FDA Issues Approvable Letter For Stavzor™ Delayed Release Valproic Acid Capsules

Noven Pharmaceuticals, Inc. (NASDAQ:NOVN) announced that the U.S. Food and Drug Administration (FDA) has issued an approvable letter related to the New Drug Application (NDA) for Stavzor™ (delayed release valproic acid capsules) in 125mg, 250mg and 500mg strengths. The approvable letter relates to the use of Stavzor™ in the treatment of manic episodes associated with bipolar disorder, adjunctive therapy in multiple seizure types (including epilepsy), and prophylaxis of migraine headaches.


The FDA states in the letter that it has completed its review of the Stavzor™ NDA and that it is approvable. The FDA has requested certain non-clinical information, including additional in vitro dissolution data, as a condition to final approval. The FDA has not requested additional human studies or clinical data.


Because the NDA for Stavzor™, submitted under Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, references Abbott Laboratories' Depakote® product, final approval is also subject to the expiration of any applicable exclusivity periods benefiting Depakote®. Based on receipt of the approvable letter, interaction with Banner Pharmacaps Inc. (the NDA holder and developer of the product), and its understanding of Depakote® exclusivity, Noven continues to expect Stavzor™ final approval, at the latest, by the end of July 2008.


Stavzor™ was developed using Banner's patent-pending EnteriCare™ enteric soft gelatin capsule delivery system. Noven acquired a license to market and sell Stavzor™ in the U.S. as part of Noven's acquisition of JDS Pharmaceuticals in August 2007. Stavzor™ will be a branded product; it is not expected to be AB-rated to or generically substitutable for Depakote®, nor will Depakote® or any Depakote® generics be substitutable for Stavzor™. Promotion of the Stavzor™ brand will target primarily high-prescribing physicians through the Noven/JDS sales force.


"We are very pleased to announce that the FDA has issued an approvable letter for Stavzor™, and we offer our congratulations to the Banner and JDS teams for this successful result," said Robert C. Strauss, Noven's President, CEO & Chairman. "We are now working with Banner to satisfy the conditions to final approval as expeditiously as possible. Banner has advised that it expects to respond to the FDA's requests in the coming weeks. Concurrently, the Noven/JDS team has begun launch and production planning in anticipation of a 2008 launch of Stavzor™."















Banner Pharmacaps Inc., headquartered in High Point, North Carolina, is a global drug delivery and specialty pharmaceutical company developing a proprietary portfolio of unique products and oral dosage forms, including soft gelatin capsules.



EnteriCare™ is a trademark of Banner; Depakote® is a registered trademark of Abbott Laboratories or its affiliates.


About Noven


Noven Pharmaceuticals, Inc., headquartered in Miami, Florida, has established itself as a leading developer of advanced transdermal drug delivery technologies and prescription transdermal products. Its commercialized transdermal products include Vivelle-Dot® (estradiol transdermal system), the most prescribed estrogen patch in the U.S., and Daytrana™ (methylphenidate transdermal system), the first and only patch approved for the treatment of ADHD.


With the acquisition of JDS Pharmaceuticals in August 2007, Noven has become a broader-based specialty pharmaceutical company with the infrastructure, products and category expertise to market and sell products itself, and with a substantially enhanced late-stage product pipeline.


Products currently marketed through the JDS psychiatry sales infrastructure include Pexeva® (paroxetine mesylate) and Lithobid® (lithium carbonate). Pipeline products in psychiatry consist of Stavzor™ (delayed release valproic acid capsule), Lithium QD (once-daily lithium carbonate), and Stavzor™ ER (extended release valproic acid capsule). Pipeline products in women's health consist of Mesafem™ (low-dose paroxetine mesylate), a non-hormonal product entering Phase 3 clinical trials for vasomotor symptoms (hot flashes). See noven for additional information.


Forward Looking Information


Except for historical information contained herein, the matters discussed in this press release contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 that involve substantial risks and uncertainties. Statements that are not historical facts, including statements which are preceded by, followed by, or that include, the words "believes," "anticipates," "plans," "expects" or similar expressions and statements, are forward-looking statements. Noven's estimated or anticipated future results, product performance or other non-historical facts are forward-looking and reflect Noven's current perspective on existing trends and information. Actual results, performance or achievements could differ materially from those contemplated, expressed or implied by the forward-looking statements contained herein.

These forward-looking statements are based largely on the current expectations of Noven and are subject to a number of risks and uncertainties that are subject to change based on factors which are, in many instances, beyond Noven's control. These risks and uncertainties include, among others, risks associated with: the difficulty of predicting FDA actions, including the timing of such actions; the risk that the FDA's request for additional information will not be fulfilled in a timely fashion or in a manner satisfactory to the FDA, which could delay or prevent final approval of the product; uncertainties in the process of obtaining regulatory approval for new products; risks related to actions that may be taken by competitors; the possibility that any product launch may be delayed; and, if Stavzor™ is approved, the many risks that face new products, including the impact of competitive products and pricing, the risk that product acceptance may be less than anticipated, the risk of unexpected adverse side effects or inadequate therapeutic efficacy of a product, risks related to compliance with extensive, costly, complex and evolving governmental regulations and restrictions, and reimbursement policies of government and private health insurers and others. For additional information regarding these and other risks associated with Noven's business, readers should refer to Noven's Annual Report on Form 10-K for the year ended December 31, 2006 as well as other reports filed from time to time with the Securities and Exchange Commission. Unless required by law, Noven undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise.


fda


View drug information on Depakote ER; Estradiol Transdermal System; Lithobid.

Targacept Initiates Phase I Clinical Trial Of TC-2216

Targacept, Inc.
(Nasdaq: TRGT), a clinical-stage biopharmaceutical company developing a new
class of drugs known as NNR Therapeutics(TM), today announced that it has
initiated a Phase I clinical trial of TC-2216, its product candidate for
the treatment of depression and anxiety disorders.


The trial is designed to evaluate the safety and tolerability of
TC-2216 and to assess its pharmacokinetic profile. The trial is a
double-blind, placebo-controlled crossover study, with sequential ascending
single oral doses administered to healthy male volunteers.



TC-2216 is a novel compound discovered using Targacept's proprietary
drug design platform known as Pentad(TM). The compound targets specific
neuronal nicotinic receptors (NNRs), a class of receptors found in the
central nervous system that play a critical role in regulating nervous
system activity. TC- 2216 selectively inhibits the alpha4beta2 NNR to
modulate the release of neurotransmitters that are involved in mood
regulation. In preclinical studies, TC-2216 showed greater potency than and
anti-depressant effects comparable to selective serotonin reuptake
inhibitors and tricyclics, which are commonly used treatments for
depression, as well as anxiety-relieving effects.



Targacept currently plans to develop TC-2216 as an oral monotherapy. In
November, the company announced positive top line results from a Phase II
clinical trial of TRIDMAC(TM), a treatment combination comprised of
mecamylamine hydrochloride as an augmentation therapy to citalopram
hydrobromide, in patients who did not respond adequately to citalopram
alone. Mecamylamine hydrochloride binds non-selectively to various NNR
subtypes, but there is a body of scientific evidence that suggests that its
anti-depressant activity is derived through its antagonism at the
alpha4beta2 NNR.



"Depression is a highly debilitating illness, and millions of people
who suffer with it are not gaining adequate relief from existing
therapies," said J. Donald deBethizy, Ph.D., Targacept's President and
Chief Executive Officer. "The results of our TRIDMAC trial not only
substantiate the promise of the NNR mechanism in the treatment of
depression and other mood disorders, but also further bolster our
enthusiasm for the potential of TC-2216."



About Targacept



Targacept is a clinical-stage biopharmaceutical company that discovers
and develops NNR Therapeutics(TM), a new class of drugs for the treatment
of central nervous system diseases and disorders. Targacept's product
candidates selectively modulate neuronal nicotinic receptors that serve as
key regulators of the nervous system activity to promote therapeutic
effects and limit adverse side effects. Targacept has product candidates in
development for Alzheimer's disease and cognitive deficits in
schizophrenia, pain and depression, and multiple preclinical programs.
Targacept is located in Winston-Salem, North Carolina. For more information
about Targacept, please visit targacept.

















Forward-Looking Statements



Any statements in this press release about expectations, plans and
prospects for Targacept, Inc., including, without limitation, statements
regarding the progress, timing and scope of research and development of TC-
2216 and related regulatory filings and clinical trials, and all other
statements that are not purely historical in nature, constitute "forward-
looking statements" within the meaning of the Private Securities Litigation
Reform Act of 1995. Without limiting the foregoing, the words "may,"
"will," "could," "would," "should," "expect," "intend," "plan,"
"anticipate," "believe," "estimate," "predict," "project," "potential,"
"promise," "continue," "ongoing" and similar expressions are intended to
identify forward-looking statements. Actual results may differ materially
from those expressed or implied by forward-looking statements as a result
of various important factors, including our critical accounting policies
and risks and uncertainties relating to: the results of non-clinical
studies and assessments and clinical trials with respect to TC-2216 or our
other current and future product candidates in development; the conduct of
clinical trials, including the performance of third parties that we engage
to execute the trials and difficulties or delays in the completion of
patient enrollment or data analysis; and the timing and success of
submission, acceptance and approval of regulatory filings. These and other
risks and uncertainties are described in greater detail under the heading
"Risk Factors" in our most recent Quarterly Report on Form 10-Q and in
other filings that we make with the Securities and Exchange Commission. As
a result of the risks and uncertainties, the results or events indicated by
the forward-looking statements may not occur. We caution you not to place
undue reliance on any forward-looking statement.



In addition, any forward-looking statements in this release represent
our views only as of the date of this release and should not be relied upon
as representing our views as of any subsequent date. We anticipate that
subsequent events and developments may cause our views to change. Although
we may elect to update these forward-looking statements publicly at some
point in the future, whether as a result of new information, future events
or otherwise, we specifically disclaim any obligation to do so, except as
required by applicable law. Our forward-looking statements do not reflect
the potential impact of any future acquisitions, mergers, dispositions,
joint ventures or investments we may make.


