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Glutamate mood disorders

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https://www.readbyqxmd.com/read/27870506/differential-neurometabolite-alterations-in-brains-of-medication-free-individuals-with-bipolar-disorder-and-those-with-unipolar-depression-a-two-dimensional-proton-magnetic-resonance-spectroscopy-study
#1
Hui Li, Haiyun Xu, Yinnan Zhang, Jitian Guan, Jie Zhang, Chongtao Xu, Zhiwei Shen, Bo Xiao, Chunlian Liang, Kaiyuan Chen, Jinling Zhang, Renhua Wu
OBJECTIVES: Bipolar disorder (BD) is a mental disorder characterized by periods of elevated mood and depression. Many individuals with BD are initially misdiagnosed and treated for unipolar depression (UD). In this study, we report direct comparisons between medication-free individuals with BD and those with UD in terms of the neurometabolites in the anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), parietal cortex (PC), and posterior cingulate cortex (PCC) of the brain...
November 2016: Bipolar Disorders
https://www.readbyqxmd.com/read/27861545/glucocorticoid-induces-incoordination-between-glutamatergic-and-gabaergic-neurons-in-the-amygdala
#2
Guang-Yan Wang, Zhao-Ming Zhu, Shan Cui, Jin-Hui Wang
BACKGROUND: Stressful life leads to mood disorders. Chronic mild stress is presumably major etiology for depression, and acute severe stress leads to anxiety. These stressful situations may impair hypothalamus-pituitary-adrenal axis and in turn induce synapse dysfunction. However, it remains elusive how the stress hormones mess up subcellular compartments and interactions between excitatory and inhibitory neurons, which we have investigated in mouse amygdala, a structure related to emotional states...
2016: PloS One
https://www.readbyqxmd.com/read/27830574/inflammation-effects-on-brain-glutamate-in-depression-mechanistic-considerations-and-treatment-implications
#3
Ebrahim Haroon, Andrew H Miller
There has been increasing interest in the role of glutamate in mood disorders, especially given the profound effect of the glutamate receptor antagonist ketamine in improving depressive symptoms in patients with treatment-resistant depression. One pathway by which glutamate alterations may occur in mood disorders involves inflammation. Increased inflammation has been observed in a significant subgroup of patients with mood disorders, and inflammatory cytokines have been shown to influence glutamate metabolism through effects on astrocytes and microglia...
November 10, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27824355/neuropathology-of-mood-disorders-do-we-see-the-stigmata-of-inflammation
#4
REVIEW
N Mechawar, J Savitz
A proportion of cases with mood disorders have elevated inflammatory markers in the blood that conceivably may result from stress, infection and/or autoimmunity. However, it is not yet clear whether depression is a neuroinflammatory disease. Multiple histopathological and molecular abnormalities have been found postmortem but the etiology of these abnormalities is unknown. Here, we take an immunological perspective of this literature. Increases in activated microglia or perivascular macrophages in suicide victims have been reported in the parenchyma...
November 8, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27781556/mood-therapeutics-novel-pharmacological-approaches-for-treating-depression
#5
Ioline D Henter, Rafael T de Sousa, Philip W Gold, Andre R Brunoni, Carlos A Zarate, Rodrigo Machado-Vieira
Real-world effectiveness trials suggest that antidepressant efficacy is limited in many patients with mood disorders, underscoring the urgent need for novel therapeutics to treat these disorders. Areas Covered: Here, we review the clinical evidence supporting the use of novel modulators for the treatment of mood disorders, including specific glutamate modulators such as: 1) high-trapping glutamatergic modulators; 2) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists; 3) NMDA receptor glycine-site partial agonists; and 4) metabotropic glutamate receptor (mGluR) modulators...
