Depression is not caused by a 'chemical imbalance' in the brain, say scientists
Summary: A new comprehensive review disputes the serotonin theory of depression, reporting there remains no clear evidence that serotonin levels or serotonin activity is responsible for low.
Source: UCL
After decades of report, there remains no clear evidence that serotonin levels or serotonin activity are responsible for depression, according to a major review of prior inquiry led by UCL scientists.
The new umbrella review – an overview of existing meta-analyses and systematic reviews – published inMolecular Psychiatry, suggests that depression is not likely caused by a chemic imbalance,and calls into question what antidepressants do.
Most antidepressants are selective serotonin reuptake inhibitors (SSRIs), which were originally said to work past correcting abnormally low serotonin levels. At that place is no other accepted pharmacological mechanism by which antidepressants bear upon the symptoms of low.
Lead author Professor Joanna Moncrieff, a Professor of Psychiatry at UCL and a consultant psychiatrist at Northward East London NHS Foundation Trust (NELFT), said: "It is always difficult to show a negative, but I call up we tin safely say that after a vast amount of research conducted over several decades, there is no convincing evidence that depression is caused by serotonin abnormalities, particularly past lower levels or reduced activity of serotonin.
"The popularity of the 'chemical imbalance' theory of depression has coincided with a huge increase in the apply of antidepressants. Prescriptions for antidepressants have risen dramatically since the 1990s, with 1 in half dozen adults in England and 2% of teenagers now being prescribed an antidepressant in a given yr.
"Many people have antidepressants because they take been led to believe their depression has a biochemical cause, only this new research suggests this conventionalities is not grounded in bear witness."
The umbrella review aimed to capture all relevant studies that have been published in the most of import fields of research on serotonin and depression. The studies included in the review involved tens of thousands of participants.
Research that compared levels of serotonin and its breakdown products in the blood or brain fluids did not find a difference betwixt people diagnosed with depression and healthy control (comparing) participants.
Research on serotonin receptors and the serotonin transporter, the protein targeted by virtually antidepressants, found weak and inconsistent evidence suggestive of college levels of serotonin activity in people with depression. However, the researchers say the findings are likely explained by the utilise of antidepressants amongst people diagnosed with low, since such effects were not reliably ruled out.
The authors too looked at studies where serotonin levels were artificially lowered in hundreds of people past depriving their diets of the amino acid required to brand serotonin.
These studies have been cited equally demonstrating that a serotonin deficiency is linked to low. A meta-assay conducted in 2007 and a sample of contempo studies found that lowering serotonin in this mode did not produce depression in hundreds of good for you volunteers, even so.
At that place was very weak testify in a small subgroup of people with a family unit history of depression, just this only involved 75 participants, and more recent evidence was inconclusive.
Very large studies involving tens of thousands of patients looked at gene variation, including the gene for the serotonin transporter. They plant no divergence in these genes betwixt people with depression and healthy controls.
These studies too looked at the effects of stressful life events and plant that these exerted a strong effect on people'due south risk of becoming depressed – the more than stressful life events a person had experienced, the more likely they were to be depressed.
A famous early on study found a relationship between stressful events, the type of serotonin transporter gene a person had and the chance of low. But larger, more comprehensive studies suggest this was a fake finding.
These findings together led the authors to conclude that there is "no support for the hypothesis that low is acquired by lowered serotonin activeness or concentrations."
The researchers say their findings are of import as studies testify that as many as 85-90% of the public believes that depression is caused by depression serotonin or a chemic imbalance. A growing number of scientists and professional bodies are recognising the chemical imbalance framing as an over-simplification.
There is also evidence that assertive that low mood is caused by a chemical imbalance leads people to have a pessimistic outlook on the likelihood of recovery, and the possibility of managing moods without medical help. This is important because most people will meet criteria for anxiety or low at some bespeak in their lives.
The authors besides constitute evidence from a large meta-analysis that people who used antidepressants had lower levels of serotonin in their blood. They concluded that some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentrations.