Targacept, Inc.

targacept

Bipolar Depression Licence Application For Seroquel(R)

AstraZeneca has submitted an application to the Medicines and Healthcare products Regulatory Agency (MHRA) for a new licence for Seroquel(R) (quetiapine fumarate) in the UK for major depressive episodes in the framework of bipolar disorder.


Quetiapine is currently licensed in the UK for the treatment of schizophrenia and manic episodes associated with bipolar disorder.1


Bipolar disorder affects about one in every 100 adults at some point in their life.2 In some cases, it can take many years to receive a diagnosis and this can have a large impact on a patient's recovery. Tragically approximately 10 to 15 per cent of people suffering from bipolar disorder will take their own lives5,В±.


The new licence submission for use in bipolar depression is based on data from the BOLDER I and II (BipOLar DEpRession) studies.3,4 These data suggested quetiapine was effective and well tolerated as monotherapy in the treatment of depressive episodes in bipolar disorder.


"The impact of having a manic or depressive episode for patients with bipolar disorder can be very serious.2 If the application is successful, Seroquel will be the first atypical antipsychotic to be licensed for monotherapy treatment of both mania & depression in bipolar disorder in the UK. We look forward to hearing the results of the license submission soon." Mathew Crowther, AstraZeneca Regulatory Team Manager



В±Lifetime risk


The Seroquel SmPC is available on request or can be found at emc.medicines.uk/


Seroquel


Launched in 1997, it is estimated that Seroquel has been prescribed to more than 25 million** patients worldwide. Seroquel is approved in 88 countries for the treatment of schizophrenia, in 77 countries for the treatment of bipolar mania, and in 11 countries including the US for the treatment of bipolar depression.


AstraZeneca


AstraZeneca is a major international healthcare business engaged in research, development, manufacturing and marketing of prescription pharmaceuticals and supplier for healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with healthcare sales of US $29.55 billion6 and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection product sales. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.


** This estimate is based upon: (1) assumptions as to persistence (the number of prescriptions per patient) based upon 2002 market research; and (2) projections of prescriptions since launch based upon information available in the US and 13 of the 50 other countries in which SEROQUEL is marketed.


References


1. Seroquel (quetiapine fumarate) Summary of Product Characteristics. November 2007


2. Royal College of Physicians. ' Bipolar disorder (manic depression)' (Accessed January 2008)


3. Calabrese JR, Keck PE, Macfadden W, et al, for the BOLDER Study Group. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry 2005;162;1351-1360.


4. Thase M, McCoy R, Chang W, Macfadden W. Efficacy of quetiapine monotherapy in bipolar depression: a confirmatory double-blind, placebo controlled study (the BOLDER II Study). Presented at the American Psychiatric Association Annual Meeting, Toronto, 2006. (Abstract)


5. Hawton K et al. Suicide and attempted suicide in bipolar disorder: A systematic review of risk factors. J Clin Psych 2005;66:693-704


6. AstraZeneca 2007 full year financial report

AstraZeneca


View drug information on Seroquel.

Two-Thirds Of Depressed Pregnant Women Not Treated

The majority of pregnant women who have full-blown major depression aren't getting any treatment for the condition, and neither are most pregnant women who have signs of milder depression or depression risk, a new University of Michigan Depression Center study finds.


Even those who are receiving some form of treatment may not be getting enough, the researchers conclude in the current issue if General Hospital Psychiatry. Without adequate treatment - medication, talk therapy, or both together - prenatal and post-partum depression can seriously impact both women and their babies.


The findings come from a study of 1,837 pregnant women who were surveyed in the waiting rooms of five Michigan obstetrics clinics, using a standard questionnaire that detects signs of depression.



Of the women in the study, 276 met the criteria for being at risk of depression. All of these women had follow-up interviews with trained mental health workers who assessed them using the standard criteria used to diagnose depression, and asked them about their mental health and treatment history.


In all, 17 percent of the 276 women were found to be experiencing a serious depression. Another 23 percent had a history of major depression, which can come and go throughout life and needs regular monitoring and treatment. Of those who were experiencing major depression at the time of the study, only 33 percent were receiving any treatment for it. And of the 276 women with high depression risk, only 20 percent were receiving treatment, despite the fact that many had a history of depression.


When the researchers analyzed data on the at-risk and depressed women who were receiving treatment, they found that only 43 percent of those taking anti-depressant medications (alone or in combination with talk therapy) had been taking them at the recommended dose for at least six weeks. Such medications often must be taken for six to eight weeks before depression symptoms ease.


Heather Flynn, Ph.D., the U-M psychologist who led the study, calls the result very troubling. "These are women who meet the formal clinical criteria for the most severe form of depression. No one would argue that these women would benefit from some form of intervention, but only 33 percent of them were," she says. "It may be impossible to closely monitor every pregnant woman at risk in the way this study did, but it certainly makes sense to ensure that women with clear depression get the help they need."


Flynn and her colleague Sheila Marcus, M.D., have led an effort to screen pregnant women for depression in the waiting rooms of obstetric clinics at U-M and elsewhere in southern Michigan. They previously published results based on the waiting-room screening tests; the new study goes much further by performing a detailed psychological assessment using the criteria of the DSM-IV, the standard text for diagnosing mental health conditions.















Their results show no significant depression or depression-treatment differences among pregnant women of different races and ethnicities, employment situations, education levels, and marital or parental situations. The only factors that were found to increase a woman's chance of treatment were severe symptoms at the time of the study, a history of major depression and a history of any psychiatric treatment.


This suggests that women who are already accustomed to accessing the mental health system may be most likely to do so if they experience depressive symptoms during pregnancy, while other women may not recognize their symptoms - or may not know, or believe, that they can get help from a mental health provider.


Flynn, who treats patients as part of the Depression Center's clinical team, says she sees this phenomenon in her own work. "A lot of the women I see don't really appreciate that the way they've been feeling isn't normal, particularly during pregnancy," she says. "They attribute their fatigue, sleep and other problems to pregnancy, or don't believe that they could be suffering from depression. Others may suspect a problem but don't believe that treatment can work. But it can."


Another major barrier to depression treatment may be the lack of awareness among the doctors who treat women during pregnancy, but this seems to have improved in recent years, says Flynn. Many women, however, still are never screened for depression or treated to prevent a recurrence of past depression.


She and her colleagues are now preparing another paper that assesses the impact of screening pregnant women for depression, based on the results from the study group. "We're hoping to see if some of the approaches used in to help link people who have other health issues with needed treatments may help women work through the ambivalence or skepticism about treatment, help them engage in the treatment process," she says.


Depression during pregnancy: Symptoms and treatment


Pregnant women who are experiencing depression may think their symptoms are just a normal part of pregnancy. But in fact, the following signs may indicate depression: two or more weeks of depressed mood, decreased interest or pleasure in activities, change in appetite, change in sleep patterns, fatigue or loss of energy, difficulty concentrating, excessive feelings of worthlessness or guilt, thoughts of suicide, extreme restlessness and irritability.


Severe depression during pregnancy can interfere with women's ability to eat properly, get enough rest, or receive prenatal care - all of which may contribute to premature and low birth-weight infants. Even mild depression during pregnancy can put a woman at risk of more severe post-partum depression, which can interfere with her ability to care for her newborn and herself. Pregnant women who are experiencing possible signs of depression, or who have a history of depression, should talk to their doctors or midwives immediately. Medications, talk therapy, stress reduction, exercise and other steps can help ease depression safely during pregnancy and beyond.


For more information on depression during pregnancy, visit the U-M Depression Center Web site at med.umich/depression/pregnancy.htm.


2901 Hubbard St., Ste. 2400

Ann Arbor, MI 48109-2435

United States


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Epilepsy, Bipolar Drug To Recommend Genetic Test For Patients Of Asian Ancestry

Manufacturers of carbamazepine (Carbatrol, Equetro, Tegretol), a drug used for the treatment of epilepsy, bipolar disorder, and neuropathic pain, have agreed to advise in their labeling that patients of Asian ancestry first have a genetic test before starting treatment. A number of people of Asian ancestry are susceptible to developing a serious skin reaction to the medication.


Janet Woodcock, M.D., Deputy Commissioner for Scientific and Medical Programs, Chief Medical Officer, Acting Director of the Center for Drug Evaluation and Research, FDA, said "Science is now letting us individually treat patients based on how their body might react to a drug. When being considered for treatment with carbamazepine, genetically high-risk patients can be given a test that will help their health care providers make personalized drug treatment decisions and help avoid potentially serious skin reactions."


The label already has a warning about a rare but severe skin reaction, which can sometimes be life-threatening - these can include toxic epidermal necrolysis and Stevens-Johnson syndrome, multiple skin lesions, blisters, fever, itching and other symptoms. However, the present labeling has no mention of patient ancestry.


The risk of developing the skin reaction for a patient of Asian ancestry is about ten times greater than for Caucasian patients - a Caucasian patient runs a 1 to 6 per 10,000 risk of developing the skin reaction.


For the test to be carried out, the doctor or health care professional will need to draw some of the patient's blood and send it to a laboratory. The FDA estimates that approximately 5% of patients being considered for treatment with carbamazepine are of Asian ancestry. An inherited gene variant, called HLA-B 1502 is found almost exclusively among people with Asian ancestry. This gene variant is strongly linked to serious skin reactions with this drug. The FDA stresses that a patient who tests positive for this should not take carbamazepine, unless the benefits stack up strongly in favor, compared to the skin reaction risk.


If you are a patient of Asian ancestry and you have been taking this medication for a few months, without any skin reaction, you will most likely not have this gene. If you are taking this medication and feel concerned about your risk you should not stop taking carbamazepine without first checking with your doctor.


