New research in Biological Psychiatry offers the first direct evidence of diminished 5-HT release cements “serotonin hypothesis.”
Researchers have postulated since the 1960s that major depression stems from disruptions in the serotonin neurotransmitter system. However, the evidence for that idea, though plentiful, was indirect. In fact, a recent comprehensive analysis of existing studies concluded that there was not strong evidence to support the “serotonin hypothesis.” In its wake, some in the field have called for a reexamination of the hypothesis. Not so fast, says a new study that provides direct evidence of disrupted serotonin release in the brains of individuals with depression.
The study was published recently in the journal Biological Psychiatry.
Depression is among the most common mental illnesses and causes of disability worldwide. Despite the lack of direct evidence for disrupted serotonin signaling in the depressed brain, medications used to treat depression overwhelmingly target the serotonin signaling system to increase extracellular serotonin, also known as 5-hydroxytryptamine (5-HT). Only about half of patients respond to antidepressants, and fewer than 30% experience total remission. A better understanding of 5-HT dynamics in depression could help guide more effective therapies.
“Our thinking about the role of serotonin in depression has evolved significantly over the past decade. We once thought that serotonin changes could account for the entirety of depression. When this simple hypothesis could no longer be supported, some were inclined to dismiss any role for serotonin in depression,” said John Krystal, MD, editor-in-chief of Biological Psychiatry. “The current study provides important new support for further exploration of the role of serotonin in depression. This is particularly timely, as drugs targeting serotonin receptors, such as psychedelics, are being explored as potential new treatments for mood disorders.”
The study, conducted by Invicro, a global, imaging contract research organization, in collaboration with researchers from Imperial College London, King’s College London, Copenhagen University, and the University of Oxford, used a novel imaging technique to look directly at the magnitude of serotonin released from neurons in response to a pharmacological challenge. In previous work, these researchers pioneered the use of positron emission tomography (PET) with the radioligand [11C]Cimbi-36 to detect serotonin release. In the current study, the researchers applied this methodology to compare serotonin release in 17 patients with depression and 20 healthy individuals.
David Erritzoe, MRCPsych, PhD, lead author of the paper, said, “This study used a new and more direct method to measure serotonin in the living human brain, and the results suggest reduced serotonin (release) functioning in depression. This imaging method, in combination with similar methods for other brain systems, has the potential to help us to better understand the varying — sometimes limited or even lacking — treatment responses that people with depression have to antidepressant medication.”
Participants with depression and healthy controls underwent PET scanning with [11C]Cimbi-36 to measure 5-HT2A receptor availability in the frontal cortex; the two groups did not differ significantly at baseline. Both groups then received a dose of d-amphetamine, a stimulant drug that works to increase 5-HT concentration outside of neurons, where it interacts with 5-HT2A receptors and reduces the binding of [11C]Cimbi-36. In a second scanning session three hours after drug administration, healthy control participants had significantly reduced 5-HT2A receptor availability, indicating an increase in serotonin levels. Participants with depression, however, did not show a significant decrease in binding potential, suggesting they had a blunted serotonin release capacity in key brain regions.
The study found no relationship between the severity of depression and the extent of serotonin release capacity deficits. Of note, all patients were free of antidepressant medication, and 11 out of the 17 had never received antidepressant treatment, indicating that low serotonin release capacity is a feature of depression rather than a result of antidepressant treatment.
This first direct evaluation of serotonin levels in the brain of individuals with depression is a major step forward in laying to rest the speculations questioning the involvement of serotonergic neurotransmission in the pathology of depression. Depression is a multifaceted disorder that may have multiple causes, and different subtypes may involve multiple neurotransmitter systems. Serotonergic dysfunction is unlikely to explain all the clinical features encountered in this disorder. Nevertheless, this study demonstrates that serotonergic deficits are present in unmedicated depressed individuals.
Eugenii Rabiner, MBBCh, FCPsych SA, at Invicro and senior author of the paper said, “It has taken our field over 20 years to develop a method that enables the measurement of serotonin release in the living human brain. I am very pleased that we managed to develop this method and apply it to clarify this important aspect of the pathophysiology of depression. I hope that we can use this technique in future to explore the different symptoms of depression, as well as serotonergic deficits found in other conditions, such as Parkinson’s disease.”
