Month: August 2015

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Research identifies biomarkers of suicide across psychiatric disorders

The ability to predict suicidal ideation by looking at the amount of expression of certain genes is quite amazing in and of itself, but what is really amazing is that lithium alters sodium transport and may interfere with ion exchange mechanisms and nerve conduction. Fluid and electrolyte metabolism are believed to be altered in affective disorders and this may be related to the therapeutic action of lithium. SLC4A4 is involved in sodium transport, and it is this protein which is a biomarker for suicidal ideation. Could this also be one of the key proteins involved in mental illness? Why isn’t anyone but me asking this question? Oh my goodness, I’m going to call my psychiatrist and run this by him. These relationships are not random, there is something quite important going on here. Na+ transporter protein predicts chances of suicide, Na+ influx and outflux, possibly the pumps that do this, are affected by lithium which treats bipolar d/o!  Read on please!

Researchers identified biomarkers of suicidal ideation across multiple psychiatric disorders and developed an application to help clinicians accurately screen for suicide risk. These researchers looked at the expression of different genes and changes in their expression between a no suicidal state to a high suicidal state, to see if one of them would signal suicidal ideation in bipolar d/o, major depressive d/o, schizoaffective d/o and schizophrenia. They looked at 217 males with bipolar d/o, major depressive d/o, schizoaffective d/o or schizophrenia.

What they found was that SLC4A4 was the best biomarker for suicidal ideation across all illnesses! This gene encodes a membrane protein transporter which transports sodium bicarbonate across cell membranes. Sodium bicarbonate cotransporters, like SLC4A4, mediate the coupled movement of sodium and bicarbonate ions across the plasma membrane of many cells. This is an electrogenic process with an apparent stoichiometry of 3 bicarbonate ions per sodium ion. SLC4A4 predicted suicidal ideation among participants with bipolar disorder with an area under the curve (AUC) of 93% and future hospitalizations with an AUC of 70%. Using questionnaires such as the simplified affective state scale (SASS) and Convergent Functional Information for Suicide (CFI-S) which measure suicidal ideation along with the biomarker SLC4A4, the AUC was 92% for all psychiatric diagnoses, 98% for bipolar disorder and 94% for future hospitalizations.

http://www.ncbi.nlm.nih.gov/pubmed/26283638

Understanding and predicting suicidality using a combined genomic and clinical risk assessment approach.
Abstract

Worldwide, one person dies every 40 seconds by suicide, a potentially preventable tragedy. A limiting step in our ability to intervene is the lack of objective, reliable predictors. We have previously provided proof of principle for the use of blood gene expression biomarkers to predict future hospitalizations due to suicidality, in male bipolar disorder participants. We now generalize the discovery, prioritization, validation, and testing of such markers across major psychiatric disorders (bipolar disorder, major depressive disorder, schizoaffective disorder, and schizophrenia) in male participants, to understand commonalities and differences. We used a powerful within-participant discovery approach to identify genes that change in expression between no suicidal ideation and high suicidal ideation states (n=37 participants out of a cohort of 217 psychiatric participants followed longitudinally). We then used a convergent functional genomics (CFG) approach with existing prior evidence in the field to prioritize the candidate biomarkers identified in the discovery step. Next, we validated the top biomarkers from the prioritization step for relevance to suicidal behavior, in a demographically matched cohort of suicide completers from the coroner’s office (n=26). The biomarkers for suicidal ideation only are enriched for genes involved in neuronal connectivity and schizophrenia, the biomarkers also validated for suicidal behavior are enriched for genes involved in neuronal activity and mood. The 76 biomarkers that survived Bonferroni correction after validation for suicidal behavior map to biological pathways involved in immune and inflammatory response, mTOR signaling and growth factor regulation. mTOR signaling is necessary for the effects of the rapid-acting antidepressant agent ketamine, providing a novel biological rationale for its possible use in treating acute suicidality. Similarly, MAOB, a target of antidepressant inhibitors, was one of the increased biomarkers for suicidality. We also identified other potential therapeutic targets or biomarkers for drugs known to mitigate suicidality, such as omega-3 fatty acids, lithium and clozapine. Overall, 14% of the top candidate biomarkers also had evidence for involvement in psychological stress response, and 19% for involvement in programmed cell death/cellular suicide (apoptosis). It may be that in the face of adversity (stress), death mechanisms are turned on at a cellular (apoptosis) and organismal level. Finally, we tested the top increased and decreased biomarkers from the discovery for suicidal ideation (CADM1, CLIP4, DTNA, KIF2C), prioritization with CFG for prior evidence (SAT1, SKA2, SLC4A4), and validation for behavior in suicide completers (IL6, MBP, JUN, KLHDC3) steps in a completely independent test cohort of psychiatric participants for prediction of suicidal ideation (n=108), and in a future follow-up cohort of psychiatric participants (n=157) for prediction of psychiatric hospitalizations due to suicidality. The best individual biomarker across psychiatric diagnoses for predicting suicidal ideation was SLC4A4, with a receiver operating characteristic (ROC) area under the curve (AUC) of 72%. For bipolar disorder in particular, SLC4A4 predicted suicidal ideation with an AUC of 93%, and future hospitalizations with an AUC of 70%. SLC4A4 is involved in brain extracellular space pH regulation. Brain pH has been implicated in the pathophysiology of acute panic attacks. We also describe two new clinical information apps, one for affective state (simplified affective state scale, SASS) and one for suicide risk factors (Convergent Functional Information for Suicide, CFI-S), and how well they predict suicidal ideation across psychiatric diagnoses (AUC of 85% for SASS, AUC of 89% for CFI-S). We hypothesized a priori, based on our previous work, that the integration of the top biomarkers and the clinical information into a universal predictive measure (UP-Suicide) would show broad-spectrum predictive ability across psychiatric diagnoses. Indeed, the UP-Suicide was able to predict suicidal ideation across psychiatric diagnoses with an AUC of 92%. For bipolar disorder, it predicted suicidal ideation with an AUC of 98%, and future hospitalizations with an AUC of 94%. Of note, both types of tests we developed (blood biomarkers and clinical information apps) do not require asking the individual assessed if they have thoughts of suicide, as individuals who are truly suicidal often do not share that information with clinicians. We propose that the widespread use of such risk prediction tests as part of routine or targeted healthcare assessments will lead to early disease interception followed by preventive lifestyle modifications and proactive treatment.Molecular Psychiatry advance online publication, 18 August 2015; doi:10.1038/mp.2015.112.

