Rethinking serotonin could lead to a shift in psychiatric care

September 5, 2017 by Ryan O'hare
Refining the model of how serotonin acts in the brain (illustrated) could help to improve treatments for mental health conditions. Credit: Imperial College London

A better understanding of how a key chemical messenger acts in the brain could lead to a radical shift in psychiatric care, according to a new paper.

Serotonin is a neurotransmitter which helps cells communicate with one another, playing important roles in stabilising mood and regulating stress.

Despite its importance, current models to explain serotonin's function in the brain remain incomplete.

Now, in a review paper published this month in the Journal of Psychopharmacology, researchers from Imperial College London suggest that serotonin pathways are more nuanced than previously thought.

They argue that the existing view should be updated to incorporate a 'two-pronged' model of how serotonin acts.

The researchers believe their updated model could have implications for treating recalcitrant mental health conditions, including depression, obsessive compulsive disorder and addiction, and could exploit the therapeutic potential of psychedelic drugs.

In the brain, serotonin acts via a number of sites called 'receptors' and serotonin has at least 14 of these. Brain drugs such antidepressants, antipsychotics and are known to interact with serotonin receptors and two of these are thought to be particularly important - the so-called serotonin 1A and 2A receptors.

For patients with depression, commonly prescribed drugs called SSRIs (Selective Serotonin Reuptake Inhibitors) can help to relieve symptoms by boosting levels of serotonin in the brain. Evidence suggests an important part of how they work is to increase activity at the serotonin 1A receptor, which reduces brain activity in important stress circuitry, thereby helping a person cope better.

In contrast, psychedelic compounds such as LSD and psilocybin (the psychoactive component of magic mushrooms), are thought to act primarily on the serotonin 2A receptor. Accumulating evidence suggests that psychedelics with psychotherapy can be an effective treatment for certain mental illnesses and, with a focus on the 2A receptor, the authors' paper attempts to explain why.

Breaking the cycle

Writing in the review paper, the researchers say that while the traditional view of developing psychiatric treatments has been focused on promoting 1A activity and often blocking the 2A, the therapeutic importance of activating the 2A pathway – the mechanism by which psychedelics have their effect – has been largely overlooked.

"We may have got it wrong in the past," said Dr Robin Carhart-Harris, Head of Psychedelic Research at Imperial and lead author on the paper. "Activating serotonin 2A receptors may be a good thing, as it makes individuals very sensitive to context and to their environment. Crucially, if that is made therapeutic, then the combination can be very effective. This is how psychedelics work – they make people sensitive to context and 'open' to change via activating the 2A receptor."

According to the researchers, the 1A and 2A pathways form part of a two-pronged approach which may have evolved to help us adapt to adversity. By triggering the 1A pathway, serotonin can make situations less stressful, helping us to become more resilient. However, they argue that this approach may not always be enough, and that in extreme crises, the 2A pathway may kick in to rapidly open a window of plasticity in which fundamental changes in outlook and behaviour can occur.

Growing evidence shows that in conditions such as treatment-resistant depression, obsessive compulsive disorder and addiction, certain brain circuitry may become 'stamped in' and resistant to change. The researchers suggest that in such cases, activating the 2A pathway – such as through psychedelics – could potentially offer a way to break the cycle, helping patients to change negative behaviours and thought patterns which have become entrenched.

By enabling the brain to enter into a more adaptive or 'plastic' state and providing patients with a suitably enriched clinical environment when they receive a drug treatment, clinicians could create a window for therapy, effectively making patients more receptive to psychotherapy.

Improving treatment

According to the authors, their updated model of how serotonin acts in the brain could lead to a shift in , with the potential to move patients from enduring a condition using current pharmacological treatments, to actively addressing their condition by fundamentally modifying behaviours and thinking.

Professor David Nutt, Director of Neuropsychopharmacology in Imperial's Division of Brain Sciences, explained: "This is an exciting and novel insight into the role of and its in recovery from depression that I hope may inspire more research into develop 5-HT2A receptor drugs as new treatments."

