September 28, 2004

Brain Chemistry and Bipolar Disorder

Source: University of Michigan

University of Michigan team finds evidence of brain chemistry abnormalities in bipolar disorder.

U-M team finds evidence of brain chemistry abnormalities in bipolar disorder
30% higher concentration of certain signaling cells may help explain, treat "manic depression"

ANN ARBOR, MI - People with bipolar disorder have an average of thirty percent more of an important class of signal-sending brain cells, according to new evidence being published by University of Michigan researchers.

The finding, in the American Journal of Psychiatry, solidifies the idea that the disorder has unavoidable biological and genetic roots, and may explain why it runs in families.

The discovery is the first neurochemical difference to be found between asymptomatic bipolar and non-bipolar people. It could help the understanding and treatment of a disease that affects as much as 1.5 percent of the population. Bipolar disorder has in the past been known as manic depression.

"To put it simply, these patients' brains are wired differently, in a way that we might expect to predispose them to bouts of mania and depression," says Jon-Kar Zubieta, M.D., Ph.D., assistant professor of psychiatry and radiology at the U-M Health System. "Now, we must expand and apply this knowledge to give them a treatment strategy based on solid science, not on the current method of trial and error. We should also work to find an exact genetic origin, and to relate those genetic origins to what is happening in the brain."

Bipolar disorder is marked by wild, cyclical mood swings, which typically begin in a person's late teens or twenties and strike men and women with equal frequency. Its milder, type II form causes depression alternating with hyperactivity, while the more severe type I disorder produces frenzied, even psychotic episodes that may send the patient to the hospital, followed by deep, crippling depressions. Current treatment uses a mix of mood-stabilizing, anti-psychotic and antidepressant drugs, but patients and physicians often struggle to strike the right combination.

Zubieta and his colleagues made the discovery in 16 patients with type I bipolar disorder using a brain imaging technique called positron emission tomography, or PET. The scans let them see the density of cells that release the brain chemicals dopamine, serotonin and norepinephrine.

These monoamines, as the chemicals are called, send signals between brain cells, or neurons. They're involved in mood regulation, stress responses, pleasure, reward, and cognitive functions like concentration, attention, and executive functions. Scientists have hypothesized their role in bipolar disorder for decades, but have never proven it.

The new U-M result points to a clear difference in the density of monoamine-releasing cells in the brains of bipolar people even when they are not having symptoms. Zeroing the PET scanner in on areas of the brain where monoamine-releasing cells are concentrated, the team looked for the faint signal of a weakly radioactive tracer, DTBZ, which they had injected into the bloodstream of the 16 participants and 16 people without bipolar disorder.

DTBZ binds only to a protein called VMAT2 inside monoamine-releasing cells, making it a good tracking device for the density of those cells. It is also often used in PET scanning to study Parkinson's disease, which is characterized by a severe shortage of cells that produce dopamine. On PET scans, DTBZ density - and therefore monoamine cell density - can be quantified by the amount of radioactive signal present in different areas.

By looking at the intensity of the DTBZ signal in all the subjects' brains, the U-M team found that bipolar patients averaged 31 percent more binding sites in the region known as the thalamus, and 28 percent more in the ventral brain stem. In the thalamus, bipolar women actually had levels nearing those of healthy comparison subjects, but bipolar men had a 42 percent higher binding rate, suggesting that there may be specific biological causes for the clinical differences in the course of the illness in men and women.

Adding in the results of functional tests, they found that the more monoamine cells patients had, the lower their scores on tests of executive function and verbal learning. This finding confirms earlier results from research at the U-M, and suggests that the altered brain chemistry due to the excess monoamine cells may directly impact the patients' cognitive and social function.

The study was carefully designed to produce consistent results. It compared brain scans and neuropsychological test results from bipolar disorder I patients who were using medications to control their symptoms, and healthy subjects matched to the bipolar subjects for age, sex, ethnicity, handedness and other factors. Careful physical and psychiatric exams ruled out differences caused by other variables.

Now, Zubieta and his colleagues hope their initial finding will lead to further research on brain chemistry and bipolar disorder. Specifically, more study is needed to examine which kinds of monoamine cells are involved - Zubieta especially suspects those that produce serotonin and norepinephrine. Those findings could help define specific subtypes of bipolar disorder, and aid development of medications and drug combinations that target a specific patient's personal brain chemistry to alleviate symptoms.

Genetic research, too, will be needed to find out why bipolar brains grow more than the usual allotment of such cells. Bipolar disorder I has a strong but still unknown tie to DNA; studies of identical twins show that if one twin has it, the other has an 80 percent chance of having it, too. Zubieta is hopeful that genetic markers will one day be found that can help people know their risk of developing bipolar disorder.

A combination of both genetic research and neuroimaging studies would help define both the genetic components of this illness, and their relationship with the expression of specific brain chemical markers in specific patients.

The U-M is launching a new trial that will enroll patients who have just been diagnosed with bipolar disorder, and those with a family history of the disease that puts them at higher risk.