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Suicide Prevention Awareness Month. National Suicide Hotline 1-800-273 TALK (8255)

One of the worst things to happen to anyone is to lose a precious, beloved family member to suicide. I know. I lost my 26 year old brother, Farooq, in 1991. It is not something that you ever get over. The loss, the emptiness, the heartache, the guilt, the devastation, they never go away. The “if only I’d …” been there, done this, held on to his hand so he couldn’t have walked away, the if onlys, they never go away. I wasn’t even in Buffalo when it happened. If only I’d been there, I may well have been able to help him. I would still give my right arm to have him here with us, with his beautiful, endearing smile, his goofy jokes, his sweetness, his sensitivity, his love.

September is Suicide prevention month. This article from NAMI is an excellent article, with a great amount of information to help people who are thinking of suicide, hotlines, it also has information for people who are friends or family of someone who is thinking of suicide. I hope my posting this will help people, will prevent this devastating loss from happening to people. Read on.

SuicidePrevention

https://www.nami.org/Get-Involved/Raise-Awareness/Awareness-Events/Suicide-Prevention-Awareness-Month

“September 2015 is also known as National Suicide Prevention Awareness Month which helps promote resources and awareness around the issues of suicide prevention, how you can help others and how to talk about suicide without increasing the risk of harm.

Suicidal thoughts can affect anyone regardless of age, gender or background. Suicide is the third leading cause of death among young people and is often the result of mental health conditions that effect people when they are most vulnerable. Suicidal thoughts and suicide occur too frequently but should not be considered common and can indicate more serious issues. In many cases the individuals, friends and families affected by suicide are left in dark, feeling shame or stigma that prevents talking openly about issues dealing with suicide.

Crisis and Information Resources

  • I’m in crisis or am experiencing difficult or sucidal thoughts: National Suicide Hotline 1-800-273 TALK (8255)
  • I’m looking for more information, referrals or support: NAMI HelpLine 800-950-NAMI (6264)

If you or someone you know is in an emergency, call The National Suicide Prevention Lifeline at 1-800-273-TALK (8255) or call 911 immediately.

If you or someone you know is in an emergency, call The National Suicide Prevention Lifeline at 1-800-273-TALK (8255) or call 911 immediately. – See more at: http://www.nami.org/suicide#sthash.GE2GI37c.dpuf

World Suicide Prevention Day

On September 10, 2015 we observe World Suicide Prevention Day to reach out to those affected by suicide, raise awareness and connect indiviudals with suicidal ideation to treatment services. It is also important to ensure that individuals, friends and families have access to the resources they need to address suicide prevention.

