PET Imaging Unveils Neuroinflammatory Mechanisms in Psychiatric Disorders: From Microglial Activation to Therapeutic Innovation
Yu-dan Liu, Yiheng Chang, Xueting Xie, Xinyao Wang, Hongliang Ma, Meichen Liu, Huimin Zhang
Abstract
Recent advancements in neuroinflammation research have significantly enhanced our understanding of its pivotal role in the pathogenesis and pathophysiology of psychiatric disorders. Positron emission tomography (PET) imaging, leveraging its unique ability to quantify biological processes in vivo non-invasively, has emerged as a transformative tool for investigating neuroimmune mechanisms. The 18 kDa translocator protein (TSPO), a biomarker of activated microglia and astrocytes during neuroinflammation, enables PET-based visualization of neuroinflammatory activity, offering novel insights into the neurobiological underpinnings of psychiatric conditions. This review synthesizes recent TSPO PET imaging findings across major psychiatric disorders, including major depressive disorder (MDD), obsessive–compulsive disorder (OCD), posttraumatic stress disorder (PTSD), schizophrenia, and psychosis. We critically evaluate how TSPO PET elucidates neuroinflammatory signatures linked to disease progression, treatment responses, and therapeutic stratification. Furthermore, we explore the translational potential of anti-inflammatory agents (e.g., celecoxib and minocycline) and TSPO-targeted ligands (e.g., etifoxine and XBD173) in modulating neurosteroid synthesis and neuroimmune interactions. By bridging methodological innovations with clinical applications, this review underscores the promise of TSPO PET in advancing diagnostic precision, personalized treatment strategies, and mechanistic insights into neuroinflammation-driven psychiatric pathologies. Challenges such as genetic polymorphisms (e.g., rs6971), partial volume effects (PVEs), and quantification biases are discussed to guide future research directions. Schematic overview of TSPO PET imaging in psychiatric disorders. (Created with BioRender.com). black diamond, consistent TSPO elevation region; black circle, conflicting findings. Abbreviations: ACC, anterior cingulate cortex; PFC, prefrontal cortex; OFC, orbitofrontal cortex; TSPO, translocator protein; PET, positron emission tomography; MDD, major depressive disorder; OCD, obsessive–compulsive disorder; PTSD, posttraumatic stress disorder; PVE, partial volume effect; HAB, high-affinity binder; MAB, mixed-affinity binder; LAB, low-affinity binder