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Glutamate mood disorders

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
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
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
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
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
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
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)...
September 9, 2016: Journal of Affective Disorders
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...
September 15, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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
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
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 25, 2016: Brain Research
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. Glutamatergic agents such as the N-methyl-D-aspartate (NMDA) antagonist ketamine are effective in treatment-resistant mood disorders, underscoring the potential importance of the glutamatergic system as a target for improved therapeutics...
August 11, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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
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
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
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
Peter Šóš
No abstract text is available yet for this article.
August 2016: Evidence-based Mental Health
Chiara Chiapponi, Federica Piras, Fabrizio Piras, Carlo Caltagirone, Gianfranco Spalletta
Third-generation neuroimaging research has been enriched by advances in magnetic resonance spectroscopy (MRS) measuring the concentration of important neurotrasmitters, such as the inhibitory amino acid GABA. Here, we performed a systematic mini-review on brain MRS studies measuring GABA concentration in patients affected by schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). We wondered whether multimodal investigations could overcome intrinsic technical limits of MRS giving a broader view of mental disorders pathogenesis...
2016: Frontiers in Psychiatry
Ema Grilo, Joana Pinto, Joana Serra Caetano, Helena Pereira, Patrícia Cardoso, Rita Cardoso, Isabel Dinis, Cristina Pereira, Isabel Fineza, Alice Mirante
Limbic encephalitis is a rare neurological disorder that may be difficult to recognize. Clinical features include memory impairment, temporal lobe seizures and affective disturbance. We report the case of a 10-year-old girl with type 1 diabetes mellitus that presented with seizures, depressed mood and memory changes. The diagnosis of glutamic acid decarboxylase 65 (GAD65) mediated limbic encephalitis relied on cerebral magnetic resonance imaging lesions and high serological and cerebrospinal fluid GAD65-antibodies titers...
August 1, 2016: Journal of Pediatric Endocrinology & Metabolism: JPEM
Y Wang, N Gu, T Duan, P Kesner, F Blaskovits, J Liu, Y Lu, L Tong, F Gao, C Harris, K Mackie, J Li, Q Tan, M N Hill, Z Yuan, X Zhang
The probability of suffering the mood disorder depression is up to 30% in women and 15% in men during their life span. Pharmacological options for depression are limited: conventional antidepressants have low efficacy and a delayed onset of action (several weeks). Here we investigate the antidepressant actions of inhibitors of monoacylglycerol lipase (MAGL), the major degradative enzyme of the endocannabinoid 2-arachidonoylglycerol. A low-dose of MAGL inhibitors produces antidepressant effects on acute stress-exposed mice, through glutamatergic synaptic long-term depression (LTD), without significant effects on chronic corticosterone-exposed mice...
March 22, 2016: Molecular Psychiatry
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