Potential biomarkers for bipolar disorder: P11 expression and PET

Bipolar disorder (BD) is a complex, chronic psychiatric condition characterized by recurring episodes of depression and mania or hypomania. It is subdivided into BD-I and BD-II, based on the nature and severity of the mood episodes experienced. Substantial evidence demonstratesthat p11 (S100A10) and positron emission tomography (PET) are potential biomarkers for BD. For example, peripheral blood mononuclear cell (PBMC) p11 mRNA was over-expressed in BD compared with non-BD controls. Comparing BD patients to healthy controls (HCs), normalized glucose metabolism (NGM) was higher in the hippocampus, parahippocampus, and amygdala, but lower in the anterior cingulate cortex (aCC), medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (dlPFC), insula and thalamus. Compared to BD-II, BD-I had hypometabolism of glucose in the aCC, bilateral middle and inferior temporal gyrus, insula and striatum, and hypermetabolism of glucose in the left parahippocampus. In addition, PBMC p11 mRNA levels were significantly positively correlated with NGM in the mPFC, aCC, left insula, bilateral orbitofrontal cortex (OFC), and left middle, inferior and superior temporal gyri, and withthe number of depressive episodes in BD patients, especially in BD-I patients. These data demonstrate that PBMC p11 mRNA expression is associated with neural activation in the brain of BD patients and warrants a larger translational study to determine its clinical utility. In this chapter, we will discuss the background information of p11 as a potential biomarker for BD. In addition, we develop the concept of combining blood p11 levels with PET as biomarkers for BD diagnosis. We will also discuss the current status of this research, including methods, such as blood sample collection, mRNA purification, real time PCR and PET data analysis for BD biomarker identification. Specifically, we will discuss the strategies for developing a blood test and PET for BD diagnosis from bench to bedside and/or from bedside to bench, a two-way approach.