Diagnostic value of structural, functional and effective connectivity in bipolar disorder.

Introduction: The aim of this systematic review is to assess the functional magnetic resonance imaging (fMRI) studies of bipolar disorder (BD) patients that characterize differences in terms of structural, functional, and effective connectivity between the patients with BD, patients with other psychiatric disorders and healthy controls as possible biomarkers for diagnosing the disorder using neuroimaging.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), guidelines a systematic search for recent (since 2015) original studies on connectivity in bipolar disorder was conducted in PUBMED and SCOPUS.

Results: A total of 60 studies were included in this systematic review: 20 of the structural connectivity, 33 of the functional connectivity, and only 7 of the studies focused on effective connectivity complied with the inclusion and exclusion criteria.

Discussion: Despite the great heterogeneity in the findings, there are several trends that emerge. In structural connectivity studies, the main abnormalities in bipolar disorder patients were in the frontal gyrus, anterior, as well as posterior cingulate cortex and differences in emotion and reward-related networks. Cerebellum (vermis) to cerebrum functional connectivity was found to be the most common finding in BD. Moreover, prefrontal cortex and amygdala connectivity as part of the rich-club hubs were often reported to be disrupted. The most common findings based on effective connectivity were alterations in salience network, default mode network and executive control network. Although more studies with larger sample sizes are needed to ascertain altered brain connectivity as diagnostic biomarker, there is a perspective that the method could be used as a single marker of diagnosis in the future, and the process of adoption could be accelerated by using approaches such as semiunsupervised machine learning.