Probiotics May Help Treat Bipolar Disorder

About 3 million people in the US are diagnosed every year with bipolar disorder, a psychiatric condition characterized by dramatic shifts in mood from depression to mania. Currently, the standard treatment includes a combination of psychotherapy and prescription medications such as mood stabilizers and antipsychotics.

However, an emerging field of research is exploring the use of probiotics — often thought of as “good bacteria” — as a potential new avenue for treatment of bipolar and other psychiatric mood disorders. And a new study from Baltimore’s Sheppard Pratt Health System, conducted by a research team led by Faith Dickerson, finds that a probiotic supplement may reduce inflammation of the gut, which is known to exacerbate bipolar disorder. Probiotic organisms are non-pathogenic bacteria that, when present in the gut flora, are known to improve the overall health of the host.

In recent years, research has demonstrated a strong link between the gastrointestinal tract and the central nervous system. This connection, named the “gut-brain axis” (GBA), allows for crosstalk between the endocrine, immune, and autonomic nervous systems. The GI tract is also home to the intestinal microbiome, a complex population of roughly 100 trillion microorganisms (more than ten times the number of cells that make up the human body) that interacts with the mucosal lining of the GI tract. Studies have shown that the intimate association between the gut microbiome and GI tissue has a significant effect on the GBA.

There is also mounting evidence linking imbalances in the microbial species that make up the gut microbiome to a number of health problems including allergies, autoimmune disorders, and psychiatric mood disorders.

In the case of bipolar disorder and the GBA, previous studies have shown that inflammation, or overstimulation of the body’s immune system, is a contributing factor in the disease. With this in mind, researchers developed a probiotic supplement aimed at reducing inflammation caused by microbial imbalances in the gut.

A group of patients recently hospitalized for mania participated in a 6-month study to track the effects of probiotic treatment on both their mood and the status of their immune system.

The patients were randomly selected to receive either the

yogurt.jpg
A picture of a milk bottle, a measuring cup, and a yogurt cup. Credit to flickr.com user Gabriel Li. Used with permission under a Creative Commons license.

probiotic supplement or a placebo in addition to their usual medications. The results showed that the group receiving the probiotic supplement, on average, didn’t return to the hospital as quickly and required less in-patient treatment time compared to the placebo group. The beneficial effects were most pronounced in those patients who exhibited abnormally high levels of inflammation at the beginning of the study.
Overall, these results indicate that changes in intestinal inflammation can alter the trajectory of psychiatric mood disorders and that modulating the intestinal microbiota may be a new avenue of treatment for patients suffering from these diseases.

Materials provided by the American College of Neuropsychopharmacology.

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National Prevention Week: How I Prevent Oncoming Bipolar Mood Episodes

The week of May 12-18 is National Prevention Week, so I’d like to talk about how I try to prevent oncoming bipolar mood episodes. Because I was diagnosed at twenty-two and started medication and therapy, I have a decade’s worth of experience in managing my bipolar disorder. Read on for a roadmap discussing how to tackle the prevention of mania and depression head on.

Fight Self-Stigma

Self-stigma is when you have absorbed the negative, inaccurate messages about your mental illness around you. This affects your perception of your mental illness and your need to treat it, which in turn affects your behaviors and actions in terms of seeking treatment. In order to face taking medication every day for the rest of your life, you need to fight stigma, especially self-stigma. The way I fought it was to recognize that I needed to be my best self for my newborn son, which entailed taking medications and going to therapy. I needed to treat my disorder so I could properly mother my son. It wasn’t just about me.

If you have a reason outside of yourself, awesome, but if you don’t, you still deserve treatment. You are better than your disease. You are a human being, a precious individual. Caring for yourself, especially in the pit of depression, is one of the hardest issues you’ll ever face. But you deserve proper care, even if it’s mostly self-care for a while.

