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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How to Spot Depression in Children, Even Preschoolers

Trigger Warning: Brief discussion of suicidal ideation.

Preschool depression is often overlooked, because the symptoms are difficult to spot or may be explained away by hopeful parents and teachers. Depression in adults is widely known, but can preschoolers suffer clinical depression? Science says they can.

Scientists began studying depression in preschoolers 20 years ago, and the research continues today. According to the conclusion of a new study led by Dr. Joan Luby of the Washington University School of Medicine in St. Louis, preschoolers suffer depression. Luby’s team examined 306 children ranging from 3 to 6 years old. This study demonstrated that 23% of the 3-year-olds endured depressive symptoms every day for two consecutive weeks. As the age of the child increased, the rate of major depressive disorder diagnoses also increased. The 4-year-olds suffered depressive symptoms at a rate of 36%, while the 5-year-olds showed a rate of 41%. The children who had suffered extremely stressful or traumatic events in their lives also had a higher incidence of depression than the controls.

Preschoolers generally can’t describe their emotional states. They’re still learning what emotions are and they lack the ability to vocalize them. This is the difficulty in diagnosing depression in preschoolers, and why you may need help spotting it. In order to allow the study participants to express how they perceive themselves and get a sense of what young children were feeling, Dr. Luby’s team asked a series of questions using puppets. How the children responded gave the researchers a clue about how the kids were feeling.

Further complicating the picture is the prevalence of other conditions along with depression, like Attention Deficit Hyperactivity Disorder (ADHD). In Dr. Luby’s study, about 40% of the study participants also dealt with ADHD, which tends to drown out symptoms of depression, because the symptoms are similar. This can even persist later in life. Children who suffer depression are more than four times as likely to suffer an anxiety disorder later in life than kids who don’t suffer depressive symptoms.

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A preschool-aged boy in blue hoodie sprawling on a parent’s lap. Credit to flickr.com user Quinn Dombrowski. Used with permission under a Creative Commons license.

But what does depression look like in a 3-to-6-year-old?How can you, as a parent, spot it? Well, depression in children looks a lot like depression in adults. For example, anhedonia, the inability to experience pleasure from normally enjoyable activities, can show up in adults as a lack of enjoyment in things like golfing or writing. Preschoolers with anhedonia find little to no joy in their toys. Both adults and children with depression are restless and irritable. Depressed kids whine a lot, and don’t want to play.

When they do play, children may decide that their stuffed animals decided to “die” today and decide to bury them. Anytime you see a preschooler demonstrate methods of suicide or death with a stuffed animal without mimicking an episode of your life, such as a death in the family, your antennae need to come up. That could indicate suicidal thoughts.

But the most common symptom of depression in children is deep sadness. Not someone who’s sad for a day, but all the time, no matter who he or see is with or what he or she is doing. Sadness in the face of goals that have been thwarted is normal. But depressed children have difficulties resolving the sadness to the point where the misery affects their ability to function regularly. If your child appears to be sad to the point of inability to enjoy anything or regulate their other emotions, then get a recommendation from your pediatrician for a child psychologist or a behavioral therapist.

Other notable symptoms of childhood depression are an exaggerated sense of guilt, shame, and insecurity. Depressed preschoolers generally feel that if they do a naughty thing or disobey, that means they are inherently bad people.

Here’s a breakdown of the symptoms of depression in children of any age, including preschoolers:

  • Deep and persistent sadness
  • Irritability or anger
  • Difficulty sleeping or focusing
  • Refusing to go to school and getting into trouble
  • Change in eating habits
  • Crying spells
  • Withdrawing from friends and toys
  • Fatigue
  • Anhedonia – inability to derive pleasure from enjoyable activities, like playing with toys
  • Whining
  • Low self-esteem and insecurity
  • Shame and guilt
  • Timidity

Preschoolers may be especially vulnerable to depression’s consequences. Young children are sensitive to emotions, but lack the ability to process strong feelings. Early negative experiences–including separation from a caregiver, abuse, and neglect–affect physical health, not just mental. Multiple studies have linked childhood depression to later depression in adulthood.

