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Glutamate mood disorders

Ioline D Henter, Rafael Teixeira de Sousa, Carlos A Zarate
Both preclinical and clinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders such as bipolar depression and major depressive disorder. In particular, rapid reductions in depressive symptoms have been noted in response to subanesthetic doses of the glutamatergic modulator ketamine in subjects with major depressive disorder or bipolar depression. These results have prompted the repurposing or development of other glutamatergic modulators, both as monotherapy or adjunctive to other therapies...
February 20, 2018: Harvard Review of Psychiatry
Li-Min Mao, John Q Wang
Major depressive disorder is a common form of mental illness. Many brain regions are implicated in the pathophysiology and symptomatology of depression. Among key brain areas is the striatum that controls reward and mood and is involved in the development of core depression-like behavior in animal models of depression. While molecular mechanisms in this region underlying depression-related behavior are poorly understood, the glutamatergic input to the striatum is believed to play a role. In this study, we investigated changes in metabotropic glutamate (mGlu) receptor expression and signaling in the striatum of adult rats in response to prolonged (10-12 weeks) social isolation, a pre-validated animal paradigm modeling depression in adulthood...
January 16, 2018: Journal of Neurochemistry
Jennifer C Felger
BACKGROUND: Studies investigating the impact of a variety of inflammatory stimuli on the brain and behavior have reported evidence that inflammation and release of inflammatory cytokines affect circuitry relevant to both reward and threat sensitivity to contribute to behavioral change. Of relevance to mood and anxiety-related disorders, biomarkers of inflammation such as inflammatory cytokines and acute-phase proteins are reliably elevated in a significant proportion of patients with major depressive disorder (MDD), bipolar disorder, anxiety disorders and post-traumatic stress disorder (PTSD)...
November 23, 2017: Current Neuropharmacology
N V Titova
Memantine is the first clinically available glutamate antagonist, with an antagonist action at the N-methyl-D-aspartate receptors in the brain, for correction of cognitive and behavioral functions in neurodegenerative disorders. Glutamate mediated excitotoxic neuronal damage has been implicated in Alzheimer's disease (AD) and other parkinsonism-related dementias and, therefore, memantine represents a novel mode of action to counteract the glutamate-mediated excitotoxicity. In moderate to severe AD, 20 mg of memantine shows a positive effect on cognition, mood, behavior and the ability to perform activities of daily living...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
R I Buji, N A Abdul Murad, L F Chan, T Maniam, M S Mohd Shahrir, M Rozita, A S Shamsul, R Mohamad Hussain, N Abdullah, R Jamal, N R Nik Jaafar
Background Systemic lupus erythematosus (SLE) patients are a high-risk population for suicide. Glutamatergic neurosystem genes have been implicated in the neurobiology of depression in SLE and suicidal behaviour in general. However, the role of glutamate receptor gene polymorphisms in suicidal behaviour among SLE patients remains unclear in the context of established clinical and psychosocial factors. We aimed to investigate the association of NR2A gene polymorphism with suicidal ideation in SLE while accounting for the interaction between clinical and psychosocial factors...
January 1, 2017: Lupus
Jae Hyeon Yoo, Tae-Woo Ha, Jin Tae Hong, Ki-Wan Oh
Sinomenium acutum has been long used in the preparations of traditional medicine in Japan, China and Korea for the treatment of various disorders including rheumatism, fever, pulmonary diseases and mood disorders. Recently, it was reported that Sinomenium acutum, has sedative and anxiolytic effects mediated by GABA-ergic systems. These experiments were performed to investigate whether sinomenine (SIN), an alkaloid derived from Sinomenium acutum enhances pentobarbital-induced sleep via γ-aminobutyric acid (GABA)-ergic systems, and modulates sleep architecture in mice...
November 1, 2017: Biomolecules & Therapeutics
Francesco Benedetti, Sara Poletti, Clara Locatelli, Elena Mazza, Cristina Lorenzi, Alice Vitali, Martina Riberto, Silvia Brioschi, Benedetta Vai, Irene Bollettini, Elisa Melloni, Veronica Aggio, Andrea Falini, Andrea De Bartolomeis, Cristina Colombo
BACKGROUND: The Homer family of postsynaptic scaffolding proteins plays a crucial role in glutamate-mediated synaptic plasticity, a phenotype associated with Bipolar Disorder (BD). Homer is a target for antidepressants and mood stabilizers. The AA risk genotype of the Homer rs7713917 A>G SNP has been associated with mood disorders and suicide, and in healthy humans with brain function. Despite the evidence linking Homer 1 gene and function to mood disorder, as well as its involvement in animal models of depression, no study has yet investigated the role of Homer in bipolar depression and treatment response...