-- Carbatrol

-- Equetro

-- Tegretol


Written by -


View drug information on Carbatrol; Tegretol XR.

Irritability Should Be Considered When Diagnosing Bipolar Disorder In Children

A new study from Bradley Hospital and The Warren Alpert Medical School of Brown University, as well as two other institutions, adds to mounting evidence that clinicians consider irritability as a symptom when diagnosing pediatric bipolar disorder.



Reporting in the July issue of the Journal of the American Academy of Child and Adolescent Psychiatry, researchers say a small percentage of children with bipolar disorder experience manic episodes without extreme elation - one of the hallmarks of the disorder - and are diagnosed based on irritable mood alone.



"Diagnosing children with bipolar disorder is challenging. One of the chief controversies is whether irritability should be included among the criteria for this diagnosis because it can also overlap with a number of other psychiatric disorders, such as attention deficit hyperactivity disorder," says lead author Jeffrey Hunt, MD, a child psychiatrist and training director at Bradley Hospital. "Our findings confirm that while irritable-only mania is uncommon, it does exist - particularly in younger children - and should be considered in a bipolar diagnosis."



Bipolar disorder is characterized by dramatic mood swings from euphoria, elation and irritability - the manic phase of the disorder - to severe depression. Bipolar disorder often begins in late adolescence or early adulthood, although it can develop as early as the preschool years. Recent studies have shown that the number of children and teens being treated for bipolar disorder has grown dramatically in the last decade. Although it is unclear what has caused this increase, experts believe it may be due in part to more aggressive diagnoses by physicians and a greater awareness of pediatric bipolar disorder in the medical community.



Hunt and colleagues studied 361 children between the ages of 7 and 17 with bipolar disorder participating in the multi-site Course and Outcome of Bipolar Illness in Youth (COBY) study at Bradley Hospital and Alpert Medical School, the University of Pittsburgh and the University of California-Los Angeles. COBY is the largest and most comprehensive study of children and adolescents with bipolar disorder to date.



Researchers quantified the frequency and severity of manic symptoms of each participant, including whether irritability and elation were present. Based on this data, the group was then reclassified into three subgroups: elation-only, irritable-only and both elated and irritable.



Approximately 10 percent of children fell into the irritable-only category, while elated-only constituted about 15 percent. Nearly three-quarters experienced both elation and irritability. The irritable-only participants were significantly younger in age than the other two groups; however, there were no other sociodemographic differences between the groups. There were also no significant differences in terms of bipolar subtype, rate of psychiatric comorbidities, severity and duration of illness, and family history of mania and other psychiatric disorders. However, depression and alcohol abuse in second-degree relatives occurred more frequently in the irritable-only subgroup.



"The fact that the irritable-only and elation-only subgroup had similar clinical characteristics and family histories of bipolar disorder provides support for continuing to consider episodic irritability in the diagnosis of pediatric bipolar disorder," says Hunt, who is an assistant professor of psychiatry and human behavior at Alpert Medical School. Hunt is also training director of the child and adolescent fellowship and triple board residency programs.



The authors say continual, long-term follow-up of this study sample will help clarify whether the presence or predominance of elation or irritability at baseline will predict future clinical outcomes.



The research was funded by a grant from the National Institute of Mental Health. Study co-authors include Jennifer Dyl and the late Henrietta Leonard from Bradley Hospital and Alpert Medical School; Christianne Esposito-Smythers, Martin Keller, Lance Swenson and Robert Stout from Alpert Medical School; Boris Birmaher, David Axelson, Neal Ryan, Benjamin Goldstein, Tina Goldstein, MaryKay Gill and Mei Yang from the University of Pittsburgh Medical Center; and Michael Strober from the David Geffen School of Medicine, University of California at Los Angeles.



Source:

Jessica Collins Grimes

Lifespan

Case Western Reserve Receives $7.8M To Study Mania In Children

The Department of Psychiatry at Case Western Reserve University School of Medicine has received a $7.8 million renewal grant from the National Institute of Mental Health (NIMH) for the long-term study of manic symptoms in children.


The grant from the NIMH, one of the National Institutes of Health (NIH), funds the continuation of a study launched five years ago in which 707 children between the ages of six and 12 years were screened and evaluated for elevated symptoms of mania (ESM), a common indicator of bipolar disease and other childhood psychiatric disorders.


By studying the course of a child's ESM over time, which can include periods of rapid mood swings and intense irritability, researchers hope to learn more about what factors make children with ESM more likely to develop a bipolar spectrum disorder.


"We want to develop the means by which to more accurately diagnose bipolar disease in children," says Robert L. Findling, MD, the Rocco L Motto, M.D. Professor of Child & Adolescent Psychiatry at the School of Medicine, and director of the Division of Child and Adolescent Psychiatry at University Hospitals (UH) Case Medical Center. He is the study's coordinating principal investigator.


From the point of enrollment, children participating in the study's initial phase have been evaluated every six months for their psychiatric diagnoses, symptoms, use of mental health services and medication, and psychosocial function. The NIMH renewal grant allows researchers to continue these six-month evaluations among participants, who will now be between eight and 17 years of age. This will enable the collection of data during a period when study participants are at greater risk of developing a bipolar spectrum disorder, Dr. Findling says.


Researchers will also incorporate both neurocognitive testing (evaluations that assess how well a person processes new data, as well as their ability to process information and pay attention) and neuroimaging. The aim is to identify possible biomarkers that signal or reflect underlying biological mechanisms that predispose individuals to bipolar disease, a type of mood disorder that affects an estimated 5.7 million Americans who often report symptoms that can be traced back to their childhood.


"We're particularly excited about adding neuroimaging to this next phase of the study to examine brain functioning in these children," Dr. Findling says. "This research component is very innovative and will lay the groundwork for future studies between the child and adolescent psychiatry and radiology departments through collaborations involving neuroimaging in children." Neuroimaging involves the use of functional magnetic resonance imaging (MRI), a type of brain scan that maps brains activity. In this area, Dr. Findling is collaborating with neuroradiologist Jeffrey Sunshine, MD, PhD, associate professor and vice chair of the Department of Radiology at the School of Medicine and UH Case Medical Center.


The continued research will further document the trajectories of children with ESM and related psychiatric disorders to better determine the most appropriate points for intervention. Study goals include assessing the nature of manic symptoms over time in relation to changes in mood. Researchers hope to enhance their understanding of the predictive value of manic symptoms, alone and in combination with other symptoms, developing evidence-based criteria for diagnosing the spectrum of bipolar disorders in children; and identifying risk factors associated with poor functional outcomes among youth with manic symptoms.


The investigators will examine the relationships between mood episodes and clinical outcomes over time. They will also evaluate neurocognitive performance, together with functional abnormalities, to better understand how these relate to ESM and the development of bipolar disorder in childhood through early adulthood.


In addition to the School of Medicine and UH Case Medical Center, children enrolled in the study have been recruited from three other collaborating sites: University of Pittsburgh Medical Center, The Ohio State University Medical Center, and Cincinnati Children's Hospital.


Source:

Case Western Reserve University

Could Extreme Irritability Be Childhood Bipolar Disorder?

Results of a new study may help improve the diagnosis and treatment of two debilitating childhood mental disorders -- pediatric bipolar disorder (BD) and a syndrome called severe mood dysregulation (SMD). When the brain's electrical signals were measured during mildly frustrating situations, researchers from the National Institute of Mental Health (NIMH), of the National Institutes of Health, found a very different pattern in children with SMD, compared with children who had BD. The results indicate that different brain mechanisms may lead to irritability in children with SMD, suggesting that they may have an illness other than BD and may require different treatments.



"These aren't children with the occasional bad moods you see in most kids. They're typically very ill, with symptoms that interfere with their lives in major ways. Establishing clear diagnostic criteria is an essential step toward making sure they get the help they need," said NIMH Director Thomas R. Insel, M.D.



Children have a comparatively low rate of BD, but the rate increases with age, to approximately 1 percent among adolescents. About 3 percent of pre-adolescent and adolescent youth are estimated to have SMD. Mood-stabilizing and antipsychotic medications are used to treat children with BD, although the data on their effectiveness are limited and several studies are underway. Since SMD was only recently defined, there are no systematic studies on its treatment, and children with SMD are often treated as if they have BD.



Defining pediatric BD is a major issue in child psychiatry, because the disorder tends to be severe in this age group and the rate of diagnosed cases is rising. Until recent years, most studies of BD were conducted in adults. Some researchers maintain that pediatric BD should be defined more broadly to include children with SMD, an assertion countered by the new finding. Results of the study were published in the February 2007 issue of the American Journal of Psychiatry.



The classic definition of BD includes extreme, sustained mood swings that range from over-excited, elated moods and irritability -- the manic phase of the disorder -- to depression. In contrast, children with SMD are extremely irritable and hyperactive, but do not have clear-cut manic episodes.



One component of irritability is the tendency to get acutely frustrated when a goal is not met. Thus, through electroencephalograms (EEGs), the researchers could observe the brain's electrical signals that occurred during frustration while children with either disorder performed simple tasks.



The new study shows that clinicians some day could use biological measurements, such as EEGs, to help make psychiatric diagnoses, in combination with clinical symptoms. Currently, clinicians diagnose mental illnesses based on symptoms alone. The difficulty of diagnosing BD in children is compounded by the frequent co-occurrence of one or more other mental disorders.
















"We're approaching the day when we'll be able to use neuroscience techniques to improve psychiatric diagnoses. Pediatric BD has some of the most pressing needs in this regard, because of its severity and because of questions about how to best make the diagnosis," said senior author Ellen Leibenluft, M.D., Chief of the Unit on Bipolar Spectrum Disorders in the Emotion and Development Branch of the NIMH Mood and Anxiety Disorders Research Program.



In this study, scientists obtained EEGs of 35 children with classic BD, 21 children with SMD, and 26 healthy children (average age 12 to 13) while they performed a task repeatedly; each time they did the task, they won or lost 10 cents. The task was frustrating because the children often lost money.