This is why properly diagnosing and treating these children early is so vital. One established intervention for treating childhood depression is called Parent-Child Interaction Therapy, or PCIT. Originally developed in the 1970s to treat violent or aggressive behaviors in preschoolers, PCIT is a program where, under the supervision of a trained therapist, caregivers are taught to encourage their children to manage their emotions and stress. The program typically lasts from 10 to 16 weeks.

The Bottom Line

Dr. Luby’s research is met with resistance. Laypeople typically think the idea of preschoolers suffering depression ridiculous, and even some doctors and scientists don’t believe children are cognitively advanced enough to suffer from depression. Preschool depression remains a controversial topic, which makes it harder to diagnose in your child.

But depression in children 6 years and older has been well established by decades of data. Is it really so hard to think that preschoolers might suffer depression as well? Dr. Luby and her team have been looking at the data for 20 years, and have concluded that preschoolers can suffer depression, just like older children and adults.

Admitting that your child is depressed may make you feel like you’re a failure. After all, if you can’t protect your children from depression, who can? But clinical depression is chemical. This is not your fault. You may have been told that depression doesn’t exist in preschoolers, or that you’re overreacting. You may be called a helicopter or hovering parent. But trust your instincts. You know your child better than anyone else. Don’t be afraid to go against stigma for your child’s benefit.

Up to 84,000 of America’s 6 million preschoolers may be clinically depressed. If your child is one of them, you are not alone. There is no shame to depression. The condition is not your child’s fault, just as in adults. No parent likes to see her child suffer, and getting help for depressed children is vital to their well-being.

If your child suffers depressive symptoms, especially anhedonia, ask your pediatrician for a recommendation for a behavioral therapist or child psychologist. Typically, the earlier the intervention, the more successful the results.

Good luck.

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How Sugar May Harm Your Mental Health

Sugar, especially refined white sugar which has been processed, inflates waistlines and contributes to obesity. But, while some studies have shown that sugar may have a detrimental effect on the mood, not a whole lot of research has been done on sugar’s effects on mental health.

In a past post, Good, Good, Good Nutrition, part II: Foods to Avoid When Managing Bipolar Disorder, we covered how sugar can cause wild mood swings in bipolar patients. And how obesity can make some bipolar medications ineffective, especially if the weight is gained around the middle. But there are other ways sugar harms mental health.

Let’s dig in.

Addictive Properties

The addictive properties of sugar have been studied in recent years, though the research is still controversial. But anyone who’s craving a chocolate fix can understand how additive sugar is. Sugar and actual drugs both flood the brain with dopamine, a feel-good chemical which changes the brain over time. Among people who binge eat, the sight of a milkshake activated the same reward centers of the brain as cocaine, according to a Yale University study. Speaking of cocaine, rats actually prefer sugar water to the hard drug. And according to a 2007 study, rats who were given fats and sugar to eat demonstrated symptoms of withdrawal when the foods were taken away.

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A spoonful of sugar on a black background. Credit to flickr.com user Gunilla G. Used with permission under a Creative Commons license.

Cognitive Effects

Sugar may also affect your ability to learn and remember things. Six weeks of drinking a fructose solution similar to soda caused the rats taking it to forget their way out of a maze, according to a University of California Los Angeles (UCLA) study. In the same study, rats who ate a high-fructose diet that also included omega-3 fatty acids found their way out of the maze even faster than the controls, who ate a standard diet for rats. The increased-sugar diet without omega 3s caused insulin resistance in the rats, which leads to diabetes and damaged brain cells crucial for memory.

Depression

Countries with high-sugar diets experience a high incidence of depression. Mood disorders may also be affected by the highs and lows of sugar consumption and subsequent crashes. In schizophrenic patients, a study has shown that eating a lot of sugar links to an increased risk of depression.

The researchers behind the study produced a couple of theories to explain the link. Sugar suppresses the activation of a hormone called BDNF, which is found at low levels in people with schizophrenia and clinical depression. Sugar also contributes to chronic inflammation, which impacts the immune system and brain. Studies show that inflammation can cause depression.

