Research Topics
Genomes and Genes | H K ManjiSummaryAffiliation: National Institutes of Health Country: USA Publications
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Publications
PKC, MAP kinases and the bcl-2 family of proteins as long-term targets for mood stabilizersH K Manji
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, MD 20892, USA
Mol Psychiatry 7:S46-56. 2002....
Riluzole in psychiatry: a systematic review of the literatureCarlos A Zarate
Mark O Hatfield CRC, Bethesda, Maryland 20892, USA
Expert Opin Drug Metab Toxicol 4:1223-34. 2008..Riluzole, a neuroprotective agent with anticonvulsant properties approved for the treatment of amyotrophic lateral sclerosis (ALS) is one such agent...
Post-receptor signaling pathways in the pathophysiology and treatment of mood disordersH K Manji
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, 10 Center Drive, 10 4N 222 MSC 1381, Bethesda, MD, 20892, USA
Curr Psychiatry Rep 2:479-89. 2000....
Signal transduction and genes-to-behaviors pathways in psychiatric diseasesHusseini K Manji
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, NIMH, Bethesda, MD 20892, USA
Sci STKE 2003:pe49. 2003..It is likely that genetic findings in severe psychiatric disorders will continue to implicate direct and indirect modulation of critical intracellular signaling pathways...
Impairments of neuroplasticity and cellular resilience in severe mood disorders: implications for the development of novel therapeuticsH K Manji
Laboratory of Molecular Pathophysiology, NIMH, Building 49, Room B1EE16, 49 Convent Dr MSC 4405, Bethesda, MD 20892 4405, USA
Psychopharmacol Bull 35:5-49. 2001..The future development of treatments that more directly target molecules involved in critical CNS cell survival and cell death pathways thus hold promise as novel, improved long-term treatments for mood disorders...
Bipolar disorder: leads from the molecular and cellular mechanisms of action of mood stabilizersH K Manji
Laboratory of Molecular Pathophysiology, Wayne State University School of Medicine, Detroit, Michigan, USA
Br J Psychiatry Suppl 41:s107-19. 2001..New research is dramatically altering our understanding of the molecular mechanisms underlying neuronal communication...
The cellular neurobiology of depressionH K Manji
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, Maryland, USA
Nat Med 7:541-7. 2001..Agents designed to directly target molecules in these pathways may hold promise as new therapeutics for depression...
The nature of bipolar disorderH K Manji
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Mich, USA
J Clin Psychiatry 61:42-57. 2000....
Neuroplasticity and cellular resilience in mood disordersH K Manji
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, USA
Mol Psychiatry 5:578-93. 2000....
Valproate robustly enhances AP-1 mediated gene expressionG Chen
Laboratory of Molecular Pathophysiology, Department of Psychiatry and Behavioral Neurosciences, WSU School of Medicine, 2301 Scott Hall, 540 E Canfield Avenue, Detroit, MI 48201, USA
Brain Res Mol Brain Res 64:52-8. 1999....
Emerging experimental therapeutics for bipolar disorder: clues from the molecular pathophysiologyJ A Quiroz
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, MD 20892, USA
Mol Psychiatry 9:756-76. 2004..While the task of developing novel medications for bipolar disorder is truly daunting, these and similar approaches will ultimately lead to better medications for the millions who suffer from this devastating illness...
Molecular mechanisms underlying mood stabilization in manic-depressive illness: the phenotype challengeO C Ikonomov
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA
Am J Psychiatry 156:1506-14. 1999..The authors critically examine the evidence supporting the hypothesis that lithium's therapeutic effects in bipolar affective disorder are mediated by alterations in the expression of specific genes in critical neuronal circuits...
Brain-derived neurotrophic factor and initial antidepressant response to an N-methyl-D-aspartate antagonistRodrigo Machado-Vieira
Mood and Anxiety Disorders Program, Laboratory of Molecular Psychiatry and Experimental Therapeutics, National Institute of Mental Health NIMH, National Institutes of Health NIH, Department of Health and Human Services, Bethesda, Maryland, USA
J Clin Psychiatry 70:1662-6. 2009..This study investigated whether changes in brain-derived neurotrophic factor (BDNF) levels are associated with the initial antidepressant effects of ketamine, a high-affinity N-methyl-D-aspartate (NMDA) antagonist...
