Study results show that bipolar disorder (BD) I patients with manic/hypomanic polarity (MP) and depressive polarity (DP) show similar temperaments but are different from patients with unipolar major depression (UP), thus supporting the “predominant polarity” concept for BD.

It has been reported that 45??”70% of all BD patients fulfill criteria for a certain predominant polarity, meaning that at least two-thirds of episodes are restricted to a single pole of the illness.

“This concept has been proven to have diagnostic and therapeutic implications, but little is known on the underlying psychopathology and temperaments,” write Eduard Vieta (University of Barcelona, Spain) and colleagues in the Journal of Affective Disorders.

The researchers therefore analyzed 124 BD I patients, and found that 69 (55.7%) presented predominant polarity criteria, with 68% meeting the criteria for MP and 32% for DP. In addition, 19 patients with UP were included in the assessment of temperament using the Temperament Evaluation of the Memphis, Pisa, Paris, and Sand Diego Autoquestionnaire (TEMPS-A).

Mixed index episodes and suicidal ideation were significantly more frequent in DP compared with MP BD patients, at 77.0% versus 17.0% and 81.8% versus 34.0%, respectively. Furthermore, DP patients had significantly more lifetime mixed episodes than MP patients, at 2.80 versus 1.36.

BD patients with MP and DP had an earlier onset but a shorter duration of depression compared with UP patients. No significant difference was seen in the number of depressive episodes between the DP and UP groups.

When Vieta and team looked at temperamental features among the groups, the distribution of mean scores on the TEMPS-A was able to differentiate bipolar from unipolar patients, as MP and DP patients scored higher on the Hyperthymic and Cyclothymic subscales but lower on the Depressive temperament scale compared with UP patients.

Furthermore, high anxious temperament traits were present in both DP and UP groups, “suggesting that this temperament could represent a link within depressive symptomatology,” according to the authors.

They suggest that “underlying temperament may separate bipolar from unipolar patients, suggesting that data on temperament could be used reliably as a bipolar screening tool in a depressive episode.”

However, the team cautions that the results must be replicated with inclusion of a BD II subgroup before any definitive conclusions may be drawn.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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Both bipolar disorder and schizophrenia patients have specific significant increases in endothelium-related inflammatory markers in comparison with healthy individuals, Norwegian scientists have discovered.

It has been demonstrated that schizophrenia patients and those with major depression have alterations in the inflammatory system. Bipolar disorder has, however, been less studied and, overall, the findings have been inconsistent in terms of the underlying mechanisms.

Sigrun Hope, from the University of Oslo, and colleagues therefore measured plasma soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin (IL)-1 receptor antagonist (IL-1Ra), IL-6, high-sensitivity C reactive protein (hs-CRP), soluble CD40L ligand (sCD40L), and von Willebrand factor (vWF) levels in 125 bipolar disorder patients, 186 schizophrenia patients, and 244 healthy controls.

The findings, published in the journal Bipolar Disorders, indicate the combined patient groups had significantly higher plasma levels of sTNF-R1 and vWF compared with healthy controls, at increases of 17% and 27%, respectively. While hs-CRP levels were significantly increased in patients versus controls, at an average of 0.95 ng/ml versus 0.80 ng/ml, there were no significant differences for the other inflammatory markers.

The team also found that unmedicated bipolar disorder and schizophrenia patients had significantly increased levels of sTNF-R1 and vWF compared with controls, at1.09 versus 0.91 ng/ml and 101 versus 77%, respectively. There were no significant differences between bipolar disorder and schizophrenia patients, regardless of medication status.

The findings were unaffected by controlling for age, gender, ethnicity, liver function, kidney function, cardiovascular disorder, diabetes, and alcohol intake, as well as for hs-CRP levels.

“The main result of the present study is a significant increase in sTNF-RI and vWf in both schizophrenia and bipolar disorders, present also after controlling for confounders,” the researchers write.

“These findings may indicate an association between severe mental illness and abnormal endothelial-related inflammation.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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Disrupted in schizophrenia 1 (DISC1) gene variants play a role in the development of psychiatric illness yet there is significant heterogeneity in clinically relevant variants between populations, say international scientists.

Although schizophrenia, schizoaffective disorder, bipolar disorder (BD), major depression, autism, and Asperger syndrome have all been linked to DISC1, no actual causal variants have been identified.

William Hennah, from the University of Edinburgh, and colleagues therefore studied 1275 individuals with schizophrenia, nearly 2000 with BD, and more than 2000 healthy controls from four European centers. All participants were genotyped for the presence of 75 single nucleotide polymorphisms (SNPs) in the translin-associated protein X and DISC1 genes, of which 67 were suitable for analysis.