February 2, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Kasper B Hansen, Feng Yi, Riley E Perszyk, Frank S Menniti, Stephen F Traynelis
NMDA-type glutamate receptors are ligand-gated ion channels that mediate a major component of excitatory neurotransmission in the central nervous system (CNS). They are widely distributed at all stages of development and are critically involved in normal brain functions, including neuronal development and synaptic plasticity. NMDA receptors are also implicated in the pathophysiology of numerous neurological and psychiatric disorders, such as ischemic stroke, traumatic brain injury, Alzheimer's disease, epilepsy, mood disorders, and schizophrenia...
2017: Methods in Molecular Biology
Wallace C Duncan, Elizabeth D Ballard, Carlos A Zarate
Ketamine, a drug with rapid antidepressant effects and well-described effects on slow wave sleep (SWS), is a useful intervention for investigating sleep-wake mechanisms involved in novel therapeutics. The drug rapidly (within minutes to hours) reduces depressive symptoms in individuals with major depressive disorder (MDD) or bipolar disorder (BD), including those with treatment-resistant depression. Ketamine treatment elevates extracellular glutamate in the prefrontal cortex. Glutamate, in turn, plays a critical role as a proximal element in a ketamine-initiated molecular cascade that increases synaptic strength and plasticity, which ultimately results in rapidly improved mood...
September 23, 2017: Handbook of Experimental Pharmacology
Edoardo Moretto, Luca Murru, Giuseppe Martano, Jenny Sassone, Maria Passafaro
Neurodevelopmental disorders (NDDs) are a group of diseases whose symptoms arise during childhood or adolescence and that impact several higher cognitive functions such as learning, sociability and mood. Accruing evidence suggests that a shared pathogenic mechanism underlying these diseases is the dysfunction of glutamatergic synapses. We summarize present knowledge on autism spectrum disorders (ASD), intellectual disability (ID), Down syndrome (DS), Rett syndrome (RS) and attention-deficit hyperactivity disorder (ADHD), highlighting the involvement of glutamatergic synapses and receptors in these disorders...
September 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
Thomas Demuyser, Lauren Deneyer, Eduard Bentea, Giulia Albertini, Teresa Femenia, Laura Walrave, Hideyo Sato, Niels C Danbolt, Dimitri De Bundel, Alex Michotte, Maria Lindskog, Ann Massie, Ilse Smolders
OBJECTIVES: The cystine/glutamate antiporter (system xc-) is believed to contribute to nonvesicular glutamate release from glial cells in various brain areas. Although recent investigations implicate system xc- in mood disorders, unambiguous evidence has not yet been established. Therefore, we evaluated the possible role of system xc- in the depressive state. METHODS: We conducted a protein expression analysis of the specific subunit of system xc- (xCT) in brain regions of the corticosterone mouse model, Flinders Sensitive Line rat model and post-mortem tissue of depressed patients...
September 8, 2017: World Journal of Biological Psychiatry
Suzan G Rosa, Ana P Pesarico, Carolina F Tagliapietra, Sônia C A da Luz, Cristina W Nogueira
Animal and clinical researches indicate that the opioid system exerts a crucial role in the etiology of mood disorders and is a target for intervention in depression treatment. This study investigated the contribution of the opioid system to the antidepressant-like action of acute or repeated m-trifluoromethyl-diphenyl diselenide administration to Swiss mice. m-Trifluoromethyl-diphenyl diselenide (50 mg/kg, intragastric) produced an antidepressant-like action in the forced swimming test from 30 min to 24 h after treatment...
August 1, 2017: Journal of Psychopharmacology
Geehoon Chung, Chae Young Kim, Yeong-Chan Yun, Sang Ho Yoon, Myoung-Hwan Kim, Yu Kyeong Kim, Sang Jeong Kim
Patients with chronic pain easily accompany the negative mood symptoms such as depression and anxiety, and these disturbances in turn affect the aversive perception of pain. However, the underlying mechanisms are largely unknown. We hypothesized that the alteration of metabotropic glutamate receptor 5 (mGluR5) in the brain region underlies such a comorbidity of aversive states. We scanned the brain of chronic neuropathic pain model rats using positron emission tomography (PET) technique with an mGluR5-selective radiotracer [11C] ABP688 and found various brain regions with higher or lower level of mGluR5 compared to control rats...
August 29, 2017: Scientific Reports
Elisabeth Lang, Anne S Mallien, Andrei-Nicolae Vasilescu, Dimitri Hefter, Alessia Luoni, Marco A Riva, Stefan Borgwardt, Rolf Sprengel, Undine E Lang, Peter Gass, Dragos Inta
A growing body of evidence supports the idea that drugs targeting the glutamate system may represent a valuable therapeutic alternative in major depressive disorders (MDD). The rapid and prolonged mood elevating effect of the NMDA receptor (NMDAR) antagonist ketamine has been studied intensely. However, its clinical use is hampered by deleterious side-effects, such as psychosis. Therefore, a better understanding of the mechanisms of the psychotropic effects after NMDAR blockade is necessary to develop glutamatergic antidepressants with improved therapeutic profile...