What else can I do?

We believe that these issues are important to address year round. Highlighting these issues during Suicide Prevention Awareness Month and World Suicide Prevention Day provides a time for people to come together and display the passion and strength of those working to improve the lives of the millions of Americans that can benefit from honest discussions about mental health conditions and suicide. In fighting for those living with mental illness there is still much more that needs to be done and more ways to get involved.

If you or someone you know may need a mental health assessment, anonymous online tools are available. Learn more and help yourself or someone you care about.

Awareness Resources

Share the images and graphics below during the month of September to help promote awareness of suicide prevention resources and promote discussion of suicide prevention awareness. You can also use #suicideprevention or #IAmStigmaFree on social media.

Facebook Cover Image and Badge:

Facebook Cover Image 851x315px

Facebook Share Image 1200x1200px

Twitter Cover Image and Badge:

Twitter Cover Image 1500x500px

Twitter Share Image 1012x512px

– See more at: https://www.nami.org/Get-Involved/Raise-Awareness/Awareness-Events/Suicide-Prevention-Awareness-Month#sthash.p0Kv0jNk.dpuf “

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Worry

Where did she go, the girl I used to be? Self sufficient, calm, observant, fun loving, resourceful? I used to read mystery books by Enid Blyton when I was young, all afternoon long, when everyone else was taking a siesta, in Lahore. I thought of nothing but what I was reading in the books, I worried about nothing, so carefree in my younger days I was. I used to, oh so quietly, sneak into the kitchen and make myself butter and jam sandwiches and then take them to my room and munch on them contentedly as I read my exciting books. I used to go out into the garden, even in the horrid afternoon heat, and talk to the flowers, and watch the butterflies alight on them, butterflies with their gossamer, iridescent wings. Even then, flowers, their brilliant colors and amazing shapes fascinated me. Then when the sun got too hot on my face and head, I would go back up to my cool, peaceful room and resume reading. It was so peaceful, no thoughts, no anxiety, no worries, just being me and doing what I was doing, in the moment. Life was fun, enjoyable, I was present and engaged in it. When and where did all this anxiety, this yearning, this restlessness and sadness come into me? I am constantly anxious about my son. I constantly miss him, worry about him, wonder if he is fine. When I cook dinner, I mourn the fact that he is not here to share it with us. I worry he is not eating right, resting enough, taking care of himself properly. I worry about my aunt, who is very sick. I’m going to visit her in December, booked my ticket already. It may be the last time I will see her, she is so thin and frail, I don’t know how long she’ll last. Yes, I know, I know, she is 75 years old, and has lived as good a life as she could have with her god awful illness. She has been surrounded by her nephew, niece and their families who love her immensely. I know, we all have to go someday, but it is still sad for the ones left behind, or to watch someone become a wraith because of their illness, it is truly a difficult thing.

Obviously, it is uncertainty that makes me anxious. Also worries about my son’s wellbeing make me anxious. Phantom worries, nothing concrete, just what ifs. Dammit, I took my Seroquel a bit ago and now I am getting very drowsy, but I have to finish this. If I wait till tomorrow, the whole timbre and tone of this piece will change.

I just wish I could recall that peaceful time. The time when I just existed and read my mystery books and munched on jam sandwiches. No other thoughts in my head, nothing worrying me, nothing upsetting me. Is it possible? Have I simply developed an anxiety disorder, a biochemical thing, and since it makes me feel anxious, I attach thoughts to the feeling? Possible. In any case, it is not a very good way to live. But I am trying to do something about it, being aware of it at least gives me the chance to address it and hopefully find a solution.

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Some Thoughts on the “Nasal spray device for mental illness” Post

I saw the article “Nasal spray device for mental illness” (http://www.neuroscientistnews.com/clinical-updates/nasal-spray-device-mental-illness) article late last night and decided to simply post it because it was so interesting (https://bipolar1blog.wordpress.com/2015/08/28/nasal-spray-device-for-mental-illness/) Somehow, even though I didn’t post it on my FB Bipolar1Blog page, my statistics show that it’s gotten 25 views! That is a huge amount of traffic in less than 12 hours! People are looking for new ways to treat mental illness, obviously, we all are. And here is a novel way, using a nasal spray. Although not so novel if you think about people whose noses are/were rimmed with white powder in rest rooms of fancy restaurants, coming out with glassy eyes and torrential conversations and activity. That would be the first intranasal “therapy” for whatever you thought ailed you. Just something that occurred to me, no disrespect to people with mental illness or old or new or developing treatments for mental illness! Anyway, we’ve known for a long time that substances can reach the brain through the nose, (nose http://www.webmd.com/brain/news/20010222/this-nasal-spray-may-clear-your-brain-not-your-sinuses) There are nerve endings in the nose from two very powerful nerves, the olfactory nerve and the trigeminal nerve. And both these nerves obviously have their roots in the brain. So if substances can travel these nerve “super highways”, they can get directly into the brain without having to go into the bloodstream, thereby avoiding the blood brain barrier. Large molecules such as Oxytocin, cannot cross the blood brain barrier. It is also faster to send molecules to the brain through the nasal route than to have them enter the bloodstream, go to the heart and then be pumped out to the rest of the body and brain.