For the combined sample, no SNP survived permutation correction or was significantly associated with schizophrenia or BD. However, the rs1538979 SNP was significantly associated with BD I males in the Finnish group and the rs821577 SNP was significantly linked with BD females in the London group, at odds ratios of 2.73 and 1.64, respectively.

Although unable to survive corrected analysis, the rs821577 SNP G allele was associated with BD in the combined group and BD females, at odds ratios of 1.28 and 1.44, respectively.

Additionally, the rs1538979 SNP T allele was a risk factor for BD in females in the London group and was protective against in schizophrenia in men in the Aberdeen group at odds ratios of 1.50 and 0.55, respectively.

Further analysis revealed that the rs821633 SNP together with the T allele of the rs1538979 SNP were associated with an increased risk for schizophrenia in females. Interestingly, the rs1538979 SNP was a risk factor only in the presence of the rs821633 SNP, while the rs821633 SNP was protective on its own.

The team concludes in the journal Molecular Psychiatry: “Our data provide further genetic support for a role of DISC1 in psychiatric illness, with the same variants on the same gene modulating risk to both BD and schizophrenia, further substantiating the hypothesis that these two separate disorders have overlapping genetic risks.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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A major breakthrough in mental health has been developed, a cooperative venture between the National Bipolar Foundation and the MedicAlert Foundation; a preventative care program called “Safe ’til Stable.” It provides vital medical information to emergency responders in time of need through our live 24-hour emergency response service. In a medical emergency, this can help reduce the trauma experienced by individuals impacted with bipolar disorder. If an individual experiences an event, first responders on the scene (e.g., law enforcement, emergency services personnel, etc.) will look for a medical ID with the “MEDIC ALERT” symbol. The “Safe ’til Stable” program is a milestone; in that, those with bipolar disorder will have a voice in times when they cannot speak for themselves, will be properly routed in times of emergency providing a sense of security for the individual and those close to them.

The National Bipolar Foundation (NBPF) was founded, in 2007 by Marc Kullman, in order to reduce stigma, educate, and seek affordable healthcare for those people living with bipolar disorder. A National Awareness Initiative has been launched to spread awareness through press releases, press conferences, proclamations, influential people, and its online campaign through social media networking. The MedicAlert Foundation, founded in 1956, is the leader in providing identification and emergency medical information. Together both foundations have developed a program that will prevent the misdirection, misdiagnosis, and mistreatments of participants; saving precious time and dollars.

Bipolar disorder is said to affect at least 1 in 100 people and some say as many as 1 in 25, including undiagnosed cases. This cooperative effort between NBPF and the MedicAlert Foundation will have widespread impact on our society. Children, adolescents, and adults living with bipolar disorder, who are involved in accidents and unable to speak for themselves will have the MedicAlert Emergency Services speaking for them, informing hospital staff and medical providers of their diagnoses, current medications in order to avoid potential dangerous withdrawal, and the acute onset of instability in regards to any symptoms of bipolar disorder. Another major benefit of the program is that when a bipolar person finds themselves in an unforeseen incident, responders will react in an appropriate manner; thus given the opportunity to defuse the situation or transport the person to an appropriate facility. The implementation of this program immediately creates jail diversion benefiting all of society. The “Safe ’til Stable” program will benefit individuals wearing the identification jewelry, reduce stress on their families, and ultimately reduce the cost of their care for all taxpayers.

Source: National Bipolar Foundation

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ADA Technologies, Inc. (ADA) received a $189,886 grant from the National Institute of Mental Health to develop a home lithiummonitor for use by patients with bipolar disorder. The testing tool would allow reliable, routine at-home monitoring of blood lithium concentrations, enabling individuals with bipolar disorder to conveniently and effectively manage their care.

Effective treatment of bipolar disorder, an inherited disease that affects 5.7 million adult Americans, is dependent on maintaining a lithium blood concentration that falls within a narrow range. Current monitoring methods are not amenable to home use by a patient, making it difficult for patients to know when their levels fall outside of this narrow range.

Testing lithium concentration in blood is extremely challenging due to the interference of sodium. ADA’s research program will overcome this problem and produce a prototypical device for testing lithium blood concentrations.

“A home-based testing tool will enable patients to monitor their lithium blood concentrations daily and adjust their medication accordingly,” said Kent Henry, Ph.D., ADA senior scientist and principal investigator on the project. “Just as home monitoring of blood sugar levels enables diabetics to manage their health, individuals with bipolar disorder will be better equipped to manage their health and overall well-being.”

