Since so many people pop them daily, and because I'm currently researching the relevant brain areas involved, I thought I'd write a relatively brief and accessible overview of how we, the sciencey types, think antidepressants actually work. The story of antidepressants is representative of other stories of drugs in the brain in that while we're pretty good at measuring if they're working from the outside, we know comparatively little about what they're doing on the inside. This article will cover with a broad stroke a bit of what we do currently know.

Antidepressants, or more specifically, SSRIs

There are a handful of different types of antidepressant drugs available that differ in terms of what they do inside the brain. The type of antidepressant I'm going to concentrate on in this article is a very popular one: the Selective Serotonin Reuptake Inhibitor (SSRI).

Let's look at these words briefly first. Selective is just a pharmacological term to mean that the drug acts only on a particular aspect of the brain as opposed to impacting on many different systems. Serotonin is a chemical in the brain that is used to send messages between cells/neurons - for this reason it's called a neurotransmitter. Reuptake is a process used by neurons in the brain to collect back chemicals that they use to send messages. And finally, Inhibitor is used to here to say that the drug blocks or inhibits this reuptake process. These concepts will be covered in more detail soon.

Serotonin: its home and function

Serotonin is a very important neurotransmitter chemical in the brain due to its chief roles of regulating mood, appetite, sleep, and learning and memory. It isn't difficult to imagine that a common theme amongst those with clinical depression is some kind of abnormality in the serotonin system.

Neurons - the cells that make up the brain - can be defined by the type of chemical they use to communicate with. Neurons that use serotonin to communicate with other neurons can therefore be called serotonin neurons. The bulk of serotonin neurons in the human brain (and most animals) can be found in a cluster of cells called the raphe nuclei. This area is roughly near the base of your brain, in the middle of your head.

From their strategic position here, the serotonin neurons project out (kind of like tentacles) and release serotonin in many other parts of the brain to regulate the functions touched on earlier, such as mood. Neurons communicate with and influence other neurons by firing and releasing their neurotransmitter. This firing is pretty much what it sounds like: the neuron builds up an electrical charge, and when a threshold is reached, it 'fires', driving the release of the neurotransmitter chemicals from the tips of the neuron's 'tentacles'/projections.

An important part of the brain are what we call receptors. You can think of how receptors work in terms of a lock and a key: the receptor is a lock that is shaped to receive a particular chemical neurotransmitter (the key). When the correct neurotransmitter/key is associated with the lock/receptor the receptor is activated, causing a physical change in the neuron, which leads to some action.

Transporters and the effect of SSRIs

Another key part of the brain are transporters. These sit on the end of the neuron's projections and collect up the neurotransmitter that is released during communication. The brain has been big on recycling for ages before it became popular, so it has this built-in function to collect and recycle neurotransmitter chemicals that have done their job in activating receptors on other neurons. This process is also called reuptake or reabsorption (in the diagram).

Accordingly, the serotonin transporter acts to take serotonin molecules back up into the end of the serotonin neuron's projections. This is the function of the brain that is inhibited by Selective Serotonin Reuptake Inhibitors! SSRI drugs inhibit the reuptake of serotonin back into the cell, causing serotonin to pool outside of the cell. Here the serotonin continues to activate the receptors in the local area - continuing to have an impact on all the things serotonin is involved in regulating.

To bring it back to the human feeling of depression, the general idea is that depressed individuals tend to have lower levels of serotonin and hence less activation by serotonin. It is thought that the outward signs of depression - lethargy, negative thoughts, lack of motivation etc. - are caused by, or at least heavily involved with, low levels of serotonin. Antidepressants, by blocking the serotonin transporter, act to increase levels of serotonin and alleviate the symptoms of depression.

This is the general idea anyway. Depression, like all mental disorders, is a roughly defined collection of symptoms and there is a relatively high degree of variation between individuals diagnosed with Major Depressive Disorder (or any other depression-related disorder). It isn't surprising then that only a proportion of patients respond well to SSRIs in comparison to other antidepressants - if they respond to any at all. But I don't want to get into all the other issues around depression and antidepressants in this article.

