Brain-Derived Neurotrophic Factor Signaling and Subgenual Anterior Cingulate Cortex Dysfunction in Major Depressive Disorder
ObjectiveThe subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their co...
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| Published in | The American journal of psychiatry Vol. 169; no. 11; pp. 1194 - 1202 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Arlington, VA
American Psychiatric Association
01.11.2012
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| Subjects | |
| Online Access | Get full text |
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| Abstract | ObjectiveThe subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known.MethodUsing polymerase chain reaction, we first assessed the degree to which BDNF controls mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and neuropeptide functions in the cingulate cortex of mice with reduced BDNF function (BDNF-heterozygous [Bdnf+/−] mice and BDNF exon-IV knockout [BdnfKIV] mice). Gene expression was then quantified in the subgenual anterior cingulate cortex of 51 postmortem subjects with major depressive disorder and comparison subjects (total subjects, N=102; 49% were women) and compared with previous amygdala results.ResultsBased on the results in Bdnf+/− and BdnfKIV mice, genes were sorted into high, intermediate, and no BDNF dependency sets. In postmortem human subjects with major depression, BDNF receptor (TRKB) expression, but not BDNF, was reduced. Postmortem depressed subjects exhibited down-regulation in genes with high and intermediate BDNF dependency, including markers of dendritic targeting interneurons (SST, NPY, and CORT) and a GABA synthesizing enzyme (GAD2). Changes extended to BDNF-independent genes (PVALB and GAD1). Changes were greater in men (potentially because of low baseline expression in women), displayed notable differences from prior amygdala results, and were not explained by demographic or clinical factors other than sex.ConclusionsThese parallel human/mouse analyses provide direct (low TRKB) and indirect (low expression of BDNF-dependent genes) evidence in support of decreased BDNF signaling in the subgenual anterior cingulate cortex in individuals with major depressive disorder, implicate dendritic targeting GABA neurons and GABA synthesis, and, together, suggest a common BDNF-/GABA-related pathology in major depression with sex- and brain region-specific features. |
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| AbstractList | Objective: The subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known. Method: Using polymerase chain reaction, we first assessed the degree to which BDNF controls mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and neuropeptide functions in the cingulate cortex of mice with reduced BDNF function (BDNF-heterozygous [Bdnf+/- ] mice and BDNF exon-IV knockout [BdnfKIV ] mice). Gene expression was then quantified in the subgenual anterior cingulate cortex of 51 postmortem subjects with major depressive disorder and comparison subjects (total subjects, N=102; 49% were women) and compared with previous amygdala results. Results: Based on the results in Bdnf+/- and BdnfKIV mice, genes were sorted into high, intermediate, and no BDNF dependency sets. In postmortem human subjects with major depression, BDNF receptor (TRKB ) expression, but not BDNF , was reduced. Postmortem depressed subjects exhibited down-regulation in genes with high and intermediate BDNF dependency, including markers of dendritic targeting interneurons (SST , NPY , and CORT ) and a GABA synthesizing enzyme (GAD2 ). Changes extended to BDNF-independent genes (PVALB and GAD1 ). Changes were greater in men (potentially because of low baseline expression in women), displayed notable differences from prior amygdala results, and were not explained by demographic or clinical factors other than sex. Conclusions: These parallel human/mouse analyses provide direct (low TRKB ) and indirect (low expression of BDNF-dependent genes) evidence in support of decreased BDNF signaling in the subgenual anterior cingulate cortex in individuals with major depressive disorder, implicate dendritic targeting GABA neurons and GABA synthesis, and, together, suggest a common BDNF-/GABA-related pathology in major depression with sex- and brain region-specific features. [PUBLICATION ABSTRACT] The subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known.OBJECTIVEThe subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known.Using polymerase chain reaction, we first assessed the degree to which BDNF controls mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and