Schizophrenia can be conceptualized as a disorder of broken brain...
Nicholas Fabiano, MD@NTFabiano
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Apr 13, 2025
~1 min read
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Schizophrenia can be conceptualized as a disorder of broken brain bioenergetics.
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These findings are from a review in @molpsychiatry which discusses the relationship between dysfunction of various metabolic pathways across different brain regions in relation to schizophrenia. nature.com/articles/s4138… 2/11
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The core psychotic and cognitive symptoms of schizophrenia may be attributed to abnormal partitioning and processing of energetic substrates. 3/11
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At baseline, perturbations of insulin signaling and glucose levels appear at the onset of psychosis. 4/11
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Glucose may be abnormally siphoned to the pentose-phosphate pathway (PPP), leading to the aberrant production of reactive oxygen species in addition to faulty mitochondrial function. 5/11
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Glucose metabolism in schizophrenia could also yield improper metabolic substrates for the tricarboxylic acid cycle (TCA) cycle, leading to an imbalance in key high-energy reductive agents and ultimately lead to deficits in oxidative phosphorylation and ATP production. 6/11
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Further, astrocytes may be compensating for neuronal metabolic deficits by transitioning away from normal, aerobic glycolysis to provide neurons with additional energetic substrates, such as lactate. 7/11
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Together, these changes may lead to an overall imbalance in energy homeostasis. 8/11
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Though antipsychotics are known to alter bioenergetic function, the reported findings in the nascent metabolic perturbations in schizophrenia are largely independent of antipsychotic therapy. 9/11
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As such, there may be some utility in targeting metabolic pathways pharmacologically to help individuals with schizophrenia. 10/11
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Overall, determining the cellular etiology of these perturbations may elucidate whether these deficits can be attributed to schizophrenia subtypes or serve as biomarkers of the disease. 11/11