Lithium up-regulates the cytoprotective protein Bcl-2 in the CNS in vivo: a role for neurotrophic and neuroprotective effects in manic depressive illnessH K Manji
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Mich 48201, USA
J Clin Psychiatry 61:82-96. 2000....
The mood stabilizer valproic acid activates mitogen-activated protein kinases and promotes neurite growthP X Yuan
Laboratory of Molecular Pathophysiology, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
J Biol Chem 276:31674-83. 2001..These data demonstrate that VPA is an ERK pathway activator and produces neurotrophic effects...
Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depressionHusseini K Manji
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, Maryland 20892-4405, USA
Biol Psychiatry 53:707-42. 2003..The development of novel, nonaminergic-based therapeutics holds much promise for improved treatment of severe, refractory mood disorders...
Pramipexole for bipolar II depression: a placebo-controlled proof of concept studyCarlos A Zarate
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institute of Health, Department of Human and Health Services, Bethesda, Maryland, USA
Biol Psychiatry 56:54-60. 2004..02). One subject on pramipexole and two on placebo developed hypomanic symptoms. CONCLUSIONS: The dopamine agonist pramipexole was found to have significant antidepressant effects in patients with bipolar II depression...
The role of the extracellular signal-regulated kinase signaling pathway in mood modulationHaim Einat
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892 4405, USA
J Neurosci 23:7311-6. 2003..These data suggest that the ERK pathway may mediate the antimanic effects of mood stabilizers...
A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depressionNancy Diazgranados
Experimental Therapeutics, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
Arch Gen Psychiatry 67:793-802. 2010..Pharmacological strategies that produce rapid antidepressant effects-for instance, within a few hours or days-would have an enormous impact on patient care and public health...
Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorderDara M Cannon
Molecular Imaging Branch, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA
Biol Psychiatry 62:870-7. 2007....
Evidence for the involvement of the kainate receptor subunit GluR6 (GRIK2) in mediating behavioral displays related to behavioral symptoms of maniaG Shaltiel
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
Mol Psychiatry 13:858-72. 2008..The molecular mechanism underlying the behavioral effects of lithium in GluR6 KO mice remains to be elucidated...
The role of hippocampal GluR1 and GluR2 receptors in manic-like behaviorJing Du
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20878, USA
J Neurosci 28:68-79. 2008..These studies provide novel insights into the role of hippocampal GluR1/2 receptors in mediating facets of the manic syndrome and offer avenues for the development of novel therapeutics for these disorders...
Targeting the BH3-interacting domain death agonist to develop mechanistically unique antidepressantsO Malkesman
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, Bethesda, MD, USA
Mol Psychiatry 17:770-80. 2012..Taken together, the results suggest that functional perturbation of apoptotic proteins such as Bid and, alternatively, enhancement of Bcl-2 function, is a putative strategy for developing novel therapeutics for mood disorders...
Enhancement of hippocampal neurogenesis by lithiumG Chen
Laboratory of Molecular Pathophysiology, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
J Neurochem 75:1729-34. 2000..These results add to the growing body of evidence suggesting that mood stabilizers and antidepressants exert neurotrophic effects and may therefore be of use in the long-term treatment of other neuropsychiatric disorders...
Lithium regulates PKC-mediated intracellular cross-talk and gene expression in the CNS in vivoG Chen
Department of Psychiatry and Behavioral Neurosciences, WSU School of Medicine, Detroit, MI 48201, USA
Bipolar Disord 2:217-36. 2000..Together, these results suggest that the PKC signaling pathway and PKC-mediated gene expression may be important mediators of lithium's long-term therapeutic effects in a disorder as complex as BD...
Modulation of synaptic plasticity by antimanic agents: the role of AMPA glutamate receptor subunit 1 synaptic expressionJing Du
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, Maryland 20892, USA
J Neurosci 24:6578-89. 2004....
