Proteomic and metabolic profiling of chronic patients with schizophrenia induced by a physical activity program:...

Schizophrenia is a chronic illness often accompanied by metabolic disorders, diabetes, obesity and cardiovascular problems often associated with unhealthy lifestyles, as well as neuroendocrine problems caused by the disease itself. Lifestyle changes, such as regular physical exercise, have a positive effect on metabolic disorders and mental health, although the molecular changes that occur in this type of patient and how they explain the changes in their response are unknown. This study wants to analyze in a novel way the proteins and molecular pathways involved in critical plasmatic proteins in plasma to reveal the pathways involved in the implementation of physical exercise and the changes that occur among patients who participate in such programs with those who leave.

Twenty-one patients with chronic schizophrenia underwent a daily, 6-month aerobic training program. We divided them into a group that completed the program (12 patients) and a second group that left the training program (9 patients). The biochemical and clinical data of each patient were analyzed and the proteomic profile of the plasma was studied using ESI-LC-MS/MS.

Proteomic analysis recognizes 21.165 proteins and peptides in each patient, of which we identified 1.812 proteins that varied between both groups linked to the metabolic and biological regulation pathways. After clinical analysis of each patient we found significant differences in weight, BMI, abdominal perimeter, diastolic blood pressure, and HDL cholesterol levels. The main change that vertebrates both groups is the Self-Assessment Anhedonia Scale, where we detected higher levels in the dropout group (no physical activity) compared to the active group.

The benefits of physical exercise are clear in chronic patients with schizophrenia, as it substantially improves their BMI, as well as their clinical and biochemical parameters. However, our study reveals the biological and molecular pathways that affect physical exercise in schizophrenia, such as important metabolic proteins such as ApoE and ApoC, proteins involved in neuronal regulation such as tenascin and neurotrophins, neuroinflammatory regulatory pathways such as lipocalin-2 and protein 14-3-3, as well as cytoskeleton proteins of cells such as spectrins and annexines. Understanding these molecular mechanisms opens the door to future therapies in the chronicity of schizophrenia.