The special session includes 12 presentations that specifically focus on the most recent and promising research developments that are of interest to the more than 1,000 participants attending the only scientific meeting devoted exclusively to bipolar disorder research.

Highlights of the these "rapid communications" presentations include the following:

CHILDHOOD GAME OF "RED LIGHT, GREEN LIGHT" ADAPTED TO STUDY BRAIN NETWORK IN BIPOLAR PATIENTS
Bipolar disorder is widely associated with behaviors including elation, hyperactivity and impulsive, often reckless behaviors during patients' manic phases. But the specifics about what in the brain actually causes these behaviors are still unclear. Researcher Stephen Strakowski, M.D., of the University of Cincinnati College of Medicine examined brain activity in response to an impulse control task that showed manic bipolar patients may have difficulties modulating the brain regions that monitor task performance, namely, those regions that detect error and promote accurate responses.

Dr. Strakowski noticed such difficulties in studies that used functional magnetic resonance imaging (fMRI), which is useful in mapping changes in the brain that correspond to mental operations. Both manic bipolar patients and healthy subjects were fitted with special goggles through which they viewed random blue letters and occasional targets, indicated by a blue letter X. Subjects were instructed to respond to the blue letter X targets by pressing a button. However, when the letter X turned from blue to red, they were asked to refrain from pressing the button.

STUDY FINDS TWO DRUGS NECESSARY TO TREAT BIPOLAR'S PHASES
While mood stabilizers and antipsychotics are essential for the treatment of bipolar disorder, both the complex nature of this illness and medication side effects pose problems for achieving an effective long-term maintenance therapy.

Researcher Allan Young, Ph.D., and colleagues from the University of Newcastle in Newcastle-upon-Tyne in the United Kingdom, finds that no single medication licensed in either the United States or the U.K. for the treatment of bipolar disorder is effective for treating both the depressive phase and the manic phase of this illness.

Dr. Young's analysis is the first to include all commonly used bipolar medications, with results suggesting the need for a two-pronged pharmacologic approach of both a mood stabilizer and an antipsychotic in order to prevent both depressive and manic recurrences.

ALTERATION IN BRAIN CHEMICAL MAY PROVIDE CLUES INTO CAUSES OF BIPOLAR DISORDER AND LEAD TO NOVEL TREATMENTS
Preliminary research has suggested that during the depressive phase, bipolar II patients have abnormally elevated metabolism, or activity, in specific regions of the brain, providing clues into the causes of the disease and suggesting novel treatment approaches. Bipolar disorder II is characterized by episodes of less severe mania, called hypomania, and major depression.

Using PET imaging, researcher Carlos Zarate, M.D., of the National Institute of Mental Health, studied the brains of patients with bipolar II depression before their symptoms emerged, and repeated the studies after the patients had received a six-week course of the antidepressant pramipexole, a drug that increases neurotransmitter activity by stimulating dopamine receptors.

Compared to patients who received placebo, pramipexole resulted in decreased brain activity in certain regions that in earlier scans had shown high activity, as well as decreased depression and anxiety symptoms. In contrast, pramipexole treatment did not alter metabolism in other brain regions, such as the amygdala, that have been implicated with conventional antidepressants but instead, pramipexole was found to increase activity in the premotor cortex, hippocampus, posterior cingulate cortex, and superior temporal gyrus.

The Sixth International Conference on Bipolar Disorder is being presented by the University of Pittsburgh School of Medicine and Western Psychiatric Institute and Clinic of the University of Pittsburgh Medical Center.

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Bipolar disorder more prevalent and costly than believed; Lithium could curb suicide rate
17-June-2005 - University of Pittsburgh Medical Center
The incidence of bipolar disorder in the general population is considerably higher than earlier studies have indicated, resulting in significantly less productivity and more days lost from work compared to the better known major depressive disorder, according to preliminary findings from a national survey presented today at the Sixth International Conference on Bipolar Disorder.

Another study has found that lithium, one of psychiatry's oldest drugs, may be the most effective solution for preventing suicide in patients with manic-depressive disorder and other types of bipolar disorders. Nearly half of all U.S. suicide deaths each year are in patients with bipolar disorders, in whom the risk is more than 20 times that of the general population.

The new prevalence estimate counts 4.3 percent of adults in the U.S. suffer from a bipolar disorder or "sub-threshold" bipolar disorder, which includes those who don't fit the precise clinical criteria for bipolar disorder but whose symptoms still severely impair their ability to perform daily tasks of living. Previous studies have placed the prevalence at 1 percent.

The findings are included in a new analysis from the National Co-Morbidity Survey Replication (NCS-R), which is the first to examine the prevalence and societal costs of bipolar disorder. As such, the summary of the survey's preliminary results presented by Ronald C. Kessler, Ph.D., professor of health care policy at Harvard Medical School and principal investigator of the NCS-R, bring into sharper focus society's shared burden from bipolar disorder.

Compared to major depressive disorder, bipolar disorder has a significantly greater impact on an individual's ability to go to work or be productive when at work, according to the NCS-R, which included face-to-face interviews with 9,282 U.S. adults. On an annual basis, the mean number of lost days for someone with bipolar disorder is 49.5, versus 31.9 for someone with major depressive disorder. Nationally, bipolar disorder carries a $25,868 billion-a-year price tag, an economic burden not before appreciated, says Dr. Kessler, who believes previous research has over-estimated the societal costs of major depression while underestimating the costs of bipolar disorder.

One significant cost associated with bipolar disorder is suicide, quantifiable in terms of both the loss of human life and its impact on society. Of particular concern is that attempts made by bipolar patients have about a one-in-five chance of being lethal, compared to a one-in-20 attempt-to-suicide rate within the general population.

According to another Harvard researcher, Ross J. Baldessarini, M.D., the number of suicides and attempted suicides, as well as their associated costs, could be reduced significantly in the United States by a return to more widespread use of lithium, as had been more common before the introduction of newer drugs and continues to be standard practice in Europe. The first modern use of lithium to treat mania was more than 55 years ago.

Dr. Baldessarini, a professor of psychiatry at Harvard Medical School, and his team conducted a comprehensive, quantitative review of studies comparing rates of suicides and attempts among patients who were undergoing different treatments, receiving a placebo as part of a clinical trial or receiving no treatment at all.

Patients taking lithium had an 80 to 85 percent lower rate of attempts or completed suicides compared to patients with manic-depressive illness not being treated with lithium, with strikingly consistent findings across a large number of dissimilar studies.

"The effect that bipolar disorder has on individuals, their families, the work place – society as a whole cannot be underestimated. While it's troubling that we are learning the burden is much greater than we even realized, we can take steps to reduce some of the hardship. One approach that may make sense, and which appears could help reduce the burden associated with suicide, is a lithium-based treatment," commented Ellen Frank, Ph.D., professor of psychiatry at the University of Pittsburgh School of Medicine.

Held every two years, the International Conference on Bipolar Disorder is the only venue in the world devoted exclusively to highlighting new research into bipolar disorder. The Sixth Conference is being held June 16 to 18 at the David L. Lawrence Convention Center, located in the heart of downtown Pittsburgh, and is being sponsored by the University of Pittsburgh School of Medicine and Western Psychiatric Institute and Clinic of the University of Pittsburgh Medical Center.

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Research zeros in on bipolar disorder genes, link with thyroid condition
16-June-2005 - University of Pittsburgh Medical Center
Despite an intensive effort, researchers have yet to identify the genes that cause bipolar disorder, yet the practical benefits of such a discovery could reap rich rewards for those suffering from the mental illness.

New research findings presented today at the Sixth International Conference on Bipolar Disorder suggest specific genetic linkages that are associated with the mental illness, bringing researchers much closer to finding the elusive gene or genes. Another study finds an association between an abnormal thyroid condition and bipolar disorder, pointing to the possibility that a simple blood test could help identify those at risk.

