity among individuals with social anxiety.
Due to the fact that previous findings suggested a decrease in binding of 5-HT autoreceptors, researchers speculated that there may actually be enhanced production of serotonin among those with social anxiety. To get a better grasp on serotonergic activity in the brains of those with social anxiety, researchers decided to track presynaptic serotonin activity (synthesis and reuptake) with neuroimaging.
How the study worked: PET Scans
For the study, researchers recruited 18 individuals with social anxiety disorder (9 men and 9 women and 18 healthy individuals without psychiatric diagnoses. All of the participants were of similar age, and brain activity was tracked with PET scans (positron emission technology). Data was collected over the course of approximately 10 years (from March 2002 to March 2012).
PET scans allow researchers to track brain activity via the usage of a radioactive tracer. The tracers are injected into a vein within your arm, absorbed by your body, and ultimately show up in the brain. In the case of this study, the PET scans were conducted using a 32-ring high-resolution scanner.
To track the brain activity of the participants, researchers used radioactive tracers [11C]5-HTP and [11C]DASB that were injected into the arm of each participant. The tracers were designed specifically to measure the rate capacity of serotonin synthesis ([11C]-5-HTP) as well as the binding potential ([11C]DASB). The PET neuroimaging scans allowed researchers to understand functional differences between the brains of those with social anxiety compared to those without it.
Following the collection of PET scan data, researchers analyzed the data from March 2013 to August 2014. Numerous calculations had to be made to determine serotonin synthesis rate and binding potential. They honed in specifically on regions of particular interest including the: anterior cingulate cortex, amygdala, caudate nucleus, hippocampus, insula cortex, putamen, raphe nuclei, and the thalamus.
Results of the study
Researchers then calculated differences between the group of individuals with social anxiety based on regional analyses of the PET scans. They then determine differences in serotonin synthesis, serotonin transporter availability, and further examined differences between males and females.
- Serotonin synthesis: Statistical analyses of the PET scans revealed an increased rate of serotonin synthesis among those with social anxiety compared to the controls. This increased synthesis was noted as occurring in the following regions: amygdala, brainstem, caudate nucleus, dorsal anterior cingulate cortex, hippocampus, and putamen. Specifically, the severity of social anxiety was in direct correlation with serotonin synthesis in the right amygdala.
- Serotonin transporter availability: It was noted that availability of serotonin transporters were significantly greater among those with social anxiety compared to healthy controls. Increased availability was specifically noted in the: amygdala, brainstem, caudate nucleus, insula, putamen, and thalamus. The severity of social anxiety symptoms was most related to serotonin transporter availability in the left dorsal anterior cingulate cortex (ACC).
- Women vs. Men: Additional analyses revealed some differences between females and males. Females had a reduced rate of serotonin synthesis, but higher serotonin transporter availability compared to men. Increases in serotonin synthesis and transporter availability were greater among individuals with social anxiety compared to both females and males.
Conclusions from the study
This is the very first neuroimaging study to analyze serotonin synthesis among individuals with social anxiety disorder. In addition, it’s one of a select few studies to use PET scans to document increased serotonin transporter binding in the thalamus region of those with social anxiety. The findings from the study in regards to serotonin transporter binding are congruent with previous data.
Researchers noted that those with social anxiety disorder tend to have significantly greater rates of serotonin synthesis in the amygdala. The greater the rate of synthesis in the amygdala, the more severe an individual’s social anxiety symptoms. They speculate that high serotonin levels results in increased amygdala reactivity, ultimately causing anxiety.
The synthesis findings from this study are consistent with preexisting data from animal studies. In animals, the chemical para-chlorophenylalanine can be administered to inhibit serotonin synthesis, resulting in low serotonin or serotonin depletion. This tends to reduce levels of anxiety, whereas administration of an SSRI actually increases their anxiety.
Based on the array of data collected and analyzed by researchers, it seems as though the more serotonin you have in your amygdala and anterior cingulate cortex (ACC), the greater the severity of your social anxiety symptoms. These findings contradict older hypotheses of reduced serotonin synthesis being the culprit for social anxiety.