Beta-catenin overexpression in the mouse brain phenocopies lithium-sensitive behaviorsTodd D Gould
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892 3711, USA
Neuropsychopharmacology 32:2173-83. 2007..By associating the behavioral effects of lithium with beta-catenin levels, these data suggest that increasing beta-catenin might be a novel therapeutic strategy for mood disorders...
The use of mood stabilizers as plasticity enhancers in the treatment of neuropsychiatric disordersNeil A Gray
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, MD 20892, USA
J Clin Psychiatry 64:3-17. 2003....
Involvement of AMPA receptors in the antidepressant-like effects of lithium in the mouse tail suspension test and forced swim testTodd D Gould
Laboratory of Molecular Pathophysiology and Experimental Therapeutics, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Neuropharmacology 54:577-87. 2008..Lithium may exert its antidepressant effects in humans through AMPA receptors, thus further supporting a role of targeting AMPA receptors as a therapeutic approach for the treatment of depression...
Increased anterior cingulate cortical activity in response to fearful faces: a neurophysiological biomarker that predicts rapid antidepressant response to ketamineGiacomo Salvadore
Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
Biol Psychiatry 65:289-95. 2009..We also investigated patterns of ACC activity to rapid presentation of fearful faces compared with the normal habituation observed in healthy subjects...
Family history of alcohol dependence and initial antidepressant response to an N-methyl-D-aspartate antagonistLaura E Phelps
Laboratory of Molecular Pathophysiology and Experimental Therapeutics, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health DHHS, 10 Center Drive, Bethesda, MD 20892 1282, USA
Biol Psychiatry 65:181-4. 2009..This study investigated whether a family history of alcohol dependence influences ketamine's initial antidepressant effect...
The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNSG Chen
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
J Neurochem 72:879-82. 1999..These novel findings represent the first report of medication-induced increases in CNS bcl-2 levels and may have implications not only for mood disorders, but also for long-term treatment of various neurodegenerative disorders...
Signalling pathways in the brain: cellular transduction of mood stabilisation in the treatment of manic-depressive illnessH K Manji
Department of Psychiatry, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
Aust N Z J Psychiatry 33:S65-83. 1999....
Temporal dissociation between lithium-induced changes in frontal lobe myo-inositol and clinical response in manic-depressive illnessG J Moore
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA
Am J Psychiatry 156:1902-8. 1999..Lithium's effects on in vivo brain myo-inositol levels were investigated longitudinally in 12 adult depressed patients with manic-depressive illness...
Evidence for selective microRNAs and their effectors as common long-term targets for the actions of mood stabilizersRulun Zhou
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
Neuropsychopharmacology 34:1395-405. 2009..These findings are the first to demonstrate that miRNAs and their predicted effectors are targets for the action of psychotherapeutic drugs...
Mood stabilizer valproate promotes ERK pathway-dependent cortical neuronal growth and neurogenesisYanlei Hao
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-4405, USA
J Neurosci 24:6590-9. 2004..This cascade of events provides a potential mechanism whereby mood stabilizers alleviate cerebral morphometric deficits associated with manic-depressive illness...
AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim testTodd D Gould
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-3711, USA
Int J Neuropsychopharmacol 7:387-90. 2004....
The anti-apoptotic, glucocorticoid receptor cochaperone protein BAG-1 is a long-term target for the actions of mood stabilizersRulun Zhou
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, Maryland 20852, USA
J Neurosci 25:4493-502. 2005....
Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptorsSungho Maeng
Laboratory of Molecular Pathophysiology and Experimental Therapeutics, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA
Biol Psychiatry 63:349-52. 2008..Understanding the mechanisms underlying the intriguing effects of N-methyl d-aspartate (NMDA) antagonists could lead to novel treatments with a rapid onset of action...