The researchers found that while both the children with BD and those with SMD became more frustrated than did healthy children performing the same task, the brain mechanisms associated with their frustration differed. Children with BD had an abnormality in the brain's P3 electrical signals, which measure ability to purposefully direct attention, but children with SMD had abnormalities in N1 signals, which occur when a stimulus grabs someone's attention. Both abnormalities suggest deficits in the brain's attention-related activity, but in different phases of that activity.



"If future research indicates that BD and SMD are two separate disorders, this could guide parents and physicians toward the right treatments," said first author Brendan Rich, Ph.D., of the NIMH Unit on Bipolar Spectrum Disorders. "A good example is that medication prescribed for symptoms seen in SMD, such as stimulant medication, might be inappropriate for a child with classically defined bipolar disorder," he said.






NIMH scientists Mariana Schmajuk, B.S., and Daniel Pine, M.D., also contributed to the research, as did University of Maryland scientists Koraly E. Perez-Edgar, Ph.D., (currently at George Mason University) and Nathan A. Fox, Ph.D.



The National Institute of Mental Health (NIMH) mission is to reduce the burden of mental and behavioral disorders through research on mind, brain, and behavior. More information is available at the NIMH website: nimh.nih/.



The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.



Contact: Susan Cahill


NIH/National Institute of Mental Health

Capsules effective in treating acute manic and mixed episodes of Bipolar I Disorder

Shire Pharmaceuticals Inc. has announced that University of North Carolina at Chapel Hill researchers studied the efficacy of carbamazepine extended-release capsules (CBZ-ERC, Equetro) in patients with manic or mixed episodes of Bipolar I Disorder over six months. Data from this open label study was presented by UNC researchers last week at the 18th annual U.S. Psychiatric and Mental Health Congress in Las Vegas.


These data complement a pooled analysis of data from two, three-week placebo-controlled phase 3 studies of CBZ-ERC, which demonstrated that CBZ-ERC significantly reduced manic and mixed symptoms for patients and was generally well tolerated. CBZ-ERC, manufactured for Shire US Inc., is the only formulation of carbamazepine approved by the U.S. Food and Drug Administration for treatment of patients with acute manic and mixed episodes associated with Bipolar I Disorder. Shire provided funding for these studies.


"Many patients still fail to find an effective medication for their bipolar disorder that is generally well tolerated with a low incidence of weight gain, which can influence their ability to stay on treatment," said Richard H. Weisler, M.D., primary investigator of both clinical trials and adjunct professor of psychiatry at UNC's School of Medicine. "A medication like CBZ-ERC that works effectively and is well tolerated in both manic and mixed patients is a very important addition to our treatment options for patients and their doctors."


Weisler also is an adjunct assistant professor of psychiatry and behavioral sciences at Duke University Medical Center and has a private practice in Raleigh.


As many as 450 million people suffer from a mental or behavioral disorder worldwide, according to the World Health Organization. A recent study demonstrated that Bipolar I Disorder is more prevalent in the U.S. than previously estimated, affecting approximately 2 percent of the population annually and 3.3 percent of the population in its lifetime. These estimates are conservative considering the difficulty in the diagnosis of bipolar disorder. In the United States, annual costs for prevalence-based bipolar disorder are estimated at $45.2 billion, while lifetime costs of incidence-based bipolar disorder amount to about $24 billion. Bipolar disorder, also known as manic depression, is an illness that causes a person to experience extreme mood changes that alternate between manic episodes of abnormally high energy and the severe lows of depression, often with periods of normal mood in between.


The six-month study was an open-label extension trial for 92 patients who previously participated in one of two large, three-week phase 3 studies in which investigators randomized a total of 263 hospitalized participants to receive either CBZ-ERC or a placebo, although neither investigators nor patients knew to which group a patient was assigned until the study ended.















Of the patients who had responded to CBZ-ERC treatment during the phase 3 trials, defined as a 50 percent decrease in scores of the Young Mania Rating Scale (YMRS), 78 percent remained responders in the extension study. Also, 73 percent of those previously on placebo responded during the extension study. Overall, only 11 (14.3 percent) of the 77 intent-to-treat study patients experienced a relapse while taking CBZ-ERC. These participants' estimated average time to relapse was 141.8 ± 5.6 days.


Weisler and his coinvestigators also pooled and analyzed the data from the two earlier phase 3 studies, confirming previous findings that CBZ-ERC is effective and generally well tolerated in patients with Bipolar I Disorder with manic or mixed episodes.


When examining the 147 patients experiencing mixed episodes, the investigators found that CBZ-ERC treatment demonstrated significantly greater improvements in average YMRS scores compared to placebo (-12.39 versus -8.84, P

One-Page Questionnaire Is Effective Screening Tool For Common Psychiatric Disorders

A one-page, 27-item questionnaire that is available free online is a valid and effective tool to help primary care doctors screen patients for four common psychiatric illnesses, a study led by University of North Carolina at Chapel Hill researchers concludes.


Results of the My Mood Monitor (M-3) checklist study are published in the March/April 2010 issue of Annals of Family Medicine.


"About one in 10 Americans who suffer from depression and anxiety-related mental health disorders never receives treatment because they don't understand what's wrong, and when they go to their family doctor these treatable illnesses are too often missed," said Bradley Gaynes, M.D., M.P.H, lead author of the study and an associate professor of psychiatry in the University of North Carolina at Chapel Hill School of Medicine.


"For these millions of people and their primary care providers, the M-3 screener is a tremendously helpful resource," Gaynes said.


The M-3 checklist is designed to screen for depression, bipolar disorder, anxiety disorders and post-traumatic stress disorder (PTSD). For most people who suffer from any of these conditions, Gaynes said, their initial diagnosis is made by a primary care provider, not by a psychiatrist. In addition, the majority of prescriptions for antidepressant medications are written by primary care physicians. For those reasons, a single tool that can screen for multiple disorders would be very helpful, Gaynes said.


To evaluate the M-3 checklist, Gaynes and study co-authors enrolled 647 adults age 18 or older who sought care at the UNC Family Medicine Center between July 2007 and February 2008. Each participant filled out a paper version of the checklist while waiting to see their doctor. Each participant's completed checklist was then given to their doctor, and the doctors used the checklist to discuss emotional health with their patients.


Researchers later interviewed each person who filled out the checklist, within 30 days of their doctor visit, and assigned final diagnoses after reviewing each interview with Gaynes. These diagnoses were then compared to the answers each participant gave on their checklists. The results showed that the M-3 was effective in screening for any mood or anxiety disorder 83 percent of the time and for a specific disorder in 76 percent of cases.


Gaynes said the research team is currently designing a second study to measure the effectiveness of the M-3 checklist when used by individuals to monitor their mental health status over time. The company has developed a mobile phone version of the checklist that will be released later.


In addition to Gaynes, authors of the study were Joanne De-Veaugh-Geiss, MA, LPA, and Hongbin Gu, Ph.D., from UNC's Department of Psychiatry; David R. Rubinow, M.D., UNC's chair of psychiatry, Sam Weir, M.D. of UNC's Department of Family Medicine; Cora MacPherson, Ph.D., of Social & Scientific Systems Inc. in Silver Spring, Md.; Herbert C. Schulberg, Ph.D., M.S.Hyg., of Weill Cornell Medical College; and Larry Culpepper, M.D., M.P.H., professor and chairman of family medicine at Boston University and chief of family medicine at Boston Medical Center.


The M-3 checklist was developed by a team of mental health practitioners and experts, including Robert M. Post, M.D., head of the Bipolar Collaborative Network; Bernard M. Snyder, M.D., assistant clinical professor of psychiatry at Georgetown University and a cognitive behavioral therapist; Michael L. Byer, director of M-3 Information; and Gerald Hurowitz, M.D., assistant clinical professor of psychiatry at Columbia University and a clinical psychopharmacologist.


UNC was invited to design and lead the study, which was funded by M-3 Information, by Robert Post, Gaynes said. Post had previously worked with David Rubinow, now UNC's chair of psychiatry, when both were at the National Institute of Mental Health, Gaynes said.


Source: University of North Carolina at Chapel Hill School of Medicine

New Scholarship For Leaders Of Bipolar Lives

What do you do when you want to let the bipolar community know about scholarships for people with bipolar disorder, but soon discover that support for bipolar students is still far too rare? Why donate a scholarship yourself of course.


The Bipolar Lives Scholarship is a new scholarship, created when journalist Sarah Freeman added a webpage on bipolar scholarships to the Bipolar Lives website, but found only a handful of suitable awards existed. "I was shocked and saddened by the lack of support and realized I could do something directly". According to scholarship donor Sarah Freeman, "Bipolar disorder is in the news constantly right now. This has done a lot of good in terms of raising awareness and shattering some of the myths about bipolar. However, this new awareness needs to be matched by practical measures that encourage and support the bipolar community. Many people with bipolar disorder are extremely talented but fail to realize their potential. Higher education seems like the right place to focus on."


The Bipolar Lives Scholarship is an annual award, and submissions for the inaugural prize opened on July 4, 2008. The scholarship encourages research, reflection, and creativity in communicating important information about bipolar disorder. According to the scholarship organizers from Bipolar-Lives, there is a shortage of higher education scholarships for mental health service consumers, and the scholarship will provide useful assistance for applicants who are enrolled in a US college, community college, or a technical or trade school.


The scholarship, which is free to apply for, offers a cash award of $500.00.


Applicants must be at least 18 years of age and studying in the United States. They must submit an original essay, article, or multimedia work in one of the stipulated formats on an important issue related to bipolar disorder. This may be a factual piece based on established research, or may be drawn from personal experience. Suggested topics include bipolar treatments, bipolar symptoms, the bipolar spouse, relationships and bipolar disorder, lithium, diet and bipolar, and many others. A complete list of suggested topics and submission requirements appears on the Bipolar Lives website. The winner will be selected on merit and chance plays no part.


