Patients with bipolar disorder and comorbid
obsessive-compulsive disorder (OCD) are more likely to have a
history of suicide attempts, rapid cycling, and alcohol dependence
compared with their peers without anxiety comorbidities, study
results show.

“The data in this report support the notion that comorbid OCD is
fairly common, is associated with disease severity, and has
important consequences regarding symptom- and patient-rated
outcomes,” comment Flávio Kapczinski (Hospital de
Clínicas de Porto Alegre, Brazil) and colleagues.

The prominence of anxiety in general and OCD in particular among
patients with bipolar disorder has long been acknowledged. Recent
studies have tried to investigate the illness burden of OCD, but
comparisons have usually been made between those with and without
OCD comorbidity.

“This is little informative because those patients with any
comorbidity tend to differ in a number of measures from those with
‘pure’ bipolar disorder,” the researchers explain in the journal
Comprehensive Psychiatry.

To address this, they performed a cross-sectional study of
lifetime comorbidities in 259 patients with bipolar disorder, using
anxiety comorbidities as a “more rigorous control group with the
aim of uncovering more specific correlates of OCD comorbidity in
bipolar disorder.”

Kapczinski et al report that lifetime prevalence of any
anxiety disorder was 55.6%, and of OCD, 12.4%. Current prevalence
of OCD was 8.5%; although no cases were detected during mania, it
was diagnosed in 8.4% of those in a euthymic phase, 13.9% of those
depressed, and 13.0% of those with mixed episodes.

The researchers note that this fits with recent studies showing
that obsessions or compulsions may remit during mania to reappear
in depression.

Compared with patients with no anxiety comorbidity, those with
lifetime OCD were more likely to be women (61.8% vs 84.4%), to have
a longer period of untreated illness (8 vs 13 years), have a
lifetime history of suicide attempts (35% vs 70%), rapid cycling
(14% vs 39%), and alcohol dependence (10% vs 31%).

Patients with OCD also had higher depression and anxiety symptom
scores than those without anxiety comorbidity, but fewer manic
symptoms.

Meanwhile, when compared with patients with other lifetime
anxiety disorders, those with OCD comorbidity had a lower quality
of life on the social domain.

Kapczinski et al comment: “Patients with OCD are troubled
by thoughts and behaviors, which seem frequently repugnant and
further restrict their social functioning.

“They also often incite friends or family members to engage in
their illness-related behaviors, which may result in conflict.”

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;
2010

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Accelerated loss of prefrontal gyrification in bipolar disorder is linked to having at least one brain-derived neurotropgic factor (BDNF) variant, although the overall rate is no higher in such patients, say UK researchers.

Studies have shown that there are structural cerebral abnormalities in bipolar disorder patients, but it is not clear whether they are present at disease-onset or develop over time. As a measure of brain morphology, the gyrification index (GI) of cortical folding has been found to be increased in patients with acute schizophrenia and decreased in those with chronic schizophrenia.

To examine GI changes in bipolar disorder, Ajay Mirakhur and colleagues, from the University of Edinburgh, performed magnetic resonance imaging at baseline and after 4 years in 18 bipolar I disorder patients and 18 healthy controls. They calculated prefrontal GI as the ratio of folded inner contour to exposed outer contour.

Both bipolar disorder patients and healthy controls had a significant decrease in GI over 4 years for dorsal and ventral prefrontal quadrants bilaterally, with no significant difference in the rate of change between patients and controls.

The team also found that bipolar disorder patients with at least one BDNF val⁶⁶met met allele experienced a significantly increased change in GI, particularly in the right dorsal prefrontal cortex, compared with patients with no copies of the BDNF val⁶⁶met met allele, with, GIs at baseline and at follow-up of 2.48 versus 2.31 and 2.47 versus 2.42, respectively.

Interestingly, the team notes in the journal Biological Psychiatry that carriers of the met allele were significantly older than non-carriers, at 43.9 years versus 35.1 years. After taking age into account, the associations between the met allele and change in GI were significant only in the dorsal quadrants. Taking into account medications had no effect on the findings.