Medication

I can’t recommend medication enough. In combination with therapy, medications saved my life. When I was first diagnosed, Depakote toned down my psychotic mania, and two years later, lithium lifted me from the black sucking hole of suicidal depression. Now I’m on Risperidone and Wellbutrin, and the combination has enabled me to be stable for over six years. Taking my medication daily has prevented the dizzying spin of mania and the pit of depression. Part of this is my fighting self-stigma, as I said above.

Therapy

Another tactic that has helped me remain stable for the past half-decade is attending counseling sessions with my therapist. Therapy has helped me learn coping mechanisms to handle my day-to-day life, including emergencies. I’ve been able to treat my manic and depressive episodes, and learn how to flourish. I am thriving, and I wouldn’t have thrived so successfully without those weekly appointments with my therapist.

Sleep

Proper sleep is crucial for managing your bipolar disorder. Sleep disturbances trigger bipolar mood episodes, especially mania, and too much sleep triggers the crash of depression–usually following mania. Problems with sleep are a common symptom of bipolar disorder; in a future post, I’ll be looking at how common insomnia is for this specific mental illness.

To ensure I sleep as well as I can, I practice what’s called good sleep hygiene. I don’t drink water or caffeinated beverages right before bed. I wind down before bed, taking a bath every night. I wake up every morning at 8:30am, if not earlier. I try to go to bed at the same time. I wake up frequently in the middle of the night with a racing mind, but I try to calm myself by praying or meditating. Generally, that works, and I’m able to get back to sleep within fifteen to thirty minutes; I recognize that I am lucky in that manner. Try to practice good sleep hygiene, and you, too, might be able to prevent oncoming bipolar mood episodes.

jessi RM
A picture of a smiling woman next to a frowning woman, in black and white. Credit to fliclr.com user Jessi RM. Used with permission under a Creative Commons license.

Final Thoughts

Fighting self-stigma, getting proper treatment for your disease (including medication and therapy), and sleeping properly are some of the best ways to prevent oncoming bipolar mood episodes. If you’re looking for a post on how to manage the most common bipolar triggers, click here.

You can do this.

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How Specific Gene Variants May Raise Bipolar Disorder Risk

cpgv level
In this data visualization, each horizontal line is an individual. Those with bipolar disorder were more likely to be on the lower end of the CPG2 protein expression scale, and more likely to have gene variants that reduced expression. Credit: Rathje, Nedivi, et. al.

A new study by researchers at The Picower Institute for Learning and Memory at MIT finds that the protein CPG2 is significantly less abundant in the brains of people with bipolar disorder (BD) and shows how specific mutations in the SYNE1 gene that encodes the protein undermine its expression and its function in neurons.

Led by Elly Nedivi, professor in MIT’s departments of Biology and Brain and Cognitive Sciences, and former postdoc Mette Rathje, the study goes beyond merely reporting associations between genetic variations and psychiatric disease. Instead, the team’s analysis and experiments show how a set of genetic differences in patients with bipolar disorder can lead to specific physiological dysfunction for neural circuit connections, or synapses, in the brain.
The mechanistic detail and specificity of the findings provide new and potentially important information for developing novel treatment strategies and for improving diagnostics, Nedivi said.

“It’s a rare situation where people have been able to link mutations genetically associated with increased risk of a mental health disorder to the underlying cellular dysfunction,” said Nedivi, senior author of the study online in Molecular Psychiatry. “For bipolar disorder this might be the one and only.”

The researchers are not suggesting that the CPG2-related variations in SYNE1 are “the cause” of bipolar disorder, but rather that they likely contribute significantly to susceptibility to the disease. Notably, they found that sometimes combinations of the variants, rather than single genetic differences, were required for significant dysfunction to become apparent in laboratory models.

“Our data fit a genetic architecture of BD, likely involving clusters of both regulatory and protein-coding variants, whose combined contribution to phenotype is an important piece of a puzzle containing other risk and protective factors influencing BD susceptibility,” the authors wrote.

