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Bipolar disorder patients, unlike those with schizophrenia, do not have an increased burden of copy number variants (CNVs) in their DNA, study results indicate.
There is extensive copy number variation in the human genome, and such variations may play an important role in disease susceptibility, including neuropsychiatric disorders such as schizophrenia and autism, explain Nick Craddock, from Cardiff University in the UK, and colleagues.
To determine associations between CNVs and bipolar disorder, the team conducted a genome-wide survey of large (>100,000 base pairs) and rare (in <1% of the population) CNVs in 1697 bipolar disorder patients and 2806 nonpsychiatric individuals, as well as in 440 schizophrenia patients.
There were no significant differences in the global CNV burden between bipolar disorder cases and controls, although there was a nominally significant decrease in the number of deletions in patients versus controls.
Furthermore, there were no significant differences in the burden of singleton CNVs between bipolar disorder patients and controls, nor in the burden of CNVs >1 Mb, whereas significant differences were observed between schizophrenia patients and controls.
The researchers report in the Archives of General Psychiatry that there were also no significant differences in the burden of CNVs that disrupt genes between bipolar disorder patients and controls, and individual CNVs previously linked to schizophrenia were not altered in bipolar disorder patients.
“We found that CNV load was not elevated in bipolar disorder compared with controls and that deletions larger than 1 Mb were less common in probands with bipolar disorder than in those with schizophrenia,” they explain.
“Our findings suggest that schizophrenia and bipolar disorder differ with respect to CNV burden in general and association with specific schizophrenia-associated CNVs in particular.”
The team concludes: “Our data are consistent with the possibility that possession of large, rare deletions may modify the phenotype in those at risk of psychosis: those possessing such events are more likely to be diagnosed as having schizophrenia, and those without them are more likely to be diagnosed as having 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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Functioning across a range of domains can be assessed in both schizophrenia and bipolar disorder patients using a brief performance-based measure, say US and Canadian researchers.
To examine the utility of the Brief University of California San Diego Performance-based Skills Assessment (UPSA-B) in the assessment of patients with bipolar disorder and schizophrenia, Brent Mausbach, from the University of California at San Diego, and colleagues studied 89 bipolar disorder patients and 116 schizophrenia patients.
In addition, the team determined functioning on the domains of independent living status, informant reports of functioning (including work and daily living skills), educational attainment and estimated premorbid intelligence quotient (IQ), and employment.
Controlling for age, psychiatric diagnosis, symptoms of psychopathology, age of illness onset, and gender, the researchers found that patients who lived independently scored significantly higher on the UPSA-B than less independent patients. For example, patients who were head of their household scored more than 80 points, on average, compared with 59 points for those living in a treatment facility.
Higher UPSA-B scores were significantly associated with better functioning in daily living skills and work skills on informant reports for both bipolar disorder and schizophrenia patients, and were significantly associated with greater estimated premorbid IQ.
Although employment was associated with significantly higher UPSA-B scores when taking into account age and diagnosis, the association was no longer significant when taking into account symptoms of psychopathology.
The researchers write in the journal Bipolar Disorders: “Our study suggests that the UPSA-B, a brief performance-based measure of functional capacity, is sensitive to impairments in multiple domains of everyday functioning in both bipolar disorder and in schizophrenia.”
They add: “These findings are consistent with recent work on the continuum of psychoses and point toward the utility of more dimensional models versus categorical distinctions between schizophrenia and 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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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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