This team has identified 7 causes for bipolar disorder. They don’t think any one gene is responsible as one has never been identified. Also people with bipolar disorder are much more likely to suffer from migraines than non diseased counter parts. This includes me, I’ve had migraines since I was 13 and was diagnosed with bipolar disorder at 25 years if age. Also childhood trauma is a factor. Fascinating article. Below for your reading pleasure.

https://m.medicalxpress.com/news/2017-12-years-bipolar-disorder-team.html

Bipolar disorder is characterized by transitions between depression and mania. Credit: Wikipedia

Nearly 6 million Americans have bipolar disorder, and most have probably wondered why. After more than a decade of studying over 1,100 of them in-depth, a University of Michigan team has an answer – or rather, seven answers.

In fact, they say, no one genetic change, or chemical imbalance, or life event, lies at the heart of every case of the mental health condition once known as manic depression.

Rather, every patient’s experience with bipolar disorder varies from that of others with the condition. But all of their experiences include features that fall into seven classes of phenotypes, or characteristics that can be observed, the team reports in a new paper in the International Journal of Epidemiology.

The team, from U-M’s Heinz C. Prechter Bipolar Research Program, collected and analyzed tens of thousands of data points over years about the genetics, emotions, life experiences, medical histories, motivations, diets, temperaments, sleep patterns and thought patterns of research volunteers. More than 730 had bipolar disorder, and 277 didn’t. Three-quarters of them are currently active research participants in the Longitudinal Study of Bipolar Disorder.

Using those findings, the team has developed a framework that could be useful to researchers studying the condition, clinical teams treating it, and patients experiencing it. The team hopes it will give them all a common structure to use during studies, treatment decisions and more.

“There are many routes to this disease, and many routes through it,” says Melvin McInnis, M.D., lead author of the new paper and head of the program based at the U-M Depression Center. “We have found that there are many biological mechanisms which drive the disease, and many interactive external influences on it. All of these elements combine to affect the disease as patients experience it.”

The Prechter program, funded by gifts from many donors, is named for a late Detroit automotive pioneer who fought bipolar even as he built a successful business.

Long-term funding from this program has made it possible to build a massive library of data from the “Prechter cohort” of patients, which is two-thirds female, and 79 percent white, with an average age at enrollment in the study of 38 years. On average, participants had had their first depressive or manic episode when they were 17, and many had other mental health conditions.

Seven classes and the key findings that shaped them

The seven phenoclasses, as the U-M team has dubbed them, include standard measures doctors already use to diagnose and track the progress of bipolar disorder.

In addition, they include:

• changes in cognition, which includes thinking, reasoning and emotion processing;

• psychological dimensions such as personality and temperament;

• measures of behaviors related to substance use or abuse – called motivated behaviors;

• aspects of the person’s life story involving family and intimate relationships and traumas;

• patterns of sleep and circadian rhythms; and

• measures of how patients’ symptoms change over time and respond to treatment.

Some of the key findings made in the Prechter cohort by the U-M team include:

• Migraine headaches are three and a half times more common among people with bipolar disorder than those without. Eating disorders, anxiety disorders and alcohol problems are also more common in those with bipolar, as is metabolic syndrome.

• More people with bipolar disorder have a history of childhood trauma than those without the condition, it is associated with changes in self-control and attention.

• People with bipolar disorder had higher levels of saturated fats in their diets, and the research also found associations between levels of certain fat molecules in the blood of patients and their mood or level of symptoms.

• Looking at the microbes living in the gastrointestinal tracts of patients and comparison volunteers, the researchers found lower levels of a key bacteria type, and less diversity of microbes in patients taking antipsychotic medications.

• Poor sleep appears to play a key role in bipolar disorder, with links found to severity of depression and mania in female, but not male, participants with the condition. Other gender differences also emerged in other aspects of the study.

• People with bipolar disorder who have a strong neurotic tendency in their personalities are more likely to have severe illness, especially among men.

• A range of cognitive abilities – including memory, executive functioning and motor skills – were poorer in participants with bipolar than those without, in general. The study found a particular link between the cognitive abilities of people who carried a particular genetic trait and were taking newer antipsychotic medicines.

• Two genes, called CACNA1 and ANK3, appear to play a role in susceptibility to developing bipolar disorder. But many genetic variations have been found to be associated with bipolar risk, and more recent findings have explored the role of having a mix of these variations in the chances a person will develop bipolar.

