Neurotransmitter regulatory networks in persistent postural-perceptual dizziness: potential mechanisms and...

Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder characterized by persistent non-spinning dizziness, subjective unsteadiness, and symptom exacerbation induced by upright posture, movement, and complex visual motion. Abnormal vestibular sensory reweighting, increased visual dependence, postural hypervigilance, and comorbid anxiety are considered to contribute to the persistence of symptoms. Neurotransmitter systems, including serotonin, norepinephrine, dopamine, gamma-aminobutyric acid, glutamate, histamine, acetylcholine and neuropeptides, may participate in the disease-related neural network imbalance by modulating vestibular signal processing, emotional responses, and central compensation. However, direct evidence for PPPD-specific neurotransmitter abnormalities remains limited. In treatment, selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are commonly employed in clinical practice, yet evidence from placebo-controlled randomized trials remains insufficient. Vestibular and balance rehabilitation therapy, cognitive behavioral therapy, and transcranial magnetic stimulation may be incorporated into comprehensive management; however, the level of evidence and long-term efficacy differ across interventions. Future studies should integrate clinical phenotypes, comorbidities, and neural network features to develop stratified diagnostic and therapeutic strategies, while also strengthening neurotransmitter-related imaging, biomarker discovery, and multicenter randomized controlled trials.