Lithium regulates total and synaptic expression of the AMPA glutamate receptor GluR2 in vitro and in vivoNeil A Gray
National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA
Ann N Y Acad Sci 1003:402-4. 2003
Possible involvement of the ERK signaling cascade in bipolar disorder: behavioral leads from the study of mutant miceH Einat
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892 4405, USA
Drug News Perspect 16:453-63. 2003....
Lithium treatment in ovo: effects on embryonic heart rate, natural death of ciliary ganglion neurons, and brain expression of a highly conserved chicken homolog of human MTG8/ETOO C Ikonomov
Laboratory of Molecular Pathophysiology, Department of Psychiatry and Behavioral Neurosciences, Wayne State University, School of Medicine, 4237 Scott Hall, 540 E Canfield, Detroit, MI 48201, USA
Brain Res Dev Brain Res 123:13-24. 2000..We propose that the induction of ETO expression, in concert with lithium-induced upregulation of other genes, such as PEBP2beta and bcl-2, is participating in the neuroprotective effect of chronic lithium treatment...
The extracellular signal-regulated kinase pathway contributes to the control of behavioral excitementS R Engel
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, MD 20892 3711, USA
Mol Psychiatry 14:448-61. 2009..Whether there is a shared mechanism through which mood stabilizers produce their clinical actions on mood, thought and behavioral symptoms of mania also requires further investigation...
Glutamate receptors as targets of protein kinase C in the pathophysiology and treatment of animal models of maniaSteven T Szabo
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Building 35, 1C912, Bethesda, MD 20892, USA
Neuropharmacology 56:47-55. 2009..These results suggest that PKC modulators or their intracellular targets may ultimately represent novel avenues for the development of new therapeutics for mood disorders...
The anterior cingulate ERK pathway contributes to regulation of behavioral excitement and hedonic activityThomas K Creson
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, NIH, Bethesda, MD 20892 3711, USA
Bipolar Disord 11:339-50. 2009..Here we investigated the extent to which perturbation of one of the affected pathways, the ERK pathway, in the ACC influences affective-related behavior...
Common effects of lithium and valproate on mitochondrial functions: protection against methamphetamine-induced mitochondrial damageRosilla F Bachmann
Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
Int J Neuropsychopharmacol 12:805-22. 2009..These agents may have potential clinical utility in the treatment of other diseases associated with impaired mitochondrial function, such as neurodegenerative diseases and schizophrenia...
A comparison of cognitive functioning in medicated and unmedicated subjects with bipolar depressionM Kathleen Holmes
Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
Bipolar Disord 10:806-15. 2008..The present study aims to compare the cognitive performance of medicated and unmedicated subjects with bipolar depression to healthy control subjects...
The female urine sniffing test: a novel approach for assessing reward-seeking behavior in rodentsOz Malkesman
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, Bethesda, Maryland 20892, USA
Biol Psychiatry 67:864-71. 2010..We describe a novel approach for monitoring reward-seeking behavior in rodents: sniffing of estrus female urine by male mice, along with number of ultrasonic vocalizations (USVs) emitted during the test...
Altered levels of extracellular signal-regulated kinase signaling proteins in postmortem frontal cortex of individuals with mood disorders and schizophreniaPeixiong Yuan
Biomarker Laboratory, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
J Affect Disord 124:164-9. 2010..The extent of the possible involvement of this pathway in psychiatric disorders remains unknown, as does its potential utility as a pharmacological target for the future development of novel therapeutics...
In vivo evidence in the brain for lithium inhibition of glycogen synthase kinase-3Todd D Gould
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD 20892-4405, USA
Neuropsychopharmacology 29:32-8. 2004..These results strongly suggest that lithium significantly inhibits brain glycogen synthase kinase-3 in vivo at concentrations relevant for the treatment of bipolar disorder...
Structurally dissimilar antimanic agents modulate synaptic plasticity by regulating AMPA glutamate receptor subunit GluR1 synaptic expressionJing Du
Laboratory of Molecular Pathophysiology, National Institutes of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-4405, USA
Ann N Y Acad Sci 1003:378-80. 2003....