CPG2 in the Bipolar Brain

During years of fundamental studies of synapses, Nedivi discovered CPG2, a protein expressed in response to neural activity, that helps regulate the number of receptors for the neurotransmitter glutamate at excitatory synapses. Regulation of glutamate receptor numbers is a key mechanism for modulating the strength of connections in brain circuits. When genetic studies identified SYNE1 as a risk gene specific to bipolar disorder, Nedivi’s team recognized the opportunity to shed light into the cellular mechanisms of this devastating neuropsychiatric disorder typified by recurring episodes of mania and depression.

For the new study, Rathje led the charge to investigate how CPG2 may be different in people with the disease. To do that, she collected samples of postmortem brain tissue from six brain banks. The samples included tissue from people who had been diagnosed with bipolar disorder, people who had neuropsychiatric disorders with comorbid symptoms such as depression or schizophrenia, and people who did not have any of those illnesses. Only in samples from people with bipolar disorder was CPG2 significantly lower. Other key synaptic proteins were not uniquely lower in bipolar patients.

“Our findings show a specific correlation between low CPG2 levels and incidence of BD that is not shared with schizophrenia or major depression patients,” the authors wrote.

From there they used deep-sequencing techniques on the same brain samples to look for genetic variations in the SYNE1 regions of BD patients with reduced CPG2 levels. They specifically looked at ones located in regions of the gene that could regulate expression of CPG2 and therefore its abundance.
Meanwhile, they also combed through genomic databases to identify genetic variants in regions of the gene that code CPG2. Those mutations could adversely affect how the protein is built and functions.

Examining Effects

The researchers then conducted a series of experiments to test the physiological consequences of both the regulatory and protein coding variants found in BD patients.

To test effects of non-coding variants on CPG2 expression, they cloned the CPG2 promoter regions from the human SYNE1 gene and attached them to a ‘reporter’ that would measure how effective they were in directing protein expression in cultured neurons. They then compared these to the same regions cloned from BD patients that contained specific variants individually or in combination. Some did not affect the neurons’ ability to express CPG2 but some did profoundly. In two cases, pairs of variants (but neither of them individually), also reduced CPG2 expression.

Previously Nedivi’s lab showed that human CPG2 can be used to replace rat CPG2 in culture neurons, and that it works the same way to regulate glutamate receptor levels. Using this assay they tested which of the coding variants might cause problems with CPG2’s cellular function. They found specific culprits that either reduced the ability of CPG2 to locate in the “spines” that house excitatory synapses or that decreased the proper cycling of glutamate receptors within synapses.

The findings show how genetic variations associated with BD disrupt the levels and function of a protein crucial to synaptic activity and therefore the health of neural connections. It remains to be shown how these cellular deficits manifest as biopolar disorder.

Nedivi’s lab plans further studies including assessing behavioral implications of difference-making variants in lab animals. Another is to take a deeper look at how variants affect glutamate receptor cycling and whether there are ways to fix it. Finally, she said, she wants to continue investigating human samples to gain a more comprehensive view of how specific combinations of CPG2-affecting variants relate to disease risk and manifestation.

Materials provided by Picower Institute at MIT.

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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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The History of the Treatment of Mental Illness

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Credit to flickr.com user Digital Collections, UIC Library. Used with permission under a Creative Commons license.

Skull drills. Exorcisms. Isolation. Lobotomies. “Happy pills.” These are all treatments which have been applied–often forcibly–to people who suffer from mental illness.

 

The first apparent “cure” for mental illness was trephining (also referred to as trepanning). People in Neolithic times would chip holes–or trephines–in each others’ skulls with stone pieces, which was thought to release evil spirits from the head. This also happened to release pressure from brain inflammation. Some people actually survived this practice, as there have been skulls found with holes in them that showed signs of healing. This practice lasted for centuries, with more sophisticated equipment being invented, such as skull saws and drills.

To ancient peoples such as the Hebrews and the Persians, mental illnesses were attributed to supernatural forces, like demons and upset deities. Practices such as exorcisms and prayer were common in the ancient world. Egyptians appeared to be the most advanced civilization when it came to treatment of mental illnesses, recommending activities such as painting and attending concerts.

