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.

For a bit of a bio on Andy Thomson...

Dr. Thomson is a psychiatrist in Charlottesville, Virginia. He has a private practice of general psychiatry and forensic psychiatry as well as serving as a staff psychiatrist at the University of Virginia's Institute of Law, Psychiatry and Public Policy and the Counseling and Psychological Services of the University of Virginia Student Health Services. Born in Washington, D.C. he received his B.A. degree from Duke University and his M.D. from University of Virginia School of Medicine. Robert Wright's book The Moral Animal introduced him to the emerging discipline of evolutionary psychology. It is that new lens of evolutionary psychology that informs his recent work on a comprehensive psychological formulation of suicide terrorism. He is a board member of the Richard Dawkins Foundation for Reason and Science.

The heavyweight Global Fund to Fight AIDS, Tuberculosis and Malaria (a.k.a. "The Global Fund") is behind this message with its Executive Director Dr. Michel Kazatchkine raising the topic at the 20th International Harm Reduction Association conference in Bangkok. In 2006, the Gates Foundation contributed $500 million to the Global Fund, calling the fund "one of the most important health initiatives in the world."

I really like Kazatchkine's key message in regard to the pointlessness of criminalising users...

"A repressive way of dealing with drug users is a way of facilitating the spread of the [HIV/Aids] epidemic," Kazatchkine said. "If you know you will be arrested, you will not go for treatment. I say drug use cannot be criminalised. I'm talking about criminalising trafficking but not users. From a scientific perspective, I cannot understand the repressive policy perspective."

And the use of harm prevention tactics...

"The one population where [Aids] mortality has been untouched - and in fact has worsened - has been IV [intravenous] drug users. It's amazing, because what we call harm reduction, such as exchanging needles, has been scientifically proven as the most effective."

I can also understand how harm prevention tactics such as needle-exchanges are limited in their adoption with the "common sense" thinking along the lines of "you're going to give those junkies what!? needles!? but they'll just go and shoot up more - you're encouraging it!"

It's one of those things that doesn't make superficial sense but after thinking about it a little and looking at the results of studies it becomes clearer. A 2003 randomised controlled trial showed that needle-exchange programmes do not cause an increase in drug administration. And a 1998 study I found quickly showed an approximately 33% decrease in HIV amongst needle-exchange users.

Additionally, we're talking about addicts here. The changes in the reward and reinforcement mechanisms in their brains caused by the drugs have more than likely put them into habitual drug-taking mode. It isn't exactly a choice any more, they are going to shoot up with dirty needles if there are no clean ones around.

Yay for studies. Boo that it takes years and years to communicate the results and make sensible policy changes.

It is in essence a collection of talks and activities for young and old around the world, and across the country, all mixed in with an education drive as well. The Brainweek website has more info.

I've seen a poster around Uni for a detailed listing of events in WLG/NZ but can't seem to find that online. There is a listing for NZ events at the US DANA website, and also Brain Days.

(the US folk have some fairly terrible logos/designs they use (as shown above))

The sentence reads...

Special "fire-polished" microelectrodes are placed on the neuron's surface and a slight vacuum applied to the pipette to attain a very tight junction with the exposed surface of the neuronal membrane, thus requiring near-nude neurons for best application.

Wait up! Did that just say near-nude neurons!? Is this a big problem in the research world - finding neurons that are not wearing too many clothes? Do scientists have to take neurons from the neuronal nude beaches of the brain?

Weirdly, after a quick google search I can't find out the actual meaning of this neuron nudity. I mostly got pages about Lindsy Lohan posing naked - super, but not helping me with study.

I'm assuming it's just referring to the fact that the neuron's membrane should be well exposed and free from other neurons or inter-neuronal things like glia cells.

And...back to studying...

Long, but it's an easy/captivating watch. Of course it's all quite full of "general public over simplifications."

If I was to be uber sensationalist, I would use this title to reflect what Susan Greenfield and other scientists are saying about video games, and social networks such as Facebook and Twitter.

Lady Greenfield does believe something along these lines however. For at least several years now she has been involved in studies to do with the impact of modern technology on attention and behaviour in general. Essentially, what changes it's making to how young people of today think.

She has written several books that deal with these topics. She's world-renowned in this area. She knows her stuff in other words.

As the BBC, NZ Herald and other news agencies are running with, she has recently been speaking to the British House of Lords on these topics, giving warning to potential consequences and urging further investigations into damage caused by things like video games, Facebook and Twitter.

She contrasts real world relationships with virtual ones, saying things such as how real world relationships...

...require a sensitivity to voice tone, body language and perhaps even to pheromones - those sneaky molecules that we release and which others smell subconsciously.

Moreover, according to the context and, indeed, the person with whom we are conversing, our own delivery will need to adapt. None of these skills are required when chatting on a social networking site.

It is hard to see how living this way on a daily basis will not result in brains, or rather minds, different from those of previous generations.

This seems all very plausable. Our behaviours tend to mould our brains in operating best to meet the needs of these behaviours - this is related to an area of neuroscience called neuroplasticity and more and more is being discovered about how our brains can and do change, even as adults to a limited extent.