To further investigate more specific genetic linkages, Marion Leboyer, M.D., Ph.D., of the University of Paris Faculty of Medicine, studied 87 bipolar sibling pairs from 70 European families who were participants in the European Collaborative Study on Early Onset Bipolar Affective Disorder and identified eight regions of genetic linkages that, while not necessarily the sole or unique ones associated with this disease, zeroed in on what may be the specific genes that predispose individuals to early onset of this debilitating disease.

According to Dr. Leboyer, his studies of families with members who developed the illness as children or adolescents reduces those genetic and clinical variabilities that can complicate efforts to identify susceptibility genes. Finding these genes would help researchers develop more effective treatments or even prevent the disorder from occurring in at-risk individuals.

Other genetic clues come from results of two related studies involving adolescent and young adult offspring of bipolar parents and of twins with bipolar disorder, suggesting a genetic link between bipolar disorder and an abnormal thyroid condition.

Willem Nolen, M.D., Ph.D., of the University of Groningen Medical Centre, Netherlands, found that bipolar patients were twice as likely as healthy subjects to develop autoimmune thyroiditis (AT). Among the offspring of parents with bipolar disorder, who usually have an increased prevalence of bipolar and other mood disorders, there also was an increased prevalence of AT. Surprisingly, this finding did not seem to be related to whether their offspring themselves had been diagnosed with a psychiatric illness.

Among identical twins (who share all their genes) with at least one twin having bipolar disorder, prevalence of AT was increased in the other twin, irrespective of whether the other twin also had bipolar disorder. However among fraternal twins (who share 50 percent of their genes) with at least one fraternal twin having bipolar disorder, prevalence of AT was increased only in the other fraternal twin who also had bipolar disorder, but was not increased in the fraternal twin without the illness.

Dr. Nolen's research highlights the increasing importance of identifying endophenotypes – clinical information unique to certain groups of individuals that may be predictive of risk for disease and course of illness. Although associated genes for bipolar disorder and AT have yet to be identified, AT may be an endophenotype for bipolar disorder. As such, the findings suggest that relatives of patients with bipolar disorder not only inherit the vulnerability for bipolar disorder and other mood disorders, but that some also may share the genetic vulnerability for developing AT.

If proven valid in further studies, the research suggests that members of families in which bipolar disorder occurs could be tested for autoimmune thyroiditis by means of a simple blood analysis, thereby helping to identify those who also may be at risk for developing bipolar disorder.

"Why hasn't a gene for bipolar disorder been identified when clearly the illness affects some families more than others and what is science telling us about who is most vulnerable and how the onset of the illness can be prevented? While a number of genes have been suspected to be associated with bipolar disorder, we thus far have failed to isolate any definitive bipolar gene, but are making sure progress that will ultimately bring answers about how and why this debilitating disease affects so many. By exploring these genetic connections, we inch closer to surer diagnosis and more rational and effective treatments," commented Michael Thase, M.D., professor of psychiatry at the University of Pittsburgh School of Medicine.

Held every two years, the International Conference on Bipolar Disorder is the only venue in the world devoted exclusively to highlighting new research into bipolar disorder. The Sixth Conference is being held June 16 to18 at the David L. Lawrence Convention Center, located in the heart of downtown Pittsburgh, and is being sponsored by the University of Pittsburgh School of Medicine and Western Psychiatric Institute and Clinic of the University of Pittsburgh Medical Center.

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Research links heavy drinking and increased mental health risk
7-July-2005 - Research Australia
Women who drink to excess are more likely to experience depression and anxiety according to new research.

Work done by Dr Rosa Alati, a research fellow from The University of Queensland's School of Population Health, and colleagues from UQ and the University of Bristol, showed women who have more than 15 drinks a week have an increased risk of experiencing mental illness.

However Dr Alati said heavy drinking was also linked to smoking and women from low income groups were more likely to be heavy drinkers.

"In part these relationships may be responsible for the association between heavy drinking and symptoms of anxiety and depression," Dr Alati said.

The research is part of the Mater–University of Queensland Study of Pregnancy (MUSP), which is Australia's largest longitudinal study tracking mothers and their children from pre-birth to early adulthood.

Dr Alati said light drinking – up to 5 drinks per week – was associated with the lowest rates of anxiety and depression when women were in their early 30s.

But at all three assessments, conducted when women were aged in their 20s, 30s and 40s, showed those who drank six or more drinks per week were more likely to have symptoms of depression and anxiety than those drinking less.

"For women in their 20s and 40s the lowest rates of symptoms were in those who did not drink any alcohol," she said.

She said the latest results point to a varying relationship between alcohol and depression and anxiety over the course of a woman's life .

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Ontario's mental health care evaluated: U of T report focuses on hospital care
27-May-2005 - University of Toronto
For the first time, Ontario hospitals have common information to help assess the quality of in-patient mental health care, with the release of a new Hospital Report by the University of Toronto-based Hospital Report Research Collaborative.

Hospital Report 2004: Mental Health is part of an ongoing series of reports on hospital care funded by the Ontario government and the Ontario Hospital Association. The researchers compiled the report after analysing data from a variety of sources.

"Including mental health in the hospital report series is a big step forward in acknowledging the treatment needs of those with mental illness," says Dr. Elizabeth Lin, who led the research team along with U of T Department of Psychiatry colleague Dr. Janet Durbin.

The report examines the overall performance of 11 psychiatric hospitals and 45 acute-care facilities in all five regions of Ontario: the north, the east, the Greater Toronto Area, the south and the southwest. In total, these facilities provide almost 1.5 million days of psychiatric care, about 25 per cent of the total days of hospital care provided in Ontario. The results are reported by region, not by individual hospital; the next mental health report in the series, slated for 2007, will provide performance data for individual hospitals.

"The introduction of this first-of-its-kind report on mental health is a positive step forward in enhancing these services across the province," says Hilary Short, president and CEO of the Ontario Hospital Association. "This report demonstrates yet another way Ontario hospitals are working with the government to lead accountability in the country."

"Overall, the news is good," agrees George Smitherman, Minister of Health and Long-Term Care. "The findings in this report indicate that for the most part patients are receiving quality mental health care. But there is always room for improvement, particularly in the area of mental illness, which for too long in our society has received neither the attention nor the understanding it requires, and that our patients deserve."

In general, the care being provided by Ontario hospitals conforms with the aims of mental health reform. However, the report identifies four key areas where more progress is possible.

Patient participation:

About 75 per cent of clients participate in discharge planning.

79 per cent of facilities/programs have clients or families represented on their steering and advisory committees. Continuity of care:

Most hospitals have partnered in some way with community providers to improve patient care, but only 52 per cent of discharged patients receive medical follow-up in the community within 30 days of discharge.

22 per cent of discharged patients are either readmitted within 30 days or visit the emergency room. Regional variation:

Regional variation in performance is considerable; while each region demonstrated strengths and weaknesses, the north scored lowest in many areas. Delivering evidence-based care:

Hospitals offer considerable support to staff for continuing education and training; but only about half the programs/hospitals report routine use of standardized care delivery approaches based on best practices.

Only 27 per cent of facilities use feedback from clients to improve program quality.

"This report provides information that will enhance our understanding of mental health care across the province," says Cliff Nordal, president and CEO of St. Joseph's Health Care in London, one of the participating hospitals. "While researchers acknowledge that there is more work to be done in future years to enhance the quality and meaningfulness of the data used to evaluate mental health care, this report is a clear signal that good progress has been made."

While highlighting areas where hospitals perform well, the data also point to areas where improvement is necessary. The suggestions for improving care include:

Regions and the province need to ensure that a continuum of supports is in place to assist clients upon discharge.

Hospitals need to improve the implementation of standardized, evidence-based approaches for delivering care.

Increased consumer participation in care planning should be promoted.

Strategies are needed to increase access to community care in the north.