neuropeptide functions in the cingulate cortex of mice with reduced BDNF function (BDNF-heterozygous [Bdnf(+/-)] mice and BDNF exon-IV knockout [Bdnf(KIV)] mice). Gene expression was then quantified in the subgenual anterior cingulate cortex of 51 postmortem subjects with major depressive disorder and comparison subjects (total subjects, N=102; 49% were women) and compared with previous amygdala results.METHODUsing polymerase chain reaction, we first assessed the degree to which BDNF controls mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and neuropeptide functions in the cingulate cortex of mice with reduced BDNF function (BDNF-heterozygous [Bdnf(+/-)] mice and BDNF exon-IV knockout [Bdnf(KIV)] mice). Gene expression was then quantified in the subgenual anterior cingulate cortex of 51 postmortem subjects with major depressive disorder and comparison subjects (total subjects, N=102; 49% were women) and compared with previous amygdala results.Based on the results in Bdnf(+/-) and Bdnf(KIV) mice, genes were sorted into high, intermediate, and no BDNF dependency sets. In postmortem human subjects with major depression, BDNF receptor (TRKB) expression, but not BDNF, was reduced. Postmortem depressed subjects exhibited down-regulation in genes with high and intermediate BDNF dependency, including markers of dendritic targeting interneurons (SST, NPY, and CORT) and a GABA synthesizing enzyme (GAD2). Changes extended to BDNF-independent genes (PVALB and GAD1). Changes were greater in men (potentially because of low baseline expression in women), displayed notable differences from prior amygdala results, and were not explained by demographic or clinical factors other than sex.RESULTSBased on the results in Bdnf(+/-) and Bdnf(KIV) mice, genes were sorted into high, intermediate, and no BDNF dependency sets. In postmortem human subjects with major depression, BDNF receptor (TRKB) expression, but not BDNF, was reduced. Postmortem depressed subjects exhibited down-regulation in genes with high and intermediate BDNF dependency, including markers of dendritic targeting interneurons (SST, NPY, and CORT) and a GABA synthesizing enzyme (GAD2). Changes extended to BDNF-independent genes (PVALB and GAD1). Changes were greater in men (potentially because of low baseline expression in women), displayed notable differences from prior amygdala results, and were not explained by demographic or clinical factors other than sex.These parallel human/mouse analyses provide direct (low TRKB) and indirect (low expression of BDNF-dependent genes) evidence in support of decreased BDNF signaling in the subgenual anterior cingulate cortex in individuals with major depressive disorder, implicate dendritic targeting GABA neurons and GABA synthesis, and, together, suggest a common BDNF-/GABA-related pathology in major depression with sex- and brain region-specific features.CONCLUSIONSThese parallel human/mouse analyses provide direct (low TRKB) and indirect (low expression of BDNF-dependent genes) evidence in support of decreased BDNF signaling in the subgenual anterior cingulate cortex in individuals with major depressive disorder, implicate dendritic targeting GABA neurons and GABA synthesis, and, together, suggest a common BDNF-/GABA-related pathology in major depression with sex- and brain region-specific features. The subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known. Using polymerase chain reaction, we first assessed the degree to which BDNF controls mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and neuropeptide functions in the cingulate cortex of mice with reduced BDNF function (BDNF-heterozygous [Bdnf(+/-)] mice and BDNF exon-IV knockout [Bdnf(KIV)] mice). Gene expression was then quantified in the subgenual anterior cingulate cortex of 51 postmortem subjects with major depressive disorder and comparison subjects (total subjects, N=102; 49% were women) and compared with previous amygdala results. Based on the results in Bdnf(+/-) and Bdnf(KIV) mice, genes were sorted into high, intermediate, and no BDNF dependency sets. In postmortem human subjects with major depression, BDNF receptor (TRKB) expression, but not BDNF, was reduced. Postmortem depressed subjects exhibited down-regulation in genes with high and intermediate BDNF dependency, including markers of dendritic targeting interneurons (SST, NPY, and CORT) and a GABA synthesizing enzyme (GAD2). Changes extended to BDNF-independent genes (PVALB and GAD1). Changes were greater in men (potentially because of low baseline expression in women), displayed notable differences from prior amygdala results, and were not explained