Depression, Serotonin, and the Mind-Gut Connection

Neuroscientists now think of the gut as a "second brain"; it independently controls your digestive processes and is in constant conversation with your main brain. What do they talk about? Depression, theorizes Dr Emeran Mayer.

Emeran Mayer: The Mind-Gut Connection is something that people have intuitively known for a long time but science has only I would say in the last few years gotten a grasp and acceptance of this concept. It essentially means that your brain has intimate connections with the gut and another entity in our gut, the second brain, which is about 100 million nerve cells that are sandwiched in between the layers of the gut. And they can do a lot of things on their own in terms of regulating our digestive processes. But there’s a very intimate conversation between that little brain, the second brain in the gut and our main brain. They use the same neurotransmitters. They’re connected by nerve pathways. And so we have really an integrated system from our brain to the little brain in the gut and it goes in both directions.

The little brain, or the second brain, in the gut you’re not able to see it because as I said it’s spread out through the entire length of the gut from your esophagus to the end of your large intestine, several layers of nerve cells interconnected. And what they do is even if you – and you can do this in animal experiments if you completely disconnect this little brain in the gut from your main brain this little brain can completely take care of all the digestive processes, the contractions, peristaltic reflex, regulation of blood flow in the intestine. And it has many sensors so it knows exactly what’s going on inside the gut, what goes on in the wall of the gut, any distention, any chemicals. All of this is being picked up by these sensory nerves, fed into the interior nervous system, the second brain. And then the second brain generates these stereotypic responses. So when you vomit, when you have diarrhea, when you have normal digestion, all of this is encoded in programs in your second brain.

What the second brain can’t do it cannot generate any conscious perceptions or gut feelings. That really is the only ability that allows us to do this and perceive all the stuff that goes on inside of us is really the big brain and the specific areas and circuits within the brain that process information that comes up from the gut. Still most of that information is not really consciously perceived. So 95 percent of all this massive amount of information coming from the gut is processed, integrated with other inputs that the brain gets from the outside, from smell, visual stimuli. And only a very small portion is then actually made conscious. So when you feel good after a meal or when you ate the wrong thing and you’re nauseated those are the few occasions where actually we realize and become aware of our gut feelings. Even though a lot of other stuff is going on in this brain-gut access all the time.

When we talk about the connection between depression and the gut there’s some very intriguing observations both clinically but also now more recently scientifically that make it highly plausible that there is an integrate connection between serotonin in the gut, serotonin in our food, depression and gut function.

On a clinical level there’s a connection because many patients with depression also complain of constipation. So a distinct dysfunction of the gut. And often the medications that people with depression take, particularly the serotonin reuptake inhibitors such as Prozac and all the other drugs in this category, they often cause transient gastrointestinal dysfunction. So that’s on the clinical level. However, what makes it particularly interesting and still an open question really more than 95 percent of all our serotonin we have in our organism is really produced and stored in the gut in specialized cells, so-called enterochromaffin cells. So our major by far the largest store of that molecule that plays such a big role in modulating our mood and our wellbeing, also appetite, pain, sensitivity is stored in the gut. And a lot of very interesting discoveries have been made more recently that makes this even more intriguing. So this serotonin is synthesized in the gut from precursors that come from our food that we ingest and the microbes that live in the gut are actually able through chemicals that they produce to stimulate the production of serotonin.

It’s been estimated based on studies in animals that 60 percent of the production is due to these signals that come from the microbes that live in our gut. So in addition another intriguing finding is that these serotonin cells, so they’re sandwiched in between the cells that make the lining of the gut. One end sticks into the inside samples, everything that goes on inside the gut. The other side very interestingly has an outgrowth which connected through a synapse with sensory nerve endings. So many vagal nerve endings. So this is a cell that sticks into the gut, samples a lot of things that go on in our digestive tract. Then it produces serotonin largely through the influence of microbes that live in our gut and then the signal when this cell is activated there’s many things chemical or mechanical stimuli associated with digestion. It signals through this synapse directly into our brain through the vagus nerve into centers that have to do with – I mean ultimately with emotional regulation and emotion generation. So even though we don’t have the proof for that it would be very difficult to mention that there’s not a significant influence on our mood and that this system if it’s out of balance does not play a significant role in the pathophysiology of depression.

There’s many food items that contain neuroreactive molecules signaling substances including oysters, chocolate and many other foods that to varying degrees contain either the precursors of serotonin or actually serotonin molecules. It’s possible that these contents of this molecule are the basis for some of these claimed effects of food items like oysters as an aphrodisiac or mood enhancer like with chocolate. People say they feel a lot better after they eat their daily piece of chocolate in the evening which is pretty true. Not just from the taste but from this chemical connection.