"All five regions have strengths and weaknesses, so the hospitals have opportunities to learn from each other," says Dr. Durbin. "There is room for improvement province-wide and we hope these data will provide hospitals with a starting point."

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Association between depression severity and poor glycemic control among Hispanics with diabetes
26-May-2005 - Columbia University's Mailman School of Public Health
In a study of more than 200 Hispanics with diabetes, researchers at Columbia University's Mailman School of Public Health and College of Physicians and Surgeons found a significant association between depression severity and poor glycemic control (PGC). The findings also confirm that less than one-half of the diabetes patients with moderate or severe depression received mental health treatment in the previous year.

"We found a steady increase in the probability of PGC with advancing categories of depression severity," according to Raz Gross, MD, MPH assistant professor of Epidemiology and Psychiatry at Columbia University's Mailman School of Public Health and College of Physicians and Surgeons and principal author of the study. "This held especially true among patients with moderate-severe depression, where likelihood for PGC was more than three-fold higher compared to patients without depression." No association was found between depression and PGC among the non-Hispanic diabetes patients.

According to Dr. Gross, there is ample evidence that among the population, in general, depressive disorders are more prevalent among adults with diabetes. However, the relationship between depression and glycemic control in patients with diabetes is less obvious. Hispanics have high rates of diabetes and are more likely to have poor glycemic control. Diabetes ranks fifth among the leading causes of death in people of Hispanic origin. Earlier research has indicated that Hispanic patients are usually less likely to have regular sources of medical care, to undergo screening, to use preventive services, to be referred to a specialist, or to receive appropriate treatment.

Says Dr. Gross, "There are important clinical and public health implications to our finding. As rates of diabetes, especially among Hispanics, continue to increase, it is important for clinicians caring for patients with diabetes to be aware of the association between depression and PGC. Our findings suggest that identification and adequate treatment of depression in this understudied, high-risk population of Hispanic primary care patients might have favorable effects on diabetic outcomes."

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Beyond lithium for bipolar disorder
23-May-2005 - Cell Press
While lithium treatment has proven to be a godsend for many of the two million Americans with bipolar disorder, it is not without its downside. People on the drug may develop hypothyroidism, tremors, cognitive impairment, and excessive thirst and urination and gain weight.

However, better treatments for bipolar disorder depend on a better understanding of the still-mysterious mechanism by which lithium damps the highs and lows of the disorder. Now, researchers led by Philip Brandish of Merck & Co., Inc., and Edward Scolnick of the Broad Institute (formerly of Merck and Co., Inc.) have identified genes whose activity appears to be switched on by lithium, suggesting more direct targets for drugs to treat the disorder.

Lithium is known to inhibit the production of an important cellular switch, called inositol monophosphate, so the researchers set out to find genes that were activated by this inhibition. They treated slices of rat brain with lithium chloride as well as a chemical that depletes inositol. The also treated other slices with the two chemicals, but added inositol.

The researchers used DNA microarrays--so-called "gene chips"--to detect genes that were unequivocally activated when inositol was depleted in the brain slices.

They discovered several genes that they concluded "suggest new directions toward the treatment of bipolar disorder."

The behavior of one such activated gene, called GPR88, has been found to be associated with a rat model of mania, they said. This gene codes for a protein that is an "orphan receptor"--that is, its cellular function in sensing external chemical signals is unknown.

The researchers also found that the gene called AD-CYAP1 was upregulated in the treated brain slices. This gene codes for a signaling molecule called PACAP in the brain and is known to be close to a chromosomal region that genetic studies have shown to be associated with a higher risk of bipolar disorder.

PACAP protein is found throughout the central nervous system, said the researchers. They cited studies demonstrating that mice in which the gene is knocked out show hyperactivity and defects in their circadian (day-night) behavior--both also characteristic of humans with bipolar disorder. Also, in animals, lithium has been shown to affect such circadian behavior. The protein also has been found to affect the activity of a key neurotransmitter, dopamine, in the brain, said the researchers. What's more, they found two other genes--PAM and GCH--that are involved in producing PACAP to be upregulated in the treated brain tissue.

Brandish and his colleagues said that such findings "suggest a coordinated upregulation of genes leading to increased dopamine signaling. In the light of the recent clinical data and human genetic linkage, it is tempting to speculate that PACAP night be a therapeutic effector of lithium in bipolar disorder."

They concluded that "the data presented here warrant further investigation of PACAP signaling in the brain and of the orphan receptor GPR88 as potential new targets in bipolar disorder."

Philip E. Brandish, Ming Su, Daniel J. Holder, Paul Hodor, John Szumiloski, Robert R. Kleinhanz, Jaime E. Forbes, Mollie E. McWhorter, Sven J. Duenwald, Mark L. Parrish, Sang Na, Yuan Liu, Robert L. Phillips, John J. Renger, Sethu Sankaranarayanan, Adam J. Simon, and Edward M. Scolnick: "Regulation of Gene Expression by Lithium and Depletion of Inositol in Slices of Adult Rat Cortex"

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Depression gene may weaken mood-regulating circuit
8-May-2005 - NIH/National Institute of Mental Health

Areas in the cingulate (right) and amygdala (left) that differed in gray matter volume between subjects with the short and long version version of the serotonin transporter gene. Short version carriers showed the greatest reductions in the red area, which previous studies have linked to depression.
Click here for a high resolution photograph.

A brain scan study suggests that a suspect gene may increase susceptibility to anxiety and depression* by weakening a circuit for processing negative emotion. People with the depression-linked gene variant showed less gray matter and weaker connections in the mood-regulating circuit. How well the circuit was connected accounted for nearly 30 percent of their anxious temperament, researchers at the National Institute of Health's (NIH) National Institute of Mental Health (NIMH) found. Dr. Daniel Weinberger and colleagues report on their brain imaging genetics study in the May 8, 2005 online edition of Nature Neuroscience.

"We discovered the mood-regulating circuit by using the gene to interrogate the imaging data," explained Weinberger. "The brain handles information much like an orchestra. So we asked questions akin to 'Are the violin and the clarinet playing the same tune and to what extent might this gene account for it?'"

In this case, it turned out that the amygdala, a fear processing hub deep in the brain and the cingulate, an emotion-dampening center located near the front of the brain, were playing a duet under the baton of the depression-linked gene.

The gene codes for the serotonin transporter, the protein in brain cells that recycles the chemical messenger after it's been secreted into the synapse, the gulf between cells. Since the most widely prescribed class of antidepressants act by blocking this protein, researchers have focused on possible functional consequences of a slight variation in its DNA sequence across individuals. Everyone inherits two copies of the gene, one from each parent, which comes in two common versions: short and long. The short version makes less protein, resulting in less recycling, increased levels of serotonin in the synapse, and more serotonin-triggered cellular activity. Previous NIMH-supported studies had shown that inheriting the short variant more than doubles risk of depression following life stresses,** boosts amygdala activity while viewing scary faces,*** and has been linked to anxious temperament. Yet, how it works at the level of brain circuitry remained a mystery.

The NIMH research team first scanned 114 healthy subjects using magnetic resonance imaging (MRI). Those with at least one copy of the short variant had less gray matter, neurons and their connections, in the amygdala-cingulate circuit than those with two copies of the long variant.

Subjects with two copies of the long version (LL) of the serotonin transporter gene showed more functional connectivity between the amygdala (yellow) and the Cingulate (red, blue), which are key components of a mood-regulating circuit.. Source: NIMH Clinical Brain Disorders Branch
Click here for a high resolution photograph.

Next, using functional magnetic resonance imaging (fMRI), the researchers monitored the brain activity of 94 healthy participants while they were looking at scary faces, which activates fear circuitry. Those with the short variant showed less functional connectivity, in the same circuit.

Nearly 30 percent of subjects' scores on a standard scale of "harm avoidance," an inherited temperament trait associated with depression and anxiety, was explained by how well the mood-regulating circuit was connected.

