Altered Lipid Landscapes Provide a Molecular Perspective on Schizophrenia-Journal of Psychiatry and Brain Science-CSCIED科技核心评价数据库-手机版

Altered Lipid Landscapes Provide a Molecular Perspective on Schizophrenia

Altered Lipid Landscapes Provide a Molecular Perspective on Schizophrenia

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DOI	10.20900/jpbs.20250016
刊名	Journal of Psychiatry and Brain Science JPBS
年，卷(期)	2025, 10(6)
作者	Robin Roychaudhuri*,
作者单位	Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA ;
摘要	Schizophrenia (SCZ) is a complex neuropsychiatric disorder characterized by disruptions in cognition, perception, and social behavior. While traditional research has focused on neurotransmitter dysregulation, growing evidence implicates altered lipid metabolism as a key contributor to the disease’s molecular pathology. Lipids are essential for maintaining neuronal membrane integrity, facilitating synaptic transmission, supporting myelination, and regulating neuroinflammation, all processes disrupted in SCZ. This review examines the molecular alterations in lipid pathways in SCZ, focusing on the dysregulated metabolism of phospholipids, sphingolipids, cholesterol, and polyunsaturated fatty acids (PUFAs). We highlight findings from genetic studies, neuroimaging, and patient-derived induced pluripotent stem cell (iPSC) models, which collectively provide a translational framework for studying lipid-related abnormalities. Evidence from postmortem brain tissue and peripheral samples consistently reveals altered lipid profiles in individuals with SCZ. Integrative models combining genetic risk variants with environmental stressors such as maternal immune activation and perinatal hypoxia offer deeper insights into how lipid dysregulation emerges during neurodevelopment and impairs neuronal function. From a clinical perspective, targeting lipid metabolism presents promising avenues for biomarker discovery, early diagnosis, and therapeutic innovation. Lipid-based interventions, including targeting of sphingolipid or phosphatidylinositol pathways, may be particularly beneficial for treatment-resistant cases. By integrating molecular lipidomics with patient-specific models and systems-level approaches, this review underscores the potential of lipid-focused strategies to advance our understanding of SCZ pathophysiology and guide the development of novel treatments.
Abstract	Schizophrenia (SCZ) is a complex neuropsychiatric disorder characterized by disruptions in cognition, perception, and social behavior. While traditional research has focused on neurotransmitter dysregulation, growing evidence implicates altered lipid metabolism as a key contributor to the disease’s molecular pathology. Lipids are essential for maintaining neuronal membrane integrity, facilitating synaptic transmission, supporting myelination, and regulating neuroinflammation, all processes disrupted in SCZ. This review examines the molecular alterations in lipid pathways in SCZ, focusing on the dysregulated metabolism of phospholipids, sphingolipids, cholesterol, and polyunsaturated fatty acids (PUFAs). We highlight findings from genetic studies, neuroimaging, and patient-derived induced pluripotent stem cell (iPSC) models, which collectively provide a translational framework for studying lipid-related abnormalities. Evidence from postmortem brain tissue and peripheral samples consistently reveals altered lipid profiles in individuals with SCZ. Integrative models combining genetic risk variants with environmental stressors such as maternal immune activation and perinatal hypoxia offer deeper insights into how lipid dysregulation emerges during neurodevelopment and impairs neuronal function. From a clinical perspective, targeting lipid metabolism presents promising avenues for biomarker discovery, early diagnosis, and therapeutic innovation. Lipid-based interventions, including targeting of sphingolipid or phosphatidylinositol pathways, may be particularly beneficial for treatment-resistant cases. By integrating molecular lipidomics with patient-specific models and systems-level approaches, this review underscores the potential of lipid-focused strategies to advance our understanding of SCZ pathophysiology and guide the development of novel treatments.
关键词	schizophrenia; lipid metabolism; D-serine; D-cysteine; phospholipids; lipidomics; astrocyte; neuron; first episode psychosis; induced pluripotent stem cell; synapse
KeyWord	schizophrenia; lipid metabolism; D-serine; D-cysteine; phospholipids; lipidomics; astrocyte; neuron; first episode psychosis; induced pluripotent stem cell; synapse
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Robin Roychaudhuri*. Altered Lipid Landscapes Provide a Molecular Perspective on Schizophrenia [J]. Journal of Psychiatry and Brain Science. 2025; 10; (6). - .

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