According to the National Institute of Mental Health, bipolar disorder is the third leading cause of death in the 15-24 age bracket and the sixth leading cause of disability in the 15-44 age bracket.

The project described was supported by Award Number R43MH090779 from the National Institute of Mental Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Metal Health or the National Institutes of Health.

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ADA Technologies, Inc.

• DISC1 gene variants show mixed associations with psychiatric illness]]>
• Two Brown Faculty To Study Brain Development In Infants And Children With Bipolar Disorder

US researchers have found that men, but not women, with bipolar disorder (BD) have larger cerebellar vermis volumes than healthy individuals.

The vermis is interconnected with brain regions linked to the pathophysiology of BD, including the hypothalamus, amygdala, hippocampus, anterior cingulate, and ventral prefrontal cortices.

Prior magnetic resonance imaging (MRI) studies have found vermis structural abnormalities in BD while others have not.

Fay Womer (Yale University School of Medicine, New Haven, Connecticut) and colleagues therefore measured volumes for total vermis and vermis subregions V1, V2, and V3 using high-resolution MRI in 44 BD patients (of whom 10 were unmedicated) and 43 healthy individuals with no history of psychiatric disorders.

The team found that total vermis volumes were significantly greater in male BD patients compared with controls, at 7500 vs 6650 mm³, respectively. By contrast, vermis volumes were nearly identical in female BD patients and controls.

Further analysis of the vermis subregions revealed significantly larger V1 volumes in the BD group compared with control group, particularly among males. No significant differences in V2 or V3 subregions were seen between groups.

“The findings reported herein raise interesting questions regarding how [gender]-related factors, such as hormonal levels, may interact with the development of the vermis in BD and whether vermis abnormalities may contribute to clinical features of BD that tend to be more characteristic of males with the disorder,” write the researchers in the journal Bipolar Disorders.

They add that since increases in vermis volume have been observed in autism and schizophrenia, which share genetic vulnerabilities with BD, commonalities in the pathophysiology of these disorders with BD are a possibility.

Womer and team call for further studies to “elucidate the role of the vermis in BD pathophysiology and the potential influences of [gender] on this role.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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Bipolar disorder (BD) patients show significant differences in serum chemokine levels compared with healthy individuals that may act as markers for the disorder, Brazilian study findings indicate.

There is evidence to suggest that BD is associated with changes in neuroplasticity and neuronal survival, which could be affected by inflammatory mediators; further evidence points to the involvement of inflammatory cytokines in BD.

To investigate, Flávio Kapczinski, from the National Institute for Translational Medicine in Porto Allegre, and colleagues measured serum levels of the cytokines CCL2, CCL3, CXCL8, CXCL9, CXCL10, CCL11, and CCL24 in 30 euthymic bipolar I disorder patients and 30 healthy controls.

There were no differences between patients and controls in terms of age, gender, ethnic group, and years of schooling, the team reports in the journal Brain, Behavior, and Immunity.

Patients were found to have significantly higher serum levels of CXCL10 than controls, at 10.00 pg/ml versus 0.00 pg/ml, and significantly lower levels of CCL24, at 1320.09 pg/ml versus 1719.54 pg/ml. There were no other significant differences in cytokine levels, and no correlation between chemokine levels and duration of disorder.

“If the present findings are corroborated by future reports, they could possibly open a new path in the field of BD treatment options and in neuroscience research as a whole, contributing to the understanding of the complex and delicate balance between neuronal life and death,” the researchers write.

“Such a complexity should be taken into account in the development of drugs that exert their effects through chemokines and that might have a therapeutic use in BD.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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The children of bipolar disorder parents face the highest risk for mood episodes during adolescence, with depression almost always the index episode, the results of a Canadian and Czech study indicate.

There is currently little information on the early clinical stages of bipolar disorder, with descriptions of onset and early course reliant largely on patient recall, explain Anne Duffy, from Dalhousie University in Halifax, Canada, and colleagues.

To investigate further, the team studied 207 children aged 8??”25 years from 105 families with parents who had known bipolar disorder. The children completed the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version at enrolment, annually, and at any time symptoms developed until their 30th birthday, with each child followed-up for 1??”15 years.

In all, 67 participants met the criteria for one or more major mood episodes. The average age at analysis was 24 years and the average age of onset was 17 years, with no child experiencing onset before 12 years of age.

