Challenges and Frontiers in Computational Metabolic Psychiatry DOI Creative Commons
Anthony G. Chesebro, Botond Antal, Corey Weistuch

et al.

Published: Aug. 13, 2024

One of the primary challenges in metabolic psychiatry is that disrupted brain functions underlie psychiatric conditions arise from a complex set downstream and feedback processes spanning across multiple spatiotemporal scales. Importantly, same circuit can have points failure, each which results different type dysregulation, thus elicits distinct cascades produce divergent signs symptoms. Here, we illustrate this challenge by examining how subtle differences perturbations lead to clinical outcomes. We also discuss computational models perform spatially heterogenous integration bridge vitro vivo paradigms. By leveraging recent methodological advances tools, integrate relevant scales (e.g., TCA-cycle, ion channel, neural microassembly, whole-brain macro-circuit) physiological systems neural, endocrine, immune, vascular), providing framework unite these mechanistic manner goes beyond conceptual descriptive, quantitative generative. These hold potential sharpen our intuitions towards circuit-based for personalized diagnostics treatment.

Language: Английский

Cognitive Impairment in Psychotic Disorders Is Associated with Brain Reductive Stress and Impaired Energy Metabolism as Measured by 31P Magnetic Resonance Spectroscopy DOI

Virginie‐Anne Chouinard,

Fei Du, Xi Chen

et al.

Schizophrenia Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Abstract Background and Hypothesis Convergent evidence shows the presence of brain metabolic abnormalities in psychotic disorders. This study examined reductive stress energy metabolism people with disorders impaired or average range cognition. We hypothesized that global cognitive impairment would be associated greater dysregulation. Study Design Participants affective non-affective psychosis (n = 62) were administered MATRICS Consensus Cognitive Battery (MCCB) underwent a 31P-magnetic resonance spectroscopy scan at 4T. used cluster-analysis approach to identify 2 clusters participants without dysfunction. compared on redox balance stress, measured by ratio nicotinamide adenine dinucleotide (NAD+) its reduced form NADH, addition creatine kinase (CK) enzymatic activity pH. Results The mean (SD) age was 25.1 (6.3) years. NAD+/NADH differed between groups, lower ratio, suggesting more cluster (t −2.60, P .01). There also significant reduction CK −2.19, .03). Intracellular pH did not differ groups 1.31, .19). significantly severity mood symptomatology other measures illness severity. Conclusions Our results demonstrate have dysregulation, decrease rate markers. provides new for potential emerging therapies treat deficits

Language: Английский

Citations

0
The Association Among Bipolar Disorder, Mitochondrial Dysfunction, and Reactive Oxygen Species DOI Creative Commons
Yuki Kageyama, Shohei Okura,

Ayaka Sukigara

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 383 - 383

Published: March 6, 2025

Mitochondria, often known as the cell’s powerhouses, are primarily responsible for generating energy through aerobic oxidative phosphorylation. However, their functions extend far beyond just production. Mitochondria play crucial roles in maintaining calcium balance, regulating apoptosis (programmed cell death), supporting cellular signaling, influencing metabolism, and synthesizing reactive oxygen species (ROS). Recent research has highlighted a strong link between bipolar disorder (BD) mitochondrial dysfunction. Mitochondrial dysfunction contributes to stress, particularly generation of ROS, which implicated pathophysiology BD. Oxidative stress arises when there is an imbalance production ROS ability neutralize them. In neurons, excessive can damage various components, including proteins neuronal membranes intracellular enzymes. Such may interfere with neurotransmitter reuptake function critical enzymes, potentially affecting brain regions involved mood regulation emotional control, key aspects this review, we will explore how types contribute ROS. These include disruptions impaired management, defects quality control mechanisms such mitophagy (the process by damaged mitochondria selectively degraded). We also examine abnormalities synaptic plasticity, lead Additionally, discuss specific dysfunctions observed BD, highlighting these disorder’s pathophysiology. Finally, identify potential therapeutic targets improve function, could pave way new treatments manage or mitigate symptoms

Language: Английский

Citations

0
Ketogenic diet, adenosine, and dopamine in addiction and psychiatry DOI Creative Commons
David N. Ruskin, Luis A. Martinez, Susan A. Masino

et al.

Frontiers in Nutrition, Journal Year: 2025, Volume and Issue: 12

Published: March 10, 2025

Adhering to the ketogenic diet can reduce or stop seizures, even when other treatments fail, via mechanism(s) distinct from available therapies. These results have led interest in for treating conditions such as Alzheimer’s disease, depression and schizophrenia. Evidence points neuromodulator adenosine a key mechanism underlying therapeutic benefits of diet. Adenosine represents unique direct link among cell energy, neuronal activity, gene expression, receptors form functional heteromers with dopamine receptors. The importance dopaminergic system is established addiction, are challenges modulating directly. A mediator that could antagonize dopamine’s effects would be useful, due its function location. Studies report improves cognition, sociability, perseverative behaviors, might improve depression. Many translational opportunities based on diet/adenosine come fore, including autism spectrum disorder, painful conditions, range hyperdopaminergic disorders.

Language: Английский

Citations

0
Challenges and Frontiers in Computational Metabolic Psychiatry DOI Creative Commons
Anthony G. Chesebro, Botond Antal, Corey Weistuch

et al.

Published: Aug. 13, 2024

One of the primary challenges in metabolic psychiatry is that disrupted brain functions underlie psychiatric conditions arise from a complex set downstream and feedback processes spanning across multiple spatiotemporal scales. Importantly, same circuit can have points failure, each which results different type dysregulation, thus elicits distinct cascades produce divergent signs symptoms. Here, we illustrate this challenge by examining how subtle differences perturbations lead to clinical outcomes. We also discuss computational models perform spatially heterogenous integration bridge vitro vivo paradigms. By leveraging recent methodological advances tools, integrate relevant scales (e.g., TCA-cycle, ion channel, neural microassembly, whole-brain macro-circuit) physiological systems neural, endocrine, immune, vascular), providing framework unite these mechanistic manner goes beyond conceptual descriptive, quantitative generative. These hold potential sharpen our intuitions towards circuit-based for personalized diagnostics treatment.

Language: Английский

Citations

1