- Source: http://archpsyc.jamanetwork.com/article.aspx?articleid=2319711
Does this mean that SSRIs don’t work for social anxiety?
Okay, so you’ve taken an SSRI or another antidepressant for your social anxiety, does this study prove that they don’t work? Not at all – they do work for many people. SSRIs and other medications are considered proven, clinically effective treatments for social anxiety. These are drugs that have been extensively studied and are regarded as first-line treatment options for those with social phobia.
This does suggest that individuals with social anxiety who don’t respond well to SSRIs or feel even more socially anxious may want to consider trying a different class of medications; possibly even one that reduces serotonin. There is clear evidence that heightened levels of serotonin can exacerbate social anxiety in animals, as well as some people with social anxiety. That said, the study in no way suggests that SSRIs are ineffective.
Why SSRIs are effective for some people…
The reason that SSRIs are effective as a first-line treatment for social anxiety is due to the fact that they can reduce excessive amygdala reactivity. In the study, researchers noted that the high serotonin levels in the amygdala makes it more reactive. Many of these medications have mechanisms by which they tone down the amygdala reactivity and anxiety is alleviated.
They also trigger a cascade of other neurophysiological changes that may contribute to their efficacy. For example, SSRIs are also known to restore prefrontal cortex response to emotional challenges, and alter blood flow in the insula and anterior cingulate cortex (ACC). The fact that SSRIs enhance overall serotonergic neurotransmission and elicit other neurochemical changes likely contributes to their efficacy in treating social anxiety disorder.
Authors of the aforementioned study note that increased serotonin availability as a result of SSRIs may reduce social anxiety. Therefore it is relatively unclear as to whether social anxiety should be considered to stem from “overactivity” or “underactivity” of serotonergic processes.
Potential problems with this study…
It seems as all the popular science blogs have taken the findings from this study and sent the internet into a frenzy. Your average person who reads any of these articles may think that they’ve been wrongfully duped into thinking that social anxiety was associated with low serotonin. In reality, this study is not flawless and should not automatically be taken as neuroscience gospel.
- Small-scale: The study compared the brains of 18 individuals with social anxiety to 18 individuals without any psychiatric conditions. This should be regarded as a very small study, and prone to error. There is a need for follow-up research with a significantly larger sample size than 18.
- First-study: It was the first study to use neuroimaging to analyze serotonin synthesis. Since it was the first study, it is unknown how this will compare to other future findings with similar methodologies. More research will need to be conducted to confirm this preliminary evidence.
- Big picture: The researchers sought out to analyze serotonin synthesis and 5-HT transporter availability among those with social anxiety. While these efforts should be applauded, they do not show a big picture of what’s actually occurring. Synthesis of serotonin and 5-HT transporter availability are two (possibly infinitesimal) factors in the “bigger picture” of social anxiety disorder.
- Potential limitations: Authors of the study noted that they could not correlate the tracers of serotonin synthesis and 5-HT transporter availability in a meaningful way due to the fact that they were collected in different individuals with social anxiety disorder. This means it’s difficult to draw conclusions by simply analyzing cumulative similarities and differences of brain scans.
- Radioactive tracers: The [11C]-5-HTP radioactive tracer that was used to analyze serotonin synthesis rates in PET scans may be problematic. Researchers noted that this radioactive tracer may have also been measuring dopaminergic and noradrenergic activity. Although this is unlikely, it is still important to avoid assuming that the radioactive tracers were without problem.
Would reducing serotonin levels help with social anxiety?
Many people may be tempted to flush their SSRIs down the toilet after reading this study (damaging the ecosystem). If you aren’t getting any relief from serotonergic antidepressants for the treatment of your social anxiety and/or they are making it even more intense, you may want to consider some alternative options. I’ve compiled a hierarchy of anxiety treatments based on scientific research and my personal experience taking them.
If you think that the results of the study are valid, you may want to reduce rate of serotonin synthesis in specific regions and decrease availability of serotonin transporters in other regions. Since it will be difficult to specifically target every region mentioned in the study with a compound that mitigates the serotonergic correlates of social anxiety, you may want to simply test something that reduces serotonin.