For additional information on the Bipolar Lives Scholarship, contact Sarah Freeman or visit bipolar-lives/bipolar-scholarships.html


About Bipolar-Lives


Bipolar Lives is one of the Internet's leading sites on bipolar disorder, and provides a unique blend of the latest research, effective bipolar management tools and techniques, and personal stories about conquering manic depression.

Bipolar-Lives

FDA Approves Lilly's Zyprexa For Two Adolescent Indications

The U.S. Food and Drug Administration (FDA) approved Zyprexa® (olanzapine) in tablet form as an option for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adolescents aged 13-17 years old.


The updated Zyprexa label states that clinicians should take into consideration the increased potential for weight gain and hyperlipidemia in adolescents compared to adults and the potential for long-term risks, which in many cases, may lead them to consider prescribing other drugs first in adolescents. Compared to patients from adult clinical trials, adolescents were also likely to experience increased sedation and greater increases in prolactin levels and hepatic transaminase (liver enzymes) levels. The recommended starting dose for adolescents is lower than that for adults.


An FDA Psychopharmacologic Drug Advisory Committee (PDAC) met in June and discussed the difficulties of diagnosing and treating these conditions in adolescents. The Zyprexa label provides additional guidance to physicians that medication therapy for pediatric schizophrenia or bipolar I disorder should be initiated only after a thorough diagnostic evaluation and careful consideration of the risks associated with medication treatment.


The updated Zyprexa label also highlights the need for a comprehensive treatment program in pediatric patients and recommends that Zyprexa be used as part of a "total treatment program for pediatric patients with schizophrenia and bipolar I disorder," which may include psychological, educational and social interventions.


This approval follows a favorable vote regarding the safety and efficacy of Zyprexa from the FDA PDAC in June on Lilly's supplemental New Drug Applications for these indications. The Committee examined findings from two pivotal clinical trials: one six-week trial in adolescents with schizophrenia and one three-week trial in adolescents with manic or mixed episodes associated with bipolar I disorder, as well as extensive Zyprexa safety data relevant to adolescents.


"There has been a recognized need in the mental health community for additional guidance on treating teens diagnosed with these serious mental illnesses," said Cherri Miner, M.D., Lilly USA Neuroscience Senior Medical Director. "Customers have been asking for data from controlled studies in these populations, and now with this information added to our label, we can help physicians make informed treatment decisions."


About Schizophrenia in Adolescents


Schizophrenia affects about 1 percent of Americans.(1) A substantial portion of first psychotic breaks for schizophrenia occur in adolescence. It has been estimated that 39 percent of males and 23 percent of females with schizophrenia experience onset of the disease before the age of 19.(2) Studies have suggested that early-onset schizophrenia is associated with worse long-term outcomes compared to onset of illness in adulthood.(3)















About Bipolar Disorder in Adolescents


Bipolar disorder affects approximately 5.7 million American adults, or about 2.6 percent of the U.S. population age 18 and older, in a given year.(4) It has an estimated prevalence of 0.1 percent to 2 percent among adolescents.(5) Lifetime prevalence of bipolar I disorder in community samples has varied from 0.4 percent to 1.6 percent.(6) It has been estimated that 20 percent of all patients with bipolar disorder experience their first episode during adolescence, with the peak age of onset for this group of patients occurring between 15 and 19 years of age.(7) Early onset of bipolar disorder is associated with greater severity of illness and more functional impairment.(8)


Safety Information for Zyprexa (olanzapine)


Zyprexa is indicated in adults in the United States for the treatment of schizophrenia, acute treatment of mixed and manic episodes of bipolar I disorder, and maintenance treatment of bipolar I disorder.


Zyprexa is indicated for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adolescents 13 to 17 years of age. When deciding among alternative treatments available for adolescents, clinicians should consider the increased potential for weight gain and hyperlipidemia compared to adults. Clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases this may lead clinicians to consider prescribing other drugs first in adolescents.


Olanzapine is not approved for the treatment of patients with dementia-related psychosis. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.


In addition, compared to elderly patients with dementia-related psychosis taking a placebo, there was a significantly higher incidence of cerebrovascular adverse events (e.g. stroke, transient ischemic attack) in elderly patients with dementia-related psychosis treated with olanzapine.


The possibility of a suicide attempt is inherent in schizophrenia and bipolar I disorder. Close supervision of high-risk patient should accompany drug therapy.


As with all antipsychotic medications, a rare and potentially fatal condition known as Neuroleptic Malignant Syndrome (NMS) has been reported with olanzapine. If signs and symptoms appear, immediate discontinuation is recommended. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.


Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics, including olanzapine. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose levels appears to fall on a continuum and olanzapine appears to have a greater association than some other atypical antipsychotics. Physicians should consider the risks and benefits when prescribing olanzapine to patients with an established diagnosis of diabetes mellitus, or having borderline increased blood glucose level. Patients taking olanzapine should be monitored regularly for worsening of glucose control. Patients starting treatment with olanzapine should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, palyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose testing.


Undesirable alterations in lipids have been observed with olanzapine use. Clinical monitoring, including baseline and follow-up lipid evaluations in patients using olanzapine, is advised. Clinically significant, and sometimes very high, elevations in triglyceride levels and modest mean elevations in total cholesterol have been observed with olanzapine use.


Potential consequences of weight gain should be considered prior to starting olanzapine. Patients receiving olanzapine should receive regular monitoring of weight.


Also, as with all antipsychotic treatment, prescribing should be consistent with the need to minimize Tardive Dyskinesia (TD). The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.


Olanzapine may induce orthostatic hypotension associated with dizziness, tachycardia, bradycardia, and in some patients, syncope, especially during the initial dose-titration period. Particular caution should be used in patients with known cardiovascular disease, cerebrovascular diseases, or those predisposed to hypotension.


Other potentially serious adverse events include decreased white blood cell count (leukopenia, neutropenia, agranulocytosis), seizures, elevated prolactin levels, cognitive and motor impairment, body temperature elevation, and trouble swallowing.


The recommended starting dose for adolescents is lower than that for adults. Compared to patients from adult clinical trials, adolescents were likely to gain more weight, experience increased sedation, and have greater increases in total cholesterol, triglycerides, LDL cholesterol, prolactin and hepatic transaminase levels. When deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential for weight gain and hyperlipidemia compared to adults. Clinicians should consider the long-term risks when prescribing to adolescents, and in many cases this may lead them to consider prescribing other drugs first in adolescents. Medication treatment for adolescent schizophrenia and bipolar I disorder should be initiated only after a thorough diagnostic evaluation and careful consideration of the risks associated with medication treatment. Medication treatment for both adolescent schizophrenia and bipolar I disorder is indicated as part of a total treatment program that often includes psychological, educational and social interventions. Safety and effectiveness of olanzapine in patients

Misdiagnosing Narcissism - The Bipolar I Disorder

Bipolar patients in the manic phase exhibit many of the signs and symptoms of pathological narcissism - hyperactivity, self-centeredness, lack of empathy, and control freakery. During this recurring chapter of the disease, the patient is euphoric, has grandiose fantasies, spins unrealistic schemes, and has frequent rage attacks (is irritable) if her or his wishes and plans are (inevitably) frustrated.


The manic phases of the Bipolar Disorder, however, are limited in time - NPD is not. Furthermore, the mania is followed by - usually protracted - depressive episodes. The narcissist is also frequently dysphoric. But whereas the Bipolar sinks into deep self-deprecation, self-devaluation, unbounded pessimism, all-pervasive guilt and anhedonia - the narcissist, even when depressed, never forgoes his narcissism: his grandiosity, sense of entitlement, haughtiness, and lack of empathy.


Narcissistic dysphorias are much shorter and reactive - they constitute a response to the grandiosity gap. In plain words, the narcissist is dejected when confronted with the abyss between his inflated self-image and grandiose fantasies - and the drab reality of his life: his failures, lack of accomplishments, disintegrating interpersonal relationships, and low status. Yet, one dose of narcissistic supply is enough to elevate the narcissists from the depth of misery to the heights of manic euphoria.


Not so with the Bipolar. The source of her or his mood swings is assumed to be brain biochemistry - not the availability of narcissistic supply. Whereas the narcissist is in full control of his faculties, even when maximally agitated, the Bipolar often feels that s/he has lost control of his/her brain ("flight of ideas"), his/her speech, his/her attention span (distractibility), and his/her motor functions.


The Bipolar is prone to reckless behaviors and substance abuse only during the manic phase. The narcissist does drugs, drinks, gambles, shops on credit, indulges in unsafe sex or in other compulsive behaviors both when elated and when deflated.


As a rule, the Bipolar's manic phase interferes with his/her social and occupational functioning. Many narcissists, in contrast, reach the highest rungs of their community, church, firm, or voluntary organization. Most of the time, they function flawlessly - though the inevitable blowups and the grating extortion of narcissistic supply usually put an end to the narcissist's career and social liaisons.


The manic phase of Bipolar sometimes requires hospitalization and - more frequently than admitted - involves psychotic features. Narcissists are never hospitalized as the risk for self-harm is minute. Moreover, psychotic microepisodes in narcissism are decompensatory in nature and appear only under unendurable stress (e.g., in intensive therapy).


The Bipolar's mania provokes discomfort in both strangers and in the patient's nearest and dearest. His/her constant cheer and compulsive insistence on interpersonal, sexual, and occupational, or professional interactions engenders unease and repulsion. Her/his lability of mood - rapid shifts between uncontrollable rage and unnatural good spirits - is downright intimidating. The narcissist's gregariousness, by comparison, is calculated, "cold", controlled, and goal-orientated (the extraction of narcissistic supply). His cycles of mood and affect are far less pronounced and less rapid.















The Bipolar's swollen self-esteem, overstated self-confidence, obvious grandiosity, and delusional fantasies are akin to the narcissist's and are the source of the diagnostic confusion. Both types of patients purport to give advice, carry out an assignment, accomplish a mission, or embark on an enterprise for which they are uniquely unqualified and lack the talents, skills, knowledge, or experience required.