The researchers say this may imply that the increment in serotonin that some antidepressants produce in the short term could lead to compensatory changes in the brain that produce the opposite effect in the long term.
While the study did not review the efficacy of antidepressants, the authors encourage further research and communication into treatments that might focus instead on managing stressful or traumatic events in people'due south lives, such as with psychotherapy, aslope other practices such as practice or mindfulness, or addressing underlying contributors such every bit poverty, stress and loneliness.
Professor Moncrieff said: "Our view is that patients should non be told that depression is acquired by depression serotonin or by a chemical imbalance, and they should not be led to believe that antidepressants work by targeting these unproven abnormalities. We practise non understand what antidepressants are doing to the brain exactly, and giving people this sort of misinformation prevents them from making an informed decision nearly whether to take antidepressants or not."
Co-author Dr Mark Horowitz, a grooming psychiatrist and Clinical Research Swain in Psychiatry at UCL and NELFT, said: "I had been taught that depression was caused by depression serotonin in my psychiatry preparation and had even taught this to students in my ain lectures. Beingness involved in this research was heart-opening and feels like everything I thought I knew has been flipped upside down.
"One interesting aspect in the studies we examined was how strong an consequence adverse life events played in depression, suggesting low mood is a response to people's lives and cannot exist boiled down to a simple chemical equation."
Professor Moncrieff added: "Thousands of people suffer from side furnishings of antidepressants, including the severe withdrawal furnishings that can occur when people endeavour to stop them, yet prescription rates continue to rise. We believe this situation has been driven partly by the false conventionalities that depression is due to a chemical imbalance. Information technology is high fourth dimension to inform the public that this conventionalities is not grounded in science."
The researchers caution that anyone because withdrawing from antidepressants should seek the advice of a health professional, given the risk of adverse effects following withdrawal. Professor Moncrieff and Dr Horowitz are conducting ongoing research into how best to gradually stop taking antidepressants.
Virtually this depression enquiry news
Author: Chris Lane
Source: UCL
Contact: Chris Lane – UCL
Epitome: The paradigm is in the public domain
Original Enquiry: Open access.
"The serotonin theory of depression: a systematic umbrella review of the evidence" by Joanna Moncrieff et al. Molecular Psychiatry
Abstract
The serotonin theory of low: a systematic umbrella review of the testify
The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research.
PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin v-HT1A receptor bounden; serotonin transporter (SERT) levels measured past imaging or at mail-mortem; tryptophan depletion studies; SERT gene associations and SERT cistron-environment interactions.
Studies of depression associated with concrete conditions and specific subtypes of low (e.g. bipolar low) were excluded. Two contained reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the Class. Nosotros did not synthesise results of individual meta-analyses because they included overlapping studies.
The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, i collaborative meta-assay, i meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic clan study and i umbrella review.
Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largestn = 1002).
I meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and prove that lowered serotonin concentration was associated with antidepressant use (n = 1869).
Ii meta-analyses of overlapping studies examining the 5-HT1A receptor (largestnorth = 561), and three meta-analyses of overlapping studies examining SERT bounden (largestn = 1845) showed weak and inconsistent prove of reduced bounden in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormally.
Withal, furnishings of prior antidepressant employ were not reliably excluded. One meta-analysis of tryptophan depletion studies establish no effect in nearly good for you volunteers (northward = 566), but weak evidence of an event in those with a family history of depression (north = 75). Another systematic review (n = 342) and a sample of ten subsequent studies (n = 407) found no effect in volunteers.
No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic clan study (due north = 115,257) and one collaborative meta-analysis (n = 43,165), revealed no prove of an clan with depression, or of an interaction between genotype, stress and depression.
The chief areas of serotonin inquiry provide no consistent bear witness of in that location existence an association between serotonin and depression, and no back up for the hypothesis that depression is acquired past lowered serotonin activity or concentrations.
Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.
Source: https://neurosciencenews.com/serotonin-depression-21074/
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