The Greek physician Hippocrates introduced the four humors–blood, bile, phlegm, and black bile–theory, which said that the combination of these fluids made up personalities. In the Middle Ages, mental illness was said to stem from an imbalance of the four humors. To bring the body back into balance, vomiting was induced, people were given laxatives, and leeches were applied. Sufferers of mental illness were also told to avoid red meat and wines. Beatings were also routinely applied to the mentally ill.

The first mental hospital was established in 792 AD, in Baghdad, followed by those in Aleppo and Damascus. However, at this time, the mentally ill were left to be cared by their families, and were often subject to abuse, concealment, or abandonment. Clergy-run facilities were soon established, which promised humane care. However, these could not handle the treatment of the entire population of the mentally ill.

Asylums were the next step, set up worldwide around the 1500s. The first in Europe is thought to be the Valencia mental hospital in Spain, 1406 AD, and though not much is known about this particular asylum, many treated their patients deplorably. Asylums, up until the mid-1800s, were places where the mentally ill slept shackled to the walls in their own waste. “Cures” ranged from bloodletting to dousing in hot and cold water to shock the system back to rationality. Physical restraints, threats, and straightjackets were common, implemented to get the sufferer to “choose” sanity. In Saint Mary of Bethlehem asylum in London, visitors could pay a penny to see violent patients in a freak show.

This all changed, starting in 1792 with a man named Philippe Pinel, in Paris. He took over La Bicentre asylum to test his hypothesis that compassion would cure the mentally ill. Patients were unchained and given clean, sunny rooms, and were no longer treated like animals. This humanitarian approach spread, kicking off a brief period of “moral management,” where patients were encouraged to perform manual labor and make moral choices.

Medical advances ended moral management. By 1939, Sigmund Freud had published twenty-four volumes of work in psychoanalysis, changing the world forever.  Freud tried hypnosis, free association, and dream interpretation. Although Freud’s work provoked criticism, psychoanalysis was popular until the mid-1900s.

During this time, psychopharmacology, surgeries, and electro-convulsive shock therapy (ECT) were common. The latter treatment was used to abuse patients in some mental hospitals, however. Because ECT is scary, patients were frequently intimidated and threatened with the practice. Some people were shocked over a hundred times. However, with reforms, this practice is still used today.

Egas Moniz performed the first lobotomy in 1935, first shocking the patient into a coma, and then hammering an instrument similar to an icepick through the top of each eye socket. This practice severs the emotional centers of the brain from the frontal lobes, producing a calm and immature patient that is unable to control their impulses or feel anything. Lobotomies were cheap, easy, and popular around the world for twenty years–until doctors started noticing the undesirable side effects.

With the introduction of the psychotropic drug Lithium in 1949, Australian psychiatrist J.F.J. Cade kicked off a wave of successful anti-psychotic medicines which effectively managed symptoms. Unfortunately, this also kicked off a wave of deinstitutionalization in the 1960s, as mental illnesses were thought to be managed entirely by medication. Thousands of the mentally ill discharged from mental wards ended up homeless. In the 1980s, over a third of all homeless individuals were severely mentally ill in America. Over 100,000 individuals who suffered from severe mental illness were imprisoned, and over a fourth of that population were held without charges as they waited for beds at one of the nation’s sole remaining mental hospitals.

Despite advancements made in therapies, many mentally ill people rely solely on psychotropic medications to avoid the shame of stigma. Mental health care is grossly underfunded in many countries around the world even today, and is widely stigmatized. The treatment of mental illness has come a long way, but we still have so much further to g

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Substance Abuse and Bipolar Disorder

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

Sometimes, the symptoms of bipolar disorder–including periods of elevated mood, depression, and irritability–are too difficult to deal with. Often, people turn to drugs and alcohol to try to cope.

“Some people attempt to treat symptoms of their mental illness with substances, but substance abuse can activate or prolong symptoms,” Marissa Krick, a writer for DrugRehab.com, said in an email.

Krick cited studies saying that up to 60 percent of people who suffer from bipolar disorder confess that they’ve also abused drugs or alcohol. People who suffer symptoms of acute mania or bipolar II disorder are significantly more likely to abuse benzodiazepine and alcohol than people who suffer from depression, according to the Zurich Cohort Study. In addition, a history of substance abuse complicates recovery from acute manic states.

