Individuals with social phobia have too much serotonin

I've had a similar experience. Taking SSRIs (Sertraline, initially 50mg/daily, now 100mg/daily) for social phobia and depression. They definitely helped increase my baseline for positive feelings (i.e., I don't spend as many days curled up in bed feeling hopeless), but it's true that it brings down other aspects of life. Decreased sexual function, loss of emotion in other areas, stuff like that.

I wonder whether serotonin is really the magic trick to increasing moods or whether it's just a stop-gap solution that works well enough for most.

> I still get bouts, but I have a mechanism in place to handle the symptoms and they mostly dissipate.

Can you tell me about the mechanism that helps you?

Yes, the paper [1] is fairly careful to point out that this is studying a neurotransmitter pathway's association with social anxiety disorder, which might be useful information in later establishing etiology, but doesn't do so on its own. Their causal hypothesis is actually (if I'm reading it correctly) the reverse of the direction people are assuming from the headline: [other physical features of] social anxiety disorder may cause excessive serotonin production, which may in turn produce additional symptoms, rather than excessive serotonin production being the root cause. That is, unusual upregulation of some pathways involving serotinin sits more towards the end of a causal chain than at its beginning. (Some of these causal chains are more like feedback loops, though, which makes it extra difficult to sort out what constitutes a root cause.)

From the paper:

> Although we cannot test causal effects in the present study, we speculate that, because raphe nuclei serotonin 1A autoreceptors exert inhibitory feedback on serotonin synthesis and firing, downregulation of inhibitory raphe serotonin 1A autoreceptors previously reported in social anxiety and panic disorder leads to increased serotonin synthesis, and augmented reuptake may be a compensatory mechanism.

[1] http://archpsyc.jamanetwork.com/article.aspx?articleid=23197...

Drugs are in a totally different category than peer reviewed articles. They go through rigorous testing that works the vast majority of the time to weed out unsuitable drugs. On the other hand peer review (having been through it a few times) is extremely sloppy and reviewers do not do due diligence. Often the reviewers can't even if they wanted to (no raw data released etc) and they have to blindly accept the authors claims.

I don't think science dies a little bit each time a dissenting or contradictory result is published. In fact it is a good thing. We need more people to try and reproduce others work. But at the moment we have is a problem of scale. In other words it only looks bad when there are two different conclusions. We need many more reproductions to come to a clear answer.

Reversals based on further evidence are part of science, inherently. Science shouldn't have a magical reputation, because it's not magic. Like all other means of explaining there material world, it's guesswork. There only difference is that science is guesswork with systematic effort to find holes in the guesses and improve them and reject there ones that don't work, while every other approach to explaining material phenomena had some form of guesswork and some method of closing which guesses to accept that is not based on what demonstrably works or fails.

I think a lot of the harm comes from people treating science as some sort of monolithic entity. Science says X! Science says Y! When really it's more like some scientists over here have found some evidence for X, some over here did some work that points to Y.

It's neat that mainstream enthusiasm for science has grown so much in the last few years, but it seems like a lot of times this kind of treatment oversimplifies things.

It's a good thing that science can change. This is what distinguishes science from dogma.

The problem is not these supposed 'reversals', but rather how this information is being reported. Pop-science media reports modest studies as absolute truths to catch eyeballs. When one study merely suggests research in one direction, it's emblazoned as fact on the tabloids.

In the example you identified: "Fatty food is bad - no it's good" the issue is not the studies flip-flopping. Rather, it's a problem of regular people taking what are likely modest reports way too far and massively integrating them into their daily lives, without ever reading the study and understanding the context or scope of it. A study indicating that, say, there may be health problems associated with consuming excess saturated fat seems to compel people to follow no-fat diets. So I'd argue that the bigger problem is people reading oversimplified reports of scientific information

I mean, I'm not terribly familiar with this field, but the study itself indicates that whether high or low serotonin levels were contributory was "a matter of debate" and that "only a few studies have used molecular neuroimaging to examine serotonin dysfunction in SAD directly."[1] So this doesn't appear to be a reversal at all, but rather a study which helps clarify the role of serotonin in SAD.

[1] http://archpsyc.jamanetwork.com/article.aspx?articleid=23197...

>But every time the accepted explanation does a 180 science dies a little bit

So let's just keep the earth flat then, shall we ;)

This is the beauty of science. If a report on memory that claims X and then another scientist is unable to replicate their results X, what can we say about the validity of X?

I suspect the reason for the reversal is the accessibility of new tools, namely the PET scan. Whereas in the past, the results were probably based on polling people about their anxiety levels while on SSRIs.

Every time something like this comes up I think of this: http://www.phdcomics.com/comics.php?n=1174

I see a lot of positive reactions to how happy we should be that science changes. I mean, look how long it took us to get out of the dark ages, right?

But no, the liberality of changes like this one is what separates fluff science from actual science. There is a vast chasm of difference between stuff like this one and, say, aether theories.