by demographic or clinical factors other than sex. These parallel human/mouse analyses provide direct (low TRKB) and indirect (low expression of BDNF-dependent genes) evidence in support of decreased BDNF signaling in the subgenual anterior cingulate cortex in individuals with major depressive disorder, implicate dendritic targeting GABA neurons and GABA synthesis, and, together, suggest a common BDNF-/GABA-related pathology in major depression with sex- and brain region-specific features. ObjectiveThe subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known.MethodUsing polymerase chain reaction, we first assessed the degree to which BDNF controls mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and neuropeptide functions in the cingulate cortex of mice with reduced BDNF function (BDNF-heterozygous [Bdnf+/−] mice and BDNF exon-IV knockout [BdnfKIV] mice). Gene expression was then quantified in the subgenual anterior cingulate cortex of 51 postmortem subjects with major depressive disorder and comparison subjects (total subjects, N=102; 49% were women) and compared with previous amygdala results.ResultsBased on the results in Bdnf+/− and BdnfKIV mice, genes were sorted into high, intermediate, and no BDNF dependency sets. In postmortem human subjects with major depression, BDNF receptor (TRKB) expression, but not BDNF, was reduced. Postmortem depressed subjects exhibited down-regulation in genes with high and intermediate BDNF dependency, including markers of dendritic targeting interneurons (SST, NPY, and CORT) and a GABA synthesizing enzyme (GAD2). Changes extended to BDNF-independent genes (PVALB and GAD1). Changes were greater in men (potentially because of low baseline expression in women), displayed notable differences from prior amygdala results, and were not explained by demographic or clinical factors other than sex.ConclusionsThese parallel human/mouse analyses provide direct (low TRKB) and indirect (low expression of BDNF-dependent genes) evidence in support of decreased BDNF signaling in the subgenual anterior cingulate cortex in individuals with major depressive disorder, implicate dendritic targeting GABA neurons and GABA synthesis, and, together, suggest a common BDNF-/GABA-related pathology in major depression with sex- and brain region-specific features. |
| Author | Guilloux, Jean-Philippe Tripp, Adam Martinowich, Keri Sibille, Etienne Lewis, David A. Oh, Hyunjung |
| Author_xml | – sequence: 1 givenname: Adam surname: Tripp fullname: Tripp, Adam email: sibilleel@upmc.edu – sequence: 2 givenname: Hyunjung surname: Oh fullname: Oh, Hyunjung email: sibilleel@upmc.edu – sequence: 3 givenname: Jean-Philippe surname: Guilloux fullname: Guilloux, Jean-Philippe email: sibilleel@upmc.edu – sequence: 4 givenname: Keri surname: Martinowich fullname: Martinowich, Keri email: sibilleel@upmc.edu – sequence: 5 givenname: David A. surname: Lewis fullname: Lewis, David A. email: sibilleel@upmc.edu – sequence: 6 givenname: Etienne surname: Sibille fullname: Sibille, Etienne email: sibilleel@upmc.edu |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26569522$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/23128924$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright © 2012 by the American Psychiatric Association 2012 2015 INIST-CNRS Copyright © 2012 by the American Psychiatric Association |
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| Keywords | Mood disorder Signal transduction Cingulate cortex Central nervous system Depression Brain derived neurotrophic factor Encephalon |
| Language | English |
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| Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 Dr. Tripp and Hyunjung Oh contributed equally to this article. |
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BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders publication-title: J Psychiatry Neurosci – volume: 156 start-page: 675 year: 1999 end-page: 682 article-title: Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness publication-title: Am J Psychiatry – volume: 25 start-page: 372 year: 2005 end-page: 383 article-title: Relationship of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia publication-title: J Neurosci – volume: 289 start-page: 3095 year: 2003 end-page: 3105 article-title: The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R) publication-title: JAMA – volume: 45 start-page: 651 year: 2005 end-page: 660 article-title: Deep brain stimulation for treatment-resistant depression publication-title: Neuron – volume: 106 start-page: 5942 year: 2009 end-page: 5947 article-title: Critical role of promoter