"Until now, it's been hard to relate amygdala activity to temperament and genetic risk for depression," said Dr. Andreas Meyer-Lindenberg, a lead author. "This study suggests that the cingulate's ability to put the brakes on a runaway amygdala fear response depends upon the degree of connectivity in this circuit, which is influenced by the serotonin transporter gene."

Since serotonin activity plays a key role in wiring the brain's emotion processing circuitry during early development, the researchers propose that the short variant leads to stunted coupling in the circuit, a poorly regulated amygdala response and impaired emotional reactivity – resulting in increased vulnerability to persistent bad moods and eventually depression as life's stresses take their toll.

Other members of the NIMH team were: Dr. Lukas Pezawas, Dr. Bhaskar Kolachana, Dr. Michael Egan, Dr. Venakata Mattay, Emily Drabant, Beth Verchinski, and Karen Munoz. Dr. Ahmad Hariri, University of Pittsburgh, also participated in the study.

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The relationship between clinical depression and chronic pain
5-May-2005 - John Wiley & Sons, Inc.
Does clinical depression bring about chronic pain? Or does pain lead to depression? Because these two conditions frequently co-exist--30 to 54 percent of patients with major depressive disorder also suffer persistent physical pain--there has been much speculation about whether one causes the other or whether a common underlying factor provokes both. Results of studies into the precise nature of this relationship, however, have been inconsistent.

To gain a clearer understanding of the depression-pain connection, researchers affiliated with the University of Michigan and the University of Cologne, Germany, focused on the underlying mechanisms in the perception of pain, physical and emotional: the brain. Their findings, featured in the May 2005 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), challenge existing notions on the interplay of emotion and sensation and have important implications for treating depression and pain as separate conditions, even when they occur simultaneously.

The study focused on 53 patients, 33 women and 20 men, with fibromyalgia (FM). This syndrome is characterized by intense widespread pain and tenderness to touch and is often accompanied by depression. Using this patient population, the research team set out to evaluate whether higher levels of symptoms of depression are associated with increased sensitivity to pressure-induced pain, as well as to determine which regions of the brain are involved in processing acute pain, chronic pain, and depressive symptoms. 42 healthy controls, 20 women and 22 men, were also included in the study. The mean age was 42 for the FM patients and 38 for the controls.

Conducted at Georgetown University's General Clinical Research Center, the study began by assessing the severity of chronic pain and depression in FM patients, through a combination of interviews, questionnaires, and measurement scales. The following day, all subjects, both FM patients and controls, participated in pressure-pain sensitivity experiments, involving the application of pressure to a thumbnail. To get a clear picture of the brain's response to painful stimuli, all subjects underwent magnetic resonance imagining (MRI) scans, before, during, and after the pressure-sensitivity sessions. FM patients were required to discontinue antidepressant medications 4 weeks prior to the study, as well as refrain from using any drugs for pain, including over-the-counter analgesics, starting 3 days before the study.

Based on the MRI results, the researchers found that FM patients required significantly less applied pressure than healthy controls to activate neurons associated with acute pain in the brain's sensory domain. This heightened sensitivity applied to FM patients in general, regardless of whether they had been diagnosed with major depressive disorder or reported any depressive symptoms. Furthermore, the researchers found only a weak correlation between the sensory regions of the brain associated with chronic pain and the affective or emotional regions of the brain associated with depression.

"Much has been made of the overlap and similarities between pain and symptoms of depression, but these and other data suggest it is also important to identify pain-processing mechanisms that are independent of mood," notes the study's leading author, Thorsten Giesecke, M.D. "The notion that sensory and affective aspects of pain may be independently processed is not just of theoretical interest," he adds.

"Evaluation of these sensory and affective dimensions in patients with chronic pain is likely to improve diagnosis, choice of treatment, and treatment efficacy." As this study affirms, prescribing a standard antidepressant medication will not necessarily relieve the suffering of a depressed patient whose pain is not only real but also intensely physical.

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'Promiscuous' area of brain could explain role of antidepressants
7-Apr-2005 - Baylor College of Medicine
A study at Baylor College of Medicine in Houston may lead to a better understanding of how antidepressants like Prozac work – and how to make them more effective.

According to results published in today's issue of the journal Neuron, a study in mice proposes that dopamine and serotonin neurotransmitter systems in the brain occasionally get their signals crossed, causing delays in stabilizing mood.

"This study provides a new site for drug discovery in one of the biggest market for drugs – those that treat symptoms of depression," said Dr. John Dani, professor of neuroscience at BCM and lead author of the study.

Dani's study, funded by the National Institutes of Health, offers an alternative explanation for the delayed effect of most antidepressants.

"Some scientists thought that you had to take an antidepressant for weeks because as serotonin is elevated, some of its receptors had to turn off and become desensitized rather than be stimulated," Dani said. "That didn't make a lot of sense to us since desensitization is usually a rapid mechanism."

Serotonin and dopamine neurotransmitter systems, which factor heavily in regulating mood, emotional balance, and psychosis, are released and reabsorbed in the striatum, an area of the brain which affects motivation and reward-based learning. Dani's findings indicate that these systems may be less selective and more "promiscuous" than previously believed.

"There has been a fundamental principal in neuroscience that a neuron releases one neurotransmitter," said Dani. "We have come to realize that neurotransmitters aren't the perfect 1-to-1signalers that we assumed – they're a little promiscuous. That is, rather than transporting one neurotransmitter, these systems may transport other neurotransmitters as well."

A better understanding of how antidepressants work would come as welcome news to those who suffer from depressive disorders, a leading cause of disability worldwide. Over 14 million adults experience depression each year in the United States alone.

"Instead of taking serotonin up as they normally would into serotonin neurons, it is taken up into the terminals for dopamine so that now when your neurons fire to send a dopamine signal, they're actually also sending a little bit of a serotonin signal," Dani said. "This kind of interaction among neurotransmitter systems alters the timing of how these neurotransmitter systems act, and in that way, it certainly impacts how you process information."

Depression is commonly treated with selective serotonin reuptake inhibitors (SSRIs) like Prozac to elevate and prolong the presence of the neurotransmitter serotonin in the brain. By blocking the uptake of serotonin after its initial release, conventional antidepressants provide the brain more serotonin for a longer period of time. An alternative approach suggested by this study is to develop antidepressant treatments that help serotonin enter dopamine terminals.

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Study shows light therapy to effectively treat mood disorders, including SAD
4-Apr-2005 - University of North Carolina School of Medicine
A study commissioned by the American Psychiatric Association and led by a psychiatrist at the University of North Carolina at Chapel Hill School of Medicine has found that light therapy effectively treats mood disorders, including seasonal affective disorder (SAD) and other depressive disorders.

A report of the study, which appeared April 1 in the American Journal of Psychiatry, also finds that the effects of light therapy, also known as phototherapy, are comparable to those found in many clinical studies of antidepressant drug therapy for these disorders.

The findings were based on a meta-analysis, a systematic statistical review of 20 randomized, controlled studies previously reported in the scientific literature. These represented only 12 percent of 173 published studies that the authors had originally considered for review.

"We found that many reports on the efficacy of light therapy are not based on rigorous study designs. This has fueled the controversy in the field as to whether or not light therapy is effective for SAD or for non-seasonal forms of mood disorders," said lead author Dr. Robert Golden, professor and chairman of psychiatry at UNC and vice dean of the medical school.

"But when you throw out all the studies that are methodologically flawed and then conduct a meta-analysis of those that are well-designed, you find that light therapy is an effective treatment not only for SAD but also for depression."

The use of bright artificial light for people with SAD, a recurring depression that develops in the fall or winter and spontaneously disappears during spring or summer, was first described in the Archives of General Psychiatry in 1984. Since then, the treatment has been tried in clinical and research programs for non-seasonal mood disorders, Alzheimer's disease, jet lag, insomnia, eating disorders and other behavioral problems.