Back to the science...there might be more to this...

We now know at a basic level what SSRIs do in the brain: increase serotonin levels and activation. That should solve the depression issue right? Turning low serotonin back into normal serotonin levels?

However, there's an interesting little fact that originally troubled researchers: serotonin levels are increased quickly within hours or days after starting to take antidepressants, however patients tend not to feel better, and can even feel worse, until around 2-3 weeks after starting with antidepressants. So what's happening during those 2-3 weeks?

Serotonin 1A receptor

One of the receptors in the brain is called the serotonin 1A receptor. The 1A receptor is found on the serotonin neurons and its 'key' is serotonin. It has been discovered by clever scientists that activating this 1A receptor causes the serotonin neuron to quieten down - to decrease the rate at which it fires and the rate at which it makes new serotonin. It essentially acts as a way to turn down serotonin's influence in the brain, and as it's activated by serotonin itself, it acts like a feedback mechanism or thermostat of sorts. You could imagine it yelling out to the serotonin neuron "hey, we've got a lot of serotonin already out here, go easy on the production and drop the firing rate."

How, you may be wondering, does this relate to what SSRIs do? Well, we've seen how SSRIs cause an increase in serotonin and hence an increase in activation of serotonin receptors. The 1A receptor therefore gets its share of extra activation. Activation that, in an almost perverse way, reduces the firing of serotonin neurons and hence the release of serotonin.

Desensitisation

At this point I need to introduce another concept of receptors: desensitisation. When receptors are bathed in an unusually high amount of neurotransmitter chemicals, as is the case when SSRI drugs block the serotonin transporter, like good little proteins they react to their changing environment. In a word, they desensitise.

Desensitisation is a complex topic, so we'll keep it simple and sweet here. The end result is that more serotonin than before is required to activate the 1A receptors - they're less sensitive to the charm of the serotonin key.

Tying it all together

The theory is then that in the 2-3 week period mentioned earlier, the increased levels of serotonin caused by SSRIs are causing the desensitisation of the serotonin 1A receptors - a process that requires 2-3 weeks. During this time of desensitisation the SSRIs are raising levels of serotonin, which causes activation of the 1A receptor and the shutting down of the serotonin neurons. Over time, the 1A receptor becomes less sensitive to the effects of these raised serotonin levels (desensitisation), so the serotonin neurons are 'less shut down' and become more active. Therefore the serotonin firing rate and communication with other neurons is improved.

This improved serotonin transmission allows serotonin neurons to have more regulatory control in all the brain areas it has projections to, which leads to improvements in the associated functions, such as mood.

This is in a simple sense the current theory of how SSRIs actually improve depression. There are lots more details, caveats and particulars that could be discussed, and much research work is being done on this and surrounding topics as you read this.

I hope you know now more about ways people use to keep the black dog on the leash.

Superstitious and religious beliefs are like walls we put up to defend ourselves and provide security from the unknown. Imagine you're in a comfortable place and you look out into the distance to see a scary looking desolate landscape of sharp peaks and precarious drops. We can think of such a landscape in the distance as representing these unknown entities. When we look out there it scares us, the sense of uncertainty looms heavy on us.

So we erect walls - walls of superstitious beliefs and myths to protect us from having to deal with all the uncertainty and fear. An example of such a wall is the general idea that a god is responsible for unknown events - e.g. "I can't explain the beauty of that rainbow, or the destructiveness of that storm, therefore God did it." Providing a global and final explanation in this way is akin to erecting a wall between the individual and the issue so that the individual doesn't have to be affected by the anxiety aroused by the uncertainty and fear the issue brings.

This analogy is backed up in part by a study that shows that when people think of randomness they are more likely to have stronger beliefs in the supernatural/God. That is, unless they can attribute the arousal and anxiety caused by thoughts of randomness to a pill which some participants were able to do.

