精神分裂症多通路精准治疗的研究进展OA

Schizophrenia is a severe and highly heterogeneous psychiatric disorder,with a lifetime prevalence of approxi-mately 0.5％-1％.It is characterized by positive and negative symptoms,as well as cognitive impairment,all of which sig-nificantly affect patients' social functioning and quality of life.Current clinical management relies primarily on dopamine D2/3 receptor antagonists.While these agents effectively alleviate positive symptoms in most patients,their efficacy in treating cognitive and negative symptoms remains limited,and they are often associated with extrapyramidal side effects and metabolic disturbances.To address these limitations,recent research has shifted toward novel therapeutic targets within and beyond the dopaminergic system.Investigations into dopamine D2 autoreceptors,trace amine-associated receptor 1 agonists,and M4 muscarinic receptor agonists have shown promising results.Among these,ulotaront and KarXT have demonstrated potential in ameliorating both positive and certain negative symptoms.For cognitive and negative symptoms,efforts have focused on precise modulation of the glutamatergic and γ-aminobutyric acid systems,involving compounds such as metabotropic glutamate receptors 2/3(mGluR2/3)agonists,N-methyle-D-aspartate(NMDA)receptor co-agonists,BI425809,and Kv3.1/Kv3.2 potassium channel modulators.Neuroimaging studies have revealed contrasting neurotransmitter abnormalities between cortical and subcortical regions,prompting the development of region-specific interventions.These include transcranial brain stimulation and pharmacological agents targeting specific γ-aminobutyric acid interneurons.In parallel,non-pharmacological interventions are increasingly recognized for their therapeutic value.Neuromodulation techniques such as transcranial magnetic stimulation and transcranial direct current stimulation show promise in addressing multidimensional symptoms.Additionally,psychosocial interventions including cognitive behavioral therapy,cognitive re-mediation training,and social skills training,contribute to improved cognitive performance,social adaptation,and quality of life.This review summarizes emerging drug targets and non-drug strategies in the treatment of schizophrenia,highlighting their underlying mechanisms and clinical relevance.It aims to provide a foundation for future advances in personalized and multidimensional treatment approaches.