Adults with bipolar I disorder are at increased risk for cardiovascular disease and hypertension, which occur over a decade earlier than in adults without the disorder, researchers have discovered.

Despite previous studies demonstrating an increase in cardiovascular risk factors and mortality in patients with bipolar disorder, there is limited evidence on the association between cardiovascular disease itself and the disorder, as most studies have been constrained by restricted analyses.

To investigate further, Benjamin Goldstein, from Sunnybrook Health Sciences Center in Toronto, Ontario, Canada, and colleagues examined data from the 2001??”2002 National Epidemiologic Survey on Alcohol and Related Conditions on 1441 patients with bipolar I disorder, 6831 patients with major depressive disorder (MDD), and 34,851 controls without MDD or bipolar I disorder.

On unadjusted analysis, bipolar I disorder patients had a significantly higher prevalence of cardiovascular disease than MDD patients, at 10.1% versus 8.0%. MDD patients in turn had a significantly greater prevalence than controls, at 4.9%. In addition, bipolar I disorder and MDD patients had a significantly greater prevalence of hypertension than controls, at 22.1% and 21.6% versus 18.4%, with no significant differences between the two patient groups.

Adjusting for age, race, and gender, the team found that the risk for cardiovascular disease in bipolar I disorder patients was increased 4.95 times compared with controls and 1.80 times compared with MDD patients.. Bipolar I disorder patients also had a significantly greater prevalence of hypertension than MDD patients or controls, at respective odds ratios of 2.38 and 1.44.

The results remained significant after also taking into account education, income, marital status, obesity, anxiety, smoking, and substance use disorders, the researchers note in the journal Bipolar Disorders.

Bipolar I disorder patients with cardiovascular disease were significantly younger than controls or MDD patients with cardiovascular disease, at approximately 14 years and 6 years younger, respectively. Among hypertension patients, those with bipolar I disorder were also younger than controls and MDD patients, at approximately 13 years and 6.5 years younger, respectively.

The team writes: “Given the complexity of bipolar I disorder itself, compounded by the high rates of psychiatric comorbidity, integration of medical care with psychiatric care is needed in order to optimize medical and psychiatric outcomes and minimize costs.

“Preliminary evidence indicates that such integration may yield improvements in both psychiatric and medical health as well as reduce both forms of service utilization.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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Impulsivity is associated with abnormal patterns of neural changes in bipolar disorder patients, with the anterior cingulate cortex (ACC) potentially involved in altered impulsivity regulation, research shows.

Euthymic, manic, and depressed bipolar disorder patients all show greater impulsivity than healthy individuals, and the trait is linked to clinical outcomes and risky behaviors. In a previous study, the team, led by Jair Soares from the University of Texas Health Sciences Center at Houston, USA, found that impulsivity is inversely related to orbitofrontal cortex (OFC) volume in healthy individuals.

Building on these findings, they administered the Barratt Impulsiveness Scale (BIS) version 11A to 63 patients with bipolar disorder, as well as the Hamilton Rating Scale for Depression (HAM-D) and the Young Mania Rating Scale (YMRS).

In addition, the participants completed a clinical interview and underwent magnetic resonance imaging to measure gray and white matter volumes in the OFC, ACC, medial prefrontal cortex, and amygdala, all of which are linked to bipolar disorder pathophysiology, the team notes in the journal Bipolar Disorders.

The average age of the patients was 38.2 years. In all, 44 patients were diagnosed with bipolar I disorder and the remainder with bipolar II disorder. Comorbid anxiety disorders were identified in 26 patients.

The average HAM-D score was 14.2, while that of the YMRS was 5.9. Twenty one patients were remitted, 32 depressed, seven manic or hypomanic, and three in a mixed state. The average total BIS score was 77.1, at 30.3 for nonplanning, 25.5 for motor, and 21.3 for attention subscales. This compares with a total BIS score of 64.2 for the general population, as derived from a previously published normative study.

MRI whole-brain analysis revealed that only the gray matter volume of the left rostral ACC was significantly inversely correlated with the BIS total scores. These findings were confirmed by small-volume false discovery rate correction. No other significant white or gray matter volume correlations with total BIS scores were detected.

Interestingly, further analysis revealed that left rostral ACC gray matter volumes were significantly inversely correlated only with BIS motor subscale scores, not with either the attention or nonplanning subscales. The findings were unaffected by any clinical variables included in the analysis.