Dr Carhart-Harris added: "I think our model suggests that you cannot just administer a drug in isolation, at least certainly not psychedelics, and the same may also be true for SSRIs.

"We need to pay more attention to the context in which medications are given. We have to acknowledge the evidence which shows that environment is a critical component of how our biology is expressed."

He added: "In psychiatry, as in science, things are rarely black and white, and part of the approach we're promoting is to have a more sophisticated model of mental healthcare that isn't just a drug or psychotherapy, it's both. I believe this is the future."

Explore further: Study suggests serotonin may worsen tinnitus

More information: RL Carhart-Harris et al. Serotonin and brain function: a tale of two receptors, Journal of Psychopharmacology (2017). DOI: 10.1177/0269881117725915

Related Stories

Study suggests serotonin may worsen tinnitus

August 22, 2017
Millions of people suffer from the constant sensation of ringing or buzzing in the ears known as tinnitus, creating constant irritation for some and severe anxiety for others. Research by scientists at OHSU shows why a common ...

Depression study finds evidence of serotonin signal transduction disturbances

August 26, 2015
Depression and anxiety disorders are the most common psychiatric disorders. Over the last few years, molecular brain imaging using Positron Emission Tomography (PET) has helped us to identify important mechanisms involved ...

The science behind many antidepressants appears to be backwards, researchers say

February 18, 2015
The science behind many antidepressant medications appears to be backwards, say the authors of a paper that challenges the prevailing ideas about the nature of depression and some of the world's most commonly prescribed medications.

Compound enhances SSRI antidepressant's effects in mice

June 21, 2013
A synthetic compound is able to turn off "secondary" vacuum cleaners in the brain that take up serotonin, resulting in the "happy" chemical being more plentiful, scientists from the School of Medicine at The University of ...

Scientists identify key receptor as potential target for treatment of autism

September 30, 2015
Scientists from the Florida campus of The Scripps Research Institute (TSRI) have uncovered a significant—and potentially treatable—relationship between a chemical that helps transmit signals in the brain and genetic mutations ...

Individuals with social phobia have too much serotonin—not too little

June 17, 2015
Previous studies have led researchers to believe that individuals with social anxiety disorder/ social phobia have too low levels of the neurotransmitter serotonin. A new study carried out at Uppsala University, however, ...

Recommended for you

Behavioral therapy increases connectivity in brains of people with OCD

September 19, 2017
UCLA researchers report that people with obsessive-compulsive disorder, when treated with a special form of talk therapy, demonstrate distinct changes in their brains as well as improvement in their symptoms.

Cognitive scientists find that people can more easily communicate warmer colors than cool ones

September 18, 2017
The human eye can perceive millions of different colors, but the number of categories human languages use to group those colors is much smaller. Some languages use as few as three color categories (words corresponding to ...

Why bad sleep doesn't always lead to depression

September 18, 2017
Poor sleep is both a risk factor, and a common symptom, of depression. But not everyone who tosses and turns at night becomes depressed.

Happiness is not determined by childhood biomarkers

September 18, 2017
Happiness is not determined by childhood biological markers such as height or body fat, according to a team of European researchers involving UCL.

People with schizophrenia have threefold risk of dying

September 18, 2017
People with schizophrenia are three times more likely to die, and die younger, than the general population, indicating a need for solutions to narrow this gap, according to research published in CMAJ (Canadian Medical Association ...

The bilingual brain calculates arithmetic differently depending on the language

September 15, 2017
People can intuitively recognise small numbers up to four; however, when calculating, they depend on the assistance of language. This presents a fascinating research question: How do multilingual people solve arithmetical ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Sep 06, 2017
So in other words the old "you need more serotonin to feel less depressed" was never true

(there are also SSREs like tianeptine which work by *decreasing* serotonin)

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.