So these researchers in Oslo decided to look at Oxytocin, a molecule that promotes social interaction, eases pregnancy, childbirth, and milk letdown after the birth of the infant. They observe that people with autism, schizophrenia, and bipolar d/o have poor social functioning, so a dose of Oxytocin will help them be better in social interactions. Since Oxytocin is a large molecule, it wouldn’t pass the blood brain barrier, so they decided to try this nasal route. It helps if you have a big nose, and if you breathe. The Oxytocin goes directly to the brain and “The research showed that only those administered a low dose of oxytocin experienced an effect on how they perceived social signals.”

The researchers say that these effects were seen in only the men who received low doses of Oxytocin intranasally. The effects were not seen in men who received Oxytocin intravenously.

Whatever the effects were, whether Oxytocin can be used as a therapy for mental illness or not, this study is important because it shows that drugs can be delivered intranasally, directly to the brain, avoiding the blood circulation and the blood brain barrier and or GI/stomach problems. More drugs can be tested for intranasal delivery. A quicker and hopefully more effective route into the brain, leading to more effective therapies for treating mental/neurological illnesses.

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Nasal spray device for mental illness

http://www.neuroscientistnews.com/clinical-updates/nasal-spray-device-mental-illness

clinical updatesAUGUST 26, 2015


Oxytocin can reach the brain in two ways: indirectly, through blood, or directly, along nerve pathways. A: nasal spray particles B: route C: mucous membrane D: sensory neuron E: blood vessel F: nerve pathway G: nerve. Credit: UiO

Researchers at the University of Oslo (UiO) have tested a new device for delivering hormone treatments for mental illness through the nose. This method was found to deliver medicine to the brain with few side effects.

About one out of every hundred Norwegians develop schizophrenia or autism in the course of their lifetime. Moreover, at any one time some 20,000 people are receiving treatment for these problems. Many psychiatric disorders such as autism, schizophrenia and bipolar disorder are characterized by poor social functioning.
Oxytocin is a hormone that influences social behavior and has shown promise for the treatment of mental illness.
Researchers at UiO have now discovered that low doses of oxytocin may help patients with mental illness to better perceive social signals. As part of this project, they have collaborated with the company OptiNose, who have developed a new device designed to improve medicine delivery to the brain via the nose.
Regulates social behavior
Oxytocin has historically been known to play a crucial role in child rearing as it facilitates pregnancy, birth, and the release of milk during nursing. Further, oxytocin helps regulate cardiac functions and fluid levels. More recent research has revealed the importance of oxytocin for social behavior.
Oxytocin is a neuropeptide and was discovered in 1953. Peptides are a group of molecules that consist of a chain of amino acids. Amino acids are also known as the building blocks of proteins, which we find in all types of cells. Oxytocin is produced in the hypothalamus, which is the brain’s coordinating center for the hormone system.
Medicine through the nose
Because of oxytocin’s role in social behavior, researchers have explored the possibility of administering the hormone for the treatment of mental illness. As oxytocin is a relatively large molecule, it has trouble crossing the barrier between the brain and circulating blood. Thus, researchers have administered oxytocin to patients through the nose as this route offers a direct pathway to the brain that bypasses this barrier.
However, researchers have a poor understanding of how oxytocin reaches and affects the brain. The most effective dose for treatment has also received little research attention.
Professor Ole A. Andreassen and his research team have collaborated with OptiNose on a project that evaluated two different doses of oxytocin and on how they affect the way in which social signals are perceived.
Low doses work best
Sixteen healthy men received two different doses of oxytocin, along with placebo. Volunteers were also given an intravenous dose of oxytocin, for a comparison of the effects of oxytocin in circulating blood. The research showed that only those administered a low dose of oxytocin experienced an effect on how they perceived social signals.
Professor Ole A. Andreassen explains: “The results show that intranasal administration, i.e. introducing oxytocin through the nose, affects the function of the brain.
As no effect was observed after intravenous treatment, this indicates that intranasally administered oxytocin travels directly to the brain, as we have long believed. The fact that we have shown the efficacy of a low dose of oxytocin on social perception is even more important.
A dose that is lower, but that still influences behavior, will entail a lower risk of affecting other regulatory systems in the body. Very high doses of oxytocin could, in fact, have the opposite effect on social behaviour.”
The scientists also discovered that individuals with larger nasal cavities had a stronger response to a low dose of oxytocin.
Breathing helps
OptiNose uses a new technology to distribute medicine to the brain, making use of the user’s breath to propel medicine deep into the nasal cavity.
The device administers oxytocin high up into the patient’s nasal cavity. When the medicine is targeted deep inside the nose, it enables brain delivery along nerve pathways from the uppermost part of the nasal cavity. Conventional nasal spray devices are not suited to consistently deliver medicine high up enough into the nose.
The device also expands the nasal cavity, facilitating nose-to-brain medicine delivery. As the user exhales into the device, this closes the soft palate and prevents the medicine from being lost down the throat.
Since less medicine is lost along the way, patients can take smaller doses and accordingly experience fewer side effects.
May yield new treatments
The next step in the research is to carry out the same tests on people with mental illness.
“We are now running tests in volunteers diagnosed with autism spectrum disorders,” says Dr Quintana.
“We hope that this research project is the first step in the development of a series of new medicines that may be of great help to more people with mental illness,” concludes Professor Andreassen.