The team writes: “The current study provides the novel finding that rostral ACC volumes are inversely associated with impulsivity, particularly motor impulsivity, in bipolar disorder patients.”

They add: “These results suggest that the ACC may participate in the neurocircuitry that regulates abnormal impulsivity in bipolar disorder patients, and the function of this neurocircuitry in bipolar disorder may be different from that in healthy volunteers.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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Damage to the brain caused by chronic stress or lead poisoning can be repaired by blocking a key molecular pathway, Yale University researchers report in the September 7-11 edition of the Proceedings of the National Academy of Sciences.

Rats subjected to chronic stress develop damage to the prefrontal cortex, an area of the brain crucial to working memory, impulse control and the ability to stay focused on tasks. Long-term stress triggers excessive activity of a family of enzymes called protein kinase C, which in turn damages the cytoskeleton of neurons and hinders their ability transmit information. This loss of the brain’s grey matter due to stress has been linked to poor impulse control, a decline in working memory and inability to focus on tasks. These findings have direct relevance to our understanding of bipolar disorder, where genetic insults increase protein kinase C signaling which may be associated with a loss of prefrontal grey matter and behavioral control.

The Yale team led by senior author Amy Arnsten, professor of neurobiology at Yale and her graduate student, Avis Brennan Hains, succeeded in protecting against the effects of stress by blocking the action of protein kinase C in rats. The researchers found that dendritic spines of neurons stayed intact and that the rats’ ability to perform a task requiring working memory and impulse control was improved.

“When you inhibit protein kinase C, cells can talk to each other again and you rescue cognition,” Arnsten said.

Blocking protein kinase C has potential for treating bipolar disorder and post-traumatic stress disorder, Arnsten said. Medications such as lithium can inhibit protein kinase C and have been shown to restore normal levels of grey matter in patients with bipolar disorder. She also noted such a therapy might help reverse the effects of lead poisoning, which causes learning disabilities and behavioral problems in tens of thousands of children. Lead, like stress, can also increase protein kinase C activity and erode grey matter in the prefrontal cortex. These findings suggest that medications that inhibit protein kinase C may help restore prefrontal brain function in children with residual problems from lead poisoning.

Other Yale researchers contributing to the study were Mai Anh T. Vu, Paul K. Maciejewski, Christopher H. Van Dyck and Melissa Grotton .

The study was funded by the National Institutes of Health and the Yale Stress Center.

Source
Yale University

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Bipolar disorder patients report more interference from pain than those with major depressive disorder (MDD) or anxiety disorders, and such pain is linked to medical and psychiatric comorbidities, conclude US researchers.

Both MDD and anxiety disorders have been associated with pain, including pain intensity, interference from pain, and pain-related role impairment. However, there has been little investigation of pain in bipolar disorder patients.

Benjamin Goldstein and colleagues from the University of Pittsburgh School of Medicine in Pennsylvania therefore studied data from the 2001??”2002 National Epidemiologic Survey on Alcohol and Related Conditions, involving a nationally representative sample of 43,093 adults.

Pain interference was determined using a question derived from the Short Form-12 version 2 questionnaire, in addition to which participants were assessed for psychiatric diagnoses, medical comorbidities, and substance use.

In all, 883 patients were diagnosed with bipolar disorder and the remaining participants were classified as non-bipolar disorder patients. There were significant differences between patients with and without bipolar disorder in terms of age, gender, education, marital status, and household income.

In addition, the team found that bipolar disorder patients were significantly more likely to report pain interference scores than other participants, at 24.8% versus 11.9%. Bipolar disorder patients were also significantly more likely than the 2579 patients with MDD and 1436 with anxiety disorders alone to report moderate or greater pain interference, at 24.8% versus 19.3% and 11.0%, respectively.

On logistic regression analysis taking into account confounding factors, bipolar disorder was significantly associated with increased pain interference, at an adjusted odds ratio of 1.57. Increased pain in bipolar disorder patients was linked to comorbid anxiety disorders, marriage, comorbid substance use disorder, white race, arthritis, and other medical disorders, at odds ratios of 1.72, 1.33, 1.91, 0.47, 2.84, and 2.21, respectively. Associations were also found with greater age and lower income.

