Plasma Fatty Acid Metabolites as Biomarkers of Metabolic Syndrome and Clinical Features in Chronic Schizophrenia
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Published on: April 7, 2023
Yeqing Dong1,2, Jinghui Chi3, Yanzhe Li1,2
1Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China.
Background And Hypothesis:
Metabolic syndrome (MetS) is a major risk factor for cardiovascular disease in schizophrenia (SCZ), yet its metabolic underpinnings, particularly in chronic SCZ, remain unclear. This study investigated plasma metabolic profiles and their associations with clinical features in chronic SCZ.
Study Design:
We recruited 374 chronic SCZ patients (222 with MetS, 152 without MetS). Plasma metabolomic profiling was conducted using ultra-high-performance liquid chromatography-high resolution mass spectrometry. Data were analyzed with orthogonal partial least squares discriminant analysis and receiver operating characteristic curves. Psychopathology and cognition were evaluated via the Positive and Negative Symptom Scale and the Repeatable Battery for the Assessment of Neuropsychological Status, respectively.
Study Results:
Metabolomic profiling revealed 37 metabolites significantly altered in MetS among chronic SCZ (variable importance projection > 1.5 and P-false discovery rate < .05). Pathway enrichment highlighted glycerophospholipid metabolism (impact = 0.1404, P<.001) and ascorbate/aldarate metabolism (impact = 0.5238, P = .044) as key contributors. A diagnostic panel comprising 12-Hydroxystearic acid (FFA (18:0-OH)) and 2-Aminoheptanoic acid, both fatty acid derivatives, showed moderate predictive accuracy for MetS (area under the curve = 0.713, 95% confidence interval = 0.660-0.765). Importantly, these fatty acids were also linked to the severity of negative symptoms and memory deficits in SCZ patients without MetS (all P<.05).
Conclusions:
Specific fatty acid metabolites may serve as early biomarkers for MetS in chronic SCZ and provide mechanistic links to negative symptoms and cognitive deficits, particularly in individuals without the syndrome.
Highlights:
Glycerophospholipid and ascorbate/aldarate metabolism are identified as the primary affected pathways in schizophrenia (SCZ) with metabolic syndrome (MetS). 12-Hydroxystearic acid (FFA (18:0-OH)) and 2-Aminoheptanoic acid demonstrated diagnostic potential for MetS. Fatty acids were linked to the severity of negative symptoms and memory impairment in SCZ without MetS.
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