A novel precision medicine framework based on the excitation-inhibition imbalance model, for treatment of schizophrenia across the life span

Schizophrenia is increasingly recognized as a neurodevelopmental disorder arising from excitation-inhibition (E/I) imbalance within cortical and subcortical networks. The E/I imbalance model posits that converging genetic, epigenetic and environmental influences act through glutamatergic (Glu) and gamma-aminobutyric acid (GABA)-ergic dysfunction, redox and immune dysregulation to destabilize neural E/I homeostasis across sequential stages of the neurodevelopmental trajectory. This framework provides a mechanistically integrated explanation for the diverse symptom dimensions and progressive course of schizophrenia, while identifying modifiable targets for intervention. Grounded in the E/I imbalance model, we outline a novel mechanistically informed framework for treatment of schizophrenia with an emphasis on prevention and recovery. Across the lifespan, this approach advocates stage-specific preventive strategies that begin well before illness onset, extend through early and chronic phases of the illness and incorporate therapeutic strategies to modify underlying neurobiology rather than simply alleviating symptoms. By connecting molecular neuroscience with clinical medicine and precision health approaches, the model outlines a realistic path towards mechanism-based prevention and recovery that is applicable not only to schizophrenia and neuropsychiatric disorders, but also to other non-communicable systemic disorders.