The team writes in the Journal of Affective Disorders: “We advocate that systematic assessment of pain should be undertaken as part of the management of bipolar disorder, and that this parameter should be monitored during the course of treatment.

“Potential benefits of early identification and treatment of pain among persons with mood and anxiety disorders include reduced pain interference, reduced healthcare costs, and improved mood and anxiety treatment outcomes.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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Bipolar disorder patients have significant brain volume changes compared with healthy individuals that are linked to age and duration of illness, but the changes do not appear to be diagnostically specific, say UK researchers.

Previous studies and meta-analyses of volumetric magnetic resonance imaging (MRI) in bipolar disorder and schizophrenia have revealed significant differences between affected individuals and healthy controls. However, there is substantial heterogeneity between the findings.

Danilo Arnone, from the University of Manchester, and colleagues therefore searched the Cochrane Library, EMBASE, PsychINFO, OVID and PubMED databases to identify volumetric MRI studies of brain regions comparing bipolar disorder patients with unrelated controls and schizophrenia patients. The team conducted a systematic review of the studies and a random-effects meta-analysis, while meta-regression was used to determine heterogeneity between the findings.

From 180 studies identified, 72 met the inclusion criteria. Of the included studies, 65 compared bipolar disorder patients and controls, with 18 of these also including patients with schizophrenia. Overall, the studies involved 1823 patients with bipolar disorder, 670 schizophrenia patients, 29 schizoaffective disorder patients, 106 unipolar depression patients, and 1940 healthy controls.

Bipolar disorder patients had, compared with healthy controls, a small but significant reduction in whole brain volume, at an effect size of -0.15, and significant increases in left and right lateral ventricles, at an effect size of 0.27. In both cases, there was no significant heterogeneity or publication bias.

It was also shown that bipolar disorder patients had significant increases in globus pallidus volumes versus controls, at an effect size of 0.57. However, there was significant heterogeneity and publication bias.

Compared with schizophrenia patients, bipolar disorder patients had significant increases in right amygdala volumes, at an effect size of 0.47, and bilateral reductions in the lateral ventricles, at effect sizes at the right and left ventricles of -0.35 and -0.26, respectively.

Heterogeneity was detected in a large number of nonsignificant brain volume changes. The effect sizes for specific volume changes compared with controls correlated with duration of illness, use of antipsychotic medication, age at onset, average age, year of publication, slice thickness, and use of mood stabilizers.

Age, percentage of male participants, and euthymia were also associated with specific volume changes in comparison with schizophrenia patients, the team reports in the British Journal of Psychiatry.

The team writes: “We found that bipolar disorder is associated with global and prefrontal volumetric brain reductions, enlarged lateral ventricles and an enlarged globus pallidus.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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Structural brain abnormalities linked to an “early” at-risk mental state may dictate an elevated susceptibility to psychosis, while those seen during a “late” state may indicate a subsequent transition to psychosis, suggest study results.

Previous studies have indicated that brain alterations exist in individuals with an at-risk mental state for psychosis. “However, the neuroanatomical underpinnings of the early and late at-risk mental state relative to clinical outcome remain unclear,” say Eva Meisenzahl (Ludwig “Maximilians University, Munich, Germany) and co-authors.

To investigate, the researchers compared voxel-based morphometry (VBM) of magnetic resonance imaging (MRI) data from 20 individuals with putatively early at-risk mental state (ARMS “E group) and 26 individuals with a late at-risk mental state (ARMS “L group).

Mesenzahl and team then compared 15 at-risk mental state individuals with subsequent transition to psychosis (ARMS “T group) with 18 participants without disease transition (ARMS “NT group). All individuals were compared with 75 healthy volunteers.

ARMS “L individuals showed a greater extent and magnitude of brain abnormalities compared with ARMS “E individuals, with extended volume losses spanning the prefrontal and orbitofrontal cortices and involving parts of the anterior cingulated cortex, insula, and medial and lateral temporal brain regions.

Structural abnormalities in the ARMS “E group did not involve the pre- or orbitofrontal areas, but were restricted to the temporolimbic structures.

Furthermore, gray matter volume abnormalities increased as symptoms progressed towards a diagnosis of psychosis.

The authors note that it was not possible to ascertain whether the differences between the groups are a result of a longitudinal course of brain changes leading to psychosis, or whether they represent two risk levels for psychosis with distinct neuroanatomical underpinnings.