Reference: “Brain Serotonin Release Is Reduced in Patients With Depression: A [11C]Cimbi-36 Pet Study With a D-Amphetamine Challenge” by David Erritzoe, Beata R. Godlewska, Gaia Rizzo, Graham E. Searle, Claudio Agnorelli, Yvonne Lewis, Abhishekh H. Ashok, Alessandro Colasanti, Iro Boura, Chloe Farrell, Hollie Parfit, Oliver Howes, Jan Passchier, Roger N. Gunn, David J. Nutt, Philip J. Cowen, Gitte Knudsen and Eugenii A. Rabiner, 28 October 2022, Biological Psychiatry.
I suppose it would be hard to justify a multi-billion dollar drug sales racket without the lie that mental illness has a “proven” biological basis.
Unfortunately peer review has long not done what it’s purported to do in psychiatry, especially regarding biological psychiatry when private funding is involved. Published or not, the results of the aforementioned study are anything but reliable.
For a more detailed criticism, please see https://www.madinamerica.com/2022/11/the-serotonin-zombie-authors-of-new-study-try-to-breathe-new-life-into-the-dead/.
I would recommend being careful with what you report. Unless you’re also receiving private funding from the funders of the study. In which case, you should make that clear.
This nonsense has been so debunk it actually showed up on Fox News Tucker Carlson. So I guess that means it’s time to put out another quote research paper proving nothing. By the way I couldn’t help but notice a lot of comments like “suggests” blah blah blah blah blah. I suggest sci-tech daily it’s nothing more than a for-profit Blog with questionable sources.
Eat a dick, Gary Graham. If you’re watching Tucker Carlson, you’re telling everyone that you read the headline and nothing else. You wouldn’t be able to tell the difference between an empirically reviewed article and a wet c*ck if they slapped you in the face. Imbecile
This article shows it’s entire point is to find some other reason than to use psychedelic therapy, while showing no actual help with depression via serotonin alone.
Gary Graham, simply by mentioning the fact that FOX “News” talking head Tucker Carlson needed to blab on about it because it was “debunked”, is evidence enough for me to trust that this is likely a legitimately groundbreaking study. Tuck’s ability to spin the truth is like a carnival ride – dizzying and disorienting. 😵💫
Mention Tucker Carlson and Science or History or anything else for that matter and you obviously don’t care for truth, justice and the American way. Lol its garbage spewing and nothing else.
“This first direct evaluation of serotonin levels in the brain of individuals with depression is a major step forward in laying to rest the speculations questioning the involvement of serotonergic neurotransmission in the pathology of depression.”
So, it is clear that this article has an axe to grind. Furthermore, this article simply supports the growing consensus–namely that none of the current research shows an unequivocal connection between serotonin levels and depression, OR that serotonin treatments effectively treat depression.
All this research did was to show that serotonin MAY be related to depression–it demonstrated correlated relationship, not a causal relationship.
One study funded by a drug company is not sufficient to prove anything. The article doesn’t comment on whether the “depressed” people were or had been taking antidepressants, a HUGE confounding factor, as ADs are well known to disrupt serotonin receptors. So we may very well be seeing that ADs cause lower serotonin problems in the long run, a hypothesis that has been put forward long ago (look up neurological down regulation).
Problem is, when this study is predictably debunked, it won’t be front page news, and most folks will never find out they were scammed.
You said, “The article doesn’t comment on whether the “depressed” people were or had been taking antidepressants”.
However, in paragraph 8, it says: “Of note, all patients were free of antidepressant medication, and 11 out of the 17 had never received antidepressant treatment, indicating that low serotonin release capacity is a feature of depression rather than a result of antidepressant treatment.”
True, only 11 out of 17 had never received antidepressant medication, so 6 had received it. The point is that your comment that the article omitted this information is incorrect….
Correlation does not equal causation. Science 101. This is like saying eating ice cream causes people to kill other people because there is a positive relationship between ice cream sales and murder rates (which actually exists; see heat hypothesis). Serotonin function may be altered, but that does nothing to show it’s a causal factor.
Do you know the damage you do to people by changing the chemicals in the brain? It’s awful. Just 1 more drug that you think is putting them in remission it doesn’t work like that everyone thinks the person has an imbalance in the brain how do you know what you are giving them will make a difference. How about finding out why the person is depressed some counseling in the hospitals to talk to. The hospitals create more depression no one to talk to and isolation worse then the COVID not knowing when you are getting out COVID-19 most of the time you will get over it. If the depression is environmental no drug on this planet is going to help that person well instead it might destroy that person’s life. Are you willing to take that chance? Do you care? There needs to be a chance in the Mental health system find out what the trauma is the person is dealing with before giving them a drug that changes the brain. I pray to God you are listening. I know it happened to ME! Email me if you want some more information