A more recent light therapy approach is "dawn simulation," which attempts to simulate an earlier dawn through exposure to artificial light. This follows the theory that SAD is triggered by the reduced period of bright daylight during winter.

The method attempts to recreate the increased intensity of sunlight that occurs in nature in the summer when the sun rises earlier in the day. "The logic here is that it might put people with seasonal affective disorder into remission," Golden said.

Still, the exact mechanisms by which light therapy works remain unclear, the researchers said.

The studies selected by the authors for inclusion in their meta-analysis were grouped into four categories: bright light for SAD, bright light for non-seasonal depression, dawn simulation for SAD and bright light as an adjunct therapy combined with conventional antidepressants for non-seasonal affective disorder.

These study groups were limited to adults ages 18 to 65 years who met a criterion-based mood disorder diagnosis.

The meta-analysis demonstrated statistically significant treatment effects for SAD, dawn simulation for SAD and bright light treatment of non-seasonal depression, the report said.

"The effect size of the light therapy intervention in our meta-analysis was comparable to what has been described in the clinical literature for conventional medications to treat depression," Golden said. "The findings are as strong or as striking."

More research is needed on the safety of light therapy, particularly among children and the elderly, Golden said. The study did not look at safety or adverse effects, as very few reports contain controlled, or comparison, data on side effects or toxicity, the authors reported.

In addition, they added, the responses of children, adolescents and the elderly to light therapy may differ, compared to non-geriatric adults. For example, at each end of the age spectrum, the requirements for light therapy dosing might differ. Also, children and adolescents may need lower doses than the elderly. "And if eye problems such as cataracts are more prevalent among the elderly, might light therapy aggravate the problem, even slightly?", Golden added.

As to efficacy of light therapy for SAD and other non-seasonal depressive mood disorders, Golden said this study largely answers the question: The treatment is effective.

"The study also points to the importance of conducting systematic literature reviews in areas of controversy using well-defined standards of what constitutes good study design, and to follow this up with meta-analyses so that the data can speak for themselves. "And when you can separate the wheat from the chaff, the findings are much more valid."

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Cognitive therapy works as well as antidepressants, but with lasting effect after therapy ends
4-Apr-2005 - University of Pennsylvania
Cognitive therapy to treat moderate to severe depression works just as well as antidepressants, according to an authoritative report appearing today in the Archives of General Psychiatry. The study, conducted by researchers at the University of Pennsylvania and Vanderbilt University, challenges the American Psychiatric Association's guidelines that antidepressant medications are the only effective treatment for moderately to severely depressed patients.

Either form of treatment worked significantly better than a placebo, but the researchers demonstrated that cognitive therapy was more effective than medication at preventing relapses after the end of treatment.

"We believe that cognitive therapy might have more lasting effects because it equips patients with the tools they need to learn how to manage their problems and emotions," said Robert DeRubeis, professor and chair of Penn's Department of Psychology. "Pharmaceuticals, while effective, offer no long term cure for the symptoms of depression. For many people, cognitive therapy might prove to be the preferred form of treatment."

The study, which follows years of debate on the relative merits of cognitive therapy versus medication for more severe forms of depression, is the largest trial yet undertaken on the topic; it involved 240 depressed patients. The patients were randomly placed into groups that received cognitive therapy, antidepressant medication or a placebo. Patients in the antidepressant group, which was twice as large as the other two, were treated with paroxetine (Paxil). Lithium or desipramine was also given, as necessary.

After 16 weeks of treatment, patients in both the medication and cognitive therapy groups showed improvement at about the same rate; however, cognitive therapy patients were less likely to relapse in the two years following the end of treatment. According to the researchers, the return of symptoms might demonstrate that the medication may have blunted the appearance of depression but did not affect underlying disease processes.

"Medication is often an appropriate treatment, but drugs have drawbacks, such as side effects or a diminished efficacy over time," DeRubeis said. "Patients with depression are often overwhelmed by other factors in their life that pills simply cannot solve. In many cases, cognitive therapy succeeds because it teaches the skills that help people cope."

The researchers also noted slight differences in the response to treatment between the two testing locations, with cognitive therapy performing better at Penn and medications performing better at Vanderbilt. Researchers surmise that the medication worked so well at the Vanderbilt clinic because more of the patients there were markedly anxious, in addition to being depressed, and the medications used in the research have anti-anxiety properties.

The researchers further believe that cognitive therapy patients might have done better at Penn due to the experience level of the therapists involved. Just as the experience of therapists may be important in cognitive therapy, so, too, can the expertise of prescribing physicians play a role in the success of antidepressant medication treatment. Studies have shown that antidepressant medication dosages are still largely a matter of physicians' discretion.

"Clearly, cognitive therapy is not for everyone, and its success could depend on variables such as the expertise of the therapist and the patient's willingness or ability to take the therapy to heart," DeRubeis said. "The key to establishing any form of treatment is rating its effectiveness in comparison to treatments currently in use, and this study has shown cognitive therapy to be a viable alternative."

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Beyond lithium for bipolar disorder
23-Mar-2005 - Cell Press
While lithium treatment has proven to be a godsend for many of the two million Americans with bipolar disorder, it is not without its downside. People on the drug may develop hypothyroidism, tremors, cognitive impairment, and excessive thirst and urination and gain weight.

The researchers used DNA microarrays--so-called "gene chips"--to detect genes that were unequivocally activated when inositol was depleted in the brain slices.

They discovered several genes that they concluded "suggest new directions toward the treatment of bipolar disorder."

They concluded that "the data presented here warrant further investigation of PACAP signaling in the brain and of the orphan receptor GPR88 as potential new targets in bipolar disorder."

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Single mothers at higher risk for depression
17-Mar-2005 - Blackwell Publishing Ltd.
A recent study showed that low-income single mothers have a very high prevalence of depressive symptoms. This research, led by Ann Peden, ARNP, BC, DSN at the University of Kentucky College of Nursing was focused on 205 volunteer women with children between the ages of 2 and 6 who were at high risk for depression.

Participants' survey results showed that more than 75% scored in the mild to high range of depressive symptoms based on well-know measurement scales. Results support previous research in this area that low- income single mothers reported a high level of depressive symptoms including negative thinking and chronic stressors. The resulting depression could interfere with their ability to parent, seek education and employment as well as significantly affect the entire families' quality of life.

This study, published in a recent issue of Journal of Nursing Scholarship suggests that with nursing intervention for depressive symptoms – particularly negative thinking – the rate at which these at-risk women develop depression could be decreased. Depression is the number one mental illness in the United States costing an estimated $44 billion with employers reporting depression as the most costly illness. Women are twice as likely as men to suffer from depression.

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Study shows depressed heart disease patients fail to take prescribed life-saving medication
9-Mar-2005 - Columbia University College of Physicians and Surgeons
Depression is known to be "hard on the heart" – now researchers are a step closer to understanding why. A new Columbia University Medical Center study examining potential links between depression and heart disease found that heart disease patients who showed symptoms of depression were substantially less adherent to taking a prescribed medicine than patients without depression. Patients who continued to show signs of depression three months after a heart attack or angina only took prescribed medications 67 percent of the time, compared to almost 90 percent in non-depressed patients.

The research, which was presented for the first time at the 63rd American Psychosomatic Society Annual Meeting is part of the Coronary Psychosocial Patient Evaluation Study (COPES), a multi-site, multi-project consortium that is funded by the National Heart, Lung, and Blood Institute. According to Karina W. Davidson, Ph.D., assistant professor of medicine at Columbia University Medical Center and principal investigator of the study, it was known that depression in heart disease patients increases the risk of death after a heart attack, but the explanation for the link had remained unclear until now.

