Gene Breakthrough on Lithium Treatment for Bipolar Disorder

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Credit to flickr.com user Berkeley Lab. Used with permission under a Creative Commons license.

Genes linked to schizophrenia in psychiatric patients suffering from bipolar disorder are the reason why such patients don’t respond to the “gold standard” treatment for bipolar – the drug lithium – according to international research led by the University of Adelaide.

Lithium has been widely used as a treatment for bipolar disorder since the 1950s because of its mood stabilising effect. It has unique protective properties against both manic and depressive episodes, and an ability to decrease the risk of suicide.

However, about 30% of patients are only partially responsive, more than a quarter show no clinical response at all, and others have significant side-effects to lithium.

Until now, researchers have not understood why these patients have not responded to the common treatment, while others have responded well to the drug.

Published in the journal JAMA Psychiatry>, an international consortium of researchers led by the University of Adelaide’s Professor Bernhard Baune reports a major discovery that could affect the future quality of treatment for people with this significant mental health condition.

Known as the international Consortium on Lithium Genetics, the group has studied the underlying genetics of more than 2500 patients treated with lithium for bipolar disorder.

“We found that patients clinically diagnosed with bipolar disorder who showed a poor response to lithium treatment all shared something in common: a high number of genes previously identified for schizophrenia,” says Professor Baune, Head of the Discipline of Psychiatry at the University of Adelaide and lead author on the paper.

“This doesn’t mean that the patient also had schizophrenia – but if a bipolar patient has a high ‘gene load’ of schizophrenia risk genes, our research shows they are less likely to respond to mood stabilisers such as lithium.

“In addition, we identified new genes within the immune system that may play an important biological role in the underlying pathways of lithium and its effect on treatment response,” Professor Baune says.

Understanding the underlying biology of people’s response to lithium treatment is a key area of research and urgent clinical need in mental health.

“These findings represent a significant step forward for the field of translational psychiatry,” Professor Baune says.

“In conjunction with other biomarkers and clinical variables, our findings will help to advance the highly needed ability to predict the response to treatment prior to an intervention. This research also provides new clues as to how patients with bipolar disorder and other psychiatric disorders should be treated in the future.”

Text provided by the University of Adelaide.

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Bipolar Patients Treated with Lithium Rehospitalized Less

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Credit to flickr.com user The Javorac. Used with permission under a Creative Commons license.

Bipolar patients treated with lithium made fewer return trips to psychiatric wards, according to a new study by Karolinska Institutet in Sweden. Long-acting injections of antipsychotics were also effective.

 

Researchers in Finland followed 18,000 patients who had previously been hospitalized for bipolar disorder. Each patient was used as their own control, observed with and without treatment.

Lithium was found to reduce the risk of rehospitalizations by 30 percent. Injections of antipsychotics were found to reduce the risk by the same number, especially when compared to oral antipsychotic medications of the same type. For example, the most prescribed antipsychotic drug, quetiapine (Seroquel), which is given in tablet form, reduced the risk by only 7 percent.

“The prescription of lithium has decreased steadily in recent years, but our results show that lithium should remain the first line of treatment for patients with bipolar disorder. Long-acting injections might offer a safe, effective option for patients for whom lithium is not suitable,” says Jari Tiihonen, specialist doctor and professor at Karolinska Institutet’s Department of Clinical Neuroscience.

Materials provided by Karolinska Institutet.

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Molecular Mechanism Behind Lithium’s Effectiveness Identified

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Credit to flickr.com user mattza. Used with permission under a Creative Commons license.

Scientists have identified the molecular mechanism behind lithium’s effectiveness in treating bipolar disorder in an international study published in Proceedings of the National Academy of Sciences (PNAS). Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP), Yokohama School of Medicine, Harvard Medical School, and UC San Diego collaborated on the study, which used human induced pluripotent stem cells (hiPS cells) to map lithium’s response pathway.

Lithium is a salt which has long been considered the gold-standard for bipolar treatment. The side effects–such as nausea, weight gain, and birth defects–are a trial for many people who take the drug. Only about one-third of people who suffer from bipolar disorder respond to lithium treatment. Before researchers at the Salk institute developed a test to predict who will respond to lithium with 92 percent accuracy, there was no test, and the drug’s effect was only found through a trial-and-error process which could take months or years.

In the study, scientists used hiPs cells created from lithium-responsive and non-responsive patience to observe a physiological difference in a protein called CRMP2: the protein was in a much more inactive state in responsive patients. However, when the researchers applied lithium, CRMP2 worked properly. So the study shows that bipolar disorder has a physiological–not necessarily genetic–cause.

