Is serotonin the happy brain chemical?

SSRI's in my opinion are not the future of antidepressants. They work by indiscriminately increasing serotonin levels in the synapse, thereby activating every single serotonin receptor (5-HT). While you get the anti-depressant effect by increasing the activation at the 5-HT1 receptor, you also get the negative side effects of SSRI's since it activates 5-HT2c receptor (weight gain), 5-HT3 receptor (nausea), and sleep issues.

The future of the antidepressants lies in chemicals that increase serotonin at the 5-HT1 receptor (lowering depression) without affecting the other receptors. Drugs like mirtazipine and nefazodone attempt to do this by blocking certain 5-HT receptors (mainly the 5-HT2a receptor, which lowers anxiety), and as a result make serotonin levels higher and more available at the 5-HT1 receptor. That's the reason these 2 drugs in particular don't have the nasty side-effects of SSRI's.

The future of anti-depressants likely lies in the ability to find a drug that increases activation at the 5-HT1 receptors in certain parts of the brain, while leaving the rest of the brain and receptors untouched.

This is the first honest article I've read on the subject of serotonin and neurotransmitters in years. It basically concludes what very few people seem to be aware of: that we do not know what causes depression or anxiety nor do we know how SSRIs, SSNRIs, or other similar chemicals work. There are, at best, hypothesis, generally untestable. The idea of chemical "imbalances" in the brain is, as it has been since its inception, complete and utter bullshit. The reality is current medical science simply doesn't know, the marketers make the rest up, and for some reason, most doctors play along. That's how you get to the popular and completely wrong idea that serotonin is the "happy" brain chemical. (Of course, if you're aware of the lack of capability in most people to process complex ideas, you could easily guess that such a simplistic idea has to be wrong simply from the number of people who talk about it like it's real.)

I would like to point out that there is a whole range of non-SSRI medicines that have significant clinical effects on depression. In particular:

Medicines that promote drowsiness (such as sleeping aids and even the antipsychotic quetiapine), as sleep deprivation and depression are highly correlated.

The atypical antidepressant wellbutrin/bupropion, which impacts a whole bunch of chemicals in the body but notably does not affect seratonin levels. My personal experience from having taken it is that it makes me more energetic, similar to a weak amphetamine.

MAOIs, which again impact a whole bunch of chemicals, including seratonin but notably also melatonin, which is well-known to promote sleep. These are well-known to be highly effective antidepressants, but are rarely used because they require the patient to alter aspects of his lifestyle.

The situation is complicated by the fact that the category of depression consists of a bunch of different symptoms that may be comorbid in many people, but are not necessarily.

Serotonine is very old. There are two different genes TPH1 and TPH2 which encode the enzyme information for serotonine-production, which happens at two sites in the body. This split is apparently very old and evolved before vertebrates did.

Serotonine controls a multitude of things including wake-night-cycle, blood pressure and temperature. It doesn't even only work as a neurotransmitter, but mechanically as well.

Further reading: http://www.ncbi.nlm.nih.gov/pubmed/8768313

After feeling very down, so much that I didn't felt like myself, I started to experiment with herbal supplements. Valerian to sleep, but my problem wasn't lack of sleep. St John's Wort for mood, but I didn't feel moody.

I tried 5-htp, which from my understanding is a precursor to the biosynthesis of Serotonin. The effect was immediate. I felt light headed, buzzed even. I felt as if I had suddenly woken up in a bright new world. I went groceries shopping could barely keep myself from gaping at all the colours, products and people. The next day, those effects were gone but I felt fine. Simply fine. I tried to take more 5-htp, but those strong effects are gone. I am no brain scientist, but to me this is anecdotal evidence that I was very much lacking in Serotonin and that this herbal supplement boosted me right back up.

It's not magical, I still feel anxious about deadlines and stressed about hard to deal with clients. However, some kind of dark blurry veil has been lifted from my perception of life.

Edit: Since then, I increased my weekly physical activities and improved my overall eating habits. I can't say if it's directly linked with my increase (or rather closer to normal) Serotonin but my instinct says yes.

The article presents a possible explaination for why SSRI antidepressants (which increase the amount of serotonine in one's synapsis) are effective: serotonine plays a role in how we learn, and

> [people with an] atypical function of the serotonin system may be at risk of developing depression or anxiety because they are too good at learning about negative outcomes

> Serotonin changes produced by the drug, combined with appropriate therapy, might work by allowing patients to learn that the world is not such a bad place rather than simply making them happy.

The article continues noting that this would explain a few things, like

> (1) why treatment with SSRI anti-depressants doesn’t tend to increase happiness until weeks after depressed patients have begun taking medication. Serotonin changes produced by the drug, combined with appropriate therapy, might work by allowing patients to learn that the world is not such a bad place rather than simply making them happy.

> (2) why some depressed patients generally do not improve when undergoing SSRI treatment. Consuming pills in the absence of improvement in life conditions or appropriate therapy might in fact make it easier for already depressed individuals to ‘learn’ more about the negative events surrounding them

> (3) [why we] have no evidence that [simply] increasing brain serotonin levels actually improves people’s mood.

The evidence shown to supports this role of serotonin in the learning process consists of two studies (cited in the article). The first showing that rats grown in the dark developed abnormal sensitivity to non-visual stimuli, and that serotinine played a role in the process. The second found that individuals with a particular genotype affecting the serotonin system were more likely than others to develop depression or anxiety only if they had experienced stressful life events.

Betteridge's law of headlines checks out: Is serotonin the happy brain chemical? No, it (probably) plays a complex role in how we learn about bad outcomes.

I'm not sure that SSRI's make me happy, but I have never believed the "chemical imbalance" story about them.

I have always been kindof anxious, maybe with a touch of GAD or even social anxiety, and I when I knew the rug was about to get pulled out from under me, I started taking an SSRI to increase my resilience.

Under the SSRI I am definitely much less anxious, perhaps even to a fault -- the big benefit I see it that I don't get upset about little things, like I don't get upset about being stuck in traffic.

By the way, triptans (drugs that increase serotonin level) can be very effective in fighting against migraines. Switching from a splitting head-ache to nothing in 20 minutes, when instead classic analgesics would do nothing, is a step towards happiness.

Edit: SSRI -> triptans

There's actually an old, effective-in-studies, and fairly obscure anti-depressant called tianeptine that works by enhancing serotonin reuptake, which lowers the levels. Effectively an Anti SSRI. I hear about it from the nootropics camp from time to time.

My main takeaway from this article was that someone also wrote an article entitled "Chemicals that activate happiness, and how to gamify them" and somehow thought this was ok.

Is the zero bit the computer happy bit?

I've noticed a strong pop-psych trend these days of referring to one's own feelings or experiences in terms of neurotransmitters. e.g. "I'm hooked on the dopamine rush of such-and-such activity," "I'm feeling blue today, my serotonin must be low," etc.

This drives me crazy. It's pure pseudoscience, and I hear it from people who should know better. Scientifically, we have very little idea what chemicals are actually behind different subjective feelings/moods/whatever. Everyone would love to believe that the brain operates in a simple, intuitive fashion, with one chemical for joy, one chemical for sadness, one chemical for anger, etc., but the reality is way more complex and nuanced.

For example, even something well-studied like dopamine, which has been strongly linked with the brain's addiction circuitry, doesn't necessarily stimulate any sort of direct pleasurable feeling as people often infer. It seems to work in a much subtler way, modulating learning, attention, and goal-seeking behavior. A recent study found that it doesn't even necessarily spike when good things happen, but tends to increase in response to unexpected events, good or bad.