We all feel things in our gut – intuitions that give us subtle physiological alerts, stress and anxiety that unsettle us, bad reactions to food, and conversely feelings of contentment from the right food, or flutters from an exciting experience. But according to Dr Emeran Mayer, what we feel is just a small fraction of what’s going on in a region of our body that is still quite mysterious – even to the experts.


In his new book, The Mind-Gut Connection,, Dr Mayer writes: "Your gut has capabilities that surpass all our other organs and even rival your brain. It has its own nervous system, known in scientific literature as the enteric nervous system, or ENS, and [is] often referred to in the media as the "second brain.""

As Mayer describes, this second brain consists of about 100 million nerve cells sandwiched between layers of the gut running all the way from the esophagus to the end of the large intestine. This ‘second brain’ and our regular brain use the same neurotransmitters and are connected through neural, endocrine, and immune pathways, so it truly is an integrated intelligent system with information flowing in both directions.

What makes the second brain unique from other organs is that – in animals at least – when it’s separated from the main brain it continues to pilot its complex activities on its own.

The system is extremely interesting to researchers because of this independent streak, and the effect that it may have on our mental health. After his many years of research, Mayer humbly says it’s "highly plausible" that there is a connection between the gut and mental health conditions such as depression. Scientists from the University of North Carolina have found that gut bacteria produce neurotransmitters like serotonin, dopamine and GABA, all of which have associations with our mood. Often the medications people with depression take are designed to adjust the uptake of these neurotransmitters, a treatment scientists at the time designed thinking only of the brain, but it may now also have implications in the microbiome.

What makes it even more intriguing is that more than 95% of our body’s serotonin is produced and stored in the gut in specialized enterochromaffin cells, says Dr Mayer, adding: "By far the largest store of the molecule that plays such a big role in modulating our mood and our wellbeing – also appetite, pain sensitivity – is stored in the gut."

In recent years, the microbiome has come to the fore of scientific research, hinting at the wide reach of its sway over the body and mind. There is still a long, long way to go in understanding direct causations, but when that happens, there is no doubt our comprehension of this second brain will affect our well-being and quality of life in a big way.

Dr Emeran Mayer's most recent book is The Mind-Gut Connection: How the Hidden Conversation Within Our Bodies Impacts Our Mood, Our Choices, and Our Overall Health

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Political division is nothing new. Throughout American history there have been numerous flare ups in which the political arena was more than just tense but incideniary. In a letter addressed to William Hamilton in 1800, Thomas Jefferson once lamented about how an emotional fervor had swept over the populace in regards to a certain political issue at the time. It disturbed him greatly to see how these political issues seemed to seep into every area of life and even affect people's interpersonal relationships. At one point in the letter he states:

"I never considered a difference of opinion in politics, in religion, in philosophy, as cause for withdrawing from a friend."

Today, we Americans find ourselves in a similar situation, with our political environment even more splintered due to a number of factors. The advent of mass digital media, siloed identity-driven political groups, and a societal lack of understanding of basic discursive fundamentals all contribute to the problem.

Civil discourse has fallen to an all time low.

The question that the American populace needs to ask itself now is: how do we fix it?


Discursive fundamentals need to be taught to preserve free expression

In a 2017 Free Speech and Tolerance Survey by Cato, it was found that 71% of Americans believe that political correctness had silenced important discussions necessary to our society. Many have pointed to draconian university policies regarding political correctness as a contributing factor to this phenomenon.

It's a great irony that, colleges, once true bastions of free-speech, counterculture and progressiveness, have now devolved into reactionary tribal politics.

Many years ago, one could count on the fact that universities would be the first places where you could espouse and debate any controversial idea without consequence. The decline of staple subjects that deal with the wisdom of the ancients, historical reference points, and civic discourse could be to blame for this exaggerated partisanship boiling on campuses.

Young people seeking an education are given a disservice when fed biased ideology, even if such ideology is presented with the best of intentions. Politics are but one small sliver for society and the human condition at large. Universities would do well to instead teach the principles of healthy discourse and engagement across the ideological spectrum.

The fundamentals of logic, debate and the rich artistic heritage of western civilization need to be the central focus of an education. They help to create a well-rounded citizen that can deal with controversial political issues.

It has been found that in the abstract, college students generally support and endorse the first amendment, but there's a catch when it comes to actually practicing it. This was explored in a Gallup survey titled: Free Expression on Campus: What college students think about First amendment issues.