Kinases as drug targets in the treatment of bipolar disorderLisa A Catapano
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, NIH, HHS, Bethesda, MD, USA
Drug Discov Today 13:295-302. 2008..This short review will focus on two of the most promising such targets: glycogen synthase-3 and protein kinase C...
Generation and behavioral characterization of beta-catenin forebrain-specific conditional knock-out miceTodd D Gould
Laboratory of Molecular Pathophysiology and Experimental Therapeutics, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Behav Brain Res 189:117-25. 2008..Alternatively, regulating beta-catenin may modulate drug effects rather than being a model of mood disorder pathophysiology per se...
Emerging experimental therapeutics for bipolar disorder: insights from the molecular and cellular actions of current mood stabilizersT D Gould
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, MD 20892, USA
Mol Psychiatry 9:734-55. 2004....
High levels of Gs alpha in platelets of euthymic patients with bipolar affective disorderP B Mitchell
Experimental Therapeutics Branch, NIMH, Bethesda, MD, USA
Am J Psychiatry 154:218-23. 1997..To determine whether such G protein abnormalities are a trait phenomenon, the authors investigated the levels of G protein alpha subunits in platelets and lymphocytes of euthymic patients with bipolar affective disorder...
Translational research in bipolar disorder: emerging insights from genetically based modelsG Chen
Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
Mol Psychiatry 15:883-95. 2010....
Sustained low-grade pro-inflammatory state in unmedicated, remitted women with major depressive disorder as evidenced by elevated serum levels of the acute phase proteins C-reactive protein and serum amyloid AMitchel A Kling
Clinical Neuroendocrinology Branch, Division of Intramural Research Programs, National Institute of Mental Health, Bethesda, MD 20892 1284, USA
Biol Psychiatry 62:309-13. 2007..Elevations of the inflammatory markers C-reactive protein (CRP) and serum amyloid A (SAA) predict increased CAD risk in populations; few data on these markers exist in MDD, particularly in remitted patients...
The role of the tripartite glutamatergic synapse in the pathophysiology and therapeutics of mood disordersRodrigo Machado-Vieira
Experimental Therapeutics, Mood and Anxiety Disorders Research Program, NIMH NIH, Bethesda, Maryland 20892, USA
Neuroscientist 15:525-39. 2009..In therapeutically relevant paradigms, ketamine preferentially targets postsynaptic AMPA/NMDA receptors, and riluzole preferentially targets presynaptic voltage-operated channels and glia...
Genetic variation in HTR2A influences serotonin transporter binding potential as measured using PET and [11C]DASBGonzalo Laje
Unit on the Genetic Basis of Mood and Anxiety Disorders, National Institute of Mental Health, Bethesda, MD 20892 3719, USA
Int J Neuropsychopharmacol 13:715-24. 2010....
In search of the Holy Grail for the treatment of neurodegenerative disorders: has a simple cation been overlooked?De Maw Chuang
Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892 1363, USA
Biol Psychiatry 62:4-6. 2007
The role of AMPA receptor modulation in the treatment of neuropsychiatric diseasesCarlos A Zarate
Laboratory of Molecular Pathophysiology and Experimental Therapeutics, Mood and Anxiety Disorders Research Program, National Institute of Mental Health/NIH, 10 Center Drive, Bethesda, MD 20892, USA
Exp Neurol 211:7-10. 2008
Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot studyCarlos A Zarate
Laboratory of Molecular Pathophysiology and Experimental Therapeutics, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
Bipolar Disord 9:561-70. 2007..In this study, we investigated whether antimanic effects can be achieved with a protein kinase C inhibitor in subjects with mania...
Neurobiology of bipolar disorderAndrew R Newberg
National Institute of Mental Health, 10 Center Drive, MSC 1282, Building 10 CRC, Room 7 5545, Bethesda, MD 20892 1282, USA
Expert Rev Neurother 8:93-110. 2008....
The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesisRodrigo Machado-Vieira
Experimental Therapeutics, Mood and Anxiety Disorders Research Program, NIMH NIH, Department of Health and Human Services, Bethesda, MD 20892, USA
Bipolar Disord 11:92-109. 2009..Continued work to decipher lithium's molecular actions will likely lead to the development of not only improved therapeutics for BD, but to neurotrophic enhancers that could prove useful in the treatment of many other illnesses...
