Neurobiological effects of aerobic exercise, with a focus on patients with schizophrenia Abstract Schizophrenia is a severe neuropsychiatric disease that is associated with neurobiological alterations in multiple brain regions and peripheral organs. Negative symptoms and cognitive deficits are present in about half of patients and are difficult to treat, leading to an unfavorable functional outcome. To investigate the impact of aerobic exercise on various neurobiological parameters, we conducted a narrative review. Add-on aerobic exercise was shown to be effective in improving negative and general symptoms, cognition, global functioning, and quality of life in schizophrenia patients. Based on findings in healthy individuals and animal models, this qualitative review gives an overview of different lines of evidence on how aerobic exercise impacts brain structure and function and molecular mechanisms in patients with schizophrenia and how its effects could be related to clinical and functional outcomes. Structural magnetic resonance imaging studies showed a volume increase in the hippocampus and cortical regions in schizophrenia patients and healthy controls after endurance training. However, results are inconsistent and individual risk factors may influence neuroplastic processes. Animal studies indicate that alterations in epigenetic mechanisms and synaptic plasticity are possible underlying mechanisms, but that differentiation of glial cells, angiogenesis, and possibly neurogenesis may also be involved. Clinical and animal studies also revealed effects of aerobic exercise on the hypothalamus–pituitary–adrenal axis, growth factors, and immune-related mechanisms. Some findings indicate effects on neurotransmitters and the endocannabinoid system. Further research is required to clarify how individual risk factors in schizophrenia patients mediate or moderate the neurobiological effects of exercise on brain and cognition. Altogether, aerobic exercise is a promising candidate in the search for pathophysiology-based add-on interventions in schizophrenia.