• Stem cells grown from skin samples taken from participants, and then coaxed to grow into nerve cells called neurons, have proven useful in studying cellular aspects of bipolar disorder. For instance, neurons derived from bipolar patients’ cells were more excitable than comparisons – but calmed down when exposed to lithium, a common treatment for bipolar. Also, the cells show differences in how they interact and function.

• Key features of speech patterns predict mood states and may be useful outcomes measures to predict the need for intervention to prevent episodes of mania or depression.

Even though bipolar disorder tends to run in families, the long-term study has revealed no one gene that ‘carries the day’ to explain it, says McInnis, who is the Woodworth Professor of Bipolar Disorder and Depression in the U-M Medical School’s Department of Psychiatry.

“If there was a gene with a strong effect like what we see in breast cancer, for instance, we would have found it,” he explains. “We hope this new framework will provide a new approach to understand this disorder, and other complex diseases, by developing models that can guide a management strategy for clinicians and patients, and give researchers consistent variables to measure and assess.”

He adds, “Bipolar disorder has a lot to teach humankind about other illnesses, because it covers the breadths of human mood, emotion and behavior like no other condition. What we can learn in bipolar about all these factors will be directly applicable to monitoring other disorders, and personalizing the approach to managing them.”

More information: Melvin G McInnis et al, Cohort Profile: The Heinz C. Prechter Longitudinal Study of Bipolar Disorder, International Journal of Epidemiology (2017). DOI: 10.1093/ije/dyx229

The Prechter Bipolar Research Program is still recruiting participants for its long-term study, and accepting donations from those who want to help the research move forward. More information is available at www.prechterprogram.org

Urea has been pinpointed as the cause of at least two, if not all, kinds of dementia. Amazing! A common metabolite of the body can cause dementia. Hopefully ways to prevent this will be forthcoming shortly.

https://www.technologynetworks.com/neuroscience/news/increased-urea-levels-in-brain-linked-with-dementia-295066

An international team of scientists have confirmed the discovery of a major cause of dementia, with important implications for possible treatment and diagnosis.

Professor Garth Cooper from The University of Manchester, who leads the Manchester team, says the build-up of urea in the brain to toxic levels can cause brain damage – and eventually dementia.

The work follows on from Professor Cooper’s earlier studies, which identified metabolic linkages between Huntington’s, other neurodegenerative diseases and type-2 diabetes.

The team consists of scientists from The University of Manchester, the University of Auckland, AgResearch New Zealand, the South Australian Research and Development Institute, Massachusetts General Hospital and Harvard University.

The latest paper by the scientists, published today in the Proceedings of the National Academy of Sciences, shows that Huntington’s Disease – one of seven major types of age-related dementia – is directly linked to brain urea levels and metabolic processes.

Their 2016 study revealing that urea is similarly linked to Alzheimer’s, shows, according to Professor Cooper, that the discovery could be relevant to all types of age-related dementias.

The Huntington’s study also showed that the high urea levels occurred before dementia sets in, which could help doctors to one day diagnose and even treat dementia, well in advance of its onset.

Urea and ammonia in the brain are metabolic breakdown products of protein. Urea is more commonly known as a compound which is excreted from the body in urine. If urea and ammonia build up in the body because the kidneys are unable to eliminate them, for example, serious symptoms can result.

Professor Cooper, who is based at The University of Manchester’s Division of Cardiovascular Sciences, said: “This study on Huntington’s Disease is the final piece of the jigsaw which leads us to conclude that high brain urea plays a pivotal role in dementia.

“Alzheimer’s and Huntington’s are at opposite ends of the dementia spectrum – so if this holds true for these types, then I believe it is highly likely it will hold true for all the major age-related dementias.

“More research, however, is needed to discover the source of the elevated urea in HD, particularly concerning the potential involvement of ammonia and a systemic metabolic defect.

“This could have profound implications for our fundamental understanding of the molecular basis of dementia, and its treatability, including the potential use of therapies already in use for disorders with systemic urea phenotypes.”

Dementia results in a progressive and irreversible loss of nerve cells and brain functioning, causing loss of memory and cognitive impairments affecting the ability to learn. Currently, there is no cure.

The team used human brains, donated by families for medical research, as well as transgenic sheep in Australia.