Some people may want to conduct an experiment biohacking their mental health by testing out an agent that may reduce serotonin. Certain supplements like BCAAs (branched-chain amino acids) have been noted to reduce serotonin synthesis in rodents – whether the same effect is achieved in humans remains unknown. Other pharmaceuticals may elicit a more pronounced effect of serotonin reduction.
If an agent that reduces your serotonin helps with your social anxiety, you may have successfully corrected an aspect of your neurochemistry that was dysfunctional. Keep in mind that reducing serotonin levels or attempting to do so may result in a cascade of other changes – some of which may be unfavorable.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23904096
Social anxiety disorder is more complicated than “serotonin”…
Serotonin is the most heavily spammed neurotransmitter in the press. It’s the one everyone and their mother knows about or has heard about. People get convinced by brilliant advertising that their brain isn’t making enough serotonin, and that’s why they have a mental disorder or brain dysfunction. While serotonergic dysfunction may play a role in the pathology of certain mental illnesses, to suggest that social anxiety disorder – or any condition stems from just one neurotransmitter is bogus.
Your body and brain are complex systems in that they respond to environmental stimuli, nutrition, and genetic inputs. The genetic underpinnings of social anxiety disorder remain unknown. It is most likely that various genes are responsible for triggering these alterations in serotonin synthesis and transporter levels.
These genetic inputs also likely elicit additional neurophysiological abnormalities (other than serotonin) that contribute to social anxiety. Even if a drug were devised to change the serotonergic synthesis and transporter densities to match the brains of healthy controls, this would merely be acting as a patch. Without correcting the root of the problem via gene therapy, all efforts (including bionic brain implants) will nothing more than a “patch.”
At this point though, it is likely that “better” patches can be developed. It is also important to consider the fact that there may be significant individual variation in regards to the pathology of social anxiety disorder. Neuroanatomical, neurotransmitter, genetic, epigenetic, nutritional, and social influences may interact to cause an individual to feel socially anxious. This is why I recommend individual assessments (including brain scans) to improve psychiatric treatment outcomes.
My initial suspicion that too much serotonin could cause social anxiety…
In no way does the aforementioned study prove that too much serotonin causes social anxiety. And in no way am I suggesting that too much serotonin is the culprit for everyone with social anxiety. In the past, I actually experienced significant relief from an SSRI drug to help combat social anxiety. The entire time I was on the drug, I felt as if I was chemically-enhanced to the point of being “high.”
Paxil and “feeling high”
The pleasurable feeling associated with using Paxil CR at 12.5 mg was significant enough to help me make friends, engage in social events, and become one of the most popular kids at my school. However, eventually the drug would stop working. As I doubled the dosage of Paxil CR to 25 mg – I became more anxious and felt worse; at this point my serotonin level was likely too high to function as a teenager.
I tried other SSRIs and SNRIs thinking that they would be a “magic bullet” for my social anxiety just like Paxil was initially. Not only did NONE of these drugs improve my anxiety, but nearly every one exacerbated it. They increased my anxiety so much, that I ended up needing to take a Xanax XR just to function throughout the day. Wasn’t I supposed to be getting some relief from the SSRI? Unfortunately I got none.
Discontinuation of SSRIs
During my initial Paxil withdrawal, I experienced high stress and became more stressed than ever. As I played antidepressant roulette, switching to other drugs, I finally decided that these drugs were making me feel significantly worse than better and that I would rather suffer without them, than further spam my brain with exogenous chemicals. The combination of Cymbalta withdrawal, a fear-inducing medical misdiagnosis, and a traumatic experience – I suffered a nervous breakdown.
As I’ve noted in a previous article, the nervous breakdown resulted in severe depression and anxiety for nearly 8 months. I’m still not sure how I managed to live through it, but I did. As my adrenaline levels continued to increase, I suspect that serotoninergic processing was altered. Although my epinephrine increase may have had a psychostimulating effect to offset depression, it may have also modified serotonergic function to offset social anxiety.