IV-driven BDNF transcription in GABAergic transmission and synaptic plasticity in the prefrontal cortex publication-title: Proc Natl Acad Sci USA – volume: 65 start-page: 1006 year: 2009 end-page: 1014 article-title: Molecular determinants of dysregulated GABAergic gene expression in the prefrontal cortex of subjects with schizophrenia publication-title: Biol Psychiatry – volume: 31 start-page: 727 year: 2011 end-page: 733 article-title: Results from 2 randomized, double-blind, placebo-controlled studies of the novel NK1 receptor antagonist casopitant in patients with major depressive disorder publication-title: J Clin Psychopharmacol – volume: 67 start-page: 258 year: 2010 end-page: 267 article-title: Increased BDNF promoter methylation in the Wernicke area of suicide subjects publication-title: Arch Gen Psychiatry – volume: 22 start-page: 409 year: 2004 end-page: 418 article-title: Limbic-frontal circuitry in major depression: a path modeling metanalysis publication-title: Neuroimage – volume: 66 start-page: 84 year: 2009 end-page: 90 article-title: Gender-specific impact of brain-derived neurotrophic factor signaling on stress-induced depression-like behavior publication-title: Biol Psychiatry – volume: 42 start-page: 116 year: 2011 end-page: 124 article-title: Reduced somatostatin in subgenual anterior cingulate cortex in major depression publication-title: Neurobiol Dis – volume: 166 start-page: 1011 year: 2009 end-page: 1024 article-title: A molecular signature of depression in the amygdala publication-title: Am J Psychiatry – volume: 157 start-page: 835 year: 1990 end-page: 841 article-title: Gender-mediated clinical features of depressive illness. The importance of temperamental differences publication-title: Br J Psychiatry – volume: 311 start-page: 864 year: 2006 end-page: 868 article-title: Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress publication-title: Science – volume: 61 start-page: 198 year: 2007 end-page: 209 article-title: Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features publication-title: Biol Psychiatry – volume: 22 start-page: 409 year: 2004 end-page: 418 article-title: Limbic-frontal circuitry in major depression: a path modeling metanalysis publication-title: Neuroimage – volume: 156 start-page: 675 year: 1999 end-page: 682 article-title: Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness publication-title: Am J Psychiatry – volume: 166 start-page: 1011 year: 2009 end-page: 1024 article-title: A molecular signature of depression in the amygdala publication-title: Am J Psychiatry – volume: 157 start-page: 835 year: 1990 end-page: 841 article-title: Gender-mediated clinical features of depressive illness. The importance of temperamental differences publication-title: Br J Psychiatry – volume: 6 start-page: e29610 year: 2011 article-title: Molecular insights into the pathogenesis of Alzheimer’s disease and its relationship to normal aging publication-title: PLoS ONE – volume: 31 start-page: 727 year: 2011 end-page: 733 article-title: Results from 2 randomized, double-blind, placebo-controlled studies of the novel NK1 receptor antagonist casopitant in patients with major depressive disorder publication-title: J Clin Psychopharmacol – volume: 92 start-page: 8856 year: 1995 end-page: 8860 article-title: Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor publication-title: Proc Natl Acad Sci USA – volume: 16 start-page: 1088 year: 2011 end-page: 1095 article-title: Serum levels of brain-derived neurotrophic factor in major depressive disorder: state-trait issues, clinical features and pharmacological treatment publication-title: Mol Psychiatry – volume: 128 start-page: 287 year: 2011 end-page: 290 article-title: The association between brain-derived neurotrophic factor polymorphism (BDNF Val66Met) and suicide publication-title: J Affect Disord – volume: 66 start-page: 84 year: 2009 end-page: 90 article-title: Gender-specific impact of brain-derived neurotrophic factor signaling on stress-induced depression-like behavior publication-title: Biol Psychiatry – volume: 22 start-page: 409 year: 2004 end-page: 418 article-title: Limbic-frontal circuitry in major depression: a path modeling metanalysis publication-title: Neuroimage – volume: 25 start-page: 372 year: 2005 end-page: 383 article-title: Relationship of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia publication-title: J Neurosci – volume: 14 start-page: 721 year: 2011 end-page: 734 article-title: GABA-related transcripts in the dorsolateral prefrontal cortex in mood disorders publication-title: Int J Neuropsychopharmacol – volume: 42 start-page: 116 year: 2011 end-page: 