The analogy can also be extended to introduce the role of science, used here in its purest sense to mean a rational and effective way of finding things out about the world. Science works in two ways: to slowly chip away at these walls of superstition, and also to paint in vivid colour and shine bright light on the distant landscape so as to not make it so bleak, dismal and uncertain. Science enhances and extends our vision of the landscape while breaking down and making superfluous the walls of superstition. Sure, the very far distance is still foggy and uncertain, although the shroud retreats by the day.

Obviously it needs glaming up by someone that is actually good at graphic design Some original and consistent graphics to represent the tap, bottle and remedy would be great.

I'm also not sure what figure to use for the cost of the homeopathic remedy. I guess it should include the cost of a consultation with a qualified (hah!) homeopath, which is around $100 average I believe. That $29 figure is a rough average of the costs of remedies I found for sale online in NZ.

Sourced from one of my new sites of moment, ffffound.com

He clearly explains why such action is necessary today...

But the situation now looks very different, even in the supposedly enlightened nations of the West. For a start, a revived Christian philosophy is well entrenched within Anglo-American philosophy of religion. More importantly, perhaps, religious organisations and leaders continue to exert social power. All too often, they seek to control how we plan and run our lives, including choices about how we die. At various times, religious lobbies have opposed a vast range of beneficial, or at least essentially harmless, activities and innovations. Even now, one religion or another opposes abortion rights; most contraceptive technologies; stem-cell and therapeutic cloning research; physician-assisted suicide; and a wide range of sexual conduct involving consenting adults. We still see intense activism from the religious lobbies of all Western democracies, and even in relatively secular countries, such as the UK and Australia, governments pander blatantly to Christian moral concerns.

Russell goes on to outline other reasons for the need of writing and speech to challenge the truth claims and moral authority of religion, considers also the criticism of the movement, and has some sage advice for those involved. He summarises with:

There are now many people who do not believe in any God or gods, or in the truth of any religious dogmas involving supernatural entities and forces, and are prepared to say so in public. Many of them have interesting reasons for their views, and it’s valuable for all of them – for all of us – to speak up. It doesn’t even matter if we don’t all entirely agree in our thinking; in fact, the last thing we should want is the hardening of contemporary forthright atheism into a kind of quasi-religious sect with its own body of orthodox dogma. We should go on scrutinising religion from all angles, while discussing our own differences thoughtfully, carefully, and often.

A very well written piece in my humble opinion. I've been thinking a lot lately about the ethics of engaging in religious debate at various levels - from the individual to the society. What's the "right thing to do" and the issue of offending people versus stating your considered position/opinion. What issues to target, and where my hypocrisies lie. Ideas slowly solidifying...

For reasons I'm not entirely sure of I've always had an affinity with Doctors Without Borders, so that's where my donation money went for Haiti. You can do the same...

If you haven't yet seen in visual form the sheer gravity of the devastation in Haiti, The Boston Globe's Big Picture series, as always, has captured some dramatic shots.

Reading this review also reminded me of a review of a ballet performance I wrote several years ago. Not your typical review I should add. I basically took proper reviews and re-jigged them to make fun of the overly-fluffy and woo-woo language ballet reviewers love to (perhaps need to) use. It cracked me up reading it again so I'll reproduce it here below...

BALLET ASTOUNDS AND AMAZES PEOPLE

The Royal Family's NZ Ballet Company performed in the prestigious Jersey Cow Theatre in Waitrahuhugrub last night to a star-speckled audience of over 37 eager Thespians.

The Tutus For Hire tour spans the entire country, with the dancing troupe splitting into two. It’s more than half a century since Poul Gnatt first dragged the NZ Ballet around the small towns in this country. Then, as now, the company’s visit was the highlight of the calendar for many of those settlements, whose other highlights included gumboot throwing and pig wrestling.