"Taking your medication as prescribed is crucial for improving your chances of good recovery after a heart attack but many doctors struggle with getting patients to take their medication on schedule," said Dr. Davidson. "Our study was designed to test if depression may be a significant factor in reducing adherence, thus potentially explaining why depression carries such a negative prognosis for the heart disease patients."

The study showed that patients who were not depressed in hospital were highly adherent – they took the correct dosage of aspirin on 88% of all monitored days. The researchers then divided the depressed patients into 2 subgroups: those who remained depressed 3 months after the ACS, and those whose depressive symptoms had remitted by then. Only patients with persistent levels of depression significantly differed in their level of adherence from non-depressed patients: they took the correct dosage only 2/3 or 67% of the time, as compared to 86% in patients whose depressive symptoms spontaneously remitted after 3 months.

"This is a huge difference that could have an impact on patient survival", concludes Dr. Davidson. "Moreover, it is of great significance to cardiologists and their patients, since medication adherence is a relatively simple, potentially modifiable behavior."

The study objectively measured adherence to aspirin, a standard medication in heart disease patients, by using an electronic Medication Event Monitoring System (MEMS) - an electronic device stored in the cap of a pill bottle that records the date and time whenever the cap is opened. The study included 53 patients from the coronary care and cardiac care step-down units of three university hospitals who had survived an Acute Coronary Syndrome (ACS), which includes either a heart attack or documented unstable angina.

Dr. Davidson's research will continue to examine the link between depression and heart disease by examining whether effectively treating depression in these patients will result in better medication adherence and subsequently a decrease in mortality.

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Olfactory receptor cells may provide clues to psychiatric disease: Nose cells provide a window into the brain
1-Mar-2005 - Monell Chemical Senses Center
In the first study to examine living nerve cells from patients with psychiatric disease, scientists from the Monell Chemical Senses Center, the University of Pennsylvania, and collaborating institutions report altered nerve cell function in olfactory receptor neurons from patients with bipolar disorder.

Like other psychiatric and neurodegenerative disorders, bipolar disorder affects nerve cells in the brain, making it difficult to study underlying neurobiological causes of the disease during its actual course.

According to senior author Nancy Rawson, PhD, a Monell cellular biologist, "Previous studies have used non-nerve cells, such as fibroblasts or red blood cells, to examine how cells function in patients with bipolar disorder. But since this is a psychiatric disorder, we need to understand what's going on in nerve cells."

Olfactory receptor neurons (ORNs), located in a small patch of epithelium inside the nose, are nerve cells that contain receptors for the thousands of odorant molecules detected by humans. Easily obtained using a simple 5-minute biopsy procedure, ORNs share many characteristics with nerve cells in the brain. These features make ORNs a useful model to study the neural effects of psychiatric disease.

Calcium is integral to properly-functioning nerves, and previous studies have implicated dysfunctions of cellular calcium metabolism as a contributing factor to bipolar disorder. Changes in how much calcium is inside ORNs and other nerve cells tell researchers how the nerves respond to stimulation.

In the study, researchers used a fluorescence imaging technique to measure basal and stimulated calcium levels in ORNs from 17 patients with bipolar disorder and age- and sex-matched healthy controls. Seven patients were medication free and 10 were being treated with mood-stabilizing drugs.

Calcium responses were predominantly decreased in nerves from patients with bipolar disease. Rawson comments, "The deceased calcium responses point to a specific set of pathways that will allow us to narrow the target for identifying the defect of calcium regulation associated with bipolar disorder. Once identified, these pathways will provide new targets for drug development."

The researchers regard the ORNs as a valuable model which will provide needed insight into the neurobiological factors underlying psychiatric disease.

Rawson notes, "The calcium dysregulation that we see in ORNs of bipolar patients is different from what has previously been reported in studies using non-neuronal cells. This suggests that nerve cells might behave differently from other cell types."

Lead author Chang-Gyu Hahn, MD, PhD, a psychiatrist at the University of Pennsylvania School of Medicine, observes, "A major issue in treating bipolar disorder – or psychiatric disorders in general – is that it is hard to predict which medication a patient will respond to. So, clinicians go through a series of trials and errors and the patient suffers until the right medication is found. It is possible that ORNs might be developed as a 'medication responsiveness test' to indicate which medication a patient should be on."

Hahn continues, "Another strength of this approach is that we can sample neurons from patients during specific stages of the illness and therefore we will be able to distinguish trait from state dependent characteristics of the disorder, which is particularly important in understanding mood disorders. "

Co-lead author was Monell neurobiologist George Gomez, PhD, currently at the University of Scranton. Also contributing to the studies were Diego Restrepo, PhD, University of Colorado; Eitan Friedman, PhD, MCP Hahnemann University; Richard Josiassen, PhD, Arthur P. Noyes Research Foundation and University of Pennsylvania; Edmund A. Pribitkin, MD and Louis Lowry MD, Thomas Jefferson University; and Robert J. Gallop, West Chester University.

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Brain stimulation treats resistant depression
28-Feb-2005 - Cell Press
Electrical deep brain stimulation can dramatically alleviate depression that is resistant to other treatments, researchers have found in an initial study on six patients. The finding is important, they said, because up to 20 percent of patients with depression fail to respond to standard treatments--requiring combinations of antidepressant drugs, psychotherapy, and electroconvulsive treatment (ECT) that still may fail. The number of resistant depression patients can be large, since depression is the leading source of disability in adults under age 50 in North America.

The 6 month study led by Helen Mayberg of Emory University School of Medicine and colleagues showed that the patients reported immediate improvements in mood when the electrical stimulation of a few volts was applied to the implanted electrodes. These effects persisted in four of the patients for the full 6 months, with three patients achieving remission or near remission of the depression. No psychological side effects were reported, and other adverse effects were limited to minor infections around the implant site, which were treatable with antibiotics, wrote the researchers.

The researchers concluded that, although the study was limited in scope and length, deep brain stimulation "may represent an effective, novel intervention for severely disabled patients with treatment-resistant depression."

The six patients who participated in the study showed severe depression according to the Hamilton Depression Rating Scale. They had all failed to respond to at least four different treatments, including drugs, psychotherapy, and ECT.

The researchers implanted the array of electrodes in a region called the "subgenual cingulate region," which their earlier studies had indicated to be overactive in treatment-resistant depression.

Precisely calibrated stimulation of a few volts produced immediate effects, the researchers wrote. "All patients spontaneously reported acute effects including 'sudden calmness or lightness,' 'disappearance of the void,' sense of heightened awareness, increased interest, 'connectedness,' and sudden brightening of the room, including a description of the sharpening of visual details and intensification of colors in response to electrical stimulation," wrote the researchers. These effects were reversed when stimulation was turned off and returned when it was resumed.

"Unexpectedly, with application of stimulation for progressively longer periods (from 1 to 3 hr), there was an increasing and correspondingly longer carry-over of the beneficial behavioral effects beyond cessation of the stimulation," reported the researchers.

During the initial weeks of stimulation, "Patients and their families described renewed interest and pleasure in social and family activities, decreased apathy and anhedonia, as well as an improved ability to plan, initiate, and complete tasks that were reported as impossible to attempt prior to surgery."

Analysis of brain activity using positron emission tomography revealed that the deep brain stimulation corrected abnormal hyperactivity in the subgenual cingulate region, which was correlated with abnormally decreased activity in the prefrontal cortex of the brain.

Psychological testing showed that the surgery did not reduce cognitive function in the patients. In fact, patients showed significant improvement in hand-eye coordination, verbal fluency, and judgment of risk.

Over a 6 month period of chronic stimulation, four of the patients continued to show significant antidepressant response, with three showing remission or near remission of illness, reported the researchers.

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Is caesarean section linked to postnatal depression? - Operative delivery and postnatal depression: a cohort study BMJ Online First
24-Feb-2005 - BMJ-British Medical Journal
Elective caesarean section does not protect women from postnatal depression, according to a study published on bmj.com today. Furthermore, neither emergency caesarean section nor assisted vaginal delivery (use of forceps or vacuum extraction) is associated with an increased risk of postnatal depression.