124 article-title: Reduced somatostatin in subgenual anterior cingulate cortex in major depression publication-title: Neurobiol Dis – volume: 106 start-page: 5942 year: 2009 end-page: 5947 article-title: Critical role of promoter IV-driven BDNF transcription in GABAergic transmission and synaptic plasticity in the prefrontal cortex publication-title: Proc Natl Acad Sci USA – volume: 165 start-page: 479 year: 2008 end-page: 489 article-title: Conserved regional patterns of GABA-related transcript expression in the neocortex of subjects with schizophrenia publication-title: Am J Psychiatry – volume: 6 start-page: e29610 year: 2011 article-title: Molecular insights into the pathogenesis of Alzheimer’s disease and its relationship to normal aging publication-title: PLoS ONE – volume: 61 start-page: 187 year: 2007 end-page: 197 article-title: Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors publication-title: Biol Psychiatry – year: 2011 article-title: Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression publication-title: Mol Psychiatry – volume: 43 start-page: 1175 year: 2009 end-page: 1184 article-title: Expression of hippocampal brain-derived neurotrophic factor and its receptors in Stanley consortium brains publication-title: J Psychiatr Res – volume: 31 start-page: 727 year: 2011 end-page: 733 article-title: Results from 2 randomized, double-blind, placebo-controlled studies of the novel NK1 receptor antagonist casopitant in patients with major depressive disorder publication-title: J Clin Psychopharmacol – volume: 48 start-page: 389 year: 2000 end-page: 397 article-title: Normal cellular levels of synaptophysin mRNA expression in the prefrontal cortex of subjects with schizophrenia publication-title: Biol Psychiatry – year: 2011 article-title: Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression publication-title: Mol Psychiatry – volume: 7 start-page: 314 year: 2008 end-page: 322 article-title: Interaction between BDNF Val66Met and childhood trauma on adult’s violent suicide attempt publication-title: Genes Brain Behav – volume: 31 start-page: 727 year: 2011 end-page: 733 article-title: Results from 2 randomized, double-blind, placebo-controlled studies of the novel NK1 receptor antagonist casopitant in patients with major depressive disorder publication-title: J Clin Psychopharmacol – volume: 311 start-page: 864 year: 2006 end-page: 868 article-title: Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress publication-title: Science – volume: 16 start-page: 1088 year: 2011 end-page: 1095 article-title: Serum levels of brain-derived neurotrophic factor in major depressive disorder: state-trait issues, clinical features and pharmacological treatment publication-title: Mol Psychiatry – volume: 157 start-page: 835 year: 1990 end-page: 841 article-title: Gender-mediated clinical features of depressive illness. The importance of temperamental differences publication-title: Br J Psychiatry – volume: 9 start-page: 712 year: 2010 end-page: 721 article-title: Lack of promoter IV-driven BDNF transcription results in depression-like behavior publication-title: Genes Brain Behav – volume: 42 start-page: 116 year: 2011 end-page: 124 article-title: Reduced somatostatin in subgenual anterior cingulate cortex in major depression publication-title: Neurobiol Dis – volume: 18 start-page: 391 year: 2007 end-page: 418 article-title: The role of neurotrophic factors in adult hippocampal neurogenesis, antidepressant treatments and animal models of depressive-like behavior publication-title: Behav Pharmacol – volume: 60 start-page: 804 year: 2003 end-page: 815 article-title: Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects publication-title: Arch Gen Psychiatry – volume: 165 start-page: 479 year: 2008 end-page: 489 article-title: Conserved regional patterns of GABA-related transcript expression in the neocortex of subjects with schizophrenia publication-title: Am J Psychiatry – volume: 289 start-page: 3095 year: 2003 end-page: 3105 article-title: The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R) publication-title: JAMA – year: 2011 article-title: Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression publication-title: Mol Psychiatry – volume: 128 start-page: 287 year: 2011 end-page: 290 article-title: The association between brain-derived neurotrophic factor polymorphism (BDNF Val66Met) and suicide publication-title: J Affect Disord – volume: 156 start-page: 675 year: 1999 end-page: 682 article-title: Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness publication-title: Am J Psychiatry – volume: 65 start-page: 1006 year: 2009 end-page: 1014 