This study is the first to explain the molecular basis of bipolar disorder. Scientists hope to use the results to develop a blood test for the disease, as well as further tests that can predict whether people who suffer from bipolar disorder will respond to lithium. Research leading from this study may also discover safer and more effective drugs to treat the disorder.

Edited to Add: Here is the link to the study, as requested.

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Scientists Predict Who Will Respond to Lithium

Lithium is a salt which treats both mania and depression in a lucky thirty percent of people with bipolar disorder. But prior to the discovery of a new method to predict who will respond to lithium, people were playing roulette.

Now scientists at the Salk Institute can predict, with 92 percent accuracy, who will be a lithium responder. All they need is five cells and a test. They discovered that the neurons of people with bipolar disorder are more excitable when exposed to stimuli and fire more rapid electrical impulses than individuals without the disorder. This means that people with bipolar are more easily stimulated.

In an old study, the scientists found that soaking skin cells from bipolar patients in a lithium solution calmed the hyperexcitability–but only for some of them. The next study proved even more fruitful. The researchers soaked lymphocytes (immune cells) rom known lithium responders in lithium solutions, and found the same results–the hyperexcitabilty was calmed. But even though both responders and non-responders had the same excitability, the electrophysiological properties were different.

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Credit to flickr.com user The Javorac. Used with permission under a Creative Commons license.

The Salk team looked for electrical firing patterns in neuronal lines, measuring the threshold for evoking a reaction, and other qualities. Overall, the patterns in responders were completely different than in non-responders.

The scientists were able to replicate the results again and again, which means that this test is proven to work. Now a blood draw is all that’s needed to test whether a patient with bipolar disorder will respond to lithium.

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Bipolar? Exercise Will Change Your Life

Many apologies for the missed posts last week! I’ve been tripping into mania, so managing my day to day life has been a struggle lately. Thank you for your patience!

When it comes to actions you can take to improve your quality of life, exercising regularly is largely considered the uncontested champion. As we covered in our post Why Weight Gain is Devastating to the Mentally Ill, a sedentary lifestyle and poor diet are linked to a worsening of bipolar and schizophrenic symptoms and decreased functioning. One of the triggers of depressive episodes is reduced physical activity, which is only the start of a vicious cycle.

A comprehensive review of research from 1966 to 2008 proved that scheduled exercise dramatically improves both the body and mind in persons with bipolar disorder. Not only does exercise flood someone with endorphins, studies indicate that it reduces the “allostatic load“, which is the damage done to your body from chronic stress.

Despite all of these good things, I know how difficult it can be to start exercising—much less follow a routine. But, starting slow is better than not starting at all. If you’re like me and can’t handle—or don’t have the time for—an hour-long workout, then just try walking for twenty minutes per day, ten minutes at a time. Eventually, you can build on your small triumphs. In our next post, we’ll cover how to squeeze in a workout around your kids’ schedules and a little bit about what to do if you have physical disabilities.

Make sure to pack plenty of healthy snacks and water to refresh yourself—and your little ones—during and after your workouts. If you are taking medications, do not become dehydrated! Lithium is especially dangerous to dehydrated persons because the body retains it when losing fluids. This can lead to lithium toxicity, which means the level in your blood has built up faster than it can be excreted by the kidneys. Side effects include dizziness, diarrhea, and vomiting, which worsens fluid loss. If the level is especially concentrated, you may slip into a coma or enter a psychotic state, both of which can damage you neurologically.

As always, please consult a physician before trying any program which involves changes to your levels of physical activity. Please ask your doctor about the effects your medications may have on your body during periods of high exertion, and to what extent you are able to work out in order to avoid symptoms like dizziness. A trained medical professional will recommend exercises tailored to your needs and health.

So start slow and good luck!

What is your favorite way to get moving and grooving?

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Good, Good, Good, Good Nutrition!

Anyone who has seen the documentary Super Size Me knows that Morgan Spurlock, who deliberately ate the most unhealthy meals at McDonald’s for a month, plunged into a deep depression by the second week of filming. Our moods are lifted by healthy food and destroyed by processed junk.

While good nutrition is vital for everyone’s health, research shows that it is especially so to those of us with mood disorders. A 2012 review by the University of Washington revealed that poor diet and a sedentary lifestyle may be coupled with “increased severity of symptoms of schizophrenia and bipolar disorder or decreased level of functioning.” 

Unfortunately, psychiatric patients tend to have “many nutrient inadequacies … and occasional excesses,” which translates to both a lack of essential vitamins and minerals and too many fats–in numbers even worse than the neurotypical population. With regard to vitamins, a broad-spectrum pre-natal with folic acid is also a boon if you’re vitamin-deficient.  Omega-3 fatty acids (fish oils) have also shown promise in helping with depression, though the research is controversial.