These findings challenge the theory that women at risk of postnatal depression should be managed differently, and should also help women make informed decisions about childbirth.

Over 14,000 pregnant women completed a questionnaire eight weeks after giving birth to a single infant at full term. Postnatal depression was also assessed using a recognised scale.

There was no evidence that elective caesarean section altered the odds of postnatal depression compared with planned vaginal delivery.

Among planned vaginal deliveries there was similarly little evidence of a difference between women who had an operative delivery and those who had spontaneous vaginal delivery.

There is no reason for women with a history of depression or those at high risk of depression to be managed differently with regard to mode of delivery, say the authors. Even if emergency caesarean section or assisted vaginal delivery is required, women can be reassured that there is no reason to believe that they are more likely to experience postnatal depression.

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Treatment guidelines for kids with bipolar disorder published - Cincinnati Children's Kowatch led effort
22-Feb-2005 - Cincinnati Children's Hospital Medical Center
Early diagnosis and treatment is important for children and adolescents with bipolar disorder, according to new treatment guidelines. The guidelines were sponsored by the Child & Adolescent Bipolar Foundation (CABF), a national parent advocacy group, and were drafted by a scientific consortium led by Robert Kowatch, M.D., director of the Pediatric Mood Disorders Center at Cincinnati Children's Hospital Medical Center.

"These new guidelines were formulated by a group of leading experts in child psychiatry and are the most up-to-date and comprehensive set of guidelines for the treatment of children and adolescents with bipolar disorder," said Dr. Kowatch. "They represent a major step towards practicing evidence-based medicine in this difficult to treat group of patients. Many of these patients require several types of medications to stabilize their moods, and these guidelines offer several treatment options that are useful for clinicians and families."

It is often necessary to use several medications in combination because these kids are very ill, often suicidal or too manic and depressed to attend school. Stabilizing their moods and allowing them to return to school as soon as possible is critical if they are to lead normal lives, said Dr. Kowatch.

"Doctors are getting somewhat better at recognizing bipolar disorder in children, but there wasn't much to guide them in terms of treatment," added Dr. Kowatch.

The guidelines are designed to help doctors identify the classic form of the illness (called Bipolar-I) in children ages 6 to 17, and suggest strategies for treatment of mania and depression, with or without psychosis, in young patients. The recommendations are based on evidence from research studies done in children and adults, case reports published in medical journals, and consensus by a group of experts as to current clinical practices.

The guidelines will be published in the March issue of the Journal of the American Academy of Child and Adolescent Psychiatry but are currently available to the public on their website at www.jaacap.com.

"Far too little research has been done on the treatment of bipolar disorder in youth," said Mina Dulcan, M.D., editor-in-chief of the journal. "The guidelines represent a consensus of existing research results and clinical experience to guide clinicians and families. We hope that the guidelines will not only facilitate clinical care but also inform and enhance new research."

Bipolar disorder (formerly called manic-depressive illness) is a heritable illness that can be diagnosed in teenagers and even in young children. Symptoms include grandiose delusions, irritable mood often accompanied by aggression and self-injury, decreased need for sleep without daytime fatigue, speech that is difficult to interrupt, racing thoughts, distractibility that varies with mood, increased goal-directed activity, hypersexuality, and in some cases, hearing voices.

"The disorder runs in families, and children with the illness are at extremely high risk of attempting suicide," said Martha Hellander, research policy director at CABF and co-author of the guidelines. "These kids suffer so badly, and deserve to have evidence-based treatment as early in life as possible. Many respond quickly to mood stabilizing medication, and parents tell us that 'we have our child back.'"

Bipolar disorder is a lifelong condition that can often be managed with medication, psychotherapy and lifestyle changes such as stress reduction, regular sleep, accommodations at school, and avoidance of caffeine, alcohol, and drugs of abuse.

"The sections on the treatment of comorbid psychiatric disorders are very helpful because having two or more disorders at the same time is common among children and adolescents with bipolar disorder," said Daniel Nelson, M.D., medical director of the Child Psychiatric Unit at Cincinnati Children's. "By far, a majority of the children we care for with bipolar disorder have high comorbidities."

Among the other disorders specific to children who have bipolar disorder, children can also suffer from ADHD, oppositional-defiant disorder, conduct disorder, anxiety and tic disorders, and substance abuse. The comorbid disorders and common side effects from treatment medications are also discussed in the guidelines.

In addition to Dr. Kowatch, other authors of the guidelines include Mary Fristad, Ph.D., director of Research & Psychological Services at Ohio State University; Boris Birmaher, M.D., head of the Children's Mood Disorders Center at Western Psychiatric Institute and Clinic in Pittsburgh; Karen Dineen Wagner, M.D., director of the division of Child and Adolescent Psychiatry at the University of Texas Medical Branch in Galveston; Robert Findling, M.D. professor of psychiatry and pediatrics at University Hospitals of Cleveland; and Martha Hellander. Participants included sixteen other experts on pediatric bipolar disorder and three family representatives from CABF.

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Research Identifies Proteins Crucial to Construction of Brain’s Information Superhighway
10-Feb-2005 - NIH
Communication in the brain travels from one nerve cell to another through critical connections called synapses. These neuron-to-neuron junctions form early in brain development, and their construction was thought to be guided by the nerve cells themselves. Now, investigators supported by the National Institute on Drug Abuse (NIDA), National Institutes of Health, have discovered that cells called glia, known to provide support for neurons in the mature brain, also play a crucial role in formation of synapses during the surge of development following birth. This key insight into the process of normal synapse development may lead to improved treatment of conditions such as drug addiction and epilepsy, which are characterized in part by too many synapses. The research, led by Dr. Ben Barres of Stanford University School of Medicine in Stanford, California, is reported in the February 11, 2005 issue of the journal Cell.

“Synapses are the key connections between cells in the brain. We know that drugs alter these connections, and that the developing brain is vulnerable to addictive drugs’ disruption of normal communication,” says NIDA Director Dr. Nora D. Volkow. “Compounds that direct synapse formation may offer a therapeutic option for people fighting drug addiction or other neurologic conditions.”

Glia account for 90 percent of the cells in a mammalian brain, but until recently scientists focused mainly on the supportive role that glial cells play in helping mature neurons survive. Dr. Barres, along with Stanford postdoctoral fellows Dr. Karen Christopherson and Dr. Erik Ullian, developed a method for growing neurons in a laboratory without glial cells. Then they isolated proteins produced by glial cells and observed the effect when they added the proteins to a culture of neurons. Two of the proteins, thrombospondin 1 and 2, led to the development of synapses — albeit functionally incomplete ones.

The synapses that developed in Dr. Barres’ laboratory dish in the presence of thrombospondin were able to transmit signals but were unable to receive them. In other words, the neuron transmitting the signal is able to secrete a chemical messenger called a neurotransmitter but the neighboring neuron receiving the signal is unable to detect the presence of the neurotransmitter. Because completely functional synapses occur in the presence of glia, “we know that glia produce at least one other protein, which we have not yet identified, that is necessary to produce a fully functional synapse,” Dr. Barres says. This yet unidentified protein enables the receiving neuron to detect the neurotransmitter sent from the neuron transmitting signal when synapses form.

To help confirm the role of the thrombospondins in synapse development, the scientists next developed a strain of mice that lacked the ability to produce thrombospondins 1 and 2; the brains of these mice had 40 percent fewer synapses than normal mice. Interestingly, glia only secrete these thrombospondins early in brain development, concurrent with the normal formation of synapses. These new findings raise the possibility that the relatively poor ability of the adult brain to form new synapses may be due to the low levels of the glial thrombospondins.

“Fully understanding the contribution made by glial thrombospondins could make possible the development of thrombospondin-based therapies to stimulate and direct synapse formation,” notes Dr. Volkow.

