Functional Magnetic Resonance Imaging And DNA Methylation Study Of Pediatric Bipolar Disorder

Objective:In the present study, we firstly investigated differences in resting-state brain activity in patients with pediatric bipolar disorder (PBD) during mania state and euthymic state and healthy controls by measuring the amplitude of low-frequency fluctuation (ALFF) of functional magnetic resonance imaging (fMRI) signals. Secondly, we explored epigenetic mechanisms in the etiology of PBD patients during mania state and euthymic state and healthy controls by measuring global leukocyte DNA methylation in peripheral blood.Methods:1. Nineteen PBD patients during mania phase,17PBD patients during euthymic phase and19gender-, age-, and education-matched healthy subjects were enrolled in this study and all participants underwent fMRI scanning. The ALFF method was used to compare the resting-state spontaneous neuronal activity between groups.2. DNA was extracted from peripheral blood leukocytes of17manic bipolar patients,15euthymic bipolar patients and19matched healthy controls. Percent of global genome DNA methylation was measured using the cytosine-extension method.Results:1. The results of variance of resting-state fMRI showed altered ALFF in the following brain regions:bilateral superior frontal gyrus, bilateral cauduate, left lenticular nucleus, bilateral globus pallidus, left amygdale, right superior temporal gyrus and inferior occipital gyrus.2. There was significant change in the global leukocyte DNA methylation in these groups. Compared with the euthymic patients or healthy subjects, the manic patients showed increased DNA methylation in peripheral blood.Conclusions:This study presents new evidence for fronto-limbic-striatal circuits in PBD patients and DNA methylation may play an important role in the etiology of PBD. Both of these new evidences may add fresh insights into pathophysiological mechanisms underlying PBD.