October 26, 2016: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27777418/the-phf21b-gene-is-associated-with-major-depression-and-modulates-the-stress-response
#6
M-L Wong, M Arcos-Burgos, S Liu, J I Vélez, C Yu, B T Baune, M C Jawahar, V Arolt, U Dannlowski, A Chuah, G A Huttley, R Fogarty, M D Lewis, S R Bornstein, J Licinio
Major depressive disorder (MDD) affects around 350 million people worldwide; however, the underlying genetic basis remains largely unknown. In this study, we took into account that MDD is a gene-environment disorder, in which stress is a critical component, and used whole-genome screening of functional variants to investigate the 'missing heritability' in MDD. Genome-wide association studies (GWAS) using single- and multi-locus linear mixed-effect models were performed in a Los Angeles Mexican-American cohort (196 controls, 203 MDD) and in a replication European-ancestry cohort (499 controls, 473 MDD)...
October 25, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27762319/midbrain-gene-screening-identifies-a-new-mesoaccumbal-glutamatergic-pathway-and-a-marker-for-dopamine-cells-neuroprotected-in-parkinson-s-disease
#7
Thomas Viereckel, Sylvie Dumas, Casey J A Smith-Anttila, Bianca Vlcek, Zisis Bimpisidis, Malin C Lagerström, Åsa Konradsson-Geuken, Åsa Wallén-Mackenzie
The ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) of the midbrain are associated with Parkinson's disease (PD), schizophrenia, mood disorders and addiction. Based on the recently unraveled heterogeneity within the VTA and SNc, where glutamate, GABA and co-releasing neurons have been found to co-exist with the classical dopamine neurons, there is a compelling need for identification of gene expression patterns that represent this heterogeneity and that are of value for development of human therapies...
October 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27756833/the-frontal-cortex-as-a-network-hub-controlling-mood-and-cognition-probing-its-neurochemical-substrates-for-improved-therapy-of-psychiatric-and-neurological-disorders
#8
Mark J Millan, Jean-Michel Rivet, Alain Gobert
The highly-interconnected and neurochemically-rich frontal cortex plays a crucial role in the regulation of mood and cognition, domains disrupted in depression and other central nervous system disorders, and it is an important site of action for their therapeutic control. For improving our understanding of the function and dysfunction of the frontal cortex, and for identifying improved treatments, quantification of extracellular pools of neuromodulators by microdialysis in freely-moving rodents has proven indispensable...
October 17, 2016: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/27699087/guanosine-a-neuromodulator-with-therapeutic-potential-in-brain-disorders
#9
Débora Lanznaster, Tharine Dal-Cim, Tetsadê C B Piermartiri, Carla I Tasca
Guanosine is a purine nucleoside with important functions in cell metabolism and a protective role in response to degenerative diseases or injury. The past decade has seen major advances in identifying the modulatory role of extracellular action of guanosine in the central nervous system (CNS). Evidence from rodent and cell models show a number of neurotrophic and neuroprotective effects of guanosine preventing deleterious consequences of seizures, spinal cord injury, pain, mood disorders and aging-related diseases, such as ischemia, Parkinson's and Alzheimer's diseases...
October 2016: Aging and Disease
https://www.readbyqxmd.com/read/27678087/in-vivo-and-in-vitro-effects-of-vortioxetine-on-molecules-associated-with-neuroplasticity
#10
Pirathiv Kugathasan, Jessica Waller, Ligia Westrich, Aicha Abdourahman, Joseph A Tamm, Alan L Pehrson, Elena Dale, Maria Gulinello, Connie Sanchez, Yan Li
Neuroplasticity is fundamental for brain functions, abnormal changes of which are associated with mood disorders and cognitive impairment. Neuroplasticity can be affected by neuroactive medications and by aging. Vortioxetine, a multimodal antidepressant, has shown positive effects on cognitive functions in both pre-clinical and clinical studies. In rodent studies, vortioxetine increases glutamate neurotransmission, promotes dendritic branching and spine maturation, and elevates hippocampal expression of the activity-regulated cytoskeleton-associated protein (Arc/Arg3...