"The reality is that we still have only sketches of what is going on in these brains, what the basic changes are, and how they are related to the course of illness," Zubieta says. "We need to look farther."


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The study was funded by the U-M's General Clinical Research Center, by the National Alliance for Research on Schizophrenia and Depression, and by the Mental Illness Research Association's Arthur Forrest Tull II Research Fund.

Posted by szadmin at 9:42 PM | Comments (0)

Seroquel - More data for Bipolar Disorder

UK pharmaceutical manufacturer AstraZeneca has released another set of data demonstrating the benefits of using its drug Seroquel (quetiapine fumarate) for the treatment of bipolar disorder, according to Reuters.

Seroquel is primarily indicated for the treatment of schizophrenia, but has shown an ability to provide relief from symptoms of rapid-cycling bipolar disorder, a form of the central nervous system (CNS) disease that affects around one in five bipolar disorder patients.

Seroquel was found to relieve depressive symptoms among patients over an eight-week period, with significant improvements recorded after the first week of treatment when compared to placebo use.

Many drug companies that sell schizophrenia drugs are now seeking additional approval for the treatment of bipolar disorder to increase sales.

For more of the Seroquel marketing speal - see:

Seroquel is significantly more effective than placebo in treating patients with rapid-cycling bipolar disorder

Posted by szadmin at 9:15 PM | Comments (6)

September 27, 2004

Author Sidney Sheldon and Bipolar Disorder

In a September 23rd CBS News show, Julie Chen interviewed Author Sidney Sheldon.

Sidney Sheldon won a Tony for co-writing "Redhead," the best musical of 1959. The Oscar came a decade earlier for writing "The Bachelor and the Bobby-Soxer."

Despite those achievements, Sheldon is best known for creating the hit situation comedy "I Dream of Jeannie" and for writing a string of sexy best-selling novels, including "The Other Side Of Midnight," "Bloodline" and his latest thriller, "Are You Afraid of the Dark?"

Despite his success, he was having many problems - sometimes he was inappropriately and extremely depressed, and other times manic. It started when he was young, as he explains briefly here:

"I was 17. I wanted to kill myself. But, please, it's all right. I didn't. I just had a lot of emotional problems. I won an Oscar for "The Bachelor and the Bobby-Soxer," and that was one of the worst nights of my life. I should have been exhilarated, and I was depressed. And I thought, you know, this is--there's something wrong. I'm not happy. And I went to a psychiatrist, and he said, `You have bipolar disorder. You're a manic-depressive.' And that's when I first learned about it. But meanwhile, I'd done a lot of bad things. I'd walked out on a lot of successes that I could have had. And I finally knew what was wrong.

CHEN: And how did they start treating it?

Mr. SHELDON: There's a medication for it, which they didn't even have back then. And the medication controls it. 'Cause now I'm perfectly normal.

The early treatment for his bipolar sounds like it allowed him to be the success that he is today.

Posted by szadmin at 10:15 PM | Comments (0)

Jane Pauley's Book "Sky Writing" - #3 on Bestseller's List

According to the New York Times review of books, the new book:

SKYWRITING, by Jane Pauley. (Random House, $25.95.) A memoir by the television personality chronicles her career, family life and recent struggle with bipolar disorder.

is now #3 on the best seller's list, up from #5 last week, and the book has been on the list for a total of 5 weeks now.

I haven't read the book yet - but the publicity that this type of book brings to the disorder is good news for better acceptance of it by the public at large, and better coverage for it by insurance companies in the US.

Posted by szadmin at 10:07 PM | Comments (12)

Valproate and Carbamazepine - Treat Acute Mania

Valproate and Carbamazepine - Treat Acute Mania but unproven in preventing mood episodes.

In a recent journal article Canadian Researchers reviewed newer anticonvulsants for the treatment of bipolar disorder. The article was published in a recent issue of the Journal of Clinical Psychiatry, and stated the following:

According to a study from Canada, "The anticonvulsants valproate and carbamazepine have efficacy in treating acute mania, but their efficacy in treating acute bipolar depression and preventing mood episodes remains uncertain. Despite this, and given their utility and widespread use, both are widely accepted as standard treatments for bipolar disorder. All the newer anticonvulsants that have become available during the last decade have been or are being assessed to determine their efficacy in the treatment of various phases of bipolar disorder."

"Among the newer anticonvulsants, some appear to have efficacy in treating core bipolar symptoms, while others have efficacy in treating psychiatric comorbidity such as substance abuse or an anxiety disorder," said Lakshmi N. Yatham at the University of British Columbia. "Lamotrigine is the most widely studied and is effective in treating and preventing bipolar depression, and it is the only anticonvulsant approved by the U.S. Food and Drug Administration as a maintenance treatment for bipolar disorder. Other newer anticonvulsants, levetiracetam, oxcarbazepine, phenytoin, and zonisamide offer promise, but further studies are required before they can be recommended for routine use to treat bipolar disorder."