However, please speak to your doctor before making any changes. Maintaining a healthy diet is made even trickier due to mood episodes. According to the Depression and Bipolar Support Alliance, cutting fat out of your diet entirely can tip you into a manic or depressed state. Sugar is terrible for the bipolar-inclined, as it is linked with severe depression. Likewise, alcohol and caffeine should be avoided like the plague. As a contrast, lean proteins and fresh produce are wonderful, but expensive.  

A rough guideline for anyone with aneurotypical brain chemistry is to look for Zinc (red meat), B-vitamins (fish), and vitamin C (oranges).  Drinking as much water as you can is incredibly useful.  And you’ll need to pay even more attention to diet if you are pregnant, something that almost goes without saying.  

Anyone who plans to make dietary changes is advised to consult a nutritionist—provided they can afford one. I know it’s difficult to stick to changes regarding food or exercise plans, especially if you have to think about making healthy lunches for your children before school. But every little bit helps.

What healthy snack or activity have you found lifts your mood the best? What tends to lower it? Do you have a comfort food, and if so, what is it?

Not meant to take the place of a treatment plan created with licensed professionals.

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Why Medicinal Weight Gain is Devastating to the Mentally Ill

“Watch out,” the mental ward’s psychiatrist gently cautioned me. “It’s true that Depakote will stabilize you, but you’ll gain a lot of weight. Plus, anything you pack on will be harder to lose. Are you sure you want this medication?”

“Pish posh,” I said, manic and therefore invincible. “I don’t care about a measly ten pounds.”

At the time, I was seething. Were we, in considering my treatment plan, really going to prioritize my weight over my mental health? In the midst of my psychotic breakdown, I’d just realized that I was insane enough to need serious medical intervention. Was that really the time to caution me about maintaining thinness—especially considering I had given birth two weeks prior? And why were there no other options to treat my condition?

Sixty pounds and a few years later, I care a great deal about my muffin top. So much so that it has started to negatively affect both my health and self-esteem.

I’ve had young children ask if I have a baby in my belly.  I’ve been laughed at and called “fattie!” when dancing.  I’ve even had a certain insensitive business owner look at my four-year-old debit card and declare, “You used to be so skinny!  You know, when you were a teen.”

Ouch.

No one can tell from looking at me what my diet is or what medications I may be taking. Despite that, they feel free to comment on my body. I fully admit that my new curves are not entirely due to my nightly med cocktail. I am largely sedentary and my diet consists of the three major food groups—Grease, Sugar, and Dairy—both issues which I am addressing. But even with that lifestyle, I should not have gained thirty pounds in a year.

Weight gain is a huge factor preventing people from complying with a long-term drug treatment plan. In a 1999 study of the adverse effects of antipsychotics, more than seventy percent of participants reported weight gain as “extremely distressing”—far greater than any other side-effect.

Depakote, a gold standard in the treatnment of bipolar disorder, is one of the worst offenders. Studies have even suggested that women on the drug crave carbohydrates up to ten percent more than men do, and tend to gain more.

This is a three-fold problem:

1.  The mental health industry is a fledgling one, even though its business is currently booming. We just don’t know what a lot of these compounds do to the body yet, especially when blended. And not all drugs work for everyone. I myself am allergic to entire families of medications, including most of the new atypical antipsychotics and serious painkillers.

2.  People stop taking their prescriptions when they feel that the diseases are easier to bear than the side-effects.  In addition, this is often done abruptly, which can be dangerous as it may trigger a severe mood episode.

3.  Despite not being able to tell how healthy someone is by looking at them, many cultures shame fat people.

There is a stigma against having a mental illness. There is a stigma against needing medications to survive. There is a stigma against being fat. But what if you are the first already and have to choose between the second and third?

This is the kind of choice that breaks a person.

What sorts of things have you had to deal with on your meds? If you can bear to part with the numbers, how many pounds have you gained?

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What is Cyclothymia?

I once met a man at a writer’s conference whose behavior screamed “hypomanic”. He spoke rapidly, walked fast, made grand gestures, and was prone to heavy drinking and smoking. I often saw him pacing or fidgeting. At any given moment, I expected him to burst out of his skin, unable to contain his elation.

He was also an inspiration to many. The great majority of his conversations consisted of probing questions about who the addressee was, and how were they going to improve themselves—today? What were their dreams, and why weren’t they acting on them already? He oozed charisma, and garnered quite a fan following.

Lucky for him, he had an amazing Team You present at the conference: a group of his friends who had all known each other since their school days. They took shifts watching over him when he inevitably crashed. They explained that their colleague would go, go, go–sometimes for up to a month and a half. Then he’d sleep for about a week, curling into himself in the throes of an awful depression.

