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January 25, 2006

Moderate alcohol use may worsen bipolar illness

Moderate alcohol use may worsen bipolar illness

The effect of alcohol consumption on bipolar disorder severity may not be confined to heavy drinkers, say researchers who found adverse effects even for those who drink alcohol at levels consistent with low-risk drinking guidelines.

In their study of patients with bipolar I or II disorder, modest levels of alcohol consumption were associated with important measures of bipolar illness severity, including emergency department visits, number of mood episodes, and current symptoms.

Benjamon Goldstein, from the University of Toronto in Ontario, Canada, and colleagues therefore stress the importance of "carefully assessing the extent of alcohol consumption and of encouraging abstinence among individuals with bipolar disorder."

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Source: J Clin Psychiatry 2006; 67: 102–106

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January 24, 2006

Bipolar disorder in the workplace

Bipolar disorder is the sixth leading cause of disability in the world, according to the World Health Organization, and depression will soon be the leading cause of sick leave in the workplace.

Awareness and accommodation from employers is crucial and yet stigma prevails. Most companies do not have a mental health policy. Employees lose their jobs over diminished functioning, while if they had flexibility to adapt to the workplace during episodes they wouldn't work incapacitated while not informing their supervisors of the issue, out of fear.

Source: Psychcentral

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Finding bipolar disorder with MRI

A special series of articles is now available on the MIT technology review web site. Their focus is "feature on brain imaging techniques that could lead to improved diagnosis of psychiatric ailments"

One of the leaders in the effort to enlist MRI in the diagnosis and treatment of psychiatric ailments is John Port at the Mayo Clinic in Rochester, MN. Port is a neuroradiologist who began his career by studying electrical engineering and computer science at MIT and later earned a PhD in cell biology and an MD from the University of Illinois. So he's in a good position to research both basic MRI technology and its applications to medicine.

Port's work on MRI could have broad application in psychiatry, but for now he is concentrating on his particular interest: bipolar disorder. Also called manic-depression, bipolar disorder is characterized by mood swings from wild exuberance to profound depression, with periods of stability in between. X-rays or conventional MRIs show no difference between the brains of people with bipolar disorder and those without it; medical journals are littered with failed attempts to use imaging to find distinctive signs of the disease.

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January 13, 2006

Pharma company announces agreement to develop treatment for bipolar disorder

In a Press/Marketing release, Memory Pharmaceuticals Corp. announced that it has entered into an agreement with The Stanley Medical Research Institute to develop MEM 1003, the company's neuronal L-type calcium channel modulator, as a treatment for bipolar disorder. Under the terms of the agreement, Memory Pharmaceuticals is eligible to receive up to $3.2 million from SMRI to fund the clinical development of MEM 1003 and will use these funds to support a Phase IIa trial of MEM 1003 in acute mania in bipolar disorder, which is scheduled to commence in the first half of 2006. Memory Pharmaceuticals also is currently conducting a Phase IIa clinical trial of MEM 1003 in Alzheimer disease.

As part of the agreement, SMRI has purchased 440,367 newly issued shares of the company's common stock, at a price of $2.18 per share, constituting $960,000 of the total funding being provided to the company under the agreement. In addition, SMRI received a 5-year warrant for the purchase of up to 154,128 additional shares of common stock at an exercise price of $2.62 per share.

The company will receive the remaining $2.24 million of funding upon the achievement of milestones related to the Phase IIa trial in bipolar disorder. These funds will be repayable to SMRI in the form of royalties, up to a specified maximum amount, on future sales of MEM 1003 for the treatment of bipolar disorder or schizophrenia.

"Abnormal calcium levels are thought to be involved in conditions such as Alzheimer disease and bipolar disorder. MEM 1003 regulates calcium abnormalities and therefore has a solid rationale as a novel potential therapeutic for such disorders," said David A. Lowe, PhD, chief scientific officer of Memory Pharmaceuticals.

"The Stanley Medical Research Institute collaborates with academic and corporate partners to advance the clinical development of promising treatments for bipolar disorder and schizophrenia," said Michael Knable, executive director of SMRI. "MEM 1003 represents a promising approach to the treatment of bipolar disorder, and we are pleased to be working with Memory Pharmaceuticals to take MEM 1003 into a proof-of-concept trial in bipolar disorder."

MEM 1003 is a neuronal L-type calcium channel modulator that Memory Pharmaceuticals is developing for the treatment of Alzheimer disease and bipolar disorder. By blocking L-type calcium channels, MEM 1003 may regulate the flow of calcium and reestablish normal levels of calcium, which may correct or prevent the severe mood swings that characterize bipolar disorder.

Memory Pharmaceuticals Corp. is a biopharmaceutical company.

The Stanley Medical Research Institute funds research for severe mental illness.

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Fat chance of becoming manic-depressive

A collaboration, led by scientists at the Garvan Institute of Medical Research and the University of New South Wales (UNSW) in Sydney, has discovered the first risk gene specifically for bipolar disorder, also known as manic-depressive illness. This means that people who have a particular form of this gene are twice as likely to develop the disease.

Lead author, Dr Ian Blair, says: "We are the first group in the world to take a multi-faceted approach to identify a bipolar risk gene - we used a number of families, unrelated patients, and therapeutic drug mouse models. Each of these three lines of investigation led us to a gene called FAT."

Contributing author Professor Phil Mitchell, Head of Psychiatry at UNSW, says: "Over the last twenty years we have collected blood samples from 67 families right across Australia. This amounts to hundreds of family members (904), some of whom are spread across four generations. This was a strong starting point in our hunt for a Bipolar gene."

"We know that the FAT gene codes for a protein that is involved in connecting brain cells together, what we need to do now is find out exactly how it contributes to the increased risk of bipolar disorder," explains Dr Blair.

While other scientists have found genes associated with Bipolar, most of them haven't stood up to scrutiny. The Sydney discovery has been verified in four independent study groups: two in the UK, one in Australia, and one in Bulgaria.

Bipolar disorder is a major psychiatric illness affecting around two people in every 100. Tragically, around one in six people suffering from the condition will commit suicide.

Mood-stabilising medications are typically prescribed to help control bipolar disorder. Lithium was the first mood-stabilising medication approved by the U.S. Food and Drug Administration (FDA) for treatment of mania. For decades it has been widely prescribed for the treatment bipolar disorder, yet no one knows for sure why it works.

"Lithium has a number of severe side effects that include tremor and weight gain. Kidney dysfunction may develop in a small proportion of patients when it is administered for long periods of time," says Professor Mitchell.

This new research has raised the possibility that lithium exerts its therapeutic affect by altering FAT gene expression, as well as the expression of genes encoding FAT's protein partners.

"Once we understand exactly what the FAT gene does, we will be able to develop better diagnostic tests for bipolar disorder. In the future, we hope our research will lead to new, targeted medicines specifically for bipolar disorder that don't have the unpleasant side effects that lithium has," says Dr Blair.

The bipolar project team has been a collaborative endeavour over the last decade involving Sydney-based scientists and clinicians from the Garvan Institute of Medical Research, the University of New South Wales and Macquarie University. Additional collaborations provided critical supporting data.

This research was E-published ahead of print on 10 January 2006 in Molecular Psychiatry
Positional cloning, association analysis, and expression studies provide convergent evidence that the cadherin gene FAT contains a bipolar disorder susceptibility allele. IP Blair, AF Chetcuti, RF Badenhop, A Scimone, MJ Moses, LJ Adams, N Craddock, E Green, G Kirov, MJ Owen, JBJ Kwok, JA Donald, PB Mitchell, PR Schofield

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