Lady Greenfield goes on to say that ADHD and Autism may be connected to the "near total submersion of our culture in screen technologies."

And this is where I feel the scaremongering comes in. It would be great to get a full copy of what she said in order to get a clearer picture. I wasn't able to find one online quickly. However I can get a decent sense going by the quotes and her other writings, along with a book of hers I've read.

One big issue with linking modern technologies with ADHD is that researchers have been unable to ascertain a reliable reason for the attention difficulties of children labelled with ADHD - or even how attention (as defined by researches) factors into the mix.

Studies comparing ADHD children and non-ADHD children in regard to computer and video game usage tend to give mixed results. For example, one study showed no differences concerning video game use, although ADHD children exhibited more problems associated with videogame playing, suggesting that some ADHD children could be vulnerable to developing dependence.

One area that is not brought up often when people go on the war path over technology's impact on children are the many studies which show the benefits of electronic media for children, such as increased coordination and actually enhanced visual attention skills.

As for technology causing autism, that is even more of a stretch it seems. In the BBC article Professor David Skuse makes clear the reverse logic of this connection, saying...

The young people with autism we see do have a problem with face-to-face communication although they can be very articulate. They need to communicate and the internet is giving them a channel that they would not otherwise have.

So, modern technology and kids...what do we do? Last year a Psychologist Tanya Byron created a paper for the UK Government called Children and New Technology. As the title suggests it outlines guidelines for dealing with issues of high modern technology usage by youth. It's a good level-headed approach as she recognises the role of technology and how it can be a force for good if managed correctly.

One thing that strikes me about these relatively sensational claims by researchers such as Lady Greenfield is how they seem to follow the "oh no, it's new and a little scary, and I don't understand it properly, and things are changing, ahgrghrhh ban it!" type of thought process. This thought process seems to be one that has long been part of the human psyche and comes up every generational change.

We should not let the exaggeration of danger get in the way of the very real issues at play however. As Lady Greenfield mentions above, this modern world where young people can be constantly stimulated by texts and tweets most likely impacts to some degree on brain functioning. And as with most areas of psychological research, it is difficult to tease the causation out of the correlations.

The key questions are how much is this modern world really different to 200 years ago in terms of stimulating events and distractions? And what strategies do we need to put in place to ensure that modern technology enriches the lives of young people.

I need to still go through the site and add some bits and pieces here and there. I haven't used WordPress much before but so far so good. I love the admin interface - compared to other CMS' it's amazing.

One change in direction for me will be to start writing neuroscience and cognitive psychology themed posts targeted at a general audience...well, probably not a "Woman's Day audience" but more of a "The Economist or New Scientist audience."

I hope to advance my skills in this area of science writing and also it will help my studies in neuroscience. That's the plan anyway.

--Philip José Farmer

I think this refers to sleep. Either way I found it cool as I've been reading a lot about sleep recently for pre-study reasons. I had to look up the Greek myth references though...

Prometheus was a God, of the race Titans, who stole fire from Zeus and gave it to the mortals. Understandably, Zeus was pissed off so he punished Prometheus by having him bound to a rock while an eagle ate his liver every day only to have it grow back to be eaten again the next day. Seems fitting.

The interesting facet comes from the fact that the woman is Italian and the man is German. She speaks a little German and he speaks 2-week-tourist Italian. English is their only real common language. The interesting point is that neither of them speaks English that fluently.

Surely it must get annoying and be unsatisfying to not be able to convey to your partner exactly what you intend to say/think with the clarity of meaning only provided by a massive vocabulary and complex sentence structures – i.e. a mother tongue or very fluent tongue at least. How can they live like this I ask!?

I know personally the inner torment of desperately wanting to say the words that perfectly encapsulate ones thoughts but one just can’t find them in the foreign tongue. Often the compromise is a watered down version lacking the full intention and meaning.

Anyway, the answer to my question it seems is “just fine thank you.” This is what I can see after one week of exposure at least. They get along and survive OK. They have been together for over a year as well, although don’t live together in the same country.

It seems that because neither of them are native English speakers all of the little mistakes they both make in their speaking wouldn’t be so glaringly obvious or irritating. I’m referring to mistakes like omitting “does” in sentences like “where does this go?”…and other classic non-native-speaker mistakes.

There are also the more subtle aspects such as intonation. I noticed that the Italian woman would say some things in an “Italian way” which come across a little rude in English, to a native speaker at least. Again, these things are probably not noticed either.

So in a way they have probably formed their own English-like language complete with their own slightly skewed word meanings and subtle intonations.

Maybe some people don’t require a native tongue connection to have a meaningful relationship. Maybe I’m putting too many of my own expectations into this.

Or maybe it helps their relationship in some ways. Being forced to reconstruct thoughts from complex and often slang-filled language into cleaner and simpler language can be a very beneficial process. I have noticed this through learning Italian. It forces one to actually think more about the meaning of what they’re saying. For example, I can’t hide behind words such as “cool” – I actually have to use an adjective that describes what I actually mean. Either that or I just use bello.

This type of issue must occur in a lot of modern day relationships, with the increasingly smaller world etc. Especially with English as it tends to be the common language in inter-country connections of all sorts.