Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

Cells, Journal Year: 2022, Volume and Issue: 11(16), P. 2607 - 2607

Published: Aug. 21, 2022

Nearly half a century has passed since the discovery of cytoplasmic inheritance human chloramphenicol resistance. The was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, number mutations in mtDNA were identified as cause severe inheritable metabolic diseases with neurological manifestation, and impairment functions been probed pathogenesis wide range illnesses including neurodegenerative diseases. Recently, growing preclinical studies have that animal behaviors are influenced possibly loss stress resilience. Indeed, high 54% patients one most common primary diseases, encephalomyopathy lactic acidosis stroke-like episodes (MELAS) syndrome, present psychiatric symptoms cognitive impairment, mood disorder, anxiety, psychosis. Mitochondria multifunctional organelles which produce cellular energy play major role other homeostasis, signaling, gene expression, among others. Mitochondrial observed be compromised become less resilient under continuous stress. Meanwhile, inflammation linked activation tryptophan (Trp)-kynurenine (KYN) system, observably contributes development pathological conditions disorders. This review discusses mitochondria Trp-KYN interaction system mitochondria, current understanding involvement clinical

Language: Английский

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Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management

World Psychiatry, Journal Year: 2023, Volume and Issue: 22(3), P. 366 - 387

Published: Sept. 15, 2023

Populations with common physical diseases – such as cardiovascular diseases, cancer and neurodegenerative disorders experience substantially higher rates of major depressive disorder (MDD) than the general population. On other hand, people living MDD have a greater risk for many diseases. This high level comorbidity is associated worse outcomes, reduced adherence to treatment, increased mortality, health care utilization costs. Comorbidity can also result in range clinical challenges, more complicated therapeutic alliance, issues pertaining adaptive behaviors, drug‐drug interactions adverse events induced by medications used mental disorders. Potential explanations prevalence above involve shared genetic biological pathways. These latter include inflammation, gut microbiome, mitochondrial function energy metabolism, hypothalamic‐pituitary‐adrenal axis dysregulation, brain structure function. Furthermore, several antecedents related social factors (e.g., socioeconomic status), lifestyle variables activity, diet, sleep), stressful live childhood trauma). Pharmacotherapies psychotherapies are effective treatments comorbid MDD, introduction interventions well collaborative models digital technologies provide promising strategies improving management. paper aims detailed overview epidemiology specific including bidirectional risk; pathways potentially implicated pathogenesis diseases; socio‐environmental that serve both protective factors; management prevention treatment. We conclude future directions emerging research optimal

Language: Английский

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Mitochondria and Brain Disease: A Comprehensive Review of Pathological Mechanisms and Therapeutic Opportunities

Biomedicines, Journal Year: 2023, Volume and Issue: 11(9), P. 2488 - 2488

Published: Sept. 7, 2023

Mitochondria play a vital role in maintaining cellular energy homeostasis, regulating apoptosis, and controlling redox signaling. Dysfunction of mitochondria has been implicated the pathogenesis various brain diseases, including neurodegenerative disorders, stroke, psychiatric illnesses. This review paper provides comprehensive overview intricate relationship between disease, focusing on underlying pathological mechanisms exploring potential therapeutic opportunities. The covers key topics such as mitochondrial DNA mutations, impaired oxidative phosphorylation, dynamics, calcium dysregulation, reactive oxygen species generation context disease. Additionally, it discusses emerging strategies targeting dysfunction, protective agents, metabolic modulators, gene therapy approaches. By critically analysing existing literature recent advancements, this aims to enhance our understanding multifaceted disease shed light novel interventions.

Language: Английский

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Major Depressive Disorder and Oxidative Stress: A Review of Peripheral and Genetic Biomarkers According to Clinical Characteristics and Disease Stages