Anxiety

Sugar consumption doesn’t cause anxiety, but it does appear to worsen anxiety symptoms. Sugar also causes the inability to cope with stress. Rats who ate sugar and then fasted showed symptoms of anxiety, according to a 2008 study. In a study in the following year, rats who ate sugar (as opposed to honey) were more likely to suffer anxiety. While you cannot cure anxiety through a change in diet, you can help the body cope with stress and minimize symptoms if you avoid sugar.

The Bottom Line

The good news is, people are consuming less sugar now that the risks to eating it are clearer. A decade ago, Americans ate sugar for 18% of their daily calories, but today that’s dropped to 13%. The more we learn about the human body and how our choices in foods affect us, the more we can tailor our diets to maximize the benefits to our health and minimize the risks.

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America Has Highest Rate of Bipolar Disorder Diagnoses in 11-Nation Study

Bipolar disorder, a disease characterized by “highs” (called mania) and “lows” (called depression), does not discriminate. It affects men and women equally, has been affecting children more and more, and appears to have a roughly similar incidence across all ethnic, racial, and socioeconomic groups. About 2.4% of people around the world are diagnosed with bipolar disorder in their lifetimes.

According to a new 11-nation study conducted by researchers around the world, the United States has the highest incidence of bipolar disorder, at 4.4%. India has the lowest rate at 0.1%, followed by Japan at 0.7%. Lower-income nations typically demonstrated lower rates. Colombia, a lower-income nation, bucked the trend with a incidence of 2.6%.

But why does the U.S. experience the highest bipolar rate among all 11 nations studied? Let’s dig in.

Wealth

Wealth may play a role. Individuals in higher-income nations were more likely to be diagnosed than those in lower-income nations. The exception is Japan, with an incidence rate of 0.7%.

Unfortunately, the U.S. also has the largest worldwide gap between the rich and the poor. The economic stressors are greater than in other Western societies. This means there are more psychological stressors among the poor of America, which may lead to substance abuse and fragmentation of the family.

Immigrant Melting Pot

Genetics may also contribute in the rate of bipolar disorder in different countries. Studies have confirmed that the condition sometimes runs in families, and that the lifetime chance of an identical twin of a bipolar twin developing the disorder is about 40% to 70%. So the genetic makeup of a country may affect the rate.

But what about immigrants? America is known as the “melting pot” of the world, due to all the immigrants that come here. Among people who have emigrated, the actual expression of bipolar disorder is the same as it is in the population that those people have left. However, what’s interesting to note is that, in those cases, their children tend to have higher rates of mental illnesses, including bipolar disorder, by a factor of as much as tenfold.

Social scientists suspect that the lack of extended family and cultural systems may result in higher incidences of bipolar disorder, as environmental stressors play a factor in the development of the disease. With a lack of familial support, immigrants have less of a buffer in terms of a social network, especially when they first arrive.

And immigrants seeking a new life in America might be more risk-taking than people who stay in their home countries. The immigrant belief that they can find success here takes a certain mindset of grandiosity and other symptoms of hypomania, which may be more common among people who suffer from bipolar disorder.

Stigma

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A stylized map of South America. Credit to flickr.com user Stuart Rankin. Used with permission under a Creative Commons license.

Stigma also plays a part in the incidence rate of bipolar disorder among different countries. Fewer than half of those suffering from the disorder sought help for it. And only a quarter of those in low-income countries were treated by a mental health professional for bipolar disorder.

Some cultures are reluctant to talk about psychiatric things. Lower-income nations experience higher rates of stigma. Fewer people are willing to come forward with their struggle with mental illnesses, which leads to a lower perceived rate of bipolar disorder.

Cultural awareness of mental illnesses also contributes to the problem of stigma. Americans are fairly aware of bipolar disorder as a disease, whereas the symptoms of the condition may be missed or ignored in lower-income nations. This leads to lower rates of diagnosis.