The writers at DrugRehab.com have penned an extensive report on substance abuse in conjunction with bipolar disorder. It’s worth a read. According to the report, “Substance abuse makes symptoms of bipolar disorder worse and decreases the benefits of standard treatment. People tend to take longer to recover, spend more time in health facilities and be more likely to contemplate suicide when they misuse substances during treatment.”

But there is hope. Rehabilitation facilities can treat both substance abuse and bipolar disorder concurrently. Treatment for substance abuse starts with a detoxification process, whereas treatment for bipolar disorder involves medication and behavioral therapy. Patients going through drug or alcohol withdrawal are kept as comfortable as possible.

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How Privilege Affects Mental Healthcare

Like many people who celebrate Thanksgiving, I’m taking a hard look at what I should be grateful for. When I was young, my family was largely feast or famine. We survived multiple job losses, costly illnesses, and bankruptcies. In my teens, all seven of us lived in a trailer no bigger than 750 sq. ft. And I was always hungry.

Now, I am steeped in obscene amounts of privilege. I am white, and I hold two college degrees. Among other things, this means I have an easier time getting and taking medication. My nursing and Latin classes specifically enable me to understand medical terminology and the effects of medications on my body and brain. I am a very insistent advocate for my health.

I am also married to a partner with a steady, middle-class job, which means my anxiety about ending up homeless or going hungry now is largely irrational. We’ve only been married for five years, but he not only held my hand when I committed myself, but he puts up with my mood episodes today. We could still get divorced, as have so many others with bipolar. But we haven’t yet. We are very awkward when people ask about our married life, because we usually exist in a different bubble than they do.

Insurance Card
Credit to flickr photographer mtsofan. Used with permission.

My partner’s job has insurance. I can—and will—write a post on this benefit alone, because without it, I wouldn’t be writing this today. I’d be dead. My hospitalization four years ago cost $6638.61—and was completely covered. I was flabbergasted. We were newlyweds at the time, and would have been put into debt. Due to growing up having Medicaid or sometimes nothing at all, the feeling is still surreal.

Speaking of jobs, I am lucky enough to be self-employed while writing my book, which means I can have as many panic attacks as I need to have without getting fired.

I’ve been in therapy for years. I’ve also changed psychiatrists five times until I found one I liked. This process of doctor-finding is actually quite common, but we could afford the doctor’s visits, the pills, and the frequent blood draws to check for liver or thyroid damage, which means I was willing to invest in my health. And my nightly cocktail of medication—found through years of trial and error—actually works. There are side effects, of course, but as I understand it, they could be significantly worse.

And finally, I was able to keep my infant despite someone threatening to report me to Child Protective Services during my psychotic break.

Is my mental illness severe? Of course. But I am lucky, to an unrealistic extent. If I wasn’t covered by my partner’s insurance, I would have had go to work immediately after my breakdown to cover costs. If I hadn’t married him when I did, I would be living with my parents, homeless, or dead—and likely one of the latter. There are so many ifs, which terrifies me.

Mental stability—which should be a basic human right—is achieved only by those who can afford it.

Homeless and cold.
Credit to flickr photographer Ed Yourdon. Used with permission.

A disproportionate amount of the homeless are returning veterans, the mentally ill, or both. Would that more shelters could provide a secure environment and treatment for any atypical brain chemistries or traumas that they may have! I would happily part with my tax dollars to ensure that more people with schizophrenia have a chance to sleep in a warm bed rather than under a bridge. Ideally, they’d also have help moving on to more permanent housing and work.

The weeks leading up to Thanksgiving and Christmas warm my heart, but not just because I’m looking forward to spending time with friends and family. The generous outpouring of help around this time is mind-boggling. But I feel I have a responsibility to use my privilege year-round to help others who are less fortunate. First, I’ll keep in mind how much I have.

What struggles have you survived? And what privileges may have helped you through them?

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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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