“These findings suggest that GI is not purely a neurodevelopmental measure and raise the possibility that GI may be a sensitive measure of morphological change with time,” the researchers conclude.

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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Novel particles identified in the first fraction of cerebrospinal fluid (CSF) from bipolar disorder patients may correlate with the degree of underlying disease processes in the central nervous system, suggests a team of Swedish scientists.

Scanning electron microscopy (SEM) has been employed to recognize potentially pathogenic structures in the CSF of schizophrenia patients. However, it has not been used to examine the CSF of patients with bipolar disorder.

To investigate further, Lennart Wetterberg, from the Karolinska Institute in Stockholm, and colleagues compared fresh CSF samples from 56 euthymic bipolar disorder patients, of whom 31 had bipolar I disorder and 25 had bipolar II disorder, with those from 20 mentally healthy controls.

The team reports in the journal Bipolar Disorders that they studied the first 0.6 ml of CSF and the following 12.0 ml for microscopic structures, rating the quantity and patterns of the particles.

No particles were identified in CSF samples from the controls, either in the first or second fraction. In contrast, 45 bipolar disorder patients were found to have morphological structures in the first CSF fraction, while just two patients had such structures in the second CSF fraction.

Forty three of the patients with morphological structures in the first fraction had either spherical particles alone or in combination with thread-like forms, or threads with micrometer-sized spherical particles closely attached. The two remaining patients had threads without any spherical particles.

Patients with morphological structures were more likely to have bipolar I disorder, a history of psychosis in manic state and certified hospitalization, and lower comorbidity than those with no structures.

The team says: “The presence of microscopic structures in CSF might be relevant for future studies of the possible causative role of inflammation in the pathogenesis of bipolar disorder.”

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; 2010

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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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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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The availability of striatal dopamine transporter (DAT) is increased in bipolar disorder patients compared with healthy individuals, even in patients in the euthymic state, the results of a Taiwanese study indicate.

DAT activity is thought to reflect the general state of dopamine function in the brain, and previous research has shown that euthymic bipolar disorder patients have regions of abnormal brain activation.

To investigate striatal DAT availability in bipolar disorder, Yen Kuang Yang, from National Cheng Kung University Hospital in Tainan, and colleagues used single photon emission computed tomography (SPECT) with [^99mTc] TRODAT-1 to approximate DAT availability in 17 drug-free euthymic bipolar disorder patients and 17 healthy controls matched for age, gender, and education level.

The team reports in the journal Bipolar Disorders that there was no correlation between the DAT ratio and the duration of bipolar disorder, number of manic episodes, or number of depressive episodes.

Patients were found to have a significantly higher binding availability of DAT in the striatum than healthy controls, at an average effect size of 1.04. There were no significant differences in DAT availability between the seven patients with bipolar I disorder and the 10 with bipolar II disorder.

While noting that the study has several limitations, the team concludes: “The present results suggest that an upregulation of DAT may be the primary alteration which progressively leads to lowered intrasynaptic dopamine concentration and then influences the emotional process and cognition in euthymic bipolar patients.”

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; 2010

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Mutations in the dystrobrevin binding protein 1 gene (DTNBP1) are associated with bipolar disorder, say European researchers in findings that reinforce the genetic overlap between schizophrenia and bipolar disorder.

As there is evidence to suggest a degree of overlap in genetic susceptibility between schizophrenia and bipolar disorder, the DTNBP1 gene, which has been linked to schizophrenia, has come under scrutiny for its potential associations with bipolar disorder.

To investigate further, Darya Gaysina, from King’s College London, UK, and colleagues genotyped 515 bipolar disorder patients and 1316 ethnically matched healthy controls for eight single nucleotide polymorphisms (SNPs), conducting an association analysis in 452 bipolar disorder patients and 956 controls.

The results, published in the American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, showed that two SNPs ??” rs760761 and rs3213207 ??” were significantly associated with bipolar disorder, at odds ratios of 1.26 and 1.41, respectively, although only the former survived Bonferroni correction with borderline significance.

