Does the Brain Matter? Cortical Alterations in Pediatric Bipolar Disorder: A Critical Review of Structural and Functional Magnetic Resonance Studies

Background: Pediatric bipolar disorder (PBD) is associated with significant psychosocial impairment, high use of mental health services and a high number of relapses and hospitalization. Neuroimaging techniques provide the opportunity to study the neurodevelopmental processes underlying PBD, helping to identify the endophenotypic markers of illness and early biological markers of PBD. Objective: The aim of the study is to review available studies assessing structural and functional brain correlates associated with PBD. Methods: PubMed, ISI Web of Knowledge and PsychINFO databases have been searched. Studies were included if they enrolled patients aged 0-18 years with a main diagnosis of PBD according to ICD or DSM made by a mental health professional, adopted structural and/or functional magnetic resonance as the main neuroimaging method, were written in English and included a comparison with healthy subjects. Results: Of the 400 identified articles, 46 papers were included. Patients with PBD present functional and anatomic alterations in structures normally affecting regulations and cognition. Structural neuroimaging revealed a significant reduction in gray matter, with cortical thinning in bilateral frontal, parietal and occipital cortices. Functional neuroimaging studies reported a reduced engagement of the frontolimbic and hyperactivation of the frontostriatal circuitry. Conclusion: Available studies on brain connectivity in PBD patients potentially indicate less efficient connections between regions involved in cognitive and emotional functions. A greater functional definition of alteration in brain functioning of PBD patients will be useful to set up a developmentally sensitive targeted pharmacological and non-pharmacological intervention.