Manchester members of the team used cutting-edge gas chromatography mass spectrometry to measure brain urea levels. For levels to be toxic urea must rise 4-fold or higher than in the normal brain says Professor Cooper.

He added: “We already know Huntington’s Disease is an illness caused by a faulty gene in our DNA – but until now we didn’t understand how that causes brain damage – so we feel this is an important milestone.

“Doctors already use medicines to tackle high levels of ammonia in other parts of the body, Lactulose – a commonly used laxative, for example, traps ammonia in the gut. So it is conceivable that one day, a commonly used drug may be able to stop dementia from progressing. It might even be shown that treating this metabolic state in the brain may help in the regeneration of tissue, thus giving a tantalising hint that reversal of dementia may one day be possible.”

This article has been republished from materials provided by The University of Manchester, UK. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference:

Handley, R. R., Reid, S. J., Brauning, R., Maclean, P., Mears, E. R., Fourie, I., . . . Snell, R. G. (2017). Brain urea increase is an early Huntington’s disease pathogenic event observed in a prodromal transgenic sheep model and HD cases. Proceedings of the National Academy of Sciences, 201711243. doi:10.1073/pnas.1711243115

This is amazing! Implanting a small bioelectronic device on the Vagus nerve in Rheumatoid arthritic (RA) patients makes markers of inflammation (such as TNF and other cytokines) go down. And not only that, the symptoms of RA are also decreased.

This can be used for other autoimmune and immune diseases as well.

https://www.technologynetworks.com/neuroscience/news/study-shows-vagus-nerve-stimulation-significantly-reduces-rheumatoid-arthritis-284383

Clinical trial data published in the Proceedings of the National Academy of Sciences (PNAS) demonstrates stimulating the vagus nerve with an implantable bioelectronic device significantly improved measures of disease activity in patients with rheumatoid arthritis (RA). RA is a chronic inflammatory disease that affects 1.3 million people in the United States and costs tens of billions of dollars annually to treat. The findings were announced by the Academic Medical Center/University of Amsterdam, the Feinstein Institute for Medical Research and SetPoint Medical.

See Also: Neurostimulation: What is being said in the media and academic literature?

The publication highlights a human study designed to reduce symptoms of RA, cytokine levels and inflammation by stimulating the vagus nerve with a small implanted device.

“This is the first study to evaluate whether stimulating the inflammatory reflex directly with an implanted electronic device can treat RA in humans,” said Professor Paul-Peter Tak, MD, PhD, FMedSci, the international principal investigator and lead author of the paper at the Division of Clinical Immunology & Rheumatology of the Academic Medical Center/University of Amsterdam. “We have previously shown that targeting the inflammatory reflex may reduce inflammation in animal models and in vitro models of RA. The direct correlation between vagus nerve stimulation and the suppression of several key cytokines like TNF as well as reduced RA signs and symptoms demonstrates proof of mechanism, which might be relevant for other immune-mediated inflammatory diseases as well.”

“Our findings suggest a new approach to fighting diseases with bioelectronic medicines, which use electrical pulses to treat diseases currently treated with potent and relatively expensive drugs,” said Anthony Arnold, Chief Executive Officer of SetPoint Medical. “These results support our ongoing development of bioelectronic medicines designed to improve the lives of people suffering from chronic inflammatory diseases and give healthcare providers new and potentially safer treatment alternatives at a much lower total cost for the healthcare system.”

“This is a real breakthrough in our ability to help people suffering from inflammatory diseases,” said co-author Kevin J. Tracey, MD, president and CEO of the Feinstein Institute for Medical Research, discoverer of the inflammatory reflex and co-founder of SetPoint Medical. “While we’ve previously studied animal models of inflammation, until now we had no proof that electrical stimulation of the vagus nerve can indeed inhibit cytokine production and reduce disease severity in humans. I believe this study will change the way we see modern medicine, helping us understand that our nerves can, with a little help, make the drugs that we need to help our body heal itself.”

Learn More: New non-invasive form of vagus nerve stimulation works to treat depression

While focused on rheumatoid arthritis, the trial’s results may have implications for patients suffering from other inflammatory diseases, including Crohn’s, Parkinson’s, Alzheimer’s and others.

