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Exercise, symptom severity, and neuroplasticity in schizophrenia Woodward, Melissa Lynn

Abstract

Schizophrenia is a debilitating disorder marked by psychosis and deficits in cognition and social functioning. It is further characterized by metabolic, neurovascular and cardiovascular deficits that interact with, or compound adverse medication-linked cardiovascular effects. Neuroanatomic deficits are seen even at early stages of illness. Reductions in frontal and temporal lobe grey matter, particularly the hippocampus, are among the most consistent findings. Prefrontal-limbic network deficits are associated with more severe positive symptoms and more cognitive impairments in psychosis patients. Additionally, reduced cardiorespiratory fitness has been linked to decreased hippocampal volume and cortical thickness. Exercise interventions are known to mitigate the negative antipsychotic-associated cardiometabolic side effects and promote hippocampal growth and cortical expansion. Yet, the efficacy of exercise as a non-pharmacological intervention to address anatomic and clinical deficits in psychosis patients is unclear. This study examines the effect of exercise on hippocampal and neocortical plasticity, and clinical outcomes in chronic schizophrenia, early psychosis and in an animal model as proof of principle. First, hippocampal volume increase and symptom severity decrease in chronically treated schizophrenia patients were observed. Compared to healthy volunteers, chronically treated patients had decreased fusiform cortical thickness. Patients who participated in the aerobic intervention had a greater increase in orbitofrontal cortical thickness compared to patients in the resistance training group. Second, early psychosis patients who completed the aerobic intervention had increased thickness in the entorhinal and fusiform cortices. For the aerobic group only, increases in the entorhinal and fusiform temporal gyri were associated with decreasing psychosis symptom severity, particularly for general psychopathology. Last, exercising rats had greater layer II entorhinal cortical thickness compared to sedentary rats, but there was no effect of exercise observed for rats treated with olanzapine. Greater entorhinal cortical thickness was associated with increased activity and improved fasting glucose and fasting insulin levels in rats. The cardiovascular burden in schizophrenia, and antipsychotic treatment has a strong negative impact on patient outcomes. Clinically appropriate exercise represents a non-pharmacologic, safe approach to reduce psychotic symptoms, and remediate neuroanatomic deficits while improving cardiovascular health, counteracting the adverse effects of antipsychotic medication.

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Attribution-NonCommercial-NoDerivatives 4.0 International