But the Bipolar's bombast is far more delusional than the narcissist's. Ideas of reference and magical thinking are common and, in this sense, the Bipolar is closer to the Schizotypal than to the Narcissistic.


There are other differentiating symptoms:


Sleep disorders - notably acute insomnia - are common in the manic phase of Bipolar and uncommon in narcissism. So is "Manic speech" - pressured, uninterruptible, loud, rapid, dramatic (includes singing and humorous asides), sometimes incomprehensible, incoherent, chaotic, and lasts for hours. It reflects the Bipolar's inner turmoil and his/her inability to control his/her racing and kaleidoscopic thoughts.


As opposed to narcissists, Bipolar in the manic phase are often distracted by the slightest stimuli, are unable to focus on relevant data, or to maintain the thread of conversation. They are "all over the place" - simultaneously initiating numerous business ventures, joining a myriad organization, writing umpteen letters, contacting hundreds of friends and perfect strangers, acting in a domineering, demanding, and intrusive manner, totally disregarding the needs and emotions of the unfortunate recipients of their unwanted attentions. They rarely follow up on their projects.


The transformation is so marked that the Bipolar is often described by his/her closest as "not himself/herself". Indeed, some Bipolars relocate, change name and appearance, and lose contact with their "former life". Antisocial or even criminal behavior is not uncommon and aggression is marked, directed at both others (assault) and oneself (suicide). Some Biploars describe an acuteness of the senses, akin to experiences recounted by drug users: smells, sounds, and sights are accentuated and attain an unearthly quality.


As opposed to narcissists, Bipolars regret their misdeeds following the manic phase and try to atone for their actions. They realize and accept that "something is wrong with them" and seek help. During the depressive phase they are ego-dystonic and their defenses are autoplastic (they blame themselves for their defeats, failures, and mishaps).


Finally, pathological narcissism is already discernible in early adolescence. The full-fledged Bipolar Disorder - including a manic phase - rarely occurs before the age of 20. The narcissist is consistent in his pathology - not so the Bipolar. The onset of the manic episode is fast and furious and results in a conspicuous metamorphosis of the patient.


More about this topic here:


Stormberg, D., Roningstam, E., Gunderson, J., & Tohen, M. (1998) Pathological Narcissism in Bipolar Disorder Patients. Journal of Personality Disorders, 12, 179-185


Roningstam, E. (1996), Pathological Narcissism and Narcissistic Personality Disorder in Axis I Disorders. Harvard Review of Psychiatry, 3, 326-340


By: Dr. Sam Vaknin


First published in my

"Narcissistic Personality Disorder" Topic Page on Suite 101


(The use of gender pronouns in this article reflects the clinical facts: most narcissists are men).


The manic phase of Bipolar I Disorder is often misdiagnosed as Narcissistic Personality Disorder (NPD).


AUTHOR BIO:


Sam Vaknin is the author of Malignant Self Love - Narcissism Revisited and After the Rain - How the West Lost the East. He served as a columnist for Global Politician, Central Europe Review, PopMatters, Bellaonline, and eBookWeb, a United Press International (UPI) Senior Business Correspondent, and the editor of mental health and Central East Europe categories in The Open Directory and Suite101.


Visit Sam's Web site at samvak.tripod

71% Report Depression Decrease After Green Walk, 22% Report Depression Increase After Urban Walk

Leading mental health charity Mind today launches a groundbreaking new report (1) which sets a new green agenda for mental health. With a mass of new and growing evidence, Mind calls for ecotherapy to be recognised as a clinically-valid frontline treatment for mental health problems. As 93 per cent of GPs have prescribed drugs due to a lack of alternatives (2) and access to Cognitive Behavioural Therapy takes up to four years in some areas of the UK (3), it is vital that ecotherapy is considered by GPs alongside these as a treatment option.


Ecotherapy involves getting outdoors and getting active in a green environment as a way of boosting mental wellbeing. Whether it's taking regular walks in the park, flying a kite or participating in a gardening therapy project, green exercise is proven to have huge benefits for mental health. The prescription of care farms as a treatment for mental distress has been highly successful on the continent but the UK is lagging far behind Europe - there are only 43 care farms in the UK, none of which are directed at mental health, compared to 600 in the Netherlands and 400 in Norway.


Ecotherapy versus retail therapy


Mind's new report Ecotherapy: the green agenda for mental health presents the findings of the first ever study looking at how green exercise specifically affects people with mental health problems. A walk in a country park was compared with a walk in an indoor shopping centre (4). The results are startling:


-- 71 per cent reported decreased levels of depression after the green walk

-- 22 per cent felt their depression increased after walking through an indoor shopping centre and only 45 per cent experienced a decrease in depression

-- 71 per cent said they felt less tense after the green walk

-- 50 per cent said their feelings of tension had increased after the shopping centre walk

-- 90 per cent had increased self-esteem after the country walk

-- 44 per cent said their self-esteem decreased after window shopping in the shopping centre.


Green activities boost mental health


Mind's second research study (5) showed the views of people who regularly partake in green activities run by Mind's network of local Mind associations:


-- 90 per cent said it was the combination of nature and exercise that had the greatest effect on them

-- 94 per cent said that green activities had benefited their mental health, lifting depression.


Farming therapy


Britain is trailing far behind other European countries in introducing care farms as a treatment for mental distress. Patients suffering from mental distress in the Netherlands, Italy, Germany, Austria, Belgium and Slovenia are prescribed agriculture work where they acquire new skills and gain increased confidence while farmers get paid for providing a health service and benefit from additional labour power.















Holland has 600 care farms that are a fully integrated part of the health service but in the UK care farming is still a relatively new concept. The National Care Farming Initiative estimates that there are 43 care farms in the UK but none aimed at mental health, the majority self-funded and there is no national framework. The expansion of UK care farms could aid thousands of people with mental health problems. It could also help rural regeneration and break down the stigma and isolation surrounding mental health problems in rural communities.


Antidepressant prescriptions soar


Antidepressant prescriptions are at an all-time high with

Depressed Employees Vulnerable To Presenteeism And Absenteeism

A new study released today in the
American Journal of Psychiatry examines the impact depression has on work
productivity. The study, conducted by researchers at Tufts-New England
Medical Center, compared depressed employees with two groups: those with
rheumatoid arthritis (RA), which is a condition associated with work
disability, and depression-free healthy employees. When compared, the
depression group was far more vulnerable to job loss, absenteeism (missed
work days) and presenteeism (impaired productivity while at work).
Furthermore, the researchers noted that even when depressed subjects
received treatment and experienced improvement in their clinical symptoms,
their work productivity was still impaired.


"In order for the United States to remain competitive and innovative,
it's vital to address the physical and emotional burden of depression,"
said Lead Author and Co-Investigator David Adler, MD, Senior Psychiatrist
at Tufts-New England Medical Center. "Depression hits at all levels of
health, and figuring out new ways for people to improve functioning is more
important than ever."


The three groups were surveyed using reliable, validated
self-administrated questionnaires. The Work Limitations Questionnaire (WLQ)
developed under the direction of Debra Lerner, MS, PhD, Study Principal
Investigator and Director of Tufts-NEMC's Institute of Clinical Research's
Program on Health, Work and Productivity, was used to measure the effect of
chronic health problems on job performance and productivity. The Patient
Health Questionnaire-9 was utilized to both screen and follow patient's
depression. The National Institute of Mental Health funded the four-year
study.


The study enrolled 572 patients who were recruited from February 2001
and March 2003 from primary care physician offices covered by Tufts Health
Plan, the Fallon Clinic and Harvard Pilgrim Health Care. Participants were
followed for 18 months. At baseline, 44 percent of the depressed group was
taking antidepressants, but were still clinically depressed.


"Depression is an issue that effects employees, their families and
employers," said Dr. Lerner. The cost of lost productivity is staggeringly
large. "There is a prevailing myth that many chronically ill people prefer
to go out on disability, but our experience is that most want to continue
to work and feel productive. Also, many realize that disability benefits
will not fully replace earnings and will result in economic hardship.


Instituting increased and improved services to help people with depression
remain productive could be a win/win for both employers and employees."



E Tufts-New England Medical Center

nemc/home/

New Dosages Of RISPERDAL(R) (Risperidone) Now Available

Physicians treating people with schizophrenia or bipolar mania now have expanded treatment options: Two additional dosages (3 mg and 4 mg) of RISPERDAL(R) M-TAB(R), the fast-dissolving form of one of the most prescribed antipsychotic medications, RISPERDAL(R) (risperidone), are now available by prescription.


RISPERDAL(R) M-TABS(R) are easy for patients to use because they dissolve in seconds when placed on the tongue. This is an alternative for health care professionals who may have patients who hide medication in their mouths to avoid taking it. Additionally, for patients who have difficulty or do not like swallowing pills, RISPERDAL(R) M-TABS(R) can be an important alternative. The new delivery option offers benefits to health care professionals because there is no mixing, measuring or beverage required for administration. The two new dosages are now available.


Schizophrenia affects more than two million Americans1 and is characterized by symptoms such as hallucinations, delusions, social withdrawal and a diminished capacity for organized thought.2


Bipolar mania is one aspect of bipolar disorder. People with bipolar mania may experience high levels of energy, unrealistic thoughts or ideas and reckless and/or impulsive behavior. Of the more than three million Americans believed to suffer from bipolar disorder, two-thirds are often under-diagnosed and under-treated, according to the National Alliance for the Mentally Ill, the leading advocacy organization for people with mental illness.3


RISPERDAL(R) has been marketed in tablet form in the United States since 1994. It is available as a standard, oral tablet in 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg and 4 mg doses; a quick-dissolving tablet (RISPERDAL(R) M-TAB(R)) in 0.5 mg, 1 mg and 2 mg doses (new 3 mg and 4 mg doses are now available); and an oral solution in a 1.0 mg/mL dose. RISPERDAL(R) CONSTA(R) (risperidone) Long-Acting Injection is also available in 25 mg, 37.5 mg and 50 mg strengths, and is given by intramuscular injection every two weeks.