September 26, 2016: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/27662572/trait-related-alterations-of-n-acetylaspartate-in-euthymic-bipolar-patients-a-longitudinal-proton-magnetic-resonance-spectroscopy-study
#11
Burç Aydin, Ayşegül Yurt, Necati Gökmen, Perry Renshaw, David Olson, Ayşegül Yildiz
BACKGROUND: Neurochemical changes are responsible for bipolar disorder (BD) pathophysiology. Despite current progress in BD research, mood- and trait-related alterations in BD continue to elicit further investigation. METHODS: In this study, we report a longitudinal proton magnetic resonance spectroscopy study evaluating dorsomedial prefrontal cortex (DMPFC) metabolites N-acetylaspartate (NAA), creatine plus phosphocreatine (total creatine [tCr]), phosphorylcholine plus glycerophosphocholine, myo-inositol, and glutamate plus glutamine levels of manic and euthymic adult BD type I patients (n=48) treated with standard antimanic medicines, compared to matching healthy controls (n=44)...
December 2016: Journal of Affective Disorders
https://www.readbyqxmd.com/read/27629368/inflammation-glutamate-and-glia-a-trio-of-trouble-in-mood-disorders
#12
Ebrahim Haroon, Andrew H Miller, Gerard Sanacora
Increasing data indicate that inflammation and alterations in glutamate neurotransmission are two novel pathways to pathophysiology in mood disorders. The primary goal of this review is to illustrate how these two pathways may converge at the level of the glia to contribute to neuropsychiatric disease. We propose that a combination of failed clearance and exaggerated release of glutamate by glial cells during immune activation leads to glutamate increases and promotes aberrant extrasynaptic signaling through ionotropic and metabotropic glutamate receptors, ultimately resulting in synaptic dysfunction and loss...
January 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27623122/-interest-of-scopolamine-as-a-treatment-of-major-depressive-disorder
#13
A Rigal, S Mouchabac, C S Peretti
INTRODUCTION: The number of patients with depression in the world is 350 millions according to estimates. The search for new treatments, particularly in forms of resistant depression, is necessary given the growing number of patients experiencing treatment failure and resistance. Scopolamine, an anticholinergic antimuscarinic molecule, is one of the treatments under evaluation. It falls within the assumptions of cholinergic disruption of the pathophysiology of depression, at different levels (genetic, receptorial [muscarinic and glutamate receptors], hormonal, synaptic…)...
September 9, 2016: L'Encéphale
https://www.readbyqxmd.com/read/27589806/possible-therapeutic-doses-of-cannabinoid-type-1-receptor-antagonist-reverses-key-alterations-in-fragile-x-syndrome-mouse-model
#14
Maria Gomis-González, Arnau Busquets-Garcia, Carlos Matute, Rafael Maldonado, Susana Mato, Andrés Ozaita
Fragile X syndrome (FXS) is the most common monogenetic cause of intellectual disability. The cognitive deficits in the mouse model for this disorder, the Fragile X Mental Retardation 1 (Fmr1) knockout (KO) mouse, have been restored by different pharmacological approaches, among those the blockade of cannabinoid type 1 (CB1) receptor. In this regard, our previous study showed that the CB1 receptor antagonist/inverse agonist rimonabant normalized a number of core features in the Fmr1 knockout mouse. Rimonabant was commercialized at high doses for its anti-obesity properties, and withdrawn from the market on the bases of mood-related adverse effects...
August 31, 2016: Genes
https://www.readbyqxmd.com/read/27569586/endocannabinoids-in-brain-plasticity-cortical-maturation-hpa-axis-function-and-behavior
#15
Diana Dow-Edwards, Lindsay Silva
Marijuana use during adolescence has reached virtually every strata of society. The general population has the perception that marijuana use is safe for mature people and therefore is also safe for developing adolescents. However, both clinical and preclinical research shows that marijuana use, particularly prior to age 16, could have long-term effects on cognition, anxiety and stress-related behaviors, mood disorders and substance abuse. These effects derive from the role of the endocannabinoid system, the endogenous cannabinoid system, in the development of cortex, amygdala, hippocampus and hypothalamus during adolescence...
