Philosophy of The Big Society

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Saturday, 24 July 2010

Evidence suggests there is more to depression than low serotonin levels

'New Scientist' Article: "Rethink Needed For Cause of Depression"

"IF YOU thought depression was caused by low serotonin levels, think again. It looks as if the brain chemistry of a depressed person is much more complex, with mounting evidence suggesting that too much serotonin in some brain regions is to blame.

If correct, it might explain some of the negative side-effects associated with selective serotonin re-uptake inhibitors (SSRIs), antidepressants like Prozac which increase the amount of the neurotransmitter serotonin in some parts of the brain.
The traditional view of depression was largely based on the observation that SSRIs boost mood- although why they do so is unknown. "Because antidepressants increase serotonin in some parts of the brain, people assumed that depression must be the result of low serotonin levels," says Christopher Lowry of the University of Boulder in Colorado. But the discovery of multiple types of serotonin-releasing neurons in the brain, along with high levels of serotonin recorded in people with depression, is prompting a rethink.

"What's more likely is that there are subgroups of serotonin neurons that are overactive in depressed patients, rather than underactive as we have all been assuming," says Lowry.

It's likely there are groups of serotonin neurons that are overactive, not underactive as assumed.

One of the first clues that something might be amiss with the traditional theory came three years ago, when Murray Esler at the Baker Heart Research Institute in Melbourne, Australia, and colleagues found that the level of serotonin in the brains of people with panic disorder was four times higher than in healthy volunteers (Stress, DOI: 10.1080/10253890701300904), and in depressed people who were not receiving treatment it was two times higher than in volunteers (Archives of General Psychiatry, vol 65, p 38). They also showed that long-term use of SSRIs in people with depression and panic disorder seemed to decrease serotonin levels through an as yet unidentified mechanism.

Now, in studies of rats and mice, Lowry has found that there are multiple types of serotonin neurons that can be independently regulated. He presented his results at the Forum of European Neuroscience in Amsterdam, the Netherlands, last week.
This fits well with findings from other groups that there are two types of serotonin receptor in the amygdala, a brain region linked to emotion and anxiety: 5-HT2A receptors that inhibit anxiety, and 5-HT2C receptors that promote it. The roles of the receptors were identified by injecting drugs that either stimulated or inhibited each receptor and observing the animals' behavioural response

Together, the findings might mean that while high levels of serotonin in some brain regions like the prefrontal cortex can lead to improved mood, high serotonin in other regions could have negative effects.

Evidence for this idea comes from Gina Forster at the University of South Dakota in Vermillion and colleagues, who injected a stress-related molecule into the brains of rats and found that it triggered two phases of serotonin release. An initial wave of serotonin appeared to increase fear-like behaviour in the rats, while a second wave decreased this behaviour, possibly because it activated a brain region called the medial prefrontal cortex, which is associated with calming of fears (Neuroscience, vol 141, p 1047).

The new findings have implications for how SSRI drugs work. In the long-term, SSRIs do tend to have a calming effect, although more research is needed to understand how they do this.

However, in the short-term some people taking SSRIs report feeling increased anxiety. This is "almost certainly due to the activation of one of these groups of serotonin neurons", says Lowry. The suicidal thoughts some people taking SSRIs claim to experience may also be linked to boosting serotonin, as suicide is thought to be associated with increased impulsivity. "It may be that certain types of SSRI are affecting these impulsivity circuits in the brain," says Lowry.

Learning more about these different groups of serotonin neurons could lead to better treatments for depression and anxiety disorders. "It might be possible to design very specific drugs that can turn on or off specific groups of neurons that are deregulated in anxiety or depression," says Lowry."


  1. for the record 80% of serotonin receptors are found in the gut

    how could a drug that was supposed to be so selective it worked on the mind (brain) turn round & ignore 80% of the places that it would be equally active?

    truth is these drugs mess up more than your mind, they mess your whole body!

    time for a rethink don't you think RETHINK

    Serotonin (pronounced /ˌsɛrəˈtoʊnən/) or 5-Hydroxytryptamine (5-HT) is a monoamine neurotransmitter, biochemically derived from tryptophan, that is primarily found in the gastrointestinal (GI) tract, platelets, and central nervous system (CNS) of humans and animals. It is a well-known contributor to feelings of well-being.

    Approximately 80 percent of the human body's total serotonin is located in the enterochromaffin cells in the gut, where it is used to regulate intestinal movements.[1][2] The remainder is synthesized in serotonergic neurons in the CNS where it has various functions, including the regulation of mood, appetite, sleep, muscle contraction, and some cognitive functions including memory and learning. Modulation of serotonin at synapses is thought to be a major action of several classes of pharmacological antidepressants.

  2. Thanks for the information. Biology is not my strong point so found it a right education to learn that 80% of my serotonin receptors are in my tummy.

    You learn something new everyday. Well, I do.

  3. Hmmmm

    I am not too impressed with the translation of complex social, family and emotional patterns of denied problems (often creating suppressed feelings and hopelessness) becoming changed distractively (I think) into neural explanations implying chemical abnormality ..

    Better to deal with causes of serious emotional flattening and pain by supportive human help and empathy as well as a better social and health system .. However that system is mad so most people are fucked anyway ...

    Yours with lurv


  4. Having said that some people need, think they need or hope they need medication.

    I am not knocking them...I am sedated most of the time meself..only way I cope with all this madness (internal and external) and that is my choice rather than the 'NIACE' guidelines cosh treatments. personal view

  5. Hell what is there after seeing there's a lousy humanly unreceiving system .. Dregging needs drugging

    Peeps must have their choices but those choices with the NHS are hemmed in and all too often cornered right up the the chemical skirting boards .. We is nailed Mandy ,nailed and failed oh so modernly ...

    Box me up for the fire party and dress me with cheeky graffiti ...

    Wamptrott will make yer oven spit ..

    Lots of Lurv


  6. This comment has been removed by a blog administrator.

  7. I don't think it matters what I say to you, Anon.

    You are the sort of person who will self victimise and I have a strange feeling you are going to keep stalking me with your grievance.

    That is why I will keep deleting you.

  8. This comment has been removed by a blog administrator.

  9. Hiya "Its"

    Gold hunting by Galaxy Rainbow on a Levitating needle has proved successful and Seratonin levels were fine too ...Purple Bunny navigated..


  10. Tiffles

    At the present time all I want on my blog is purple bunnies and snowy, big eyed, owls so ta muchly :>)