The study also showed that prefrontal structural alterations in ARMS “T participants were seen on average 6 months prior to disease transition, and overlapped with abnormalities of the ARMS “L sample.

Further analysis showed that ARMS “T participants had more pronounced prefrontal gray matter volume reductions compared with those in the ARMS “L group. Individuals in the ARMS “NT group also showed gray matter volume reductions similar to those seen in the ARMS “T group.

“Based on [previous] results and our own findings, we may cautiously interpret prefrontal brain alterations pre-dating psychosis as a marker of clinical outcome and not only as a marker of liability to attenuated or transient psychotic symptoms,” write the authors in the British Journal of Psychiatry.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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In addition to its established effectiveness for treating unipolar (UP) depression, electroconvulsive therapy (ECT) is a viable treatment for bipolar (BP) I and II depression resistant to pharmacologic treatment, suggest study results.

“Several studies on responsiveness to ECT compared UP and BP depression, but differences among UP, BP II, and BP I depressive subtypes have not been discussed before,” say Giulio Perugi (University of Pisa, Italy) and co-authors.

They add: “The distinction between BP I and II has shown relevant clinical and prognostic impact that might influence response to ECT.”

To investigate, Perugi and team administered twice-weekly bilateral ECT to patients with UP depression (n=17), BP II (n=67), and BP I (n=46) disorder who were currently depressed and showed resistance to pharmacologic treatment. The total number of lifetime episodes was greater in patients with BP I than UP and BP II (6.7 vs 5.5 and 5.2, respectively), while current episode length was similar in all three diagnostic subtypes.

Patients were assessed at baseline and a week after the ECT course using a set of standardized measures. The mean number of ECT sessions was 7.2 per patient.

All patients showed a significant improvement after the ECT course, with global response rates (defined as a final Clinical Global Improvement [CGI] severity score of less than 2) of 94.1%, 79.1%, and 67.4% for UP, BP II, and BP I, respectively. Similar results were obtained when response rate was defined as a 50% reduction on the Hamilton Rating Scale for Depression (HAM-D), with corresponding values of 88.2%, 73.1%, and 69.6%.

However, the rate of remission ??” defined as a final CGI severity score of 1 ??” was nearly twice as high in UP (70.6%) than in BP I (41.3%). No significant differences were seen between UP and BP II and between BP II and BP I.

Defining remission according to a final HAM-D score of less than 8 showed that remission rates were higher in the UP group (70.6%) than in BP II (43.3%) and in BP I (34.8%).

At the final evaluation BP I patients showed a less complete response, with residual manic and psychotic symptomatology after ECT compared with BP II and UP patients.

“It is possible that this residual symptomatology may account for a worse outcome, utilizing subjective measures,” write the authors in the Journal of Affective Disorders.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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Only a small proportion of bipolar disorder patients switch from mania to depression, say European researchers in findings that suggest atypical antipsychotics may protect against the switch to depression.

Switching in mood polarity in bipolar disorder patients has been identified as a predictor for poor long-term outcomes. However, while the switch from depression to mania has received a great deal of attention, the risk for switching from mania to depression is poorly understood.

Eduard Vieta, from the University of Barcelona, and colleagues therefore examined data from the 2-year, prospective, observational European Mania in Bipolar Longitudinal Evaluation of Medication study on 2390 patients who took part in the maintenance phase of the investigation, which lasted for up to 24 months.

The participants completed the Clinical Global Impression-Bipolar Disorder scale (CGI-BP), the Young Mania Rating Scale (YMRS), and the 5-item Hamilton Depression Rating Scale, the team reports in the Journal of Affective Disorders.

During the first 12 weeks of follow-up, 5.0% of the patients switched from mania to depression. Patients who switched to depression were, compared with non-switchers, significantly older at disease onset, presented less often with a mixed episode at baseline, had more depressive episodes, hospital admissions, and suicide attempts in the previous 12 months, had more substance abuse, had higher CGI-BP scores, and were more likely to be taking antidepressants and typical antipsychotics.

Cox analysis demonstrated that higher/faster switching to depression was significantly associated with more previous depressive episodes, at relative risks of 1.83, 2.58, and 3.29 for 1, 2, and ?3 episodes, respectively, substance abuse other than alcohol or cannabis, at a relative risk of 2.39, greater CGI-BP severity, at a relative risk of 1.26, and benzodiazepine/other hypnotic use, at a relative risk of 1.69.