Antioxidants, Journal Year: 2023, Volume and Issue: 12(4), P. 942 - 942

Published: April 17, 2023

Major depressive disorder (MDD) is currently the main cause of disability worldwide, but its pathophysiology remains largely unknown, especially given high heterogeneity in terms clinical phenotypes and biological characteristics. Accordingly, management still poor. Increasing evidence suggests that oxidative stress, measured on various matrices such as serum, plasma or erythrocytes, has a critical role MDD. The aim this narrative review to identify erythrocyte biomarkers stress MDD patients according disease stage features. Sixty-three articles referenced PubMed Embase between 1 January 1991, 31 December 2022, were included. Modifications antioxidant enzymes (mainly glutathione peroxidase superoxide dismutase) highlighted. Non-enzymatic antioxidants uric acid) decreased depressed compared healthy controls. These changes associated with an increase reactive oxygen species. Therefore, increased damage products (principally malondialdehyde, protein carbonyl content 8-hydroxy-2′-deoxyguanosine) present patients. Specific modifications could be identified stages Interestingly, antidepressant treatment corrected these changes. remission from depression, markers globally normalized. This particular interest for care may contribute provide opportunity find new therapeutic targets.

Language: Английский

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Genetic Relationships between Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, and Intelligence

Neuropsychobiology, Journal Year: 2022, Volume and Issue: 81(6), P. 484 - 496

Published: Jan. 1, 2022

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum (ASD) commonly co-occur; both traits exert an influence on intelligence scores. Genetic relationships between these three are far from being clear.The summary results of genome-wide association studies ADHD (20,183 cases 35,191 controls), ASD (18,381 27,969 (269,867 participants) were used for the analyses. Local genetic correlation analysis polygenic overlap to explore shared components ADHD, ASD, intelligence. Mendelian randomization (MR) was examine causal associations A cross-trait meta-analysis performed identify pleiotropic variants across traits.Our showed that has a positive negative with respectively, including hub genomic regions showing correlated effects traits. Polygenic indicated all risk contributing overlapped half those intelligence, majority have opposite effect directions them. The (80%) almost (97%). Notably, some ASD/intelligence overlapping displayed opposing two conditions. MR liability higher associated increased (OR = 1.12) decreased 0.78). Cross-trait meta-analyses identified 170 loci traits, 12 novel loci. Functional analyses genes support their potential involvement in neurodevelopment.Our suggest is inheriting reduced set low-intelligence alleles, whereas incongruous mixture high-intelligence alleles summed up additional, ASD-specific not

Language: Английский

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Potential Role of Curcumin for the Treatment of Major Depressive Disorder

CNS Drugs, Journal Year: 2022, Volume and Issue: 36(2), P. 123 - 141

Published: Feb. 1, 2022

Curcumin is the major biologically active polyphenolic constituent in turmeric plant (Curcuma longa) that has been shown to have antioxidant, anti-inflammatory, neuroprotective, anticancer, antimicrobial, and cardioprotective effects. Interest curcumin as a treatment for mental health conditions increased there an expanding body of preclinical clinical research examining its antidepressant anxiolytic In this narrative review, human trials investigating effects depression or depressive symptoms are summarised. Using findings from vitro, animal, trials, possible biological mechanisms associated with also explored. To increase understanding depression, directions future proposed.

Language: Английский

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The metabolic overdrive hypothesis: hyperglycolysis and glutaminolysis in bipolar mania

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(5), P. 1521 - 1527

Published: Jan. 25, 2024

Evidence from diverse areas of research including chronobiology, metabolomics and magnetic resonance spectroscopy indicate that energy dysregulation is a central feature bipolar disorder pathophysiology. In this paper, we propose mania represents condition heightened cerebral metabolism facilitated by hyperglycolysis glutaminolysis. When oxidative glucose becomes impaired in the brain, neurons can utilize glutamate as an alternative substrate to generate through phosphorylation. Glycolysis astrocytes fuels formation denovo glutamate, which be used mitochondrial fuel source via transamination alpha-ketoglutarate subsequent reductive carboxylation replenish tricarboxylic acid cycle intermediates. Upregulation glycolysis glutaminolysis manner causes brain enter state excitatory activity underlie subjective experience mania. Under normal conditions, mechanism serves adaptive function transiently upregulate response acute demand. However, when recruited long term counteract it may become pathological process. article, develop these ideas detail, present supporting evidence novel avenue investigation understand biological basis for

Language: Английский

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Mitochondria in the Central Nervous System in Health and Disease: The Puzzle of the Therapeutic Potential of Mitochondrial Transplantation