Furthermore, the G-C-G haplotype of the combined SNPs rs16876571-rs2619539-rs3213207, and the G-C-G-T haplotype of the combined SNPs rs16876571-rs2619539-rs3213207-rs760761, were significantly associated with bipolar disorder.

“Our results are consistent with previous studies in terms of a general association between the DTNBP1 and bipolar disorder,” the researchers conclude.

“They also provide additional molecular genetic evidence that a portion of the genotypic overlap between schizophrenia and bipolar affective disorder is attributable to this gene.”

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 and major depressive disorder (MDD) patients have differences in amygdala and orbitomedial prefrontal cortex (OMPFC) effective connectivity (EC) in response to happy faces, say researchers.

Bipolar depression is the most common presentation of bipolar disorder and often leads to a misdiagnosis of MDD. However, as emotional dysregulation is a central feature of bipolar disorder, neural dysfunction in systems supporting emotional regulation may help to discriminate the two groups.

To investigate further, Mary Phillips, from the University of Pittsburgh in Pennsylvania, USA, and colleagues studied 15 bipolar depressed and 16 MDD patients matched for age, age of illness onset, illness duration, and depression severity, and 16 age- and gender-matched healthy controls.

The participants were administered two event-related paradigms labeling the emotional intensity of happy and sad faces, respectively, during which OMPFC and amygdala blood oxygen level dependent signals were measured. Dynamic causal modeling was then used to examine significant among-group alterations in EC between right- and left-sided neural regions.

There were no differences among the groups in the labeling of emotional faces in either experiment, with no significant differences between the two depressed groups, the team notes in the journal Biological Psychiatry.

Compared with controls, both bipolar disorder and MDD patients had significantly reduced left-sided top-down OMPFC-amygdala EC during the happy experiment. EC values were positive for controls, close to zero for bipolar disorder patients, and negative for MDD patients.

Whereas bipolar disorder patients had significantly reduced right-sided bottom-up OMPFC-amygdala EC in response to the happy experiment, there were no significant differences between MDD patients and controls. EC values were positive for controls and MDD patients but negative for bipolar disorder patients.

The results also showed that, compared with controls, both MDD and bipolar disorder patients had significantly reduced left-sided top-down OMPFC-amygdala EC during the sad experiment.

“We show that bipolar depression and major depression are associated with different patterns of abnormal functional integration between different regions in neural systems supporting emotion regulation, in both hemispheres during happy emotion processing,” the team writes.

“This finding in turn suggests that different pathophysiological mechanisms might underlie these two types of depression and is a promising step forward toward identifying biological markers to distinguish between these different illnesses.”

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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It appears that variations in the CLOCK gene do not play a major role in the development of schizophrenia, bipolar disorder, or major depressive disorder (MDD), conclude Japanese investigators.

Clock genes not only regulate circadian rhythms but also have an influence on dopamine neural transmission, and it is thought that abnormalities in both of these systems are associated with schizophrenia, bipolar disorder, and MDD. Furthermore, there is evidence that CLOCK is linked to these conditions.

To investigate further, Taro Kishi, from Fujita Health University School of Medicine in Aichi, and colleagues genotyped 733 schizophrenia patients, 149 bipolar disorder patients, 324 MDD patients, and 795 healthy controls for the six tagging single nucleotide polymorphisms (SNPs) in CLOCK.

There were no overall associations between the tag SNPs and schizophrenia, bipolar disorder, or MDD. Exploration of gender differences revealed an association between one SNP and schizophrenia in women, although this did not survive Bonferroni correction.

The researchers also report in the European Archives of Psychiatry and Clinical Neuroscience that that there were no gender associations between any of the studied SNPs and MDD or bipolar disorder.

They suggest: “CLOCK may not play a major role in the pathophysiology of schizophrenia, bipolar disorder, and MDD in the Japanese population. However, it will be important to replicate and confirm these findings in other independent studies using larger samples.”

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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