PET Imaging in Psychiatric Disorders.

Abstract

Positron emission tomography (PET) has emerged as a pivotal imaging modality in the investigation of psychiatric disorders, enabling in vivo assessment of regional cerebral metabolism, neurotransmitter dynamics, receptor binding, synaptic density, and neuroinflammation. This comprehensive review synthesizes current evidence on the utility of PET imaging in elucidating the pathophysiology of major psychiatric conditions-including schizophrenia, mood disorders, autism spectrum disorder, attention-deficit/hyperactivity disorder, and addiction and its potential in clinical decision-making. ¹⁸F-FDG-PET has consistently demonstrated regional metabolic abnormalities, most notably prefrontal hypometabolism in schizophrenia and major depressive disorder, with implications for negative symptomatology, cognitive dysfunction, and treatment resistance. Functional FDG-PET (fPET) has recently enabled dynamic metabolic mapping with high temporal resolution, allowing the evaluation of stimulus-induced changes in neuronal activity. Receptor-specific PET tracers have provided further insights into dopaminergic, serotonergic, glutamatergic, and GABAergic dysregulation across psychiatric spectra. Notably, schizophrenia is associated with a increased striatal dopamine (DA) synthesis capacity and DA release, and disrupted frontolimbic connectivity, while depression shows reduced serotonergic transporter binding and lower mGluR5 availability, supporting neurotransmitter system-based subtyping. PET imaging has also revealed neuroinflammatory signatures, such as altered TSPO binding, as well as synaptic density reductions via SV2A tracers in early psychosis, emphasizing shared neurobiological underpinnings and disease progression markers. In pediatric and neurodevelopmental disorders, including ASD, PET and multimodal approaches have contributed to identifying heterogeneous neurochemical phenotypes, linking abnormal glucose metabolism and receptor availability to specific behavioral domains. Clinically, PET imaging aids in the differential diagnosis of primary psychiatric disorders from neurodegenerative conditions, including behavioral variant frontotemporal dementia (bvFTD), by detecting disease-specific metabolic patterns and supporting biomarker-informed diagnostics. Furthermore, PET has been employed to predict and monitor treatment response across pharmacological and neuromodulatory interventions, including antidepressants, electroconvulsive therapy (ECT), and cognitive behavioral therapy (CBT), enabling strides toward personalized psychiatric care. Despite its promise, widespread clinical integration of PET in psychiatry remains limited by high cost, accessibility barriers, and the need for standardized acquisition and interpretation protocols. Ongoing advancements in radiopharmaceutical development, artificial intelligence, and normative imaging databases are expected to facilitate the incorporation of PET into routine psychiatric assessment and therapeutic planning. This review underscores the transformative role of PET in precision psychiatry and advocates for its expanded research and clinical application.