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Bacteria 101… sort of… and some musings…

Many things affect the growth of bacteria. Many things affect what kind of bacteria grow. Some of these things are pH, temperature, the type of nutrients. The immune system can also determine which bacteria survive in our bodies, if the immune system attacks and kills a certain type of bacteria, then it cannot survive (unless we are very weakened). If the immune system does not react against a type of bacteria, then that type can grow. Same goes for fungi and viruses as well. All the friendly bacteria in our gut, like Lactobacillus or Enterobacter (which synthesizes Vitamin K for us) are not attacked by our immune system and live in symbiosis (mutual benefit) in our gut.

Illness can change what bacteria live in our bodies by changing the above things I mentioned. How is it that the type of bacteria living in the throats of people who have schizophrenia is different from controls (those who do not have schizophrenia)? Is is related to the onset or continuity of the illness or is it simply incidental? Even if it is incidental, at the very least, it may be useful in the diagnosis of this illness, which is very complex and very difficult to treat.

Could it be that the different microbiome in people with schizophrenia can affect the gut neuronal tissue and alter the types or amounts of neurotransmitters produced and this then affects the brain neuronal tissue and then is involved in generation of disease? The immune system is also in intimate contact with the gut, in fact a part of the immune system is called Gut Associated Lymphoid Tissue or GALT. The gut associated neurons aka the gut brain or gut nervous system line the cells of the gut. The immune system, and neuronal tissue come into intimate contact in the gut, exactly where there are trillions of bacteria living, in the gut. So much is happening in the gut. The importance of GALT, the gut nervous system, the microbiome, and the gut itself cannot be overlooked. It’s a puzzle, but a puzzle whose pieces are slowly coming together to form a picture. Let’s see what the picture will show us.

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Researchers identify signature of microbiomes associated with schizophrenia (!!!)

Oh my god! Could it be that simple? Fix the microbiomes of patients and they’ll be cured of schizophrenia? No, I doubt it, but still this is a phenomenal discovery! That the throat microbiomes of schizophrenia patients and people who don’t have schizophrenia (controls) are significantly different. The microbiome is the collection of bacteria, viruses, and fungi that live in our bodies with us. Once again this brings the immune system into the picture, and as I posted in my very last post, it also brings the gut nervous system (aka gut brain) and gut immune system into play. Why are different bacteria, fungi, viruses growing in the throats of people who have schizophrenia? Is their immune system different? If so, why is their immune system different? How is it different? Are the bacteria in the gut also different since the throat all the way to the anus is about 9 feet of the alimentary canal. If the microbiome is different, what affect is it having on the gut nervous system and also ultimately on the brain, also known as the central nervous system? Phenomenal discovery! Also shows how interconnected everything is! Studying the brain or the gut or the immune system in isolation is all well and good, but we have to study relationships within these systems and how they affect one another and us. Also a very important question for me: Is this also the case for people who have bipolar d/o? Do we also have microbiomes that are different from control individuals? And again, all the questions I asked above apply in this case too.

http://www.neuroscientistnews.com/research-news/researchers-identify-signature-microbiomes-associated-schizophrenia

“Recent studies have shown that microbiomes—the communities of microbes living within our bodies—can affect the immune system and may be connected to mental health.

