Support for progranulin role in bipolar disorder

By Lucy Piper, Senior medwireNews Reporter

Researchers have found reduced levels of plasma progranulin in patients with bipolar disorder, strengthening evidence for its possible role as a biomarker for the condition.

But they caution against the use of decreased progranulin levels alone as a reliable means of establishing a bipolar disorder diagnosis.

“Larger studies however might be able to delineate a subgroup of [bipolar disorder] patients characterized by drastically decreased progranulin levels and other (neuro-)inflammatory markers in an attempt to better characterize an ‘inflammation subgroup’ of [bipolar disorder],” they suggest.

Progranulin is encoded by the granulin gene (GRN), variants of which have been confirmed in autosomal dominant fronto-temporal lobar degeneration. It is involved in several physiological and pathophysiological processes in peripheral blood as well as the central nervous system.

Enzyme-linked immunosorbent assay of blood plasma showed that 104 patients with bipolar disorder had significantly lower levels of progranulin than 80 mentally healthy individuals, at an average of 141.3 ng/mL versus 152.4 ng/mL.

This association was independent of bipolar subtype and polarity. But progranulin levels were significantly affected by increasing age and treatment with mood stabilisers; the former correlation being positive and the latter negative.

Sarah Kittel-Schneider (University of Würzburg, Germany) and co-workers also assessed the influence of several genetic variations of GRN on progranulin plasma levels and found that one, rs5848, had a significant effect on progranulin levels in bipolar disorder patients only.

“Genetic variation located at this binding site […] leads to a changed binding of this [micro]RNA and subsequently altered translational processing,” the researchers comment in the Journal of Affective Disorders.

They call for further studies to determine whether such genetic risk variants and lower progranulin levels make bipolar disorder patients more susceptible to fronto-temporal lobar degeneration.

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