Abnormal hippocampal functioning and impaired spatial navigation in depressed individuals: evidence from whole-head magnetoencephalographyBrian R Cornwell
Mood and Anxiety Disorders Program, NIMH, 15K North Dr, MSC 2670, Bethesda, MD 20892, USA
Am J Psychiatry 167:836-44. 2010..The authors aimed to link spatial navigation deficits previously documented in depressed patients to abnormal hippocampal functioning using a virtual reality navigation task...
Strain differences in lithium attenuation of d-amphetamine-induced hyperlocomotion: a mouse model for the genetics of clinical response to lithiumTodd D Gould
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, NIH, HHS, Bethesda, MD 20892 3711, USA
Neuropsychopharmacology 32:1321-33. 2007....
Targeting glycogen synthase kinase-3 in the CNS: implications for the development of new treatments for mood disordersTodd D Gould
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, NIH, Bethesda, MD 20892 3711, USA
Curr Drug Targets 7:1399-409. 2006..The evidence described in this review suggests that regulating GSK-3 may represent a target for novel medications to treat mood disorders...
Verapamil augmentation of lithium treatment improves outcome in mania unresponsive to lithium alone: preliminary findings and a discussion of therapeutic mechanismsAlan G Mallinger
Mood and Anxiety Disorders Program, National Institutes of Health Intramural Research Program, Building 10, Room 3N210, MSC 1290, Bethesda, MD 20892, USA
Bipolar Disord 10:856-66. 2008..Verapamil has shown antimanic activity in some but not all studies. Therefore, we investigated verapamil, used alone or as an adjunctive treatment, in manic patients who did not respond to an initial adequate trial of lithium...
Amygdala volume in depressed patients with bipolar disorder assessed using high resolution 3T MRI: the impact of medicationJonathan Savitz
Section on Neuroimaging in Mood and Anxiety Disorders, NIH NIMH MAP, Bethesda, MD 20892, USA
Neuroimage 49:2966-76. 2010..Here we extend these results to the amygdala. We raise the possibility that neuroplastic changes in the amygdala associated with BD are moderated by some mood stabilizing medications...
Glycogen synthase kinase-3: a target for novel bipolar disorder treatmentsTodd D Gould
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA
J Clin Psychiatry 65:10-21. 2004..We conclude with a discussion of the GSK-3 inhibitors furthest in development and the clinical trials that may emerge...
An open-label trial of the glutamate-modulating agent riluzole in combination with lithium for the treatment of bipolar depressionCarlos A Zarate
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, Maryland, USA
Biol Psychiatry 57:430-2. 2005..This study was conducted to determine the efficacy and safety of riluzole, a glutamate-modulating agent, in bipolar depression...
New approaches to modeling bipolar disorderHaim Einat
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, Maryland, US
Psychopharmacol Bull 37:47-63. 2003..These new models hold much promise in delineating the underlying pathophysiology of bipolar disorder and for the development of novel, improved therapeutics. Psychopharmacology Bulletin...
Regulation of cellular plasticity cascades in the pathophysiology and treatment of mood disorders: role of the glutamatergic systemCarlos A Zarate
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, Maryland 20892, USA
Ann N Y Acad Sci 1003:273-91. 2003....
Discovering endophenotypes for major depressionGregor Hasler
Mood and Anxiety Disorders Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, USA
Neuropsychopharmacology 29:1765-81. 2004....
Neural circuitry and neuroplasticity in mood disorders: insights for novel therapeutic targetsPaul J Carlson
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, Maryland 20892, USA
NeuroRx 3:22-41. 2006....
An open-label trial of riluzole in patients with treatment-resistant major depressionCarlos A Zarate
Laboratory of Molecular Pathophysiology and Experimental Therapeutics and the Pathophysiology Branch, Mood and Anxiety Disorders Program, NIMH, Department of Health and Human Services, NIH, Bethesda, MD 20892, USA
Am J Psychiatry 161:171-4. 2004..This study was conducted to determine the efficacy and safety of riluzole, a glutamate-modulating agent, in patients with recurrent major depression...
