No clear link between low serotonin and depression - study

In summary, this study has been criticised for its methodology, with some questioning whether the findings actually support the serotonin theory of depression. However, it is still widely accepted and has influenced clinical guidelines.f
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TL;DR Summary
A major international study has found no clear evidence that low serotonin levels are responsible for depression.

The idea that depression is the result of abnormalities in brain chemicals, particularly serotonin (5-hydroxytryptamine or 5-HT), has been influential for decades, and provides an important justification for the use of antidepressants. A link between lowered serotonin and depression was first suggested in the 1960s [1], and widely publicised from the 1990s with the advent of the Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants [2,3,4]. Although it has been questioned more recently [5, 6], the serotonin theory of depression remains influential, with principal English language textbooks still giving it qualified support [7, 8], leading researchers endorsing it [9,10,11], and much empirical research based on it [11,12,13,14]. Surveys suggest that 80% or more of the general public now believe it is established that depression is caused by a ‘chemical imbalance’ [15, 16]. Many general practitioners also subscribe to this view [17] and popular websites commonly cite the theory [18].
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"Serotonin can be measured in blood, plasma, urine and CSF..."

I didn't look into the details but are the only assessing systemic levels? I think it's known that chemical imbalances in the brain can have local misregulations in different parts of the brain for, rather than systemic imbalances which is why systemic additions of medications have side effects on other parts of the brain while some parts benefit from it, how do they interpret systemic samplings?

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This study has already attracted a great deal of criticism and the lead author is a well known critic of biochemical theories.

Having said that, It's difficult to know why it's generated such concern, its now very widely accepted that explaining mental life in terms of the actions of single neurotransmitters is a simplistic nonsense. The drug treatment of depression has remained controversial for decades, with many trials reporting results little better than placebo. A wide range of new drugs have also been developed that target other transmitters and virtually all the drugs have other effects (particularly sedation) that might act as confounders. It also appears that the effects of drug toxicity has been underrated. Many of these issues are also the cause of debate much more widely in the treatment of mental illness. I'm not sure that this adds to the debate really, it simply confirms what many already believe and antagonises others. I suspect issues of ease and convenience are the most important factors in choosing first line treatments

These issues have informed clinical guidelines for some time, though it's interesting how the evidence has been used in different countries, the US for example seems to favour biological treatments. In the UK, patient choice is stressed but in less severe depression antidepressants are avoided and psychological therapies advocated. For more severe depression, therapies may be combined with antidepressants, the evidence for effectiveness seems better for the more serious mood disorders.

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