People who came up with aether theories were the brightest of their ages. That is really the best they could come up with -- and the reason why it took us so long to disprove aether-based theories was that they had some bloody solid science behind them -- at least back in those ages. People were unable to come up with anything better because, for a very long time, they lacked both theoretical and experimental tools with which to conclusively prove (or disprove) their hypotheses.

We needed significant developments in mathematics, fluid mechanics and optics in order to test these theories, and we needed special relativity to come up with something better.

Whereas claims like the one this article refutes need only a correct application of double-blind testing and not falling into well-known (at least to statisticians) traps in order to be tested.

The fact that we have 180 degree spins in understanding such matters every six months is not a testament to how modern science cares only about truth. It's a testament of how important it is to publish papers.

These aren't fully contradictory results. The paper is referring in serotonin in one brain structure, the amygdala. The article was wrong to cast such a broad stroke.

That assumes the latest info from science is right. Maybe the earlier info was right, and this is the incorrect interpretation.

Either way it does get frustrating though.

People are asserting that these reversals are a normal part of science and therefore good. I think they are a normal part of science but reveal a huge flaw in the method: scientists frequently over extrapolate and end up drawing erroneous conclusions based on limited data. The widespread presence of basic methodological flaws in many scientific papers such as misunderstanding the meaning of p values means a lot of so-called science is built on faulty reasoning. This is worse than merely presenting a model that imperfectly represents the data, it is simply wrong: reaching conclusions that the data do not justify and never could.

You see this most often with efforts to reduce complex systems down to the effect of single variables; such efforts are almost guaranteed to miss the point. The serotonin story is a good example. The notion that the complexity of human psychology that led to depression could be reduced to the activity level of a single neurotransmitter should strike us as an absurd exercise on its face. It's not even wrong, it's a basic misreading of the problem space.

I wouldn't treat this as a complete reversal just yet. These kinds of "paradigm changing" studies get shown to be flawed all the time. It's just that the press rarely reports when that happens.

Most of those things you mention were not based on any solid science in the first place if you look into them so no conundrum here.

>> Previous studies have led researchers to believe that individuals with social anxiety disorder or social phobia have too low levels of the neurotransmitter serotonin. A new study, however, shows that the situation is exactly the opposite.

> It's stuff like this that is destroying the reputation of science in general.

the actual paper contains no such language of course, let me quote the introduction:

> Anxiety disorders are debilitating psychiatric conditions that impose a considerable burden on patients1 and society,2 and social anxiety disorder (SAD) is one of the most common of these conditions.3 The neural underpinnings of excessive social anxiety are not fully characterized, although serotonin (5-hydroxytryptamine) has been suggested to be involved etiologically.4,5

> However, only a few studies have used molecular neuroimaging to examine serotonin dysfunction in SAD directly. A single-photon emission tomography study6 found increased serotonin transporter availability in the thalamus, but not in the raphe nuclei, in patients with SAD relative to healthy control individuals. Also, a positron emission tomography (PET) study7 showed that SAD is associated with reduced serotonin 1A receptor binding. Somatodendritic serotonin 1A autoreceptors in the raphe nuclei, which inhibit serotonin synthesis and release,8 and postsynaptic serotonin 1A heteroreceptors, which convey inhibitory signals in the amygdala, anterior cingulate cortex (ACC), and insula cortex, were downregulated.7 In addition, functional neuroimaging studies of SAD9 have demonstrated heightened, fear-induced neural reactivity in the amygdala, which is densely innervated by serotonin,10 with alterations in the hippocampus, ACC, insula cortex, and striatum.9,11 Moreover, the first line of pharmacologic treatment for SAD consists of selective serotonin reuptake inhibitors (SSRIs),12- 14 which reduce excessive amygdala reactivity, restore initially suppressed ventromedial prefrontal cortex response to emotional challenge,15- 18 and attenuate resting brain perfusion in the ACC and insula.19 Thus, findings from molecular and functional neuroimaging and treatment studies indicate that serotonergic neurotransmission in the amygdala, raphe nuclei, striatum, thalamus, hippocampus, insula cortex, and ACC may be compromised in SAD.

> Given the inhibitory role of serotonin 1A autoreceptors on serotonin synthesis,8 previous findings of decreased autoreceptor binding in SAD7 may indicate increased serotonin formation and enhanced serotonergic activity. On the other hand, because blocking the serotonin reuptake with SSRIs attenuates social anxiety symptoms12,13 and because posttreatment dietary depletion of the serotonin precursor tryptophan reverses the anxiolytic effects of SSRIs,20 the notion that increased serotonin availability is pivotal for anxiety reduction also has support. Indeed, whether anxiety conditions such as SAD are best characterized by serotonin overactivity or underactivity remains a matter of debate.5

Note there are at least 14 known serotonin receptors:

https://en.wikipedia.org/wiki/5-HT_receptor

and this is responsible for the rich pharmacology of serotonin-affecting drugs such as the SSRIs, hallucinogens such as LSD, and MDMA which delivers an entirely different experience, atypical antipsychotics, antimigraine drugs, anti-emetic drugs such as Ondansetron, etc. It doesn't matter "how much" serotonin you have as where it is. Note that serotonogenic drugs have radically different modes of actions such as agonist, antagonist, partial agonist as well as the reuptake inhibitors, and that many serotonin receptors are actually autoreceptors on the other side of the junction which suppress the production of serotonin at the terminals.