The Bottom Line

No matter where people live, bipolar disorder causes serious impairment among those who suffer from it. People need to be less afraid about seeking help for their mental illnesses. Educating individuals about the disease may help combat stigma. Greater awareness among cultures will only help people get much-needed treatment.

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Can Early Symptoms Predict Bipolar Disorder? Evidence Shows Differing Patterns of Risk Factors

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A picture of pink pills in a bubble pill container. Credit to flickr.com user Kris A. Used with permission under a Creative Commons license.

Two patterns of antecedent or “prodromal” psychiatric symptoms may help to identify young persons at increased risk of developing bipolar disorder (BD), according to a new analysis in the Harvard Review of Psychiatry.

Early signs of BD can fall into a relatively characteristic “homotypic” pattern, consisting mainly of symptoms or other features associated with mood disorders; or a “heterotypic” pattern of other symptoms including anxiety and disruptive behavior. Environmental risk factors and exposures can also contribute to BD risk, according to the analysis by Ciro Marangoni, MD, at the Department of Mental Health, Mater Salutis Hospital, Legnato, Italy; Gianni L. Faedda, MD, Director of the Mood Disorder Center of New York, NY, and Co-Chairman of a Task Force of the International Society for Bipolar Disorders on this topic; and Professor Ross J. Baldessarini, MD, Director of the International Consortium for Bipolar & Psychotic Disorders Research of the Mailman Research Center at McLean Hospital in Belmont, Mass.

The authors reviewed and analyzed data from 39 studies of prodromal symptoms and risk factors for later development of BD. Their analysis focused on high-quality evidence from prospective studies in which data on early symptoms and risk factors were gathered before BD was diagnosed.

BD is commonly preceded by early depression or other symptoms of mental illness, sometimes years before BD develops, as indicated by onset of mania or hypomania. Nevertheless, the authors note that “the prodromal phase of BD remains incompletely characterized, limiting early detection of BD and delaying interventions that might limit future morbidity.”

The evidence reviewed suggested two patterns of early symptoms that “precede and predict” later BD. A homotypic pattern consisted of affective or mood-associated symptoms that are related to, but fall short of, standard diagnostic criteria for BD: for example, mood swings, relatively mild symptoms of excitement, or major depression, sometimes severe and with psychotic symptoms.
The authors note that homotypic symptoms have “low sensitivity” — that is, most young people with these mood symptoms do not later develop BD. However, this symptom pattern also had “moderate to high specificity” — homotypic symptoms do occur in many patients who go on to develop BD.

The heterotypic pattern consisted of other types of prodromal symptoms, such as early anxiety and disorders of attention or behavior. This pattern had low sensitivity and specificity: relatively few patients with such symptoms develop BD, while many young people without heterotopic symptoms do develop BD.

The study findings also associate several other factors with an increased risk of developing BD, including preterm birth, head injury, drug exposures (especially cocaine), physical or sexual abuse, and other forms of stress. However, for most of these risk factors, both sensitivity and specificity are low.

Although many elements of the reported patterns of prodromal symptoms and risk factors have been identified previously, the study increases confidence that they are related to the later occurrence of BD. The researchers note that the findings of high-quality data from prospective studies are “encouragingly similar” to those of previous retrospective and family-risk studies.

“There was evidence of a wide range of [psychiatric] symptoms, behavioral changes, and exposures with statistically significant associations with later diagnoses of BD,” the authors conclude. With further study, the patterns of prodromal symptoms and risk factors may lead to new approaches to identifying young persons who are likely to develop BD, and might benefit from early treatment. The investigators add that predictive value might be even higher with combinations of multiple risk factors, rather than single predictors.

Materials provided by Wolters Kluwer Health

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The Links Between Bipolar Disorder and Fibromyalgia

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A statue holding its head. Credit to flickr.com user leadfoot. Used with permission under a Creative Commons license.

On the surface, fibromyalgia and bipolar disorders aren’t very similar diseases. Fibromyalgia is a physical illness that causes joint and muscle aches, and fatigue, as well as depression for up to 90% of patients. Bipolar disorder is a mental illness with symptoms of extreme ups and downs, known respectively as mania and depression.