When I explained his behavior to my therapist, she said, “That sounds like cyclothymia.”

Cyclothymia is largely considered to be a “weaker” form of bipolar disorder. Episodes of mania and depression are not as severe and do not last as long. Psychotic features aren’t usually present. Some people with the weaker form eventually develop full-blown bipolar. It is suspected that cyclothymia is passed down genetically.

The disorder is difficult to diagnose because it shares so many characteristics with Attention Deficit Hyperactivity Disorder (ADHD), including, “increased energy, distractibility, and impulsive or risk-seeking behavior.” The symptoms also overlap with certain personality disorders. In addition, cyclothymia is frequently comorbid with other disorders, which means that a doctor may have one or more diagnoses to sift through.

Symptoms are usually treated with lithium carbonate and Seroquel, provided the patient desires treatment. Most people with cyclothymia are productive, sometimes to extremes.

Disclaimer: I do not claim to know enough to have diagnosed my friend, nor do I expect or want my therapist to do the same.

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The Importance of Team You, Part V

Team You, a term coined by advice writer Captain Awkward, is a group of people who support you in times of emergency. If you are fighting the grips of mania or coping with isolating depression, these allies are invaluable.

This is part one of a five-part series.
Part I | Part II | Part III | Part IV | Part V

Who Shouldn’t Be On Team You

If you’re like me, you’ve found that there are only a few precious people who can uphold the coveted Team You title, and a lot who can’t. Sometimes even close friends and family fit into that description. Even worse, they may insist on “helping” you, when all they do is harm. Cut them off at the knees. Deflect, deflect, deflect.

Phrases include:

  1. “Thank you, but I’ll be able to handle it. Specific, positive example of a Thing recently accomplished.”
  2. “Thanks for the suggestion to try [remedy which contradicts my medications]. I’ll think on that (for ten seconds).”

Then there are the maliciously ignorant. These are the people who loudly declare that conquering depression is just a matter of willpower, and if you’d just get out of bed, you’d be able to see how lazy you’ve been. Avoid these people like the plague they are.

Next is the person who actually wants to help, but always feels uncomfortable doing so and skirts around the fact that you have one or more mental illnesses. They may note, innocuously, that you’re “sick” quite often. Phrases include the ones above, but also: “It seems like you’ve noticed I have a problem today. Do you have any concrete and specific ideas about how to help me?”

Make sure they are as detailed as possible about the extent they’re willing to go, otherwise you’ll find it difficult to take their help—-or they’ll give more than they want to.

Someone who makes you feel guilty for needing their support is almost worse than the maliciously ignorant person. Try not to let them touch you, and if you find one one your Team You, boot them.

Others who shouldn’t be on Team You fall into the category of super passive-aggressives and “extreme” advice givers. Our brains are fragile enough as it is. Don’t let others fill them up with more toxins. If possible, excise these harmful influences from your life.

Thanks for reading our series on finding allies! Did we miss anything?

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The Importance of Team You, Part IV

Team You, a term coined by advice writer Captain Awkward, is a group of people who support you in times of emergency. If you are fighting the grips of mania or coping with isolating depression, these allies are invaluable.

This is part one of a five-part series.
Part I | Part II | Part III | Part IV | Part V

How to Avoid Burning Out Your Team

As everyone with bipolar disorder knows, living with a mental illness is exhausting. And although the people around us may not feel the exact effects that we do, dealing with someone who can’t stop talking or can’t get out bed is exhausting, too. Like many people with this disorder, I have lost friends due to either:

      1. relying on them too much
      2. driving them away with an overbearing manner during my manias
      3. losing touch with them during my depressions

The last two are subjects for different days, but please keep them in mind. The first is crucial to avoiding friend burn out. If our friends are to be our supporters and allies, we must support them, too. This means we can’t overwhelm them with bragging or obsessions or negative complaints, especially during periods of mania.

We also have to listen to their successes and problems in return. Every relationship is based around give and take. Strive for a healthy balance. Make sure to ask your friends to tell you when they need a break—and try not to be offended. This is exhausting for everyone, remember? I promise that it’s not personal.

Ideally, you’d have several friends’ brains to pick. If you don’t, please try to be patient. Journal your thoughts and feelings so that you don’t dump them on the few friends who have stuck around.

It might not seem fair to have to manage your effect of your mental illness on your friends. You’re right. It’s not. But, unfortunately, learning your limits and your friends’ is part of the whole. The more self-aware you are about your disorder, the better you’ll be able to control it—or react when an episode gets the best of you.

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