Study methodology and results

In the study, a stimulation device was implanted on the vagus nerve during a surgical procedure, then activated and deactivated based on a set schedule to measure response over 84 days, with primary endpoints measured at day 42 using DAS28-CRP, a standard disease activity composite score for RA that includes counts of tender and swollen joints, patient’s and physician’s assessment of disease activity and serum C-reactive protein (CRP) levels.

Of 17 patients with active RA in the study, several patients that had failed to respond to multiple therapies, including biologicals with different mechanisms of action, demonstrated robust responses. The findings indicate that active electrical stimulation of the vagus nerve inhibits TNF production in RA patients and significantly attenuates RA disease severity.

Don’t Miss: The neurons in our gut help the immune system keep inflammation in check

Several patients reported significant improvements, including some who had previously failed to respond to any other form of pharmaceutical treatment. In addition, no serious adverse side effects were reported.

The emerging field of bioelectronic medicine aims to target disorders traditionally treated with drugs and instead uses advanced neuromodulation devices that may offer significant advantages. SetPoint is developing a novel proprietary bioelectronic medicine platform to treat a variety of immune-mediated inflammatory diseases, using an implanted device to stimulate the vagus nerve.

Note: Material may have been edited for length and content. For further information, please contact the cited source.

Just had one of the best experiences of my life at the Louisville Zoo. He came right up to me and did the head butt on the glass, which means basically “Pet me”!!! I am madly in love. I’ll be visiting him often 🐅😄

Why is it that when we are physically ill, as in for example having the flu, we are allowed to rest and recuperate. However when the illness is mental, as for example a mixed episode of bipolar disorder, we are not allowed to rest. We must keep going as if we are not sick at all. If we are housewives, dinner must be on the table when the family gets home. If we don’t make dinner (just an example of work) then why didn’t we? People might say “You don’t look sick, why don’t you do your work?” I have been in a mixed phase, as I generally am in the Fall. I feel terrible, emotional, terribly anxious, weepy, nothing good. Can’t eat. Yet I’m not given much of a chance to rest. I don’t look sick.

I’ve been away from my blog. Was having a pretty rough time of it as usual upon the changing of the seasons. Increased meds. Feeling a bit better. Will be back soon with more. In the meantime, makin ‘ lemonade 🙂

I saw this on Instagram and I think it’s a wonderful idea so I’m sharing it with all of you. 🤗😊💐😻👍

Everything old is constantly new again. The realization that this hellish illness has stolen so much from me personally, it’s even taken my brother.

My marriage almost ended, and hellishly, I have traumatized my precious son because of this illness.

The five years I was on *Lamictal, constantly in hypomania, almost destroyed my life.

*Lamictal, the best new drug for bipolar disorder in the early 2000’s. Everyone was being put on it, including myself. Later they realized it only works for Bipolar 2 Disorder and should never be given to people with Bipolar 1 Disorder as it puts these people in hypomania. Yes I was one of the early experimental subjects, though without my consent. And being in hypomania for 5-6 years, imagine what that does to someone’s life! Nothing good, I can tell you that. So not only has this illness tried to destroy me but the medications which were prescribed to control its symptoms, those very medications have exacerbated the illness, made it worse, tested my mettle and my strength. Anyway, enough about that, I’m still here.

And I’m on the path to reclaim my life, reclaim myself from the awful effects of this illness as well as some medications.

I have lived in fear and constant anxiety for at least the last two years. I’m ready to let that go and really reclaim my life and myself. Let go of the devastation, let in the light and take control of my life.

I am on Lithium, have been since 2009. My mood’s been pretty stable except for the massive anxiety. Dealing with it.

I feel like I have to forgive myself for my behavior when I was hypomanic for 5-6 years while on Lamictal. I feel I have to let go of the guilt for the pain I caused my family, especially my darling son. And my dear husband. Of course they bore the brunt of it because I lived with them.

I will make amends. I will ask their forgiveness.

I will forgive myself.

And I will go on with as little fear and anxiety as I can possibly manage.

I will take positive actions in my life, not just remediate the negative past.

I have some very positive actions in mind.

The main thing is that like an earthquake, one feels the aftershocks days after the main one, well the aftereffects of being hypomanic for years last a long time as well. Realizing how one’s life was almost destroyed is horrendous, truly it is!

But moving past that is miraculous. It is pure strength and confidence. And that is what I’m working on now.

Wish me luck.