To investigate peripheral metabolic alterations in patients with schizophrenia using a two-stage metabolomic workflow of untargeted analysis and targeted re-analysis,explore the associated metabolic pathways, identify potential peripheral metabolic biomarkers, and elucidate the underlying metabolic dysregulation mechanisms.
Plasma samples were collected from 24 schizophrenia patients and 10 healthy controls for non-derivatized targeted metabolomics analysis. Differential metabolites were identified and visualized using box plots. Hierarchical clustering analysis was performed to evaluate expression pattern differences across samples, and KEGG pathway enrichment analysis was conducted to map the involved biological pathways. False discovery rate (FDR) correction was applied for multiple comparisons.
Among the 21 quantified metabolites, four exhibited significant differences after FDR correction (FDR < 0.05). α-Ketoglutarate was significantly elevated in the patient group, whereas succinic acid, tryptamine, and amino butyric acid were significantly reduced. The opposite variations of α-ketoglutarate and succinic acid suggest a peripheral TCA cycle metabolic bottleneck. Hierarchical clustering based on these four metabolites effectively distinguished patients from healthy controls. KEGG enrichment demonstrated that these metabolites converged predominantly on amino acid metabolism, energy metabolism, and most notably the GABAergic synapse pathway, offering peripheral evidence supporting the core position of GABAergic dysfunction in schizophrenia.
Schizophrenia patients display significant peripheral metabolic disturbances characterized by dysregulated amino acid metabolism, synaptic transmission abnormalities, and energy metabolism imbalance. The four-metabolite panel (α-ketoglutarate, succinic acid, tryptamine, and amino butyric acid) may provide experimental basis for further mechanistic research and therapeutic development.
Bing Han, Yu Guo, Baie Feng et al.· Frontiers in Psychiatry· 0 citations
Depression represents a multifaceted neuropsychiatric disorder distinguished by disruptions in cerebral energy metabolism, neurotransmitter communication, neuroplasticity, and cognitive processes. An increasing body of literature indicates that integrative non-pharmacological interventions aimed at metabolic and neurochemical pathways may present promising adjunctive strategies for ameliorating depressive manifestations and concomitant cognitive impairments. This review explores the prospective combined effects of creatine supplementation, branched-chain amino acids (BCAAs), and physical exercise as a multimodal bioenergetic intervention for the management of depression. Creatine is pivotal in maintaining neuronal energy equilibrium via the phosphocreatine system, thereby facilitating mitochondrial functionality and adenosine triphosphate availability within neural cells. BCAAs may influence central fatigue and exercise performance through competitive inhibition of tryptophan transport across the blood-brain barrier. Importantly, this mechanism primarily reflects acute exercise-related serotonergic responses associated with central fatigue and should not be considered mechanistically equivalent to the chronic serotonergic dysfunction observed in major depressive disorder. Accordingly, within the context of depression, BCAAs are discussed as indirect modulators of mental health outcomes through their effects on fatigue perception, exercise tolerance, and adherence to physical activity, rather than as direct serotonergic antidepressant interventions. Concurrently, consistent engagement in physical exercise activates critical neuroplasticity-associated signaling pathways, which are instrumental in promoting hippocampal neurogenesis and enhancing stress resilience. Emerging empirical evidence derived from both experimental and clinical investigations suggests that the combined application of these interventions may exert complementary influences on brain bioenergetics, neuroplasticity, exercise capacity, and cognitive function. Collectively, this integrative paradigm highlights the potential of creatine supplementation, BCAAs, and physical exercise to support depression-related outcomes through distinct yet complementary mechanisms involving bioenergetic regulation, enhanced exercise capacity, neuroplastic adaptations, and improved cognitive and emotional functioning.
Xiaoqin Xu, Li Liu· Frontiers in Psychiatry· 0 citations
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