Understanding depression and anxiety
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# 4.2 Evidence for the monoamine hypothesis

Serotonin is eventually broken down by the body and new serotonin is made by neurons. The breakdown products can be detected in the cerebrospinal fluid (CSF), which bathes the brain and spinal cord. Levels of serotonin breakdown products appear to be low in the CSF of people suffering from serious depression.

What do low levels of serotonin breakdown products suggest about levels of serotonin in the brain?

## Answer

That levels of serotonin in the brain are low – the less there is, the less there is to break down.

Other evidence supporting the monoamine hypothesis comes from post-mortem studies of the brains of depressed people who unfortunately committed suicide. Some studies have found abnormally high numbers of serotonin receptors in the prefrontal cortex in suicide cases (Stanley and Mann, 1983; Yates et al., 1990). The significance of increased numbers of serotonin receptors in the brain is that it may enhance neuron to neuron communication when serotonin levels are low, by facilitating the capture of as much of the available serotonin as possible.

However, such effects are not always found in those who are depressed or have committed suicide. It has also become clear that not all those with depression respond to antidepressants such as SSRIs. One possibility is that the category of ‘major depression’ lumps together different kinds of depression (for instance early onset, late-onset and chronic or recurrent), which may differ in their biological bases. However, any such differences are not currently well-understood, in part because they have not been well-explored.

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