Research linking immune disorders and schizophrenia has also been published, and this study furthers the possibility that shifts in oral communities are associated with schizophrenia.

Mr. Castro-Nallar’s research sought to identify microbes associated with schizophrenia, as well as components that may be associated with or contribute to changes in the immune state of the person. In this study, the group found a significant difference in the microbiomes of healthy and schizophrenic patients.

“Our results suggesting a link between microbiome diversity and schizophrenia require replication and expansion to a broader number of individuals for further validation,” said Keith Crandall, director of the CBI and contributing author of the study. “But the results are quite intriguing and suggest potential applications of biomarkers for diagnosis of schizophrenia and important metabolic pathways associated with the disease.”

The study helps to identify possible contributing factors to schizophrenia. With additional studies, researchers may be able to determine if microbiome changes are a contributing factor to schizophrenia, are a result of schizophrenia or do not have a connection to the disorder.

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“Think Twice: How the Gut’s “Second Brain” Influences Mood and Well-Being”

olympic butterflies gut second brain

There are a 100 billion neurons, on average, in the human brain, the one in our skulls. There are an additional 100 million neurons in out guts, this is called the enteric nervous system. The butterflies in our stomach? Yes, generated here. Gut feelings? Yes generated in the enteric nervous system! Why do we have 100 million neurons embedded in the walls of our gut? Well one function, perhaps the primary function is digestion and excretion of food. However, there is more, these neurons also produce Serotonin, in fact they produce the majority of Serotonin in the body. They also produce 30 neurotransmitters, just like the brain in our heads. So, as neurotransmitters are the communication molecules between neurons, also between neurons and other cells, there is communication going on between the enteric brain and the main brain. A large part of our emotions are most likely influenced by this enteric brain! Most of the nerve impulses generated in the vagus nerve are headed towards the brain in our heads, that means there is a lot of information going from the gut to our brain! The enteric brain also exists to deal with the trillions of gut bacteria that reside in the gut! The gut has been implicated in Autism, osteoporosis, perhaps depression and mood disorders as well, as the large production of Serotonin points to. There is already a field called psychoneuroimmunology, which looks at the relationship of neurons, immune systems, and our psychological state. Now we can add gastroenterology to that!

http://www.scientificamerican.com/article/gut-second-brain/ Full text below:

The emerging and surprising view of how the enteric nervous system in our bellies goes far beyond just processing the food we eat

As Olympians go for the gold in Vancouver, even the steeliest are likely to experience that familiar feeling of “butterflies” in the stomach. Underlying this sensation is an often-overlooked network of neurons lining our guts that is so extensive some scientists have nicknamed it our “second brain”.

A deeper understanding of this mass of neural tissue, filled with important neurotransmitters, is revealing that it does much more than merely handle digestion or inflict the occasional nervous pang. The little brain in our innards, in connection with the big one in our skulls, partly determines our mental state and plays key roles in certain diseases throughout the body.

Although its influence is far-reaching, the second brain is not the seat of any conscious thoughts or decision-making.

“The second brain doesn’t help with the great thought processes…religion, philosophy and poetry is left to the brain in the head,” says Michael Gershon, chairman of the Department of Anatomy and Cell Biology at New York–Presbyterian Hospital/Columbia University Medical Center, an expert in the nascent field of neurogastroenterology and author of the 1998 book The Second Brain(HarperCollins).

Technically known as the enteric nervous system, the second brain consists of sheaths of neurons embedded in the walls of the long tube of our gut, or alimentary canal, which measures about nine meters end to end from the esophagus to the anus. The second brain contains some 100 million neurons, more than in either the spinal cord or the peripheral nervous system, Gershon says.

This multitude of neurons in the enteric nervous system enables us to “feel” the inner world of our gut and its contents. Much of this neural firepower comes to bear in the elaborate daily grind of digestion. Breaking down food, absorbing nutrients, and expelling of waste requires chemical processing, mechanical mixing and rhythmic muscle contractions that move everything on down the line.

Thus equipped with its own reflexes and senses, the second brain can control gut behavior independently of the brain, Gershon says. We likely evolved this intricate web of nerves to perform digestion and excretion “on site,” rather than remotely from our brains through the middleman of the spinal cord. “The brain in the head doesn’t need to get its hands dirty with the messy business of digestion, which is delegated to the brain in the gut,” Gershon says. He and other researchers explain, however, that the second brain’s complexity likely cannot be interpreted through this process alone.

