US researchers have found significant white matter tract alterations in adolescent patients with bipolar disorder (BD) within pathways involved in emotional, behavioral, and cognitive regulation.

“These results suggest that alterations in white matter are present early in the course of disease in familial BD,” say Naama Barnea??”Goraly (Stanford University, California) and co-authors.

A number of studies indicate that white matter abnormalities are present in BD. To investigate further, the researchers analyzed diffusion tensor imaging (DTI) images using a whole-brain voxel-by-voxel analysis to investigate white matter structure in 21 adolescents with familial BD and 18 age- and intelligence quotient-matched healthy individuals.

BD patients had lower white matter fractional anisotropy (FA) values than healthy individuals within the limbic system (the fornix and the left mid-posterior cingulated gyrus), which has been hypothesized to contribute to the combination of affective, cognitive, and vegetative symptomatology in BD.

The researchers point out that the fornix findings in their study should be interpreted with caution due to the thin nature of the fornix, which could result in partial volume effects.

BD patients also had lower FA values than controls throughout the corpus callosum, in fibers extending from the fornix to the thalamus, and in parietal and occipital radiata bilaterally.

Barnea??”Goraly and team say that their finding of reduced FA in the corpus callosum is at odds with a previous study in adults, which “may indicate an abnormal maturation process in the corpus callosum occurring in individuals with BD, with lower FA in adolescence representing reduced coherence or aberrant myelination with increasing FA with age.”

No significant differences were seen between groups in apparent diffusion coefficient values, a measure of overall diffusivity. Furthermore, there were no significant correlations between behavioral measures or medication exposure and FA values.

“An intriguing and important follow-up study will be to investigate whether early treatment of BD normalizes the development of these pathways and if improvement of particular symptoms is associated with structural changes in regional white matter anatomy,” suggest the researchers.

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

Free abstract

• FDA Issues Complete Response Letter For RISPERDAL(R) CONSTA(R) For Adjunctive Maintenance Treatment Of Bipolar Disorder
• Cephalon Announces Positive Results From A Phase Two Study Of NUVIGIL In Bipolar Depression
• Brain activity determines risk or resilience in bipolar disorder

Patients with bipolar disorder are more likely to be admitted to hospital with a cardiovascular (CV) event than individuals without the disorder, results of a longitudinal study suggest.

Crucially, the present study, published in the Journal of Affective Disorders, is one of the few that have measured the incidence of actual CV morbidity in bipolar disorder patients, rather than simply the prevalence of CV risk factors.

“These findings add weight to current treatment guidelines… stressing the importance of integrated psychiatric and somatic care for persons with bipolar disorder,” comment study authors Russell Callaghan and Anbreen Khizar from the Centre for Addiction and Mental Health in Toronto, Ontario, Canada.

Individuals with bipolar disorder are vulnerable to a wide range of metabolic medical conditions, which in turn impacts on CV health. Yet almost all of the research linking bipolar disorder and CV morbidity has come from cross-sectional or case-series studies.

Noting a lack of longitudinal data, Callaghan and Khizar identified all hospital discharges of patients with bipolar disorder (n=5999) in the Ontario area between 2002 and 2006. They also recorded discharges of an equal number of patients with appendicitis, to serve as a matched population-proxy group of control individuals.

They then assessed incidence of readmission to hospital for CV events in both groups of patients in the 4 years after the original admission.

In all, there were 156 CV events in the appendicitis group and 280 in the bipolar group. Regression analysis revealed that after adjustment for age, tobacco use, diabetes, and lipid disorders, patients with bipolar disorder faced a significant 66% increased risk for readmission for CV events relative to patients with appendicitis.

Discussing their findings, the researchers note a recent Veteran’s Affairs study showing that only 50% of patients with bipolar disorder on atypical antipsychotics received the recommended lipid tests and about two-thirds received glucose testing for routine CV disease.

“In light of the elevated risk for CV morbidity among persons with bipolar disorder, our findings add to the importance of screening and intervention programs for metabolic disorders and known CV risk factors among patients with bipolar disorder,” Callaghan and Khizar comment.

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

Free abstract

• FDA Advisory Committee Votes In Favor Of Zyprexa For Two Adolescent Indications
• Schering-Plough Submits Response To FDA For SAPHRIS(TM) (asenapine) In The Acute Treatment Of Both Schizophrenia And Bipolar I Disorder
• New Research Under Way To Study Treatment For Older Adults With Bipolar Disorder

A variant in the 5-hydroxytryptamine (serotonin) receptor 5A (HTR5A) gene may be involved in the pathogenesis of bipolar disorder, says an international team of scientists, although they urge caution in interpreting the findings.

Despite a wealth of research into the etiology of bipolar disorder and evidence to suggest that it is the result of an interaction between genetic and environmental factors, no single gene has been identified as being definitively associated with the disorder.

Yusuke Nakamura, from the University of Tokyo in Japan, and colleagues genotyped 94 bipolar disorder patients and 184 healthy controls from Bulgaria for 191 single nucleotide polymorphisms (SNPs) in 65 candidate genes using TaqMan and/or Invader assays.

In all, 17 SNPs were significantly associated with bipolar disorder and these were further genotyped in an additional set of 78 bipolar disorder patients and 372 controls, with the results pooled with the previous analysis to give a combined set of 172 patients and 556 controls.

The most significant association with bipolar disorder was found for the rs1800883 SNP in a promoter region of the HTR5A gene, which was unaffected by sequential Bonferroni correction, the team notes in the Journal of Affective Disorders.

Analysis revealed that 56.7% of the patients were homozygous for the G risk allele, compared with 42.1% of controls, giving an odds ratio of 1.80. In addition, the risk allele was more common in patients than in controls, at 73.7% versus 62.1%.

A weak association was also found for the rs6265 SNP located in exon 2 of the brain-derived neurotrophic factor gene, with the risk C allele more frequently seen in patients than controls, while a possible association was observed for the rs5443 SNP in exon 10 of the guanine nucleotide binding protein, beta polypeptide 3 gene. However, neither survived Bonferroni correction.

“In conclusion, our findings suggest that HTR5A gene could be one of many genes of importance in the etiology of bipolar disorder in the Bulgarian population, but the effect by the genetic substitution seemed to be small even if the association is further confirmed,” the team writes.

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

Free abstract

• Eighth International Conference On Bipolar Disorder To Be Held In Pittsburgh, June 25 To 27
• A Combination Of Common Genetic Variations Can Lead To Schizophrenia
• Long-Term Tolerability And Safety Data Of Abilify(R) In Combination Treatment For Patients With Bipolar I Disorder