RISPERDAL(R) is indicated for the treatment of schizophrenia and for the short term treatment of bipolar mania in acute manic or mixed episodes of Bipolar I Disorder (manic depression). As with all other psychotropic medications, RISPERDAL(R) is associated with side effects.


Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Neither RISPERDAL(R) or RISPERDAL(R) CONSTA(R) is approved for the treatment of patients with Dementia-Related Psychosis.


The most common side effects that occurred with RISPERDAL(R) in the treatment of Schizophrenia were: anxiety, sleepiness, restlessness, tremors and muscle stiffness; dizziness, constipation, nausea, indigestion, runny nose, rash and rapid heartbeat; in the treatment of Bipolar Mania either alone or in combination with a mood stabilizer (lithium or valproate) were: sleepiness, muscle stiffness, restlessness, tremor, indigestion, nausea, abnormal vision, muscle aches, dizziness, runny nose, diarrhea, increased saliva, stomach pain and urinary incontinence. In a study of people taking RISPERDAL(R) CONSTA(R), most common side effects were: sleepiness, restlessness, tremors and muscle stiffness, stomach upset, constipation, dry mouth, feeling tired and weight increase.















Studies suggest an increased risk of elevated blood sugar-related side effects, and sometimes potentially fatal, in patients treated with this class of medications, including RISPERDAL(R). Some people may need regular blood sugar testing.


Some people may have heard the term "tardive dyskinesia." These are usually persistent, uncontrollable, slow or jerky facial or body movements that can be caused by all medications of this type. A rare, but serious, side effect that has been reported with this kind of medicine, including RISPERDAL(R), is known as NMS, or neuroleptic malignant syndrome. NMS is characterized by muscle rigidity, fever and can be serious. Phenylketonurics: RISPERDAL(R) M-TAB(R) contains phenylalanine. RISPERDAL(R) M-TAB(R) is bioequivalent to RISPERDAL(R) Tablets.


Based in Titusville, NJ, Janssen, L.P., focuses exclusively on pioneering solutions for healthy minds and currently markets prescription medications for the treatment of schizophrenia and bipolar mania. For more information about RISPERDAL(R) please see the accompanying full prescribing information or visit janssen.


References:

1 Schizophrenia Research Fact Sheet. National Institute of Mental Health, Washington, D.C. nimh.nih/publicat/NIMHschizresfact.pdf.

2 Schizophrenia. National Institute of Mental Health, Washington, D.C. nimh.nih/publicat/NIMHschizoph.pdf.

3 The National Alliance for the Mentally Ill, "Understanding Bipolar Disorder," page 1 SOURCE Janssen, L.P.

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FDA Approves AstraZeneca's Seroquel(c) For Bipolar Depression Treatment

AstraZeneca today announced that the U.S. Food and Drug Administration (FDA) has approved SEROQUEL(c) (quetiapine fumarate) for the treatment of patients with depressive episodes associated with bipolar disorder. SEROQUEL already is approved for the treatment of acute manic episodes associated with bipolar I disorder and for the treatment of schizophrenia. SEROQUEL is now the first and only single medication approved by the FDA to treat both depressive and manic episodes associated with bipolar disorder.


he FDA approval was based primarily on results from the clinical trial programme known as BOLDER (BipOLar DEpRession), which comprises the BOLDER I and BOLDER II studies. In these studies, patients taking SEROQUEL showed an improvement in depressive symptoms starting at week one compared to those taking placebo, and this improvement continued throughout the eight-week study. The recommended dose is 300 mg once-daily, to be achieved by day four of treatment.


More than seven million American adults are affected by bipolar disorder, a serious psychiatric condition also known as manic depressive illness. Patients with bipolar disorder are symptomatic almost half of their lives, and approximately two-thirds of that time is spent in the depressed phase of the illness. For many people with bipolar disorder, the depressive symptoms are significantly more debilitating than the manic symptoms associated with the illness.


"The new indication for SEROQUEL provides physicians and their patients with a single medication to treat both the depressive and manic episodes associated with bipolar disorder," said John Patterson, Executive Director Development, AstraZeneca. "Treating acute bipolar disorder with a single medication may help patients adhere to their medication regimen."


Both studies in the BOLDER programme were double-blind, placebo-controlled trials of outpatients (N=1,045) with bipolar I or II disorder. Patients were randomized to receive eight weeks of treatment with fixed doses of SEROQUEL(c) (300 mg or 600 mg) or placebo administered once-daily. Efficacy in bipolar depression was demonstrated in the studies at both 300 mg a day and 600 mg a day. No additional benefit was seen in the 600 mg a day dose groups. Therefore, the recommended dose is 300 mg once-daily, to be achieved by day four of treatment.


SEROQUEL was generally well tolerated, with adverse event types similar to those seen in other clinical trials of SEROQUEL in bipolar mania and schizophrenia. The most frequent adverse events seen in the bipolar depression trials were dry mouth, sedation, somnolence, dizziness and constipation.


Because the depressive symptoms associated with bipolar disorder are also seen in major depressive disorder, a proper diagnosis can be difficult to achieve. In fact, studies show that as many as 69 percent of people with bipolar disorder were misdiagnosed, with the most frequent misdiagnosis being major depressive disorder. This misdiagnosis can lead to unfocused treatment that may exacerbate the disease.


Beyond schizophrenia, bipolar mania and bipolar depression, the ongoing clinical development programme includes investigations of the use of SEROQUEL in bipolar maintenance. Regulatory filings for the treatment of schizophrenia with a sustained release formulation of quetiapine fumarate, SEROQUEL SR(c), were submitted this year to regulatory authorities in the US, EU and other markets. Ongoing SEROQUEL SR(c) clinical studies also cover major depressive disorder and generalized anxiety disorder. SEROQUEL is the number 1 prescribed atypical antipsychotic in the United States. With a well-established safety and efficacy profile, SEROQUEL has had more than 19 million patient exposures worldwide since its launch in 1997. In 2005, global sales for SEROQUEL reached $2.8 billion.


astrazeneca


View drug information on Seroquel.

Key To New Treatment Of Depression: Ever-happy Mice May Hold Key

A new breed of permanently 'cheerful' mouse is providing hope of a new treatment for clinical depression. TREK-1 is a gene that can affect transmission of serotonin in the brain. Serotonin is known to play an important role in mood, sleep and sexuality. By breeding mice with an absence of TREK-1, researchers were able create a depression-resistant strain. The details of this research, which involved an international collaboration with scientists from the University of Nice, France, are published in Nature Neuroscience this week.



"Depression is a devastating illness, which affects around 10% of people at some point in their life," says Dr. Guy Debonnel an MUHC psychiatrist, professor in the Department of Psychiatry at McGill University, and principal author of the new research. "Current medications for clinical depression are ineffective for a third of patients, which is why the development of alternate treatments is so important."



Mice without the TREK-1 gene ('knock-out' mice) were created and bred in collaboration with Dr. Michel Lazdunski, co-author of the research, in his laboratory at the University of Nice, France. "These 'knock-out' mice were then tested using separate behavioral, electrophysiological and biochemical measures known to gauge 'depression' in animals," says Dr. Debonnel. "The results really surprised us; our 'knock-out' mice acted as if they had been treated with antidepressants for at least three weeks."



This research represents the first time depression has been eliminated through genetic alteration of an organism. "The discovery of a link between TREK-1 and depression could ultimately lead to the development of a new generation of antidepressant drugs," noted Dr. Debonnel.



According to Health Canada and Statistics Canada, approximately 8% of Canadians will suffer from depression at some point in their lifetime. Around 5% of Canadians seek medical advice for depression each year; a figure that has almost doubled in the past decade. Figures in the U.S. are comparable, with approximately 18.8 million American adults (about 9.5% of the population) suffering depression during their life.






Funding for this research was provided by the CNRS (Centre National de la Recherche Scientifique) and the Canadian Institutes for Health Research (CIHR).



The Research Institute of the McGill University Health Centre (RI MUHC) is a world-renowned biomedical and health-care hospital research centre. Located in Montreal, Quebec, the institute is the research arm of the MUHC, a university health center affiliated with the Faculty of Medicine at McGill University. The institute supports over 500 researchers, nearly 1000 graduate and post-doctoral students and operates more than 300 laboratories devoted to a broad spectrum of fundamental and clinical research. The Research Institute operates at the forefront of knowledge, innovation and technology and is inextricably linked to the clinical programs of the MUHC, ensuring that patients benefit directly from the latest research-based knowledge. For further details visit: muhc.ca/research.



About the McGill University Health Centre (MUHC)

The MUHC is a comprehensive academic health institution with an international reputation for excellence in clinical programs, research and teaching. The MUHC is a merger of five teaching hospitals affiliated with the Faculty of Medicine at McGill University - the Montreal Children's, Montreal General, Royal Victoria, and Montreal Neurological Hospitals, as well as the Montreal Chest Institute. Building on the tradition of medical leadership of the founding hospitals, the goal of the MUHC is to provide patient care based on the most advanced knowledge in the health care field, and to contribute to the development of new knowledge. muhc.ca/



Contact: Ian Popple


McGill University

Blocked Enzyme Reverses Schizophrenia-like Symptoms - MIT Study Of Mice Could Lead To Drug Treatments For The Brain Disorder

Researchers at MIT's Picower Institute for Learning and Memory have found that inhibiting a key brain enzyme in mice reversed schizophrenia-like symptoms. The finding, reported in the March 20 issue of Cell, identified how a particular gene controls this brain enzyme. Better understanding of the relationship could lead to new drug treatments for schizophrenia, the severe brain disorder that affects about 1 percent of the population and is characterized by hallucinations, delusions, poor social and emotional functioning and disorganized thoughts.


