TY - JOUR
T1 - Metabolic Insights into Neuropsychiatric Illnesses and Ketogenic Therapies: A Transcriptomic View
T2 - A Transcriptomic View
AU - Sahay, Smita
AU - Pulvender, Priyanka
AU - Rami Reddy, Madhu Vishnu Sankar Reddy
AU - McCullumsmith, Robert E
AU - O'Donovan, Sinead M
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/8
Y1 - 2024/8
N2 - The disruption of brain energy metabolism, leading to alterations in synaptic signaling, neural circuitry, and neuroplasticity, has been implicated in severe mental illnesses such as schizophrenia, bipolar disorder, and major depressive disorder. The therapeutic potential of ketogenic interventions in these disorders suggests a link between metabolic disturbances and disease pathology; however, the precise mechanisms underlying these metabolic disturbances, and the therapeutic effects of metabolic ketogenic therapy, remain poorly understood. In this study, we conducted an in silico analysis of transcriptomic data to investigate perturbations in metabolic pathways in the brain across severe mental illnesses via gene expression profiling. We also examined dysregulation of the same pathways in rodent or cell culture models of ketosis, comparing these expression profiles to those observed in the disease states. Our analysis revealed significant perturbations across all metabolic pathways, with the greatest perturbations in glycolysis, the tricarboxylic acid (TCA) cycle, and the electron transport chain (ETC) across all three disorders. Additionally, we observed some discordant gene expression patterns between disease states and ketogenic intervention studies, suggesting a potential role for ketone bodies in modulating pathogenic metabolic changes. Our findings highlight the importance of understanding metabolic dysregulation in severe mental illnesses and the potential therapeutic benefits of ketogenic interventions in restoring metabolic homeostasis. This study provides insights into the complex relationship between metabolism and neuropsychiatric disorders and lays the foundation for further experimental investigations aimed at appreciating the implications of the present transcriptomic findings as well as developing targeted therapeutic strategies.
AB - The disruption of brain energy metabolism, leading to alterations in synaptic signaling, neural circuitry, and neuroplasticity, has been implicated in severe mental illnesses such as schizophrenia, bipolar disorder, and major depressive disorder. The therapeutic potential of ketogenic interventions in these disorders suggests a link between metabolic disturbances and disease pathology; however, the precise mechanisms underlying these metabolic disturbances, and the therapeutic effects of metabolic ketogenic therapy, remain poorly understood. In this study, we conducted an in silico analysis of transcriptomic data to investigate perturbations in metabolic pathways in the brain across severe mental illnesses via gene expression profiling. We also examined dysregulation of the same pathways in rodent or cell culture models of ketosis, comparing these expression profiles to those observed in the disease states. Our analysis revealed significant perturbations across all metabolic pathways, with the greatest perturbations in glycolysis, the tricarboxylic acid (TCA) cycle, and the electron transport chain (ETC) across all three disorders. Additionally, we observed some discordant gene expression patterns between disease states and ketogenic intervention studies, suggesting a potential role for ketone bodies in modulating pathogenic metabolic changes. Our findings highlight the importance of understanding metabolic dysregulation in severe mental illnesses and the potential therapeutic benefits of ketogenic interventions in restoring metabolic homeostasis. This study provides insights into the complex relationship between metabolism and neuropsychiatric disorders and lays the foundation for further experimental investigations aimed at appreciating the implications of the present transcriptomic findings as well as developing targeted therapeutic strategies.
KW - Humans
KW - Diet, Ketogenic
KW - Transcriptome
KW - Mental Disorders/metabolism
KW - Animals
KW - Energy Metabolism
KW - Gene Expression Profiling
KW - Bipolar Disorder/metabolism
KW - Metabolic Networks and Pathways
KW - Ketone Bodies/metabolism
KW - Brain/metabolism
UR - https://doi.org/10.3390/ijms25158266
U2 - 10.3390/ijms25158266
DO - 10.3390/ijms25158266
M3 - Article
C2 - 39125835
SN - 1661-6596
VL - 25
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 15
M1 - 8266
ER -