Factors associated with a significantly lower/slower rate of switching to depression were greater CGI-BP depression scores, YMRS severity, and atypical antipsychotic use, at relative risks of 0.71, 0.97, and 0.64, respectively.

The team concludes: “These findings, particularly the fact that atypical antipsychotics were associated with a lower switch risk, may have important implications for the treatment of patients with mania.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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5-HT_1A receptor binding is not reduced in medicated euthymic bipolar disorder patients versus healthy individuals, say researchers in findings that contrast with the reductions seen in unipolar and bipolar depressed patients.

Previous studies of 5-HT_1A receptor binding have focused on unipolar and bipolar depressed patients, with mixed results, but the greatest reductions observed have been in patients with a family history of bipolar disorder.

To examine binding reductions in euthymic bipolar disorder patients, Peter Sargent, from Warneford Hospital in Oxford, UK, and colleagues performed positron emission tomography using the selective 5-HT_1A receptor ligand [carbonyl-¹¹C]WAY-100635 in eight medicated euthymic bipolar disorder patients and eight healthy controls.

Although the team found a significant negative correlation between age and global postsynaptic parametric binding potential, there was no significant difference in binding potential between patients and controls, at averages of 4.24 and 4.34, respectively.

The results, published in the Journal of Affective Disorders, also demonstrated no significant differences in regional parametric binding potentials between the groups. There was no significant correlation between global binding potentials and depression scores in patients.

The team concludes: “Longitudinal studies examining 5-HT_1A binding in both medicated and unmedicated patients with bipolar disorder are warranted to clarify whether there may be effects of medication on 5-HT_1A binding or whether there is an effect of mood state in bipolar disorder with normalization of 5-HT_1A binding in the euthymic state.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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Bipolar disorder, or manic-depression, causes severe and unusual shifts in mood and energy, affecting a person’s ability to perform everyday tasks. With symptoms often starting in early adulthood, bipolar disorder has been thought of traditionally as a lifelong disorder. Now, University of Missouri researchers have found evidence that nearly half of those diagnosed between the ages of 18 and 25 may outgrow the disorder by the time they reach 30.

“Using two large nationally representative studies, we found that there was a strikingly high peak prevalence of bipolar disorders in emerging adulthood,” said David Cicero, doctoral student in the Department of Psychological Sciences in the College of Arts and Science and lead author of the paper. “During the third decade of life, the prevalence of the disorder appears to resolve substantially, suggesting patients become less symptomatic and may have a greater chance of recovery.”

By examining the results of two large national surveys, MU researchers found an “age gradient” in the prevalence of bipolar disorder, with part of the population appearing to outgrow the disorder. In the survey results, 5.5 to 6.2 percent of people between the ages of 18 and 24 suffer from bipolar disorder, but only about 3 percent of people older than 29 suffer from bipolar disorder.

“Young adults between the ages of 18 and 24 are going through significant life changes and social strain, which could influence both the onset and course of the disorder,” said Kenneth J. Sher, Curators’ Professor in the Department of Psychological Sciences and co-author of the study. “During this period of life, young adults are exploring new roles and relationships and begin to leave their parents’ homes for school or work. By the mid 20s, adults have begun to adjust to these changes and begin to settle down and form committed relationships.”

Researchers predict the prevalence of the disorder also could be affected by brain development, particularly the prefrontal cortex. The prefrontal cortex, the very front part of the brain, is thought to control perception, senses, personality and intelligence. In particular, it controls reactions to social situations, which can be a challenge for people with bipolar disorder.

“The maturing of the prefrontal cortex of the brain around 25 years of age could biologically explain the developmentally limited aspect of bipolar disorder,” Cicero said. “Other researchers have found a similar pattern in young adults with alcohol or substance abuse disorders.”

While some scholars suggest that the difference could be due to discounting factors such as early mortality, the sheer number of those who are recovering rules out this possibility, Sher said.

The study, “Are There Developmentally Limited Forms of Bipolar Disorder?” was published in the Journal of Abnormal Psychology. It was co-authored by Cicero, Sher and Amee Epler, a doctoral student in the Department of Psychological Sciences.

Source:
Kelsey Jackson

University of Missouri-Columbia

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