“The system is way too complicated to have evolved only to make sure things move out of your colon,” says Emeran Mayer, professor of physiology, psychiatry and biobehavioral sciences at the David Geffen School of Medicine at the University of California, Los Angeles (U.C.L.A.). For example, scientists were shocked to learn that about 90 percent of the fibers in the primary visceral nerve, the vagus, carry information from the gut to the brain and not the other way around. “Some of that info is decidedly unpleasant,” Gershon says.

The second brain informs our state of mind in other more obscure ways, as well. “A big part of our emotions are probably influenced by the nerves in our gut,” Mayer says. Butterflies in the stomach—signaling in the gut as part of our physiological stress response, Gershon says—is but one example. Although gastrointestinal (GI) turmoil can sour one’s moods, everyday emotional well-being may rely on messages from the brain below to the brain above. For example, electrical stimulation of the vagus nerve—a useful treatment for depression—may mimic these signals, Gershon says.

Given the two brains’ commonalities, other depression treatments that target the mind can unintentionally impact the gut. The enteric nervous system uses more than 30 neurotransmitters, just like the brain, and in fact 95 percent of the body’s serotonin is found in the bowels. Because antidepressant medications called selective serotonin reuptake inhibitors (SSRIs) increase serotonin levels, it’s little wonder that meds meant to cause chemical changes in the mind often provoke GI issues as a side effect. Irritable bowel syndrome—which afflicts more than two million Americans—also arises in part from too much serotonin in our entrails, and could perhaps be regarded as a “mental illness” of the second brain.

Scientists are learning that the serotonin made by the enteric nervous system might also play a role in more surprising diseases: In a new Nature Medicine study published online February 7, a drug that inhibited the release of serotonin from the gut counteracted the bone-deteriorating disease osteoporosis in postmenopausal rodents. (Scientific American is part of Nature Publishing Group.) “It was totally unexpected that the gut would regulate bone mass to the extent that one could use this regulation to cure—at least in rodents—osteoporosis,” says Gerard Karsenty, lead author of the study and chair of the Department of Genetics and Development at Columbia University Medical Center.

Serotonin seeping from the second brain might even play some part in autism, the developmental disorder often first noticed in early childhood. Gershon has discovered that the same genes involved in synapse formation between neurons in the brain are involved in the alimentary synapse formation. “If these genes are affected in autism,” he says, “it could explain why so many kids with autism have GI motor abnormalities” in addition to elevated levels of gut-produced serotonin in their blood.

Down the road, the blossoming field of neurogastroenterology will likely offer some new insight into the workings of the second brain—and its impact on the body and mind. “We have never systematically looked at [the enteric nervous system] in relating lesions in it to diseases like they have for the” central nervous system, Gershon says. One day, perhaps there will be well-known connections between diseases and lesions in the gut’s nervous system as some in the brain and spinal cord today indicate multiple sclerosis.

Cutting-edge research is currently investigating how the second brain mediates the body’s immune response; after all, at least 70 percent of our immune system is aimed at the gut to expel and kill foreign invaders.

U.C.L.A.’s Mayer is doing work on how the trillions of bacteria in the gut “communicate” with enteric nervous system cells (which they greatly outnumber). His work with the gut’s nervous system has led him to think that in coming years psychiatry will need to expand to treat the second brain in addition to the one atop the shoulders.

So for those physically skilled and mentally strong enough to compete in the Olympic Games—as well as those watching at home—it may well behoove us all to pay more heed to our so-called “gut feelings” in the future.

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After my vacation…

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It was a wonderful vacation, a perfect vacation. Nine out of ten beach days! The best part was to have my son with us, he is so sweet and funny and intelligent! It is just a pleasure to be with him. It was also wonderful for me because I didn’t have to worry about him. I worry about him much too much. The beginnings of an anxiety disorder? I don’t know. What I do know is that he is fine, but I still worry about him and of course I miss him a lot. I know all about how children have to separate from their parents to individuate and grow up. I’m not sure I quite buy it though, I think families are meant to stay together, not in the same house, but close by, perhaps in the same town, so they can stay in touch and be there for each other if the need arises. But the American culture is all about individuality, about the nuclear family and not the extended family. It’s about individual rights. It separates us instead of bringing us together. As a mother, there is nothing that makes me happier than to be with my son and know that he is happy, healthy, well loved and living a productive, self sufficient life. That is what I wish for all my friends and family and their children as well.

