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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Patients with bipolar disorder have reduced serum levels of glial cell line-derived neurotrophic factor (GDNF), suggesting this neurotrophic factor plays a role in the pathophysiology of the condition, say researchers in China.

“This finding suggests that peripheral GDNF synthesis or release is decreased during acute episodes of bipolar disorder,” Zhijun Zhang (Affiliated ZhingDa Hospital of Southeast University, Nanjing) and colleagues report.

They add: “It is unclear whether this represents a pathologic or compensatory mechanism.”

The team also found that 8 weeks of bipolar disorder treatment increased the bipolar patients’ GDNF levels to around normal levels.

As reported in the Journal of Affective Disorders, serum GDNF concentrations were measured in 40 patients with bipolar disorder before and after 8 weeks of drug treatment.

Before treatment, GDNF levels were significantly lower in bipolar disorder patients, both during manic and depressive episodes, at 466 pg/ml and 312 pg/ml, respectively, compared with an average of 750 pg/ml in 50 mentally healthy individuals.

The researchers note that serum GDNF levels in manic or depressive patients did not correlate significantly with age at onset, length of illness, or severity of symptoms.

“Thus, we speculate that the changes of GDNF may be state-related rather than trait-related,” say Zhang et al.

After 8 weeks of treatment, GDNF levels in the bipolar disorder patients rose significantly to 769 pg/ml in manic patients and to 809 pg/ml in depressive patients.

In turn, average scores on the Young Mania Rating Scale and on the Hamilton Depression Rating Scale decreased significantly in manic and depressive patients, respectively, from 31.9 to 7.0 and from 27.8 to 7.6.

“GDNF may be considered as a non-specific peripheral marker that can respond to drug treatment,” say Zhang and colleagues.

“This finding further supports the current hypothesis that neurotrophins are involved in the pathophysiology 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

Free abstract

Adding psychosocial therapy to standard drug treatment improves global functioning in patients with refractory bipolar disorder, study results demonstrate.

“Although these findings are preliminary, psychotherapy conducted in a group format seems both effective and efficient, at least with respect to quality of life, and it can easily be implemented in the setting of a mental health center or day hospital,” Ana González-Isasi (Santiago Apóstol Hospital, Spain) and colleagues comment.

In around half of patients with bipolar disorder, drug treatment alone fails to control the illness, with significant subsyndromal symptoms persisting beyond the acute stage.

“The use of psychosocial therapy in resistant bipolar disorder in combination with psychoactive drugs has received scant attention to date, with very few long-term controlled studies,” González-Isasi et al comment in the journal Psychiatry Research.

To investigate, the researchers recruited 20 bipolar disorder patients who had a history of poor disease course with two or more relapses in the preceding year, rapid cycling, hospitalizations in the past year, suicide attempts, or severe difficulties in social??”occupational functioning.

All patients received psychoactive drugs including mood stabilizers, antipsychotics, and benzodiazepines on an individual basis as indicated, and half the group was randomly assigned to receive a course of psychosocial treatment.

This consisted of 13 weekly group sessions, each lasting 1.5 hours, based on a cognitive-behavioral model.

In terms of depression and mania relapses, the proportion of patients with severe symptoms in the control group remained stable at 20% throughout follow-up, whereas in the combined treatment group the proportion fell from 20% to 10%. The difference between the groups was not, however, significant.

By contrast, patients in the combined group showed a significantly greater improvement in Global Assessment of Functioning than the standard treatment group, with baseline to 12-month improvements of 71.9 to 75 and 70.3 to 85, out of a maximum of 100, in the respective groups.

“A larger and better controlled study design is needed in future research and, depending on the mood instability found in this type of patients, more continuous follow-up visits and more specific variables for this disorder are required,” the researchers conclude.

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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