August 26, 2016: Brain Research
https://www.readbyqxmd.com/read/27510426/genetic-studies-on-the-tripartite-glutamate-synapse-in-the-pathophysiology-and-therapeutics-of-mood-disorders
#16
Rafael T de Sousa, Alexandre A Loch, André F Carvalho, André R Brunoni, Marie Reine Haddad, Ioline D Henter, Carlos A Zarate, Rodrigo Machado-Vieira
Both bipolar disorder (BD) and major depressive disorder (MDD) have high morbidity and share a genetic background. Treatment options for these mood disorders are currently suboptimal for many patients; however, specific genetic variables may be involved in both pathophysiology and response to treatment. Agents such as the glutamatergic modulator ketamine are effective in treatment-resistant mood disorders, underscoring the potential importance of the glutamatergic system as a target for improved therapeutics...
September 28, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27449360/adverse-childhood-experiences-associate-to-reduced-glutamate-levels-in-the-hippocampus-of-patients-affected-by-mood-disorders
#17
Sara Poletti, Clara Locatelli, Andrea Falini, Cristina Colombo, Francesco Benedetti
Adverse childhood experiences (ACE) can possibly permanently alter the stress response system, affect the glutamatergic system and influence hippocampal volume in mood disorders. The aim of the study is to investigate the association between glutamate levels in the hippocampus, measured through single proton magnetic resonance spectroscopy (1H-MRS), and ACE in patients affected by mood disorders and healthy controls. Higher levels of early stress associate to reduced levels of Glx/Cr in the hippocampus in depressed patients but not in healthy controls...
November 3, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/27354525/epigenetics-and-energetics-in-ventral-hippocampus-mediate-rapid-antidepressant-action-implications-for-treatment-resistance
#18
Benedetta Bigio, Aleksander A Mathé, Vasco C Sousa, Danielle Zelli, Per Svenningsson, Bruce S McEwen, Carla Nasca
Although regulation of energy metabolism has been linked with multiple disorders, its role in depression and responsiveness to antidepressants is less known. We found that an epigenetic and energetic agent, acetyl-l-carnitine (LAC, oral administration), rapidly rescued the depressive- and central and systemic metabolic-like phenotype of LAC-deficient Flinders Sensitive Line rats (FSL). After acute stress during LAC treatment, a subset of FSL continued to respond to LAC (rFSL), whereas the other subset did not (nrFSL)...
July 12, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27345143/hippocampal-dysfunction-and-cognitive-impairment-in-fragile-x-syndrome
#19
REVIEW
Crystal Bostrom, Suk-Yu Yau, Namat Majaess, Mariana Vetrici, Joana Gil-Mohapel, Brian R Christie
Fragile-X Syndrome (FXS) is the most common form of inherited intellectual disability and the leading genetic cause of autism spectrum disorder. FXS is caused by transcriptional silencing of the Fragile X Mental Retardation 1 (Fmr1) gene due to a CGG repeat expansion, resulting in the loss of Fragile X Mental Retardation Protein (FMRP). FMRP is involved in transcriptional regulation and trafficking of mRNA from the nucleus to the cytoplasm and distal sites both in pre- and post-synaptic terminals. Consequently, FXS is a multifaceted disorder associated with impaired synaptic plasticity...
September 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27268280/effect-of-desipramine-and-fluoxetine-on-energy-metabolism-of-cerebral-mitochondria
#20
Roberto Federico Villa, Federica Ferrari, Antonella Gorini, Nicoletta Brunello, Fabio Tascedda
Brain bioenergetic abnormalities in mood disorders were detected by neuroimaging in vivo studies in humans. Because of the increasing importance of mitochondrial pathogenetic hypothesis of Depression, in this study the effects of sub-chronic treatment (21days) with desipramine (15mg/kg) and fluoxetine (10mg/kg) were evaluated on brain energy metabolism. On mitochondria in vivo located in neuronal soma (somatic) and on mitochondria of synapses (synaptic), the catalytic activities of regulatory enzymes of mitochondrial energy-yielding metabolic pathways were assayed...
August 25, 2016: Neuroscience
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