article-title: Molecular determinants of dysregulated GABAergic gene expression in the prefrontal cortex of subjects with schizophrenia publication-title: Biol Psychiatry – volume: 22 start-page: 409 year: 2004 end-page: 418 article-title: Limbic-frontal circuitry in major depression: a path modeling metanalysis publication-title: Neuroimage – volume: 60 start-page: 804 year: 2003 end-page: 815 article-title: Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects publication-title: Arch Gen Psychiatry – volume: 61 start-page: 187 year: 2007 end-page: 197 article-title: Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors publication-title: Biol Psychiatry – volume: 22 start-page: 409 year: 2004 end-page: 418 article-title: Limbic-frontal circuitry in major depression: a path modeling metanalysis publication-title: Neuroimage – year: 2011 article-title: Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression publication-title: Mol Psychiatry – volume: 128 start-page: 287 year: 2011 end-page: 290 article-title: The association between brain-derived neurotrophic factor polymorphism (BDNF Val66Met) and suicide publication-title: J Affect Disord – volume: 156 start-page: 675 year: 1999 end-page: 682 article-title: Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness publication-title: Am J Psychiatry – volume: 128 start-page: 287 year: 2011 end-page: 290 article-title: The association between brain-derived neurotrophic factor polymorphism (BDNF Val66Met) and suicide publication-title: J Affect Disord – volume: 42 start-page: 116 year: 2011 end-page: 124 article-title: Reduced somatostatin in subgenual anterior cingulate cortex in major depression publication-title: Neurobiol Dis – volume: 67 start-page: 258 year: 2010 end-page: 267 article-title: Increased BDNF promoter methylation in the Wernicke area of suicide subjects publication-title: Arch Gen Psychiatry – volume: 45 start-page: 651 year: 2005 end-page: 660 article-title: Deep brain stimulation for treatment-resistant depression publication-title: Neuron – volume: 16 start-page: 383 year: 2011 end-page: 406 article-title: The GABAergic deficit hypothesis of major depressive disorder publication-title: Mol Psychiatry – volume: 311 start-page: 864 year: 2006 end-page: 868 article-title: Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress publication-title: Science – volume: 7 start-page: 314 year: 2008 end-page: 322 article-title: Interaction between BDNF Val66Met and childhood trauma on adult’s violent suicide attempt publication-title: Genes Brain Behav – volume: 311 start-page: 864 year: 2006 end-page: 868 article-title: Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress publication-title: Science – volume: 49 start-page: 741 year: 2001 end-page: 752 article-title: Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder publication-title: Biol Psychiatry – volume: 202 start-page: 245 year: 2009 end-page: 251 article-title: Deficit in BDNF does not increase vulnerability to stress but dampens antidepressant-like effects in the unpredictable chronic mild stress publication-title: Behav Brain Res – volume: 43 start-page: 1175 year: 2009 end-page: 1184 article-title: Expression of hippocampal brain-derived neurotrophic factor and its receptors in Stanley consortium brains publication-title: J Psychiatr Res – volume: 48 start-page: 830 year: 2000 end-page: 843 article-title: Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response publication-title: Biol Psychiatry – volume: 25 start-page: 372 year: 2005 end-page: 383 article-title: Relationship of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia publication-title: J Neurosci – volume: 156 start-page: 675 year: 1999 end-page: 682 article-title: Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness publication-title: Am J Psychiatry – volume: 289 start-page: 3095 year: 2003 end-page: 3105 article-title: The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R) publication-title: JAMA – volume: 45 start-page: 651 year: 2005 end-page: 660 article-title: Deep brain stimulation for treatment-resistant depression publication-title: Neuron – volume: 52 start-page: 404 year: 2002 end-page: 412 article-title: Low glial numbers in the amygdala in major depressive disorder publication-title: Biol Psychiatry – year: 2011 article-title: Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression publication-title: Mol Psychiatry – volume: 202 start-page: 245 year: 2009 end-page: 251 article-title: Deficit in BDNF does not increase vulnerability to stress but dampens antidepressant-like effects in the unpredictable chronic mild stress publication-title: Behav Brain