Large, rare CNV burden reduced in bipolar disorder

By Ingrid Grasmo, medwireNews Reporter

Large and rare chromosomal copy number variants (CNVs) are uncommon in patients with bipolar disorder (BD), even those with early-onset disease, study findings confirm.

Large, rare CNVs have been shown to increase the risk for developing schizophrenia and other neuropsychiatric disorders, and often predispose individuals to persistent brain dysfunction and poor disease prognosis.

"We postulate that one difference between some schizophrenia and [bipolar disorder] cases is the co-occurrence of a neurodevelopmental abnormality that can be caused by certain large and rare CNVs," say Nick Craddock (MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff, UK) and colleagues.

Craddock and team collated genotyping data from 1650 previously reported bipolar disorder cases and 10,259 individuals without a known psychiatric disorder who took part in the Wellcome Trust Case Control Consortium study.

Findings revealed that the rate of CNVs larger than 100 kb was not significantly different between bipolar disorder patients and individuals without psychiatric illnesses. Furthermore, the rate of very large (>1 Mb) and rare (<1% incidence) CNVs was significantly lower among bipolar disorder patients than among individuals without psychiatric disorders.

The results of the study, published in Bipolar Disorders, also showed that patients with bipolar disorder did not have an increased rate of CNVs commonly associated with schizophrenia. In fact, the incidence of these CNVs was nonsignificantly lower in bipolar disorder patients compared with controls, at 0.49% versus 0.86%.

This was true even for patients with early-onset bipolar disorder, who would have been hypothetically at greater risk for CNVs, according to Craddock and team.

They say that their observation of lower levels of large, rare CNVs in bipolar disorder patients supports the notion that individuals at the upper end of brain functioning distribution are more likely to fulfill criteria for a mood disorder rather than schizophrenia.

“[A]n individual who develops episodic psychosis in the context of non-compromised brain functioning may be able to cope more effectively with the disturbance of mental state, make more sense of symptomatology, and tend not to have persistent impairment between episodes. In current diagnostic practice, such an individual is more likely to attract a diagnosis of psychotic mood disorder,” they explain.

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