Bipolar disorder patients do not have accelerated prefrontal gyrification index (GI) loss, but having at least one brain-derived neurotrophic factor (BDNF) gene variant may increase loss, UK scientists have found.

Brain structural abnormalities, including temporal lobe and prefrontal cortex volume reductions, have been identified in bipolar disorder patients. However, it is not clear whether the abnormalities are present at disease onset or whether they develop over time.

Noting that the BDNF valine (val)⁶⁶methionine (met) variant has been linked to such brain changes, Ajay Mirakur and colleagues from the University of Edinburgh performed magnetic resonance imaging (MRI) at baseline and after 4 years in 18 bipolar I disorder patients and 18 healthy controls.

The GI was calculated as the ratio of folded inner contour to exposed outer contour. In addition, the participants underwent clinical assessment and were genotyped for BDNF val⁶⁶met.

Both bipolar disorder patients and healthy controls were found to have a significant decrease in GI over 4 years in all prefrontal quadrants, and there was no significant difference in the rate of change of GI between patients and controls.

Comparing bipolar disorder patients with and without at least one BDNF val⁶⁶met met allele, the team discovered that having at least one met allele was associated with a significantly increased change in GI over 4 years in all four prefrontal quadrants, but particularly in the right dorsal prefrontal cortex.

Carriers of a met allele were significantly older than val/val homozygotes, at 43.9 years versus 35.1 years. When taking age into account, there was a trend toward a significant difference in change in GI between met carriers and val/val homozygotes in the ventral quadrants, and a significant difference in dorsal quadrants.

The researchers conclude in the journal Biological Psychiatry: “We show that GI decreases significantly over time and that the rate of change in GI is not different in bipolar patients compared with control subjects but is accelerated in bipolar participants possessing at least one BDNF allele.

“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.”

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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The pathological process of bipolar disorder and schizophrenia may be due, in part, to oxidative damage, say Canadian researchers in findings that may point to novel treatment approaches.

There is increasing evidence to suggest that mitochondrial dysfunction is present in the brains of bipolar disorder patients. Furthermore, the mitochondrial electron transport chain is a major source of reactive oxygen species, which cause oxidative stress.

To examine associations between bipolar disorder and oxidative stress, Jun-Feng Wang and colleagues from the University of British Columbia in Vancouver studied postmortem anterior cingulate brain sections from 15 bipolar disorder patients, 15 major depressive disorder (MDD), patients, 15 schizophrenia patients, and 15 controls matched for age, gender, postmortem interval (PMI), pH, and messenger RNA quality.

As a surrogate for oxidative stress, levels of 4-hydroxynonenal (4-HNE), which s a major product of lipid peroxidation, were determined via immunohistochemical analysis of 4-HNE protein adducts.

Compared with controls, 4-HNE levels were significantly increased in bipolar disorder and schizophrenia patients by 59% and 47%, respectively. Although levels were 33% higher in MDD patients than in controls, the difference was not significant.

Studying medication-free patients only, the team found that 4-HNE levels were increased significantly compared with controls in both bipolar disorder and schizophrenia patients, at 94% and 72%, respectively, with no change recorded in MDD patients.

Four-HNE levels were unaffected by age, gender, and PMI. In all brain samples, 4-HNE levels were negatively correlated with pH, the team says in the journal Bipolar Disorders.

However, 4-HNE levels were still significantly increased in bipolar disorder patients and there was a trend for an increase in schizophrenia patients when pH was used as a covariate. In addition, 4-HNE levels were negatively correlated with pH only in bipolar disorder patients.

“Oxidative damage in the brain may contribute to the pathological process of bipolar disorder and schizophrenia, and anti-oxidative stress may well serve as an alternative approach to pharmacological treatment of these psychiatric disorders, 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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A new study from Thomson Reuters found that patients with bipolar disorder were at greater risk for a wide range of medical conditions than a control group of patients with no mental health diagnoses.

The study analyzed de-identified insurance claims for more than 600,000 Americans with employer-sponsored insurance. It is available here and an interactive graphic charting bipolar patients’ risk of comorbid disorders is available here. Key findings include the following:

– Trauma or Adverse Reactions to Treatment: Patients diagnosed with bipolar disorder were 3.13 times more likely than the control group to have a trauma or adverse reaction to treatment. Approximately 7 percent of bipolar cases had at least one such episode in the two-year study period.

– Neurological Episodes: Neurological conditions — such as headaches and spinal cord injuries — occurred 2.27 times more frequently among bipolar patients. Approximately one-fourth of all enrollees with a bipolar episode also had at least one episode involving the neurological system.

– Female Reproduction: Conditions involving the female reproductive system — such as dysfunctional uterine bleeding and breast cancer — were 25 percent more common among bipolar patients.

The study is based on data contained in the 2006-2007 MarketScan(R) Commercial Claims and Encounters Database. The Thomson Reuters Medical Episode Grouper was used to group each enrollee’s claims into distinct episodes of care based on the disease for which treatment was received.

“Medication use and behavioral characteristics are known to increase the risk of disease among bipolar patients, but much is still unknown about the reasons for increased rates of comorbidities among this population and ways to reduce them,” said William D. Marder, Ph.D., senior vice president and general manager for the Healthcare & Science business of Thomson Reuters and one of the study’s authors. “Our analysis underscores the urgent need for further exploration of how to best increase providers’ capacity to address, monitor and ultimately improve the psychiatric and physical health of their bipolar patients.”

About Thomson Reuters

Thomson Reuters is the world’s leading source of intelligent information for businesses and professionals. We combine industry expertise with innovative technology to deliver critical information to leading decision makers in the financial, legal, tax and accounting, scientific, healthcare and media markets, powered by the world’s most trusted news organization. With headquarters in New York and major operations in London and Eagan, Minnesota, Thomson Reuters employs more than 50,000 people in 93 countries

Source: Thomson Reuters

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