Yes, our vacation was wonderful, so coming back has been difficult. Yes, I am dealing with emotions, the downfall for those of us who have mood disorders. Separation from my son and the ensuing anxiety are definitely triggers that plunge me into an anxious, depressed phase. Other triggers can make my adrenaline spike and possibly contribute to an angry, manicky response. Yes, I have to start my “Choosing to do Something Different” course with Pema Chödrön again. It was truly helping me when I was reading a section daily. It’s really a matter of use it or lose it. Must keep at it, must keep practicing. I will start again tonight and start posting about it again.

Also one of my triggers which is really simple to avoid is hunger. Yes I said hunger. When I am hungry, my anxiety can get to pretty high levels pretty quickly. For example in a well fed state (haha) I might find someone like Donald Trump (ugh) mildly annoying. But expose me to this annoying boor in a hungry state and I will react much more strongly, maybe even call him a gargantuan fool… which he might be… but what’s important here is my reaction to something, not the something. My reaction, that is what I am trying to control with Pema Chödrön’s course. Of course I won’t stop just with that course, I will read, follow, meditate, use other techniques as well.

I’m back. My son’s fine. I’m controlling my emotions. Hurrah!

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Disruption of Communication Between Two Regions of the Brain Contributes to Symptoms of Psychiatric Illnesses

Basically, when the synaptic transmission between the hippocampus and the prefrontal cortex is disrupted, symptoms of mental illnesses such as schizophrenia are seen. This has been known for a long time. What wasn’t known was how is this communication between the hippocampus and prefrontal cortex disrupted? That is, what are the mechanisms responsible for the disruption of communication between these two regions of the brain? Well, in this paper below, they show over activation of the D2-like Dopamine receptors leads to a decrease in another type of receptor called the NMDA receptor. This leads to a marked disruption of synaptic transmission between the two brain regions. This newly discovered relationship between the Dopamine and NMDA receptors may lead to treatment options for people with mental illnesses like schizophrenia.

“Synaptic transmission between the hippocampus and prefrontal cortex is required for many executive cognitive functions. It is believed that disruption of this communication contributes to symptoms observed in psychiatric disorders including schizophrenia. Hyperdopaminergic tone and hypofunction of NMDA receptor-mediated glutamate transmission are distinctive elements of schizophrenia. Here we demonstrate that activation of low-affinity D2-like dopamine receptors leads to a lasting depression of NMDA receptors at the hippocampal– prefrontal projection of juvenile rats, leading to a marked disruption of synaptic transmission. These data demonstrate a link between dopamine and hypofunction of NMDA receptormediated transmission with potential implications for psychiatric disease.”

http://www.pnas.org/content/early/2015/08/18/1512064112.full.pdf

“New research has identified the mechanisms that trigger disruption in the brain’s communication channels linked to symptoms in psychiatric disorders including schizophrenia. The University of Bristol study, published in the Proceedings of National Academy of Sciences, could have important implications for treating symptoms of brain disorders.

Many of our everyday cognitive functions such as learning and memory rely on normal communication between the two regions of the brain – the hippocampus and prefrontal cortex. While previous studies have identified disruption to communication channels in these two areas of the brain contribute to symptoms in psychiatric disorders, the mechanisms that lead to these disturbances have been largely unknown, until now.

In this study, led by Professor Zafar Bashir from Bristol’s School of Physiology and Pharmacology, the researchers studied the neurotransmitters glutamate and dopamine, which work together in controlling normal transmission between these brain regions by communicating chemical information throughout our brain and are disrupted in schizophrenics.

The team found that subtle changes in the interplay of these transmitters completely altered the flow of information from the hippocampus to prefrontal cortex. Over-activation of the D2 class of dopamine receptors led to suppression of the function of NMDA receptors, which are activated by the neurotransmitter glutamate, at the synaptic connection between hippocampus and prefrontal cortex. This in turn leads to a marked disruption of communication between these brain regions.

Dr Paul Banks, one of the researchers, said: “Our findings demonstrate a mechanism for how dopamine neurotransmission can influence NMDA receptor function at a connection in the brain needed for complex mental tasks which are disrupted in schizophrenic patients. It has been known for some time that dopamine and NMDA receptor function are altered in schizophrenic patients – our data mirror the direction of these changes and therefore might give insight into how these changes come about mechanistically.”

http://www.neuroscientistnews.com/research-news/study-identifies-cause-disruption-brain-linked-psychiatric-disorder