In their findings the authors state:

"The vast majority say free speech is important to democracy and favor an open learning environment that promotes the airing of a wide variety of ideas. However, the actions of some students in recent years — from milder actions such as claiming to be threatened by messages written in chalk promoting Trump's candidacy to the most extreme acts of engaging in violence to stop attempted speeches — raise issues of just how committed college students are to
upholding First Amendment ideals.

Most college students do not condone more aggressive actions to squelch speech, like violence and shouting down speakers, although there are some who do. However, students do support many policies or actions that place limits on speech, including free speech zones, speech codes and campus prohibitions on hate speech, suggesting that their commitment to free speech has limits. As one example, barely a majority think handing out literature on controversial issues is "always acceptable."

With this in mind, the problems seen on college campuses are also being seen on a whole through other pockets of society and regular everyday civic discourse. Look no further than the dreaded and cliche prospect of political discussion at Thanksgiving dinner.

Talking politics at Thanksgiving dinner

As a result of this increased tribalization of views, it's becoming increasingly more difficult to engage in polite conversation with people possessing opposing viewpoints. The authors of a recent Hidden Tribes study broke down the political "tribes" in which many find themselves in:

  • Progressive Activists: younger, highly engaged, secular, cosmopolitan, angry.
  • Traditional Liberals: older, retired, open to compromise, rational, cautious.
  • Passive Liberals: unhappy, insecure, distrustful, disillusioned.
  • Politically Disengaged: young, low income, distrustful, detached, patriotic, conspiratorial
  • Moderates: engaged, civic-minded, middle-of-the-road, pessimistic, Protestant.
  • Traditional Conservatives: religious, middle class, patriotic, moralistic.
  • Devoted Conservatives: white, retired, highly engaged, uncompromising,
    Patriotic.

Understanding these different viewpoints and the hidden tribes we may belong to will be essential in having conversations with those we disagree with. This might just come to a head when it's Thanksgiving and you have a mix of many different personalities, ages, and viewpoints.

It's interesting to note the authors found that:

"Tribe membership shows strong reliability in predicting views across different political topics."

You'll find that depending on what group you identify with, that nearly 100 percent of the time you'll believe in the same way the rest of your group constituents do.

Here are some statistics on differing viewpoints according to political party:

  • 51% of staunch liberals say it's "morally acceptable" to punch Nazis.
  • 53% of Republicans favor stripping U.S. citizenship from people who burn the American flag.
  • 51% of Democrats support a law that requires Americans use transgender people's preferred gender pronouns.
  • 65% of Republicans say NFL players should be fired if they refuse to stand for the anthem.
  • 58% of Democrats say employers should punish employees for offensive Facebook posts.
  • 47% of Republicans favor bans on building new mosques.

Understanding the fact that tribal membership indicates what you believe, can help you return to the fundamentals for proper political engagement

Here are some guidelines for civic discourse that might come in handy:

  • Avoid logical fallacies. Essentially at the core, a logical fallacy is anything that detracts from the debate and seeks to attack the person rather than the idea and stray from the topic at hand.
  • Practice inclusion and listen to who you're speaking to.
  • Have the idea that there is nothing out of bounds for inquiry or conversation once you get down to an even stronger or new perspective of whatever you were discussing.
  • Keep in mind the maxim of : Do not listen with the intent to reply. But with the intent to understand.
  • We're not trying to proselytize nor shout others down with our rhetoric, but come to understand one another again.
  • If we're tied too closely to some in-group we no longer become an individual but a clone of someone else's ideology.

Civic discourse in the divisive age

Debate and civic discourse is inherently messy. Add into the mix an ignorance of history, rabid politicization and debased political discourse, you can see that it will be very difficult in mending this discursive staple of a functional civilization.

There is still hope that this great divide can be mended, because it has to be. The Hidden Tribes authors at one point state:

"In the era of social media and partisan news outlets, America's differences have become
dangerously tribal, fueled by a culture of outrage and taking offense. For the combatants,
the other side can no longer be tolerated, and no price is too high to defeat them.
These tensions are poisoning personal relationships, consuming our politics and
putting our democracy in peril.


Once a country has become tribalized, debates about contested issues from
immigration and trade to economic management, climate change and national security,
become shaped by larger tribal identities. Policy debate gives way to tribal conflicts.
Polarization and tribalism are self-reinforcing and will likely continue to accelerate.
The work of rebuilding our fragmented society needs to start now. It extends from
re-connecting people across the lines of division in local communities all the way to
building a renewed sense of national identity: a bigger story of us."

We need to start teaching people how to approach subjects from less of an emotional or baseless educational bias or identity, especially in the event that the subject matter could be construed to be controversial or uncomfortable.

This will be the beginning of a new era of understanding, inclusion and the defeat of regressive philosophies that threaten the core of our nation and civilization.