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Mother's depression associated with increased risk of child's antisocial behavior
7-Feb-2005 - JAMA and Archives Journals
Significantly higher levels of antisocial behavior were found in seven-year-old children whose mothers were depressed during the child's first five years of life, according to an article in the February issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

"Children of depressed mothers have elevated conduct problems, presumably because maternal depression disrupts the caregiving environment," according to background information in the article. Researchers have identified three possible explanations for the association between a mother's depression and antisocial behavior (ASB) in their children: 1) depressed women are likely to have antisocial personality traits related to depression, 2) are likely to bear children with antisocial men, 3) and the children of depressed mothers may inherit a genetic predisposition for antisocial disorders.

Julia Kim-Cohen, Ph.D., from King's College London, and colleagues investigated the association between maternal depression and children's ASB. Participants were members of the Environmental Risk (E-Risk) Longitudinal Twin Study, which examined how genetic and environmental factors affected the development of 1,116 sets of twins in England and Wales. The mothers categorized the timing of their depression as: never depressed (n = 728), depressed only before twins' birth (n = 68), depressed only after twins' birth (n = 193), and depressed before and after twins' birth (n = 124). Children's ASB at ages five and seven was determined from mother and teacher reports.

The researchers found that children of mothers who were depressed during the child's first five years of life had significantly higher ASB levels at seven years of age. A mother's depression taking place after the children's birth was associated with children's ASB, although depression before the children's birth was not. Maternal depression combined with symptoms of antisocial personality disorder in mothers posed the greatest risk for children's ASB.

"We found that familial liability for ASB accounted for approximately one third of the observed association between maternal depression and children's ASB," the authors write. "However, our findings also suggested that children exposed to maternal depression were significantly likely to have conduct problems through a risk process that operates environmentally over any contributions of their parents' antisocial personality."

(Arch Gen Psychiatry. 2005; 62: 173 – 181. Available post-embargo at www.archgenpsychiatry.com)

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Over-the-counter supplement appears effective in treatment of midlife-onset depression
7-Feb-2005 - JAMA and Archives Journals
The over-the-counter hormonal therapy known as DHEA may be an effective treatment of midlife-onset minor and major depression, according to a study in the February issue of The Archives of General Psychiatry, one of the JAMA/Archives journals. DHEA (dehydroepiandrosterone), an adrenal androgen and neurosteroid is available as a supplement in the U.S.

Complementary and alternative medicine is a multimillion dollar industry, reflecting a growing number of people who avoid traditional medication, including anti-depressants, according to information provided in the article. Alternative therapies may have potential as second- or third-line treatments but controlled evaluations of these potential therapeutic agents are needed, the study's authors suggested. DHEA has been previously reported to have antidepressant-like effects. The current study was designed to evaluate DHEA as a treatment for depression with a midlife onset.

Peter J. Schmidt, M.D., from the Behavioral Endocrinology Branch of the National Institute of Mental Health, Rockville, Md. and colleagues, evaluated 23 men and 23 women aged 45 to 65 with midlife onset major or minor depression of moderate severity. They were randomly assigned to either receive six weeks of DHEA therapy, three weeks each of two dosages, or six weeks of placebo treatment. Following the six weeks of DHEA therapy and a period of one or two weeks without any therapy, the treatment groups were reversed. The participants in the study were evaluated at three and six weeks during the treatment phases with standard measures of depression and a sexual functioning scale.

A 50 percent or greater reduction in the baseline of their score on a depression rating scale was observed in 23 patients after DHEA and in 13 patients after placebo. Six weeks of DHEA treatment was associated with significant improvements in measures of depression and sexual functioning compared to both baseline and six weeks of placebo treatment, the researchers found.

In conclusion the authors write, "At present, there are no predictors of response, and with a 50 percent response rate one would obviously select more reliable first-line treatments for this condition. However, in the 50 percent of depressed outpatients who do not respond to first-line antidepressant treatment, or in those unwilling to take traditional antidepressants, DHEA may have a useful role in the treatment of mild to moderately severe midlife-onset major and minor depression."

(Arch Gen Psychiatry. 2005;62:154-162. Available post-embargo at archgenpsychiatry.com)

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More homeless mentally ill than expected according to UCSD study: Interventions urged
1-Feb-2005 - University of California - San Diego
The prevalence of homelessness in persons with serious mental illness is 15 percent, a higher percentage than suggested in previous studies, according to new research by investigators at the University of California, San Diego (UCSD) School of Medicine.

Published in the February 2005 issue of the American Journal of Psychiatry, the study noted that homelessness in this population might potentially be reduced or prevented with substance abuse treatment and help in obtaining public-funded health benefits (Medicaid, or MediCal in California). Because homeless mentally ill were more than twice as likely to be hospitalized as non-homeless patients, the investigators said improved care for homeless persons with serious mental illness may be cost effective or at least result in improved patient outcomes with only moderate increases in total costs.

The research was conducted among an ethnically diverse population of 10,340 San Diegans with serious mental illness (both homeless and those with housing) who were treated by San Diego County Adult Mental Health Services (AMHS). While one-fourth to one-third of homeless persons are estimated to have a serious mental illness, this is one of the first studies to document and describe the other side of the picture – the number of mentally ill who are homeless.

"Homelessness is more common in patients with serious mental illness than I would have guessed," said the study's first author, David Folsom, M.D., co-director of the UCSD Combined Family Medicine-Psychiatry Residency Program and the assistant medical director of St. Vincent de Paul Village's Family Health Center, a free medical clinic located in one of San Diego's largest homeless service agencies.

According to the UCSD researchers, homelessness was most frequently associated with people who were diagnosed with schizophrenia or bipolar disorder, who were substance abusers, and who had no public-funded health care. Men were also more likely to be homeless than women, as were African Americans. Latinos and Asian Americans were less likely to be homeless.*

"Homelessness is an increasingly important public health issue, with seriously mentally ill persons most at risk for homelessness," said the study's senior author, Dilip Jeste, M.D., UCSD Estelle and Edgar Levi Chair in Aging, professor of psychiatry and neurosciences, director of the UCSD Sam and Rose Stein Institute for Research on Aging, and a geriatric psychiatrist at the VA San Diego Healthcare System. "In addition to the trauma experienced by these individuals, there is also a cost to society. Homeless persons have a significantly more-frequent use of expensive emergency services** and are more likely to spend more time in jail."

The study noted that in San Diego, African Americans comprise 5 percent of the general population, 11 percent of the AMHS population with serious mental illness, and 16 percent of the homeless patients with serious mental illness treated in AMHS. Latinos contribute 23 percent of the general population, 19 percent of the AMHS patients, and 12 percent of the homeless.

"It is possible that the higher rate of homelessness among African Americans may be in part due to fewer community resources for this group of patients, whereas the larger Latino community may be able to provide more resources to protect against homelessness," the study said. "However, African Americans have been found to be at higher risk of homelessness in other cities with larger African American populations, such as New York and Philadelphia***."

The authors also said that an investigation of homeless persons in Los Angeles, only some of whom had mental illness, found lower rates of homelessness in Caucasians and Latinos than in African Americans.

Noting that treatment for substance abuse has been reported to improve outcomes, the researchers said "access to substance abuse treatment is more difficult for homeless persons with serious mental illness than for other homeless persons. Similarly, patients who did not have MediCal insurance were twice as likely to be homeless as patients with MediCal; homeless persons with psychotic disorders have been reported to have greater difficulty obtaining and maintaining entitlement benefits than non-psychotic homeless persons."

The authors concluded that "although it would be naïve to assume that treatment for substance use disorders and provision of MediCal insurance could solve the problem of homelessness among persons with serious mental illness, further research is warranted to test the effect of interventions designed to treat dually diagnosed patients and to assist homeless persons with SMI obtain and maintain entitlement benefits."

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