Bcl-2 polymorphism influences gray matter volume in the ventral striatum in healthy humansGiacomo Salvadore
Mood and Anxiety Disorders Program, National Institute of Mental Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA
Biol Psychiatry 66:804-7. 2009..We tested the hypothesis that this SNP would modulate gray matter (GM) volume in the limbic-cortical-striatal-pallidal-thalamic circuitry that plays major roles in mood regulation...
Protein kinase C inhibitors: rationale for use and potential in the treatment of bipolar disorderCarlos A Zarate
Laboratory of Molecular Pathophysiology and Experimental Therapeutics, Bethesda, Maryland, USA
CNS Drugs 23:569-82. 2009..The development of CNS-penetrant PKC inhibitors may have considerable benefit for this devastating illness...
G protein-coupled receptors in major psychiatric disordersLisa A Catapano
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, NIH, HHS, Bethesda, MD 20892, USA
Biochim Biophys Acta 1768:976-93. 2007..The future development of novel agents targeting GPCR signaling cascades remains an exciting prospect for patients refractory to existing therapeutics...
Regional cerebral glucose metabolic abnormalities in bipolar II depressionLinda Mah
Section on Neuroimaging in Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA
Biol Psychiatry 61:765-75. 2007..This study investigated whether cerebral metabolic abnormalities previously reported in unmedicated BD subjects are evident in depressed bipolar disorder type II (BD II) subjects receiving lithium or divalproex...
The anticonvulsants lamotrigine, riluzole, and valproate differentially regulate AMPA receptor membrane localization: relationship to clinical effects in mood disordersJing Du
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
Neuropsychopharmacology 32:793-802. 2007....
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depressionCarlos A Zarate
Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD 20892, USA
Arch Gen Psychiatry 63:856-64. 2006..Converging lines of evidence suggest the role of the glutamatergic system in the pathophysiology and treatment of mood disorders...
Serotonin transporter binding in bipolar disorder assessed using [11C]DASB and positron emission tomographyDara M Cannon
Mood and Anxiety Disorders Program, Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892 2670, USA
Biol Psychiatry 60:207-17. 2006..This study used PET and [(11)C]DASB, a radioligand that afforded higher sensitivity and specificity for the 5-HTT than previously available radioligands, to compare 5-HTT binding between BD and control subjects...
The extracellular signal-regulated kinase pathway: an emerging promising target for mood stabilizersGuang Chen
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Research Program, National Institute of Mental Health, National Institute of Health, Bethesda, Maryland 20892 3711, USA
Curr Opin Psychiatry 19:313-23. 2006....
MicroRNAs in mental health: from biological underpinnings to potential therapiesJoshua G Hunsberger
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, 9000 Rockville Pike, Building 35, 1C912, Bethesda, MD 20892, USA
Neuromolecular Med 11:173-82. 2009..Clearly, considerable research is required to better determine any therapeutic potential of targeting miRNAs; however, these agents may provide the next generation of effective therapies for psychiatric illnesses...
Cellular plasticity cascades: targets for the development of novel therapeutics for bipolar disorderCarlos A Zarate
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Research Program, National Institute of Mental Health, Bethesda, Maryland, USA
Biol Psychiatry 59:1006-20. 2006....
Life stress, genes, and depression: multiple pathways lead to increased risk and new opportunities for interventionDennis S Charney
Mood and Anxiety Disorders Research Program, National Institute of Mental Health, 15K North Drive, Room 101, MSC 2670, Bethesda, MD 20892 2670, USA
Sci STKE 2004:re5. 2004....
Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stressR J Schloesser
Laboratory of Molecular Pathophysiology, National Institute of Mental Health NIMH, National Institutes of Health NIH, Bethesda, MD 20892, USA
Mol Psychiatry 15:1152-63. 2010....