Fibromyalgia and bipolar disorder appear to be linked in several different ways. Up to 25% of patients with fibromyalgia show bipolar symptoms, and the two diseases share many characteristics.

A new study out of the Federal University of Ceará in Brazil examined the shared pathophysiology–how the diseases work in the body–of fibromyalgia and bipolar disorder. The researchers found that there were “remarkable” similarities between the two sicknesses.

In the study, the scientists discovered that the brains of people with either disease are very, very similar. While the causes of bipolar disorder are numerous–ranging from environmental to genetic–and the causes of fibromyalgia aren’t known, the researchers found that both bipolar disorder and fibromyalgia shared brain structures that might contribute to the cause of other illnesses.

The study also found that both bipolar disorder and fibromyalgia are characterized by “functional abnormalities in the hypothalamic-pituitary-adrenal axis.” This means that patients of both illnesses suffer from difficulties managing their hypothalamus, pituitary gland, and adrenal glands. These abnormalities can cause depressive symptoms, as well as other symptoms like cold intolerance.

Both fibromyalgia and bipolar disorder are associated with increased markers of inflammation in the blood and the brain. This causes a dysfunction in the cells of your nervous system, hormonal abnormalities, and leads to changes in your brain’s ability to regulate moods. Higher levels of inflammation also contributes to sleep disturbances.

Bipolar disorder and fibromyalgia patients both suffer from mitochondrial dysfunction. The mitochondrion, an organelle found in every cell in the human body–except red blood cells–that produces the power needed for growth and cell division, is also affected in both disorders. Because mitochondria perform so many different functions in different tissues, there are literally hundreds of different mitochondrial diseases. Dysfunction in them–found in bipolar disorder and fibromyalgia–can cause fatigue, among other abnormalities.

In addition, patients with either bipolar disorder or fibromyalgia have difficulties producing serotonin and melatonin, feel-good chemicals which help with sleep and the ability to handle pain. Bipolar disorder and fibromyalgia are also both associated with impaired neuroplasticity, which is the brain’s ability to handle new information and adapt to circumstances.

Fibromyalgia and bipolar disorder share a number of characteristics–mostly negative ones for the people who have to endure either disease. The researchers of the study urge that future studies explore these similarities, in the hopes that both sicknesses can be treated with targeted medications.

This all means that if you have bipolar disorder, you share characteristics with fibromyalgia patients–enough so that you might want to get checked out for the latter disorder. Similarly, if you have fibromyalgia, you may want to talk to your doctor about bipolar disorder. Medications which treat fibromyalgia have been found to trigger mania in bipolar patients, which means that you need to be cautious in taking medications to treat the former disease.

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Scientists Link Bipolar Disorder to Unexpected Brain Region

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A painted black brain on a rainbow background. Credit to flickr.com user Anders Sandberg. Used with permission under a Creative Commons license.

While bipolar disorder is one of the most-studied neurological disorders—the Greeks noticed symptoms of the disease as early as the first century—it’s possible that scientists have overlooked an important part of the brain for its source.

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have shown for the first time that ensembles of genes within the striatum—a part of the brain that coordinates many primary aspects of our behavior, such as motor and action planning, motivation, and reward perception—could be deeply involved in the disorder. Most modern studies of bipolar disorder have concentrated on the brain’s cortex, the largest part of the brain in humans, associated with higher-level thought and action.

“This is the first real study of gene expression in the striatum for bipolar disorder,” said Ron Davis, chair of the Department of Neuroscience at TSRI, who directed the study. “We now have a snapshot of the genes and proteins expressed in that region.”

The study, published recently online ahead of print in the journal Molecular Psychiatry, also points to several pathways as potential targets for treatment.

Bipolar disorder is a mental illness that affects about 2.6 percent of the U.S. adult population—some 5.7 million Americans—with a sizable majority of these cases classified as severe. The disease runs in families, and more than two-thirds of people with bipolar disorder have at least one close relative with the illness or with unipolar major depression, according to the National Institute of Mental Health.