January 2018: Neuroscience and Biobehavioral Reviews
Yanqiong Zhang, Xia Mao, Jing Su, Ya Geng, Rui Guo, Shihuan Tang, Junfang Li, Xuefeng Xiao, Haiyu Xu, Hongjun Yang
BACKGROUND: QiXueHe Capsule (QXHC) is a Chinese patent drug that is extensively used for the treatment of menstrual disorders. However, its underlying pharmacological mechanisms have not been fully elucidated. METHODS: A list of QXHC putative targets were predicted using MetaDrug. An interaction network using links between QXHC putative targets and the known therapeutic targets of menstrual disorders was constructed. QXHC candidate targets were also identified via calculating the topological feature values of nodes in the network...
2017: Chinese Medicine
Claudio D'Addario, Maria Carlotta Palazzo, Beatrice Benatti, Benedetta Grancini, Mariangela Pucci, Andrea Di Francesco, Giulia Camuri, Daniela Galimberti, Chiara Fenoglio, Elio Scarpini, A Carlo Altamura, Mauro Maccarrone, Bernardo Dell'Osso
Bipolar Disorder (BD) is a prevalent and disabling condition, determined by gene-environment interactions, possibly mediated by epigenetic mechanisms. The present study aimed at investigating the transcriptional regulation of BD selected target genes by DNA methylation in peripheral blood mononuclear cells of patients with a DSM-5 diagnosis of type I (BD-I) and type II (BD-II) Bipolar Disorders (n=99), as well as of healthy controls (CT, n=42). The analysis of gene expression revealed prodynorphin (PDYN) mRNA levels significantly reduced in subjects with BD-II but not in those with BD-I, when compared to CT...
August 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
Christy Duan, Jessica Cosgrove, Kristina M Deligiannidis
PURPOSE OF REVIEW: Imaging research has sought to uncover brain structure, function, and metabolism in women with postpartum depression (PPD) as little is known about its underlying pathophysiology. This review discusses the imaging modalities used to date to evaluate postpartum depression and highlights recent findings. RECENT FINDINGS: Altered functional connectivity and activity changes in brain areas implicated in executive functioning and emotion and reward processing have been identified in PPD...
August 19, 2017: Current Psychiatry Reports
Caren J Blacker, Charles P Lewis, Mark A Frye, Marin Veldic
Glutamatergic dysregulation is implicated in the neuropathology of bipolar disorder (BD). There is increasing interest in investigating the role of metabotropic glutamate receptors (mGluRs) in BD and as a target for treatment intervention. Bipolar mGluR studies (published January 1992-April 2016) were identified via PubMed, Embase, Web of Science, and Scopus. Full-text screening, data extraction, and quality appraisal were conducted in duplicate, with strict inclusion and exclusion criteria. The initial literature search for mGluRs in BD, including non-bipolar mood disorders and primary psychotic disorders, identified 1544 articles...
November 2017: Psychiatry Research
Puja K Parekh, Darius Becker-Krail, Poornima Sundaravelu, Shinsuke Ishigaki, Haruo Okado, Gen Sobue, Yanhua Huang, Colleen A McClung
BACKGROUND: Disruptions in circadian rhythms are associated with an increased risk for bipolar disorder. Moreover, studies show that the circadian protein CLOCK (circadian locomotor output cycles kaput) is involved in regulating monoaminergic systems and mood-related behavior. However, the molecular and synaptic mechanisms underlying this relationship remain poorly understood. METHODS: Using ex vivo whole-cell patch-clamp electrophysiology in ClockΔ19 mutant and wild-type mice we characterized alterations in excitatory synaptic transmission, strength, and intrinsic excitability of nucleus accumbens (NAc) neurons...
June 27, 2017: Biological Psychiatry
Carlo Cattaneo, Thomas Müller, Erminio Bonizzoni, Gabriele Lazzeri, Ioannis Kottakis, Charlotte Keywood
BACKGROUND: Mood disorders are very frequent in Parkinson's Disease (PD), and their effective treatment is still a major unresolved issue: growing evidence suggests that glutamatergic system dysfunction is directly involved. Safinamide is a drug with an innovative mechanism of action, dopaminergic and non-dopaminergic, that includes the reversible inhibition of the monoamine oxidase-B (MAO-B) enzyme and the modulation of excessive glutamate release through the use- and state-dependent blockade of the sodium channels...
2017: Journal of Parkinson's Disease
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