Abstract: Schizophrenia is a severe and complex psychiatric disorder with high heterogeneity, characterized by positive symptoms (such as hallucinations and delusions), negative symptoms (including emotional blunting and social withdrawal), and extensive cognitive impairments, which severely affect patients’ cognitive, emotional, and behavioral functions. Among its core neurophysiological features, abnormal sensory processing—especially deficits in sensory attenuation—has attracted increasing attention in academic circles. Sensory attenuation plays a crucial role in regulating individuals’ adaptive responses to environmental stimuli: it enables the brain to dynamically adjust the responses of neuronal populations to repetitive sensory inputs, filter out irrelevant information, and prioritize the processing of important signals, thereby ensuring the efficient allocation of cognitive resources. However, schizophrenia patients often exhibit significant abnormalities in sensory attenuation, manifested as hypersensitivity to environmental stimuli and reduced ability to screen information. This neurophysiological disturbance not only directly leads to cognitive control deficits and abnormal subjective experiences but also is closely associated with the emergence of core symptoms like hallucinations, potentially serving as the neurobiological basis for the disease’s cognitive and behavioral abnormalities. Neurotransmitters, as key substances for information transmission between neurons, are critical regulators of sensory attenuation mechanisms. A large body of research has confirmed that functional abnormalities in multiple neurotransmitter systems—including glutamate, dopamine, and γ-aminobutyric acid (GABA)—are closely related to the pathogenesis of schizophrenia and are important factors contributing to the disruption of sensory attenuation mechanisms, though their specific regulatory mechanisms have not yet been fully and systematically clarified. Glutamate, the main excitatory neurotransmitter in the brain, affects sensory attenuation through abnormal activity of glutamatergic neurons (e.g., reduced activity in the prefrontal cortex and hippocampus) and dysfunction of N-methyl-D-aspartate (NMDA) receptors, which impairs synaptic plasticity and the brain’s adaptive responses to repetitive stimuli. Dopamine, a major modulatory neurotransmitter, exerts complex effects on sensory attenuation: abnormal activity of dopaminergic neurons in brain regions such as the striatum and prefrontal cortex, along with dysfunction of dopamine receptors (particularly D1 receptors), leads to biased processing and integration of sensory information, resulting in hypersensitivity to sensory stimuli. GABA, the primary inhibitory neurotransmitter in the brain, contributes to sensory attenuation deficits through reduced numbers or impaired function of GABAergic neurons in key brain regions (e.g., prefrontal cortex, hippocampus) and dysfunction of GABA-A receptors, disrupting the inhibitory regulation of neuronal excitability and thus the normal sensory attenuation process. Genetic factors further modulate the function of these neurotransmitter systems. For instance, the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene affects dopamine metabolism, while polymorphisms in GRIN genes (which encode NMDA receptor subunits) regulate glutamate signaling; both ultimately influence sensory attenuation by altering neurotransmitter function. From a cognitive neuroscience perspective, neurotransmitter abnormalities disrupt the normal activity of visual, auditory, and tactile sensory pathways and impair the functional integrity of the default mode network (DMN), further exacerbating sensory attenuation deficits in schizophrenia patients. This review integrates multimodal evidence from neurobiology, molecular genetics, and cognitive neuroscience to systematically discuss the regulatory roles of neurotransmitters in abnormal sensory attenuation in schizophrenia. It emphasizes the need for future longitudinal studies combining dynamic neuroimaging techniques (e.g., fMRI, PET) to clarify the temporal relationship between neurotransmitter abnormalities and sensory attenuation deficits. Additionally, it proposes that future research should focus on developing targeted interventions (such as D1 receptor modulators and NMDA receptor partial agonists) and constructing individualized prediction models using multi-omics data and machine learning algorithms, with the goal of providing a scientific basis for precise intervention in schizophrenia and promoting improvements in patients’ prognosis and social function recovery.

Key words: schizophrenia, sensory attenuation, neurotransmitter, neural pathway