In the new research, tissue samples from 35 bipolar and non-bipolar control subjects were analyzed. The number of genes differentially expressed in tissue samples from the two groups turned out to be surprisingly small—just 14 in all. However, co-expression network analysis also revealed two modules of interconnected genes that were particularly rich in genetic variations associated with bipolar disorder, suggestive of a causal role in the disorder. One of these two modules was particularly striking, as it seemed to be highly specific to the striatum.

“Our finding of a link between bipolar disorder and the striatum at the molecular level complements studies that implicate the same brain region in bipolar disorder at the anatomical level, including functional imaging studies that show altered activity in the striatum of bipolar subjects during tasks that involve balancing reward and risk,” said TSRI Research Associate Rodrigo Pacifico, who was first author of the new study. Analyzing reactions to risk was important because bipolar patients may act impulsively and engage in high-risk activities during periods of mania.

Pathway analysis also found changes in genes linked to the immune system, the body’s inflammatory response, and cells’ energy metabolism. Davis noted, “We don’t know if these changes are a cause of the disease or the result of it. But they provide additional gene markers in bipolar disorder that could potentially lead to the future development of diagnostics or treatments.”

The study, “Transcriptome Sequencing Implicates Dorsal Striatum-Specific Gene Network, Immune Response and Energy Metabolism Pathways in Bipolar Disorder,” was supported by funding from the State of Florida.

Text</a< from the Scripps Research Institute.

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A Quarter of People With Fibromyalgia Show Bipolar Disorder Symptoms

Fibromyalgia and bipolar disorder appear to be connected. New research shows that a quarter of fibromyalgia patients who were screened tested positive for bipolar symptoms. Because these diseases are found in tandem, it’s known as comorbidity. If you have one disorder going on, despite their differences, you might have both.

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Credit to flickr.com user CJS*64. Used with permission under a Creative Commons license.

The causes of fibromyalgia are yet to be discovered, and up to 5% of the population may be affected. More common in women, fibromyalgia is a disorder that causes muscle and joint aches. Other symptoms are fatigue, and, occasionally, depression.

Dr. William Wilke from the Cleveland Clinic in Ohio and his colleagues gave 128 patients with fibromyalgia four questionnaires. The first was the Mood Disorder Questionnaire (MDQ) for bipolar disorder, to determine the link between bipolar and fibromyalgia. Next was the Beck Depression Inventory (BDI) for depression. The scientists also used the Epworth Sleepiness Scale (ESS) for daytime sleepiness, and the Fibromyalgia Impact Questionnaire Disability Index (FIQ‐DI) to assess for functional capacity.

According to the MDQ screen, just over 25% of the patients were likely to have bipolar disorder, demonstrating a clear link between fibromyalgia and bipolar disorder. People who showed symptoms of bipolar also suffered from more severe depressions than people who didn’t show symptoms of bipolar disorder, which is really no surprise, given bipolar disorder’s depressions.

The BDI’s results were also of interest: 79% of the fibromyalgia patients were clinically depressed. Of those people, up to a third of the people who suffered from depression also reported symptoms of bipolar disorder.

The ESS showed that 52% of the patients with fibromyalgia–just over half–experienced daytime sleepiness, which doesn’t relate to bipolar disorder, but is interesting nonetheless.

Wilke’s team pointed out that some medications that treat fibromyalgia may also trigger mania in bipolar patients, and therefore doctors are urged to be cautious.

So, if you have fibromyalgia, you might want to talk to your doctor about the potential for bipolar disorder before you take medications to treat the disease, because those medications can trigger manic episodes. Similarly, if you have bipolar disorder, those muscle aches and fatigue might be something more; get screened for fibromyalgia.

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Tackling the Clutter Demon With Bipolar Disorder

For those of us living with bipolar disorder, the battle to control the mess in our houses is very real.