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 410 - 410

Published: Feb. 27, 2024

Mitochondria, the energy suppliers of cells, play a central role in variety cellular processes essential for survival or leading to cell death. Consequently, mitochondrial dysfunction is implicated numerous general and CNS disorders. The clinical manifestations include metabolic disorders, immune system, tumorigenesis, neuronal behavioral abnormalities. In this review, we focus on CNS, which has unique characteristics therefore highly dependent mitochondria. First, review mitochondria development, synaptogenesis, plasticity, behavior as well their adaptation intricate connections between different types brain. Then, sparse knowledge mechanisms exogenous uptake describe attempts determine half-life transplantation long-term effects sprouting, proteome, behavior. We further discuss potential serve tool study causal link activity Next, transplantation’s therapeutic various Finally, basic reverse—translation challenges approach that currently hinder use transplantation.

Language: Английский

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The effects of ketogenic metabolic therapy on mental health and metabolic outcomes in schizophrenia and bipolar disorder: a randomized controlled clinical trial protocol

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: Aug. 21, 2024

Background Schizophrenia, schizoaffective disorder, and bipolar affective disorder are debilitating psychiatric conditions characterized by a chronic pattern of emotional, behavioral, cognitive disturbances. Shared psychopathology includes the pre-eminence altered states, disorders thoughts, behavioral control. Additionally, those share epidemiological traits, including significant cardiovascular, metabolic, infectious, respiratory co-morbidities, resulting in reduced life expectancy up to 25 years. Nutritional ketosis has been successfully used treat range neurological preclinical data have convincingly shown potential for its use animal models psychotic disorders. More recent from open clinical trials pointed toward dramatic reduction psychotic, affective, metabolic symptoms both schizophrenia disorder. Objectives investigate effects nutritional via modified ketogenic diet (MKD) over 14 weeks stable community patients with or schizophrenia. Design A randomized placebo-controlled trial 100 non-hospitalized adult participants diagnosis who capable consenting willing change their diets. Intervention Dietitian-led medically supervised compared following Australian Guide Healthy Eating weeks. Outcomes The primary outcomes include measures, reported as symptom improvement functional changes Positive Negative Symptoms Scale (PANSS), Young Mania Rating (YMS), Beck Depression Inventory (BDI), WHO Disability Schedule, Affect Lability Cambridge Cognitive Battery. secondary body weight, blood pressure, liver kidney function tests, lipid profiles, markers insulin resistance. Ketone glucose levels will be study correlation between outcomes. Optional hair cortisol analysis assess long-term stress variations fecal microbiome composition. Autonomic nervous system activity measured wearable devices (OURA ring EMBRACE wristband) form skin conductance, oximetry, continuous pulse monitoring, rate, movement tracking, sleep quality. Based on encouraging results established research, other neurodevelopment disorders, schizophrenia, we predict that therapy well tolerated result improved global measures social functioning. We additionally may exist level achieved cognitive, intervention group.

Language: Английский

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Mitochondrial Metabolism in Major Depressive Disorder: From Early Diagnosis to Emerging Treatment Options

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(6), P. 1727 - 1727

Published: March 17, 2024

Major Depressive Disorder (MDD) is one of the most disabling diseases in world. MDD traditionally diagnosed based on a patient’s symptoms, which can lead to misdiagnosis. Although pathogenic mechanisms are unknown, several studies have identified mitochondrial dysfunction as central factor onset and progression MDD. In context MDD, alterations metabolism imbalances energy production oxidative stress, contributing disorder´s underlying pathophysiological mechanisms. Consequently, identification key biomarker for early accurate diagnosis represents significant challenge. Faced with limits traditional treatments antidepressants, new pharmacological therapeutic targets being investigated such ketamine/esketamine, psychedelics, or anti-inflammatories. All these drugs show potential antidepressant effects due their speed action ability modulate neuroplasticity and/or motor processing. parallel, non-pharmacological studied, like Transcranial Magnetic Stimulation (TMS) Deep Brain (DBS), recognized neuronal activity offer treatment alternatives. As cellular directly related respiration, aim this review examining link between assessing how biomarkers could provide more objective precise diagnostic tool, exploring other addition specific focus emerging targets. Finally, detailed analysis strengths, weaknesses, opportunities, threats approaches was carried out, highlighting challenges that must be addressed.

Language: Английский

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