Studies have documented that PTSD decreases serotonin transporter availability in the amygdala – this is opposite to the finding among individuals with social anxiety. In theory, I may have “traded” in my social anxiety for PTSD. It is likely more complex than the simplistic interpretation I’ve made regarding serotonin, but to suggest that altered serotonin wasn’t responsible is relatively short-sighted.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21855859
My theory: Traumatic stress can override neural correlates of social anxiety
In attempt to interpret my situation, I believe that the neurophysiological impact of PTSD overrode the homeostatic state of social anxiety. This is due to the fact that the traumatic experience ramped up production of various neurochemicals, sped up cortical activity (brain waves), and lead to changes in functioning of the autonomic nervous system.
Specifically, the sympathetic nervous system became overactive, whereas the parasympathetic branch became underactive. This lead to an increased in anxiety related to bodily functions (e.g. somatic anxiety), ultimately contributing to hypersensitivity and hypochondria. In overcoming PTSD, I’ve noticed that social anxiety has returned as physiological (genetic) homeostasis has been reestablished.
I’m not alone in my experience either, there are many other anecdotes of individuals reporting that in cases of severe “fear-based” anxiety associated with somatic preoccupation (e.g. hypochondria), their previously debilitating social anxiety vanishes. This suggests that various homeostatic mechanisms of social anxiety are overruled by PTSD-induced neurophysiological alterations.
Could new drugs be developed for social anxiety?
There are many new medications for anxiety in the works, but they aren’t necessarily engineered for the treatment of social anxiety. Many of these drugs attempt to target anxiety via selective targeting of neurotransmitters and/or hormones. While they may be effective for anxiety reduction, there’s no telling whether they will improve the specific pathology of social anxiety.
Should more research surface to confirm results from the aforementioned study, pharmaceutical companies may work to develop compounds that selectively reduce serotonin synthesis and 5-HT transporter availability in certain regions. These may behave significantly different than standard SSRIs and may yield improved outcomes for individuals diagnosed specifically with social anxiety disorder.
Have SSRIs helped your social anxiety?
If you’ve been specifically diagnosed with social anxiety disorder (or “social phobia”), have you found serotonergic drugs helpful in mitigating symptoms? To help others better understand your situation, feel free to mention the specific serotonergic drugs that you’ve found most impactful in reducing social anxiety – also include the dosage. Also chime in with a comment if you’ve found that SSRIs have done nothing but exacerbate your social anxiety.
I’ve personally used drugs like Adderall for anxiety and found that the dopaminergic effect can elicit a pro-social effect. High amounts of serotonin may result in a decrease in dopamine levels, resulting in psychomotor slowing and ultimately increased anxiety and/or brain fog. As thought speed increases via increases in dopamine, serotonin may be indirectly reduced or slightly reduced.
It could be speculated that increasing concentrations of stimulatory neurotransmitters like dopamine, norepinephrine, epinephrine, and/or cortisol – may mitigate social phobia, but increase other anxieties stemming from sympathetic overactivation.
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612120/
Mechanistic theories: Serotonin too high vs. too low and social anxiety
After these findings, there are several theories circulating regarding whether low serotonin, high serotonin, or a combination of both (in certain regions) may influence social anxiety.
Low serotonin synthesis: When serotonin levels are reduced, certain regions of your brain may not be able to communicate efficiently. In other words, the communication may be compromised as a result of reduced levels. As your amygdala signals “fear” – other regions of your brain (e.g. prefrontal cortex) may attempt to suggest that there’s no need to feel “fear” in this situation.
However, since the communication is impaired, the “fear” response of the amygdala continues to promote fear. It could also be speculated that the fear-signaling from the amygdala may be weaker than usual, meaning it triggers a fear-based response in social situations, but the weak signaling cannot be overruled by other regions because they never get the signal.
High serotonin synthesis: When serotonin levels are increased, perhaps regional signaling and communication may be hypersensitive. In other words, your amygdala may overreact at even the slightest thought of fear, which sends it into a frenzy. This overreaction from the amygdala cannot be overridden because even the slightest hint of fear perpetuates the existing response.
