Physical exercise as a non-pharmacological adjunct in schizophrenia: Effects on molecular and biochemical parameters

• Exercise enhances antioxidant and anti-inflammatory mechanisms in schizophrenia. • Physical activity modulates BDNF signaling and synaptic plasticity. • Exercise improves serotonergic function and depressive symptoms. • Adjunct exercise may potentiate antipsychotic therapeutic effects. • Feasibility, adherence, and supervision are critical for intervention success. Schizophrenia is a severe mental disorder affecting approximately 20 million people worldwide. It is characterized by positive symptoms (such as hallucinations and delusions) and negative symptoms (including demotivation, anhedonia, and sociality). These behavioral manifestations are associated with molecular alterations in inflammatory molecules, impaired glutamatergic and dopaminergic pathways, and disruptions in mitochondrial redox balance and neurotrophic factor levels. Antipsychotic medications are the primary treatment for managing schizophrenia symptoms; however, they often have limited efficacy on negative symptoms and can cause significant side effects. In this context, physical exercise has emerged as a promising non-pharmacological adjunctive strategy. Physical exercise has been shown to modulate peripheral and central biochemical pathways, including antioxidant and anti-inflammatory mechanisms. Additionally, it enhances neurotrophic factor expression, improves mitochondrial function, and influences glutamatergic and dopaminergic signaling. This narrative review highlights the beneficial effects of incorporating physical exercise into traditional antipsychotic treatment regimens.