Personally I think of the SSRI drugs as "antineurotics" and what they seem to do is help me keep compensated under stress. That is, rather than going to pieces, I stay rational under provocation. This might be why Scientology hates SSRIs so much, because it really does seem to make your "reactive mind" much weaker.

With most biological systems, it's a pretty safe bet that things are more complicated than that.

honest question: is that phobia a real problem for you? or did somebody tell you it is?

One thing that has become increasingly clear is that the simplistic "too much x" or "too little y" theory of Mental illness as a "neurotransmitter imbalance" is flawed to the point of uselessness. Neurotransmitters certainly do mediate synapse growth and activity, but the brain is a complex adaptive organ, and it will adapt to modifications to neurotransmitter levels. This is why antidepressnts become less effective and require stronger doses, and why their sudden withdrawal leads to the massive exacerbation of symptoms. The problem isn't simply that patients "go off their meds". The problem is that meds stop working, and withdrawing them leaves the poor patient with a brain that was adapted to their presence suddenly unable to cope. The meds make the organic problem worse, but it dorsn't show until you withdraw them. We're still basically at the witch-doctor stage of "try it and see" with most if these drugs, with nothing like a proper pathology model or functional description of how the meds work to even do proper long-term studies.

No, an important aspect of mental diagnosis is that the patient is actively troubled by the problem but is unable to change on his own; otherwise it is more of personality. If you just hate socializing, you don't have social phobia. If you sincerely believe that washing your hands every ten minutes make you cleaner and do so, you don't have OCD.

Psychologists are not as eager to judge as you might imagine.

When an irrational fear prevents you from doing something, that's basically a definition of psychiatric disorder.

It doesn't matter if you have no great desire to do it in the first place. If someone thinks an activity isn't useful then that can mitigate a phobia, but it's orthogonal to the actual existence or not of a phobia.

Nobody is judging you for your preferences. "won't" and "can't" are different things.

So if you're calling the overuse of chemicals bullshit, fine. But don't call a clear diagnosis bullshit.

The article was certainly a bit casual with its terms, but as a human being, you shouldn't be generally nervous about mere socialization with others. You may be specifically nervous, if you need to impress the others, or if you're in a foreign land for the first time, but you should not generally be nervous about all social interaction. If you are, you have a problem. It may not be something that we should necessarily throw medication at, we've all got problems of one sort or another, the benefits of medication may not outweigh the costs, but it is a problem.

Nervousness is different than boredom, lack of desire, or lack of seeking it out. I can cover those bases quite well. I often don't want to socialize. But I'm not fearful of it, I just find it boring in most groups.

On the other hand, "public speaking", as in, getting up in front of a crowd and making any sort of speech, well, I've heard multiple people who make a living doing it that they never actually stop being nervous about it before hand. They learn how to get through it, but they're always nervous. Heck, I daresay such nerves are rational, really. That would seem to be a different category of issue.

So, you clearly do not have social phobia. Yes, it is a legitimate disorder, and it can be quite disabling when it's severe.

It's not about not being able to speak in public. Imagine suffering from panic attacks and not being able to leave your house for days, because you're afraid someone will say hi to you. That's social anxiety.

Your attitude "STOP IT. tell them to fit in" is the reason many people with social anxiety, and many other psychiatric disorders end up committing suicide.

Cognitive Behaviour Therapy - a short course of between 6 to 14 hours (one hour per week). Find a reputable therapist (in England you'd look for BACP).

Or meditation and mindfulness would probably help.

You may find sleep hygiene helps, but if you're not having trouble the rest of the time it might not.

http://www.nhs.uk/Conditions/Insomnia/Pages/Treatment.aspx

For rare events, not trying to cure insomnia, consider zopiclone (or any of the Z drugs). You'd take one before the event; you'd get a good night sleep; you avoid the addiction problems that are risked if you take it every night.

(Obviously I'm not a doctor and this isn't medical advice).

Sleep deprivation is one of the most reliable and strong antidepressants, but also one of the least practical. Some clinics actually make patients stay awake for a period of time. I don't recommend "self-medicating" on purpose, though... In many case this makes everything worse.

Isn't it more that we don't understand why it works (i.e. what kind of connection serotonin has with these mental illnesses) rather than the mechanism of action itself, which is believed to be serotonin staying longer in the synaptic cleft by way of inhibiting reuptake, leading to repeated stimulation of the post-synaptic receptors?

I was under the impression that SSRI's were specifically designed to target the serotonin system.

What if those with social phobia are creating those serotonins to counter-act other social-phobia-causing stuff?

IMHO, this article really shouldn't say serotonin causes social phobia based on 'social-phobiacs have lots of serotonin'

Definitely not, it's not the same mental state, one is pleasant the other one not.