"Gabapentin and topiramate do not appear to have efficacy in treating acute mania, but their utility in bipolar depression and prevention of mood episodes has not been studied in double-blind trials," stated Yatham. "Pregabalin has utility in treating generalized anxiety disorder, but it has not been studied in bipolar disorder. Given the success of lamotrigine in treating bipolar disorder, further double-blind controlled trials of the newer anticonvulsants in treating bipolar disorder are warranted. This article summarizes current evidence from trials of anticonvulsants in bipolar disorder and makes recommendations for their clinical use."

Yatham published the study in the Journal of Clinical Psychiatry (Newer anticonvulsants in the treatment of bipolar disorder. J Clin Psychiat, 2004;65(Suppl. 10):28-35).

Posted by szadmin at 10:03 PM | Comments (0)

September 21, 2004

Teens and Mental Illness

Teens and Mental Illness

This week NPR had a good program on Teens and Mental Illness. Mental illness in kids affects the whole family. Parents and their children have to balance medical treatments, therapy and stigma with the not-so-simple act of growing up.

Excerpt from the program:

"Finding the right treatment for mental illness is never easy. For parents who have children with mental health problems, deciding what to do is even thornier. Picking the right therapist, determining whether a child needs medication takes time. Many kids are resistant to intervention, and parents often struggle to identify the warning signs. For some families, the rising cost of health care means deciding whether to pay out of pocket for extended treatment or costly prescription drugs. To add to that, the information about the effects that medication has on young people is confusing and can be frightening. Last week, a panel of medical experts concluded that a group of antidepressants known as SSRIs should come with stronger warnings that they raise the risk of suicide among young people.

This hour, a look at how families make decisions about mental illness in children and adolescents. We're going to talk to one family that successfully navigated through the complicated web of options. And we want to hear from your calls a little later. If you're a parent whose child has a mental illness, tell us about your decision-making process. Where did you get your information from? Did you involve your child in the process? If you're a young person who's been diagnosed with a mental illness, how did you decide what to do?"


NPR Audio Recording - Teens and Mental Illness

Posted by szadmin at 11:51 PM | Comments (1)

New Book: Heather's Rage: A Mother's Chronicle of Daughter's Journey of Mental Illness

A new book has just been released on Bipolar Disorder - the story of a Mother's experience in getting treatment for her 10 year old daughter. Following is a quote from the book's press release:

"Imagine as a mother being forced to relinquish custody of your daughter in order for the child to receive the proper treatment for mental illness. That�s just what Omahan Leslie Byers did in 1996 when her daughter was 10 years old.

In her newly published book, �Heather�s Rage,� author Leslie Byers chronicles the years of frustration experienced as she and her husband struggled to find answers to their daughter�s manic-induced rages and suicidal depressions brought on by a mental illness called bipolar disorder. At the same time, Byers, an information technology consultant, and her husband had to cope with the challenges of getting help for their daughter, from working through the educational system to dealing with something that they least expected because of their daughter�s illness--the juvenile court system. Through it all, the Byers greatest agony came from being forced to give up custody of their little girl because they could not afford the proper treatment.

Byers' daughter finally received the right diagnosis and treatment she needed and today, she is living successfully with the disease. Byers wrote about her family�s story to help erase the stigma of mental illness, to create a better understanding of the disease, and to raise awareness that there needs to be better systems in place aimed at children for early detection and intervention.

�As the mother of a daughter who has struggled with mental illness for more than 16 years, I know first-hand the stigma and ignorance of mental illness and the challenges that families face as a result of that stigma,� said Byers. �I chose to write a book about how we overcame our challenges through faith and perseverance, recovered and healed as a family. I hope our story will replace ignorance of mental illness with understanding, and offer help, suggestions and inspiration for those in similar situations.�

To read a sample of Byers� �Heather�s Rage,� visit Brown Books� Web site at http://www.brownbooks.com/authors/byers. The book is available nationwide. If a local bookstore does not carry it, the book can be ordered online at http://www.amazon.com or http://www.brownbooks.com. The paperback book is $14.95.

Posted by szadmin at 9:51 PM | Comments (1)

September 15, 2004

Bipolar 1 Gene Search Intensifies

It was reported today that the Indiana University School of Medicine has embarked on a massive search to isolate the specific gene responsible for bipolar I disorder.

The School's Institute for Psychiatric Research is continuing a collaboration with the National Institute for Mental Health and 11 other U.S. academic centers. Their goal is to narrow the field from suspect areas of chromosomes to isolate genes that affect the mental health of thousands of Americans.

The Institute began the collaborative research 15 years ago and has successfully identified areas of genetic linkage on specific chromosomes. With new funding from the NIMH, the IU researches hope to hone in on the specific gene by collecting genetic information from 5,000 people with bipolar I disorder. This multi-center trial has received a five-year, $16 million NIMH grant.


Source: NIMH

Posted by szadmin at 10:06 PM | Comments (0)