According to a new study published in Nature, depression may not be caused by a serotonin imbalance in the brain as previously assumed.
For the past three decades, people have been bombarded with material that suggests depression is brought on by a “chemical imbalance” in the brain, namely an imbalance of serotonin. The evidence, however, does not support it, according to our most recent examination of the research (pdf below).
The pharmaceutical industry began heavily promoting the serotonin theory of depression in the 1990s in conjunction with its efforts to sell a new class of antidepressants known as selective serotonin-reuptake inhibitors, or SSRIs, despite the fact that it was initially put forth in the 1960s. The American Psychiatric Association, which continues to warn the public that “differences in certain chemicals in the brain may contribute to symptoms of depression,” supported the theory as well.
Numerous doctors have spread the word throughout the world in their private clinics and in the media. People believed what was told to them. And many people began using antidepressants because they thought there was a problem with their brain that needed to be fixed by an antidepressant. Antidepressant use increased considerably during this marketing campaign; today, one in six adults in England, for instance, receives a prescription for one.
Some academics, including some eminent psychiatrists, have long argued that there isn’t enough proof to back the theory that depression is caused by abnormally low or inactive serotonin. Others still support the theory. However until now there hasn’t been a thorough analysis of the studies on serotonin and depression that would have allowed for definitive findings.
At first glance, the serotonin system-targeting properties of SSRI-type antidepressants seem to corroborate the serotonin theory of depression. Although SSRIs momentarily raise serotonin levels in the brain, this does not always mean that depression is brought on by the opposite effect.
The effects of antidepressants can also be explained by other factors. Drug studies actually reveal that when it comes to treating depression, antidepressants are hardly distinguishable from a placebo (fake tablet). Additionally, antidepressants seem to have a generalized emotion-numbing effect that may affect people’s moods, while neither the cause nor the details of this impact are well understood.
First comprehensive review
Since the 1990s, there has been a lot of study on the serotonin system, but it has never been systematically collected. We performed a “umbrella” review, which involves carefully locating and compiling existing summaries of the data from each of the key domains of serotonin and depression research. Although there have previously been systematic studies of certain fields, none have pooled the information from all the fields using this approach.
Research comparing the levels of serotonin and the byproducts of its breakdown in the blood or brain fluid was one area of study we included. Overall, this study found no distinction between those who suffer from depression and those who do not.
Serotonin receptors, which are proteins on the terminals of the nerves that serotonin connects with and which can transmit or suppress serotonin’s actions, have also been the subject of research. The most often studied serotonin receptor revealed either no differences between depressed and non-depressed individuals or, contrary to the serotonin theory’s prediction, higher serotonin activity in depressed individuals.
Research on the protein known as a serotonin “transporter,” which helps to end the effects of serotonin and is the protein that SSRIs operate on, also revealed that, if anything, serotonin activity was increased in depressed individuals. However, these results could be explained by the fact that numerous study participants had used or were currently using antidepressants.
We also reviewed studies that investigated whether serotonin levels could be intentionally lowered in order to produce depression in volunteers. At the time the current research was completed, a sample of the ten most recent studies and two systematic reviews from 2006 and 2007 revealed that reducing serotonin did not cause depression in a large number of healthy volunteers. A small subset of individuals with a family history of depression showed very flimsy evidence of an effect in one of the reviews, however there were only 75 participants.
Gene variation, including the gene that contains the instructions for creating the serotonin transporter, was studied in extremely large studies including tens of thousands of patients. They discovered no variation in the frequency of this gene’s variants between individuals with depression and healthy controls.
Despite the fact that a well-known early study linked the serotonin transporter gene to stressful life events, larger, more thorough investigations indicate no such link exists. However, stressful life events had a significant impact on people’s likelihood of later developing depression.
Antidepressants may actually diminish the concentration or activity of serotonin, according to certain research in our review that involved participants who were currently taking or had previously taken antidepressants.
Not supported by the evidence
One of the most popular and well-researched scientific ideas about the causes of depression is the serotonin theory. Our research demonstrates that there is no evidence to back up this viewpoint. It also questions the rationale of using antidepressants.
It is assumed that the majority of antidepressants in use today work by influencing serotonin. Some also have an impact on noradrenaline, a brain chemical. However, experts concur that there is less support for noradrenaline’s role in depression than there is for serotonin.
No additional pharmacological mechanism for how antidepressants might effect depression is accepted at this time. Antidepressants may not do more good than harm if they act as placebos or by numbing the emotions.
Although it might appear that treating depression as a biological disorder would lessen stigma, research has shown that this is not the case. Additionally, those who think their personal melancholy is brought on by a chemical imbalance are less optimistic about their chances of recovery.
It’s crucial for people to understand that the notion that depression is caused by a “chemical imbalance” is purely speculative. Furthermore, we do not fully comprehend the effects of antidepressants’ briefly elevated serotonin levels or other biochemical changes on the brain. We come to the conclusion that it is impossible to establish whether using SSRI antidepressants is beneficial or even entirely safe.
It’s critical that you talk to your doctor before stopping any antidepressants you’re taking. But in order to decide whether or not to use these drugs, patients need all of this information.
Read the study given below: