Brain Training Shows Promise For Patients With Bipolar Disorder

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Researchers at McLean Hospital, an affiliate of Harvard Medical School, have discovered for the first time that computerized brain training can result in improved cognitive skills in individuals with bipolar disorder.

In a paper published in the October 17, 2017, edition of The Journal of Clinical Psychiatry, the researchers suggest that brain exercises could be an effective non-pharmaceutical treatment for helping those with bipolar disorder function more effectively in everyday life.

“Problems with memory, executive function, and processing speed are common symptoms of bipolar disorder, and have a direct and negative impact on an individual’s daily functioning and overall quality of life,” said lead investigator Eve Lewandowski, PhD, director of clinical programming for one of McLean’s schizophrenia and bipolar disorder programs and an assistant professor at Harvard Medical School. “Improving these cognitive dysfunctions is crucial to helping patients with bipolar disorder improve their ability to thrive in the community,” Lewandowski added.

Lewandowski and her colleagues knew from previous studies that this type of intervention had helped patients with schizophrenia improve cognitive functions. “There is considerable overlap in cognitive symptoms between bipolar disorder and schizophrenia,” Lewandowski noted.

The researchers therefore decided to test the impact of brain exercises in the bipolar population. They randomly assigned patients with bipolar disorder, aged 18-50, to either an intervention group or an active comparison group (used as a control). The intervention group was asked to use a special regimen of neuroplasticity-based exercises from Posit Science — maker of the BrainHQ online exercises and apps — for a total of 70 hours over the course of 24 weeks. These exercises use a “bottom-up” approach, targeting more basic cognitive processes early in the treatment to strengthen cognitive foundations, then moving on to training focused on more complex cognitive functions later in the program. The control group was asked to spend an equivalent amount of time on computerized exercises that focused on quiz-style games, like identifying locations on maps, solving basic math problems, or answering questions about popular culture.

At the end of the study, the participants in the intervention group displayed significant improvements in their overall cognitive performance as well as in specific domains, such as cognitive speed, visual learning, and memory. “The intervention group maintained cognitive improvements six months after the end of the treatment, and in some areas even showed continued improvements,” Lewandowski reported.

Lewandowski is encouraged by the findings, as they demonstrate that “this type of non-pharmaceutical intervention can significantly improve cognition in patients with bipolar disorder,” she said. “These findings suggest that once the brain is better able to perform cognitive tasks, it will continue to strengthen those processes even after patients stop using the treatment.” In addition, Lewandowski said, “The study indicates that affordable and easily accessible web-based interventions can be effective for a broad group of patients.”

Lewandowski noted that further research is needed to determine how the improvements in these cognitive skills impact work and leisure activities and daily functioning in patients with bipolar disorder.

Text provided by McLean Hospital.

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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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Brain Protein Targeted to Develop New Bipolar Disorder Therapies

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A new study by scientists from the Florida campus of The Scripps Research Institute (TSRI) has identified specific genetic variations closely associated with increased susceptibility to bipolar disorder and other conditions. The discovery may provide a target for new therapies.

 

In the new study, the researchers focused on a gene known as PDE10A, one of the many genes that has been linked to bipolar disorder, and the proteins this gene produces. These proteins help regulate intracellular levels of a messenger molecule called cAMP (cyclic adenosine monophosphate), which is involved in a variety of biological processes including learning and memory.

“We began with the idea that behavioral changes in bipolar subjects might be due to these genetic variations in the cAMP messenger pathway,” said Ron Davis, chair of TSRI’s Department of Neuroscience. “We did find that this was the case and, indeed, that these variations were in one specific gene for the cAMP messenger pathway called PDE10A. The variations that we found in the gene may alter the function of one form of PDE10A and lead to susceptibility to bipolar disorder.”

The research, published recently by the journal Translational Psychiatry, examined human brain tissue from patients with bipolar disorder, as well as brain tissue from individuals without the psychiatric disorder.

“The PDE10A19 protein is interesting because we previously didn’t know it even existed in the human brain and because it’s found only in other primates—not mice or rats,” said Research Assistant Courtney MacMullen, the first author of the study. “Once we understand how this protein helps neurons remain healthy, we might be able to develop medications to treat neurons when they function abnormally, such as in patients with bipolar disorder and schizophrenia.”

The results suggested abnormal variations in PDE10A19 might alter cAMP signaling by interacting with another protein known as PDE10A2, restricting its activity and disrupting the entire process.

Davis said that the complexity of gene expression in the human brain is greatly underestimated, and that future neurogenetic studies ought to begin with a deep study of each gene’s ability to code for proteins to avoid false conclusions, particularly when it comes to the development of potential therapies.

“We need to know much more about this large family of enzymes and the roles they play in disorders like bipolar disorder,” he said.

Text taken from the Scripps Research Institute.

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People At-Risk for Bipolar Disorder May Age Faster

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People at-risk for bipolar disorder may age faster, according to a study by Timothy R Powell, Danai Dima, Sophia Frangou, and Gerome Breen. The findings were published in Neuropsychopharmacology, a scientific journal.

 

Telomeres are DNA repeat structures (TTAGGG) at the end of chromosomes. When telomeres are critically shortened, cell death occurs, which makes these structures a biomarker for aging. Lifestyle changes, cellular stressors, and social adversity all contribute to telomere shortening.

Shorter telomere length is associated with cardiovascular disease, type-2 diabetes, and age-related memory dysfunction. Telomere length is associated with the hippocampus, a sea-horse-shaped brain region which controls inhibition and emotion, and helps contribute to episodic memory.

Previous studies have shown reduced telomere length in schizophrenia, dementia, and major depressive disorder. But with regards to bipolar disorder, however, studies have demonstrated both reduced and increased telomere length in patients compared to healthy controls.

According to the Powell study, patients with bipolar disorder taking lithium have longer telomeres. The researchers used DNA sampling as well as magnetic resonance imaging (MRIs) of close relatives to bipolar disorder sufferers to determine whether people with the illness age faster.

The scientists found that lithium has a protective effect on telomere length, whereas other medications, such as antidepressants, don’t. Also, the relatives of patients with bipolar disorder had significantly shorter telomeres than healthy volunteers.

This is the first study to demonstrate a link between shorter telomere length and relatives with bipolar disorder. Understanding telomere biology may lead to therapies to maintain telomere length or reverse the shortening process, which means slower aging. Studying the effect of lithium on telomeres may also contribute to further psychological medications which can help patients who suffer from bipolar disorder.

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Men and Women Differ When it Comes to Bipolar Biomarkers

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According to a new study by an international team of researchers, men and women have different reactions to compounds associated with immune system response to bipolar disorder. This is exciting news! The findings mean that bipolar disorder can one day be diagnosed by biological measurements in the body, and that approaches to treatment can be tailored differently for the sexes.

 

Researchers have long known that bipolar disorder manifests differently in men and women. This suggests that different biological processes underlie the condition in the two sexes. Additionally, the immune system activates during periods of mania or depression, and previous studies have demonstrated that immune system activation starts low-level inflammatory process in the brain, which is harmful. This inflammation may contribute to poor function among bipolar sufferers.

The immune system works differently in men and women as well. Researchers decided to measure immune system factors in men and women with bipolar disorder to see if reliable markers for the diseases could be found.

Scientists measured concentrations of zinc and neopterin–both associated with inflammatory processes–in blood samples of both men and women experiencing manic or depressive episodes, as well as from healthy controls. Zinc is a mineral needed by a healthy immune system to function properly, while neopterin is an immune marker secreted by white blood cells when the immune system is activated.

The 27 people with bipolar disorder recruited for the study had lower levels of zinc in their blood than the 31 healthy controls. There was no difference in neopterin levels. However, when women had more zinc in their blood, their depression was worse, whereas men’s mania was worse if they had higher concentrations of neopterin.

Zinc deficiencies have been associated with depression in the past, so the findings were surprising. Scientists are now measuring zinc levels in the brains of mice with inflammatory depression to see if higher levels of zinc in the blood means less in the brain.

The findings do not suggest that people suffering depression should take zinc, however.

What the international team that contributed to this study is ultimately hoping for is to discover a blood marker that can help predict bipolar episodes, and whether treatment is working. Exciting news!

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Researchers Create Global Map of How Bipolar Disorder Affects the Brain

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In the largest magnetic resonance imaging (MRI) study to date, researchers have created a roadmap of bipolar disorder and how the illness affects the brain. Scientists found that people who suffer from bipolar disorder possessed differences in the brain regions that control inhibition and emotion.

 

Using MRI scans of 6,503 individuals, including 2,447 adults with bipolar disorder and 4,056 healthy controls, the researchers created a map of bipolar disorder. Also measured was the age of onset for the disorder, history of psychosis, mood state, age, sex, and commonly used prescription medications.

According to the study, patients with bipolar disorder showed thinning of grey matter in the frontal and temporal regions of the brain, which control motivation and inhibitions. The research also demonstrated that lithium has a protective effect on the brain, associated with less thinning of gray matter.

The international report includes research from 76 centers and 26 different groups around the world. Published in Molecular Psychiatry, the findings demonstrate the underlying mechanisms of bipolar disorder.

Researchers hope to use the study in early detection efforts, as well as to determine which medications will protect the brain.

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Bipolar? Your Brain is Wired to Make Poor Decisions

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Struggling to plan and make decisions while depressed or manic are common problems. But have you ever had trouble doing the same while relatively stable? New research may show why.

 

Researchers examined ninety patients’–forty-five with bipolar disorder in stable moods, and forty-five controls without bipolar disorder–brains, and discovered that, in the bipolar sufferers, there are certain areas of the brain that have reduced activation regardless of mood due to structural damage.

This is the first study to look at the relationship between functional magnetic resonance imaging (MRIs) and structural MRIs in bipolar disorder. The scientists found that the patients with bipolar suffered from reduced cortical thickness and thus had less activity in areas of the brain that controlled impulses, or contributed to making decisions.

The study was published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, and conducted by scientists at the University of California, Los Angeles.

As this is the first study to find a link between structure and function, the results are exciting. The research proves that bipolar disorder damages your brain. You’re not stupid; your brain is just wired to make impulsive decisions and be poor at planning.

The scientists who conducted the study hope that their research will be used in future intervention studies. Good news!

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Molecular Mechanism Behind Lithium’s Effectiveness Identified

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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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Hippocampus Volume Decreases Linked to Bipolar Disorder

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In a new study by researchers at The University of Texas Health Science Center at Houston (UTHealth) , damage to the hippocampus–the brain’s seahorse-shaped center for mood and memory–was linked to bipolar disorder. This study is groundbreaking; it’s one of the first to link volume decreases in specific parts of the hippocampus to bipolar, something scientists have been trying to answer.

 

Different subfields of the hippocampus may have different functions and may be affected differently by mood disorders like depression or anxiety disorders. The researchers at UTHealth used magnetic resonance imaging (MRI) and segmentation approaches–which includes the delineation of brain features using image contrasts–to discover differences in the volumes of subfields of the hippocampus. Patients with bipolar disorder were compared to healthy controls as well as patients with major depressive disorder.

The study found that people who suffer from bipolar disorder had reduced volumes in subfield 4 of the cornu ammonis (CA) of the hippocampus. In patients with bipolar I disorder, the reduction was even more severe. Also, as the illness went on, the volumes of areas such as the right CA 1 decreased. People who had manic episodes had even more reduced volumes in the hippocampal tail and other CA areas.

The researchers hope that the study will be able to encourage more research pinpointing the details of the hippocampus as it relates to bipolar disorder, thus creating better treatments for the disease.

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Bipolar Disorder is Toxic–Literally

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Apparently the blood of people with bipolar disorder is toxic to their brains. Let me explain.

Bipolar disorder, also known as manic-depressive illness, is a brain disorder characterized by changes in mood and energy levels, affecting a sufferer’s ability to function. People affected by the disorder endure periods of both mania–with elevated mood, irritability, and rapid thoughts–and depression.

Lately, researchers have begun classifying patients as early or late-stage. Early-stage patients have dealt with fewer mood episodes; late-stage patients have dealt with more frequent and more severe episodes.

A recent study compared neurons exposed to blood serum from bipolar patients to neurons exposed to blood serum from healthy controls. Researchers Fabio Klamt and Flávio Kapczinski found that the first neurons suffered a significant loss in the density of neurites, which estimate the number of brain connections. However, neurons exposed to serum from early-stage bipolar disorder patients showed no difference in neurite density compared to the healthy controls’. The scientists also found that, except for those neurons exposed to serum from patients at very late stages of the disease, the number of neurons weren’t that different between samples.

Previous studies have shown that people with bipolar disorder have lower neurotrophins–proteins that promote brain growth. Also lowered is the early-growth response 3 (EGR3), a protein which helps the brain cope with stressors such as environmental changes and overstimulation. In addition, another study showed that bipolar patients have abnormally low levels of chemokines–proteins that signal other cells, so reactions to stimuli are slower.

So, what does that all mean? In short: researchers have found definitive proof that the blood of people with bipolar disorder is toxic to their brains. The more mood episodes a person has, the fewer brain connections he or she will create, and the slower their brains will grow. People in later stages of the disease also produce more cells which impair the brain’s ability to deal with environmental changes, inflammation, and stress.

Further studies will concentrate on creating drugs which can offset the toxicity of the bipolar patients’ blood.

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