Question: Is social anxiety caused by “too much” or “not enough” serotonin?
It is known that social anxiety is incredibly more complex than serotonin. However, since we are in the Stone Age of neuroscience, research needs to start somewhere. Among individuals with social anxiety, do you believe that too much serotonin is a bigger problem than not enough serotonin – or vice-versa? If you feel strongly one way or the other in regards to serotonin, feel free to share some logic behind your belief.
You may want to also discuss a potential hybrid perspective that low serotonin synthesis in certain regions, coupled with high serotonin synthesis in others may play a role in the pathology of social phobia. I personally am not overly-excited about neurotransmission findings, I would rather identify the genetic correlates and (possibly) modify those genes. However, it’s going to take “baby steps” like this study to advance brain research and neuroscience.
3 thoughts on “Social Anxiety Disorder Caused By Too Much Serotonin?”
To add something else useful to the discussion (I didn’t mean to completely dismiss the premise earlier):
In the study, metergoline reduced anxiety even after the metergoline has been fully metabolized and excreted.
Granted this is not an effect from reducing monoamine levels of 5-HT, but rather directly antagonizing receptors. There are too many good metabolites (useful stuff like normelatonin, melatonin for example needed for sleep, and restorative sleep is fundamental for any mental health issue) downstream of serotonin to make me believe that abnormally low levels of 5-HT can be a good thing. High 5-ht vs “normal” 5-ht levels may be another issue, however.
Metergoline is basically a pan-serotonin antagonist at most of the 5-ht receptors:
My guess is that 2a and 2c antagonism presents most of metergoline’s benefit. It always makes me sad that research chemicals such as ritanserin are not explored for clinical use due to obvious economic reasons.
If this were the case then there would probably be at least a few case reports of social anxiety improved by high dose tamoxifen depleting 5-HT, which I haven’t yet seen any such reports of. Plus, there is MDMA and other serotonin releasing agents to consider which supposedly temporarily relieves social anxiety as it also fries neurons. Tonic increases in 5-HT tends to downgrade DA-ergic, while short bursts of NT may be more desirable.
Rapid depletion of 5-HT can also cause aggression in animal studies. But genetically modified low 5-HT animals are relatively normal in terms of aggression. Social behavior is a complex behavior so it is doubtful any single system is responsible. Anxiogenics are also under-explored. Pro-psychotic amphetamines can temporarily relieve social anxiety in a handful of stimulant naive cohorts, that is until tolerance and toxicity sets in.
Non-hallucinogenic 5-ht2a agonists, 5-ht1a full agonists, OXT at vasopressin 1a, NPS, anxiogenic ACTH releasing agents (w/feedback modulation), the glutamate and DA systems in general may or may not be worth investigating. Asociality and social anxiety likely have multiple complex causes.
This is an interesting take on SAD and serotonin. With personal experience of Lexapro, Dexedrine, Seroquel, Risperdal, lamictal, Xanax, Klonopin, Propranolol, Clonidine, the list continues. I have found that Dexedrine, is counterintuitively effective as well. I experience little noticeable effect on anxiety from SSRI antidepressants. And have had mixed results from many other alternative/adjunct/off label treatments.
The possibility that deficits, and surplus on serotonegric activity occur on a very localized basis, within regions of the brain. I expect (perhaps research will soon confirm) that social anxiety is a phenomena that occurs as a result of serotonegric abnormalities in one or more likely, many different areas of the brain. Though I agree it would not be safe to rest the entire cause of anxiety on 5-HT transmission alone.
This is speculative, but a general trend in efficacy for SSRI’s may indicate the the human brain has increased tolerance to excessive serotonin and related functioning, as opposed to deficiencies in serotonin. I would support this on the basis that if a particular region of the brain is the source of anxiety and can be considered deficient, it would be logical to assume that SSRIs would help alleviate the symptom.
But in addition it cannot be ruled out that normally functioning non-problematic areas will be buffered by the same treatment. Yet adverse reactions to SSRIs remain minimal. That to me hints at the brains ability to function better with excess serotonegric activity.