Antidepressants, metabolites, and apparent drug resistanceW Z Potter
Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, MD 20892
Clin Neuropharmacol 13:S45-53. 1990..Finally, principles are deduced for identifying those cases in which metabolic considerations are most likely to be relevant to observed drug resistance...
Molecular and cellular mechanisms underlying mood stabilization in bipolar disorder: implications for the development of improved therapeuticsH K Manji
Laboratory of Molecular Pathophysiology, NIMH, Bethesda, MD 20892-4405, USA
Mol Psychiatry 7:S1-7. 2002
Signal-transducing G proteins and antidepressant drugs: evidence for modulation of alpha subunit gene expression in rat brainK P Lesch
Section of Neuropharmacology, National Institute of Mental Health, Bethesda, Maryland
Biol Psychiatry 32:549-79. 1992..The development of novel drugs with G proteins as primary targets remains an attractive prospect for the future...
Increased anxiety-like behaviors and mitochondrial dysfunction in mice with targeted mutation of the Bcl-2 gene: further support for the involvement of mitochondrial function in anxiety disordersHaim Einat
College of Pharmacy, Duluth, University of Minnesota, 376 Kirby Plaza, 1208 Kirby Drive, Duluth, MN 55812, USA
Behav Brain Res 165:172-80. 2005..Our study, therefore demonstrates that Bcl-2 may be a key factor in anxiety disorders and that its effects may possibly originate from its role in the mitochondria...
Glycogen synthase kinase-3: a putative molecular target for lithium mimetic drugsTodd D Gould
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, MD 20892, USA
Neuropsychopharmacology 30:1223-37. 2005..In this regard, as is discussed, there is a major effort underway to develop novel, specific, GSK-3 inhibitors...
Effects of a glycogen synthase kinase-3 inhibitor, lithium, in adenomatous polyposis coli mutant miceTodd D Gould
Laboratory of Molecular Pathophysiology, National Institutes of Mental Health, 49 Convent Drive, Room B1EE16, Bethesda, MD 20892, USA
Pharmacol Res 48:49-53. 2003..These results are consistent with the available epidemiological evidence that long-term lithium therapy does not increase cancer morbidity or mortality, but rather is associated with reduced overall mortality in bipolar disorder...
Timing is everything: does the robust upregulation of noradrenergically regulated plasticity genes underlie the rapid antidepressant effects of sleep deprivation?Jennifer L Payne
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, Maryland 20892 1283, USA
Biol Psychiatry 52:921-6. 2002....
Mood disorders: treatment-induced changes in brain neurochemistry and structureDebra A Glitz
Neuropsychiatric Research Unit, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA
Semin Clin Neuropsychiatry 7:269-80. 2002....
The Wnt signaling pathway in bipolar disorderTodd D Gould
Neuroscientist 8:497-511. 2002..The future development of selective GSK-3beta inhibitors may have considerable utility not only for the treatment of bipolar disorder but also for a variety of classical neurodegenerative disorders...
Getting balance: drugs for bipolar disorder share targetJoseph T Coyle
Nat Med 8:557-8. 2002
Endophenotypes in bipolar disorderRobert H Lenox
Neuropsychopharmacology Program, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Am J Med Genet 114:391-406. 2002..Furthermore, lithium has been shown to regulate circadian cycles in diverse species, including humans, possibly through inhibition of glycogen synthase kinase 3-beta (GSK-3beta), a known target of lithium...
Mood stabilizers target cellular plasticity and resilience cascades: implications for the development of novel therapeuticsRosilla F Bachmann
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, MD, USA
Mol Neurobiol 32:173-202. 2005..This article also discusses approaches to develop novel treatments specifically for bipolar disorder...
A double-blind, placebo-controlled study of memantine in the treatment of major depressionCarlos A Zarate
Mood and Anxiety Disorders Program, National Institute of Mental Health, Department of Human Health Services, Bethesda, MD, USA
Am J Psychiatry 163:153-5. 2006..This study was designed to assess possible antidepressant effects of memantine, a selective N-methyl-D-aspartate (NMDA) receptor antagonist in humans...