The dancers are no longer billeted with the locals due to reports of indecent exposure and overfeeding, but they are, for 48 hours, welcomed as family. This is unique among other world-renowned ballet companies, who would view such a tour as below them.

The opening, Pas de Quatre, is a feminine cameo of four leading dancers from the romantic ballet era. They are here given a poetic perfume, which helps mask the smell of sweat emanating out from the stage. However, this fragrance does not deliberately distinguish the contrasting qualities of the original ballerinas who were arch-rivals.

The second work, Theme and Deviations, is choreographed by company dancer Andrew Simmons, here in its premier performance. As a piece, it is awash with temperate colours which give it an almost prosaic texture while maintaining an effervescent glow reminiscent of a turtle at night. Brendan Bradshaw identifies with this turtle particularly well.

The most astounding and amazing part of the evening was the Concerto Pas de Deux by Kenneth MacMillan. Immaculately crafted sequences and positions that melt and flow highlight this piece, illuminated further by the Shostakovich score. Catherine Eddy’s line is, as per usual, absolutely amazing. It’s not hard to see why it’s been called the best line in the country. Her line shines with the light of a thousand gypsies, while at the same time, holds the austere presence of several sheep in a barn. Qi Huan is good too.

Equilibrium is choreographed by Cameron McMillan, returning to New Zealand after several years with Thug Dance Company in Harlem, to stage this premier. Borrowing from quantum physics the notion of a “superposition of states”, the work makes uncompromising metaphysical demands on the performers – proposing the question through dance of how fundamental elements can exist as waveforms and matter in symbiotic duality, and what this means for multiple realities or universes. The striking costumes designed by Moana Nepia support the choreographic concept, although the Philip Glass score was a terrible choice of accompaniment. Philip just doesn’t get it.

The final work, Raymonda Variations, re-staged by Craig Lord and Nadine Tyson, evokes the grandeur of the Russian Mafia, though here, in splendidly styled tutus with hidden gun holsters and hammer and sickle imprints. Designed by Gary Harris, the work is not weighed down by the bloody history of the Russian Mafia, which is a good thing; it would have really brought down the tone of the piece. Qi Huan delivers great pyrotechnics with bravura, although concerns were raised about her use of fireworks in an indoor theatre. Abigail Boyle, trying to one-up Qi and her use of pyrotechnics, brings crazy arm movements to the party, which grace her impressive technique. There’s also the fresh meat, Ingrid Gow, who offers an aristocratic line coupled with a naturalness that already makes her one to watch. Ingrid’s line is no match for Catherine Eddy’s however, whose line is so powerful she can catch Fish with it.

From the forced smiles seen on stage, the dancers seemed to really enjoy the programme. It is a good balance between the antiquated and beautiful to something new and edgy. Tutus For Hire will be hitting your town soon!

I can definitely recommend the July Mix - it's huge.

I find these mixes a welcome change sometimes from the more "mainstream" (if I can use that word) dubstep mixes from the likes of Skream and Benga. Good to sus out the smaller producers and what not.

To explain why I don't like this one, I need to introduce a few ideas. Well, just one actually. Basically that a meme can be divided up into its "concept" and its "content". The concept refers to a meme's central idea, its uniqueness. The content refers to a meme's actual substance.

The thing is, a good meme has a disconnection between its concept and content. This allows the concept to continue being recognised with fresh content every time. Instant lol. For example, see Xzibit Yo Dawg and You're Doing It Wrong.

Keyboard Cat however has no disconnection between concept and content - both are the same every time. Not so instant lol after the 3rd or 4th times viewing. Lame.

Phew...glad to get that uber important thought out there.

This is essential to prevent the wide scale unnecessary use of the drug which tilts the balance from prevention over to significantly increasing the risk of Tamiflu-resistant mutations developing. That'd be a bad thing mmmkay.

Plus it lessens the chance of swine flu hysteria where people storm the pharmacy wanting the magic cure.