Neuroimaging Evidence of Mitochondrial Dysfunction and Inflammation in Psychiatric Disorders: A Review

Abstract Mitochondrial dysfunction and neuroinflammation are two fundamental pathological processes underlying the development of psychiatric disorders. These processes are interconnected and may jointly contribute to disease progression. This article systematically reviews the progress of multimodal imaging approaches for assessing mitochondrial function, including magnetic resonance spectroscopy (MRS), PET tracers targeting mitochondrial complexes, MRI-based cerebral metabolic rate of oxygen (CMRO₂), and emerging techniques such as T1ρ imaging and manganese-enhanced MRI (MEMRI), as well as neuroinflammation, including translocator protein (TSPO) PET, monoamine oxidase B (MAO-B) PET, novel tracers targeting C3aR/IL-1β, and diffusion imaging techniques reflecting white matter microstructural alterations. These approaches have been applied to various psychiatric disorders, including schizophrenia (SZ), major depressive disorder (MDD), bipolar disorder (BD), post-traumatic stress disorder (PTSD), autism spectrum disorder (ASD), sleep disorders, and substance use disorders (SUD). Based on imaging evidence across different psychiatric disorders and cohorts, this review summarizes three transdiagnostic imaging features: impaired mitochondrial energy metabolism, alterations in glial cell immune status, and white matter microstructural alterations associated with neuroinflammation. However, although individual imaging techniques have independently identified mitochondrial dysfunction and neuroinflammation, few studies have applied dual-target imaging within the same research cohort. The direct relationship between these processes remains unverified by in vivo studies. This review outlines the shared imaging features of various psychiatric disorders and examines the utility of multimodal imaging techniques in investigating mitochondrial and neuroinflammatory pathologies. It aims to provide new insights into the diagnosis and treatment of psychiatric disorders.