In 90% of cases, the first episode was major depression, and 61 patients had a remitting or partially remitting episode course. Among remitting patients, 89% of first episodes were depressive, compared with 68% of second episodes, 78% of third episodes, and 58% of fourth episodes.

The average duration of first depressive episodes among remitting or partially remitting patients was 6.1 months, compared with 1.7 months for the first hypomanic/manic or mixed episode. The average cycle length was 26.3 months.

Analysis revealed an increase risk for new onsets of major mood episodes from age 12 years that continued to 30 years of age. A similar pattern was seen for recurrence risk, at a risk for recurrence of 61% by 5 years.

The researchers write in the British Journal of Psychiatry: “These findings emphasize the need to identify children at familial risk for bipolar disorder and to provide continuity of expert psychiatric surveillance and assessment over this period.

“This involves programs spanning child and adult institutions, and close collaboration between child and adult psychiatry services.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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• DISC1 gene variants show mixed associations with psychiatric illness]]>
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Malfunctioning circadian clock genes may be responsible for bipolar disorder in children. Researchers writing in the open access journal BMC Psychiatry found four versions of the regulatory gene RORB that were associated with pediatric bipolar disorder.

Alexander Niculescu from Indiana University School of Medicine, Indianapolis, US, worked with a team of researchers at Harvard, UC San Diego, Massachusetts General Hospital and SUNY Upstate Medical University to study the RORA and RORB genes of 152 children with the condition and 140 control children. They found four alterations to the RORB gene that were positively associated with being bipolar. Niculescu said, “Our findings suggest that clock genes in general and RORB in particular may be important candidates for further investigation in the search for the molecular basis of bipolar disorder”.

RORB is mainly expressed in the eye, pineal gland and brain. Its expression is known to change as a function of circadian rhythm in some tissues, and mice without the gene exhibit circadian rhythm abnormalities. According to Niculescu, “Bipolar disorder is often characterized by circadian rhythm abnormalities, and this is particularly true among pediatric bipolar patients. Decreased sleep has even been noted as one of the earliest symptoms discriminating children with bipolar disorder from those with attention deficit hyperactivity disorder (ADHD). It will be necessary to verify our association results in other independent samples, and to continue to study the relationship between RORB, other clock genes, and bipolar disorder”.

Pediatric bipolar disorder is a controversial diagnosis characterized by alternating bouts of depression and mania in children, although it does not affect all young people in the same way and the duration and severity of the disorder can vary enormously.

Notes:

Evidence for Genetic Association of RORB with Bipolar Disorder
Casey L McGrath, Stephen J Glatt, Pamela Sklar, Helen Le-Niculescu, Ronald Kuczenski, Alysa E Doyle, Joseph Biederman, Eric Mick, Stephen V Faraone, Alexander B Niculescu and Ming T Tsuang
BMC Psychiatry (in press)

http://www.biomedcentral.com/bmcpsychiatry/

Source: Graeme Baldwin

BioMed Central

Removing the PKCI/HINT1 gene from mice has an anti-depressant-like and anxiolytic-like effect. Researchers writing in the open access journal BMC Neuroscience applied a battery of behavioral tests to the PKCI/HINT1 knockout animals, concluding that the deleted gene may have an important role in mood regulation.

Elisabeth Barbier and Jia Bei Wang, from the School of Pharmacy at the University of Maryland, USA, carried out the experiments to investigate the role of the gene in regulating mood function. Wang, the corresponding author of the paper, said, “The knockout mice displayed behaviors indicative of changes in mood function, such as increased perseverance and reduced anxiety in open spaces”.

The causes of mood dysfunction, as seen in depressive and bipolar disorders, are still not fully understood. They are believed to be multifactorial, involving heredity, changes in neurotransmitter levels, altered neuro-endocrine function, and psychosocial factors. Speaking about these results, Wang said, “Although we don’t yet know why the deletion of the gene altered the mood status of the mice, what we have learned about the importance of this gene in mood function and its involvement in human mental disorders is interesting. The protein encoded by this gene could be a potential drug target for development of diagnostic or therapeutic agents that one day might be used for depression, bipolar or schizophrenia disorders. In addition, the knockout mice might be useful as a model to study mania, as there is no other animal model available yet.

Notes:

Anti-depressant and anxiolytic like behaviors in PKCI/HINT1 knockout mice associated with elevated plasma corticosterone level
Elisabeth Barbier and Jia Bei Wang
BMC Neuroscience (in press)

http://www.biomedcentral.com/bmcneurosci/

Source: Graeme Baldwin

BioMed Central

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