The Picower research focused on a gene known as DISC1 (short for "disrupted in schizophrenia 1"), which was first identified in the 1990s by researchers studying the genetic makeup of a large Scottish family with mental and behavioral disorders. DISC1 has since been shown to help brain neuronal cells migrate to their correct positions and to help new neurons grow in the developing brain, but its role was not well understood.


Now, Li-Huei Tsai, the Picower Professor of Neuroscience in MIT's Department of Brain and Cognitive Sciences, and colleagues have shown for the first time that DISC1 directly inhibits the activity of a brain enzyme called glycogen synthase kinase 3 beta, also known as GSK3B.


Lithium chloride, the mood-stabilizing drug often prescribed for schizophrenia and bipolar disorder, also acts on GSK3B.


"This work for the first time provides a detailed explanation of how DISC1 functions normally in our brains," said Tsai, a Howard Hughes Medical Institute investigator and director of the neurobiology program of the Stanley Center for Psychiatric Research at the Broad Institute of Harvard and MIT.


"With this new knowledge of the DISC1-GSK3B interaction, one of the goals is to develop new drugs targeting schizophrenia, providing some hope that this devastating disease will be treated more effectively in the near future," she said.


Growing new neurons


Working with mice, Tsai and colleagues found that DISC1 regulates the growth of neural stem cells in both developing and adult brains. "During brain development, a fine-tuned mechanism regulates when neural stem cells divide and replenish their own population and when they turn into newborn neurons that will mature and grow appropriate connections with other neurons," Tsai said.


Tsai and colleagues found that halting expression of the DISC1 gene in neural stem cells causes them to stop dividing and prematurely turn into newborn neurons.


Eliminating DISC1 in adult mouse neural stem cells caused similar defects and produced behavioral changes such as hyperactivity, a symptom of schizophrenia in mice models of the disease. "Giving a chemical inhibitor of GSK3B to these mice completely reversed their abnormal behavior," Tsai said.


DISC1 works by directly inhibiting the activity of GSK3B, a target of the drug lithium. "It seems that DISC1 regulates the balance between neural stem cell self-renewal and turning into neurons, which impacts overall brain circuitry and can lead to compromised cognition and behavioral abnormalities," Tsai said. "Understanding the normal function of DISC1 in the brain could lead to new information on how schizophrenia arises due to genetic predisposition and environmental factors."


In addition to Tsai, co-authors are Picower Institute postdoctoral fellow Yingwei Mao; MIT Brain and Cognitive Sciences graduate student Xuecai Ge, Picower Institute postdoctoral associate Christopher L. Frank; Broad Institute researchers Jon M. Madison, Erin M. Berry, Takahiro Soda and Karun K. Singh; and colleagues at Massachusetts General Hospital, the Harvard-MIT Division of Health Sciences and Technology and the University of Washington School of Medicine.


This work was supported by the National Institutes of Health, the Stanley Center, the National Alliance for Research on Schizophrenia and Depression (NARSAD) and the Human Frontier Science Program.



Written by Deborah Halber, Picower Institute

Source
MIT

Indiana U Study May Alter Approach To Psychiatric Treatment

Indiana University School of Medicine researchers have isolated biomarkers in the blood that identify mood disorders, a breakthrough that may change the way bipolar illness is diagnosed and treated. The report will be published in the February 26 advance online edition of the journal Molecular Psychiatry.



The panel of markers is present in differing amounts in individuals suffering from high or low mood states. The concentration of the blood markers also varies depending on the severity of the depression or mania the individual experiences.



"This discovery is a major step towards bringing psychiatry on par with other medical specialties that have diagnostic tools to measure disease states and the effectiveness of treatments," said Alexander B. Niculescu III, M.D., Ph.D., lead author and assistant professor of psychiatry, medical neurobiology and neuroscience at the IU School of Medicine Institute of Psychiatric Research.



"Although psychiatrists have been aware that bipolar illness and other psychiatric conditions produced molecular changes in the brain, there was no way to measure those changes while the patient was living," Dr. Niculescu said. "Blood now can be used as a surrogate tissue to diagnose and assess the severity of the illness."



The researchers discovered that the molecular changes in the brain are reflected in the blood producing biomarkers whose levels correlated with the severity of the symptoms. This gives psychiatrists an objective tool to assess the effectiveness of a medication on individual patients without the typical lengthy waiting period, said Dr. Niculescu.



The researchers isolated the blood biomarkers in 96 patients involved in the initial research, which was supported by National Institutes of Health grant funding, NAESAD and funds from Eli Lilly and Company. Next the Indiana University researchers are planning a larger study looking at these mood markers in response to treatments, and they will use their unique methodology to seek biomarkers for other psychiatric diseases.







Dr. Niculescu, who also is a staff psychiatrist at the Richard L. Roudebush VA Medical Center, said the discovery could have an impact on how a wide range of mood disorders are treated including post-partum depression, post-traumatic stress disorder and assessments for bereavement interventions. This research also may facilitate the development by pharmaceutical companies of much needed targeted new medications with greater efficacy and decreased side-effects.



Other IU faculty involved in the research are Helen Le-Niculescu, Ph.D., John I. Nurnberger, M.D., Ph.D. and Howard J. Edenberg, Ph.D. National collaborators in this study are Daniel R. Salomon, M.D. and colleagues from Scripps Research Institute in La Jolla, Calif., and Ming T. Tsuang, M.D., Ph.D. from the University of California, San Diego.



Source: Mary L. Hardin

New Understanding Of Schizophrenia Could Lead To New Treatment Approaches

New research helps bridge an important gap in understanding schizophrenia, providing the best evidence to date that defects in the brain's white matter are a key contributor to the disease, which affects about 1 percent of people worldwide. The findings, published online by the Proceedings of the National Academy of Sciences, also demonstrate how two of the dozen or more genes previously linked with schizophrenia may contribute to the disease.



Prior genetic studies had linked schizophrenia to the genes for neuregulin 1 (NRG1), a growth factor involved in brain development, and erbB4, a receptor on brain cells through which NRG1 exerts its action. But until now it hadn't been shown that alterations in these genes lead to psychiatric disorders. Working in a mouse model, researchers led by Gabriel Corfas, PhD, Kristine Roy, PhD, and Joshua Murtie, PhD, in the Children's Hospital Boston Neurobiology Program now demonstrate, for the first time, that alterations in NRG1-erbB signaling induce pathologic changes in the brain's white matter. They further show that these changes lead to alterations in biochemical signaling and to behaviors suggestive of mental illness.



"We show that causing a defect in white matter is sufficient to cause biochemical and behavioral changes resembling those seen in neuropsychiatric disorders," says Corfas, the study's senior author. "I think this will provide a new way of thinking about the causes of, and possibly, therapies for schizophrenia."



The findings could also have implications for bipolar disorder, which has also been linked with NRG1 and also involves white matter defects, he adds.



Working with mice, the researchers blocked NRG1-erbB signaling in oligodendrocytes - the cells that form the fatty sheath, known as myelin, which insulates nerve fibers. These myelinated nerve fibers make up the brain's white matter. When NRG1-erbB signaling was blocked, the mice had more oligodendrocytes than normal mice, but these cells had fewer branches and formed a significantly thinner myelin sheath around nerve fibers. As a result, the nerve fibers conducted electrical impulses more slowly, the researchers found.



The mice also had changes in the nerve cells that make and use dopamine, a key chemical in the brain that transmits messages from one nerve cell to another. The dopamine system has long been known to be altered in schizophrenia, and is the target of many antipsychotic drugs.



"Changing the white matter in the brain apparently unbalanced the dopamine system, something that also occurs in patients with neuropsychiatric disorders," says Corfas.



Finally, mice whose NRG1-erbB signaling was blocked showed behavioral changes that appeared to be consistent with mental illness. They explored their environment less than normal mice and had reduced social interaction, thought to be a manifestation of so-called "negative" schizophrenic symptoms such as decreased initiative and social withdrawal. The mice also showed behaviors suggestive of anxiety, a symptom seen in patients with schizophrenia and bipolar disorder, and increased sensitivity to amphetamine, also seen in many schizophrenia patients.
















Is it possible to modify NRB1-erbB signaling with drugs, or otherwise protect oligodendrocytes (and white matter) as a way of treating or preventing schizophrenia?



"This is something that should be investigated," says Corfas. "People are thinking about ways to repair white matter as a treatment for multiple sclerosis, which is also a disease of white matter. That research could now be used in thinking about neuropsychiatric disorders."



Schizophrenia is typically diagnosed in late adolescence or early adulthood, but it is almost always preceded by subtle affective, cognitive or motor problems, Corfas adds. "We need to investigate whether the white-matter defects emerge early, before psychotic symptoms are evident," he says. "If they do, that raises the possibility of early diagnosis and preventive treatment."



The idea of schizophrenia arising from white-matter defects may also help explain the timing of its emergence, Corfas notes. Recent evidence suggests that myelination of the prefrontal cortex (a brain area that has been implicated in schizophrenia) occurs not only during infancy and toddlerhood, but also during late adolescence or early adulthood - just when schizophrenia strikes.



"We now need to go back to patients with schizophrenia and see whether those with variants of the NRG1 and erbB4 genes have differences in their white matter," Corfas says. "It may be that there are different kinds of schizophrenia, arising from alterations in different genes, and that directed treatments could be developed for the different forms."



Corfas and colleagues also plan to investigate other genes linked with schizophrenia, studying whether they interact with NRG1-erbB signaling and how they may alter brain function.







The research was funded by the National Institute of Neurological Disorders and Stroke (NINDS), the National Multiple Sclerosis Society, the National Institute of Mental Health (NIMH), NARSAD: The Mental Health Research Association, and an NIH Development Disability Research Center Grant.



Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 11 members of the Institute of Medicine and 10 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 347-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital and its research visit: childrenshospital/newsroom.



Contact: James Newton


Children's Hospital Boston