Anyone who has ever been depressed knows that cleaning is a struggle, to put it mildly, especially when you can’t even shower or feed yourself. And when we’re manic, we either can’t concentrate to clean the clutter, start new tasks without picking up our messes, or purchase frivolous items to soothe anxiety. In persons with bipolar I specifically, the wiring in their frontal lobes is so tangled that they suffer these executive functioning difficulties even during stable periods.

konmari
The Life-Changing Magic of Tidying Up: The Japanese Art of Decluttering and Organizing, by Marie Kondo. Also known as the Kon Mari Method.

Studies have even shown that hoarding is linked to bipolar, for the same reasons. We’re just wired to create messes.

But there is hope. I’ve just started decluttering using the KonMari method, based on the book The Life-Changing Magic of Tidying Up: The Japanese Art of Decluttering and Organizing, by Marie Kondo. In short, you tidy by category. In order to start the process, you first search the house for items (clothes, books, papers, miscellany, and then sentimental clutter). Then you lay them out on the floor. Then you hold each item and ask if it “sparks joy” before making a decision to keep it and put it away, donate it, or toss it.

I feel a little silly doing this, but so far the method has really worked to tidy up my clothes closet. I got through my closet and dresser in three hours, and donated two full garbage bags. I now only have five items hanging up, one full-sized drawer full of clothes, and an underwear drawer. I’m exhausted.

One caveat to the method for bipolar I people especially is that I can easily see how it could trigger a hypomanic episode. The elation from throwing things out is very real, and it might be difficult for a person with mental illness to stop once he or she has started. It’s almost ritualistic, which might spell trouble for people suffering from Obsessive Compulsive Disorder.

This is also not a method to use when you’re depressed. Laying out all my clothes on the floor was overwhelming, and I was fortunate to have my sister to walk me through the KonMari process. I confess that first, we had to clean up the floor to make enough room to sort through the clothes, which took half the time we’d allotted to going through them (three hours total).

So, I have a mixed review of the KonMari method. It’s effective, but dangerous. I’ll hold off on giving a full review until I’ve completed the six months the book says the method takes.

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Family Study Emphasizes Distinct Origins for Bipolar Disorder Subtypes

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

The most common subtypes of bipolar disorder, bipolar I and bipolar II, stem—at least in part—from different biological causes, according to a new study published in Biological Psychiatry. Despite genetic overlap between the two subtypes, each subtype tended to cluster within families, suggesting a distinction between bipolar disorders I and II.

The study, by Dr. Jie Song of the Department of Clinical Neuroscience, Karolinska Institutet, Sweden, and colleagues helps settle controversy over the relationship between bipolar I and bipolar II disorders. Although genetic similarities indicate overlap between the subtypes, the new findings emphasize different origins. According to Song, this is contrary to a common notion among many clinicians that bipolar II disorder is merely a milder form.

“We have tended to view the two forms of bipolar disorder as variants of the same clinical condition. However, this new study highlights important differences in the heritable risk for these two disorders,” said Dr. John Krystal, Editor of Biological Psychiatry.

The study is the first nationwide family study to explore the difference between the two main subtypes of bipolar disorder. Dr. Song and colleagues analyzed the occurrence of the bipolar disorder subtypes in families from the Swedish national registers. Although a strong genetic correlation between bipolar I and bipolar II disorder suggests that they are not completely different, the family occurrence for each subtype was stronger than co-occurrence between the subtypes, indicating that bipolar I and bipolar II disorders tend to “run” in families separately, rather than occurring together.

“Within the context of our emerging appreciation of polygenic risk, where gene variations are implicated in several disorders, the new findings point to only partial overlap in the risk mechanisms for these two forms of bipolar disorder,” said Dr. Krystal.

The study also provided some additional clues that bipolar I and II disorders have distinct origins. Only bipolar disorder II showed gender differences—the proportion of females to males was higher in bipolar disorder II but not bipolar disorder I. And bipolar I clustered together in families with schizophrenia, which was not apparent for bipolar disorder II.

“Hopefully, our findings increase awareness of the need for refined distinctions between subtypes of mood disorder,” said Dr. Song. The distinction between the subtypes also has implications for treatment strategies for patients. Dr. Song added that future research is warranted to characterize new biomarkers to improve treatment and prognosis.

Text provided by Elsevier.

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