Deficits of Neurotransmitter Systems and Altered Brain Connectivity in Major Depression: A Translational Neuroscience Perspective

Abstract

Recent studies that examined brain characteristics for major depressive disorder (MDD) have reported deficient neurotransmitter system, altered brain morphology and patterns of white matter-based brain inter-regional connections, and differential brain inter-regional coherence of oscillatory patterns during resting and task performance status compared to healthy controls. For better understanding of the MDD pathophysiology that underlies clinical symptoms, the current review provides practical approaches of multimodal brain imaging encompassing the regional deficiency of neurotransmitter receptors or synaptic density to altered patterns of brain inter-regional connection or communication for MDD. First, to elucidate the deficits of neurotransmitter system in MDD, the current review illustrates how to acquire the brain molecular positron emission tomography (PET) images and estimate the synaptic density in addition to the binding potential (or receptor availabilities) of serotonergic (5-HT transporter and 5-HT1A autoreceptor), glutamatergic (metabotropic glutamate receptor 5), and dopaminergic (D2 receptor) system across the whole brain. Second, the current review demonstrates how to explore the possible associations between the regional deficits of neurotransmitter binding potential and altered resting-state functional connectivity [voxel-to-whole brain (intrinsic functional connectivity) or region-to-region (seed-based functional connectivity)], structural connectivity [brain white matter-based region-to-region structural connectivity, estimated using the probabilistic fiber tracking system], and directed functional connectivity [region-to-region] during task performance in MDD. Third, opened resources of software and pipelines that could be applied in running these analytical procedures are also provided. © 2022, The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.