Res – volume: 52 start-page: 404 year: 2002 end-page: 412 article-title: Low glial numbers in the amygdala in major depressive disorder publication-title: Biol Psychiatry – volume: 36 start-page: 195 year: 2011 end-page: 203 article-title: Decreased BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders publication-title: J Psychiatry Neurosci – volume: 92 start-page: 8856 year: 1995 end-page: 8860 article-title: Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor publication-title: Proc Natl Acad Sci USA – volume: 4 start-page: 11 year: 2011 article-title: Activity-dependent brain-derived neurotrophic factor expression regulates cortistatin-interneurons and sleep behavior publication-title: Mol Brain – volume: 311 start-page: 864 year: 2006 end-page: 868 article-title: Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress publication-title: Science – volume: 166 start-page: 1011 year: 2009 end-page: 1024 article-title: A molecular signature of depression in the amygdala publication-title: Am J Psychiatry – volume: 7 start-page: 314 year: 2008 end-page: 322 article-title: Interaction between BDNF Val66Met and childhood trauma on adult’s violent suicide attempt publication-title: Genes Brain Behav – volume: 289 start-page: 3095 year: 2003 end-page: 3105 article-title: The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R) publication-title: JAMA – volume: 157 start-page: 835 year: 1990 end-page: 841 article-title: Gender-mediated clinical features of depressive illness. The importance of temperamental differences publication-title: Br J Psychiatry – volume: 61 start-page: 198 year: 2007 end-page: 209 article-title: Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features publication-title: Biol Psychiatry – volume: 289 start-page: 3095 year: 2003 end-page: 3105 article-title: The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R) publication-title: JAMA – volume: 31 start-page: 727 year: 2011 end-page: 733 article-title: Results from 2 randomized, double-blind, placebo-controlled studies of the novel NK1 receptor antagonist casopitant in patients with major depressive disorder publication-title: J Clin Psychopharmacol – volume: 67 start-page: 258 year: 2010 end-page: 267 article-title: Increased BDNF promoter methylation in the Wernicke area of suicide subjects publication-title: Arch Gen Psychiatry – volume: 289 start-page: 3095 year: 2003 end-page: 3105 article-title: The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R) publication-title: JAMA – volume: 45 start-page: 651 year: 2005 end-page: 660 article-title: Deep brain stimulation for treatment-resistant depression publication-title: Neuron – volume: 48 start-page: 389 year: 2000 end-page: 397 article-title: Normal cellular levels of synaptophysin mRNA expression in the prefrontal cortex of subjects with schizophrenia publication-title: Biol Psychiatry – volume: 106 start-page: 5942 year: 2009 end-page: 5947 article-title: Critical role of promoter IV-driven BDNF transcription in GABAergic transmission and synaptic plasticity in the prefrontal cortex publication-title: Proc Natl Acad Sci USA – volume: 166 start-page: 1011 year: 2009 end-page: 1024 article-title: A molecular signature of depression in the amygdala publication-title: Am J Psychiatry – volume: 7 start-page: 314 year: 2008 end-page: 322 article-title: Interaction between BDNF Val66Met and childhood trauma on adult’s violent suicide attempt publication-title: Genes Brain Behav – volume: 45 start-page: 651 year: 2005 end-page: 660 article-title: Deep brain stimulation for treatment-resistant depression publication-title: Neuron – volume: 25 start-page: 372 year: 2005 end-page: 383 article-title: Relationship of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia publication-title: J Neurosci – volume: 202 start-page: 245 year: 2009 end-page: 251 article-title: Deficit in BDNF does not increase vulnerability to stress but dampens antidepressant-like effects in the unpredictable chronic mild stress publication-title: Behav Brain Res – volume: 311 start-page: 864 year: 2006 end-page: 868 article-title: Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress publication-title: Science – volume: 45 start-page: 995 year: 2011 end-page: 1004 article-title: Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: a systematic review and meta-regression analysis publication-title: J Psychiatr Res – volume: 67 start-page: 258 year: 2010 end-page: 267 article-title: Increased BDNF promoter methylation in the Wernicke area of suicide subjects publication-title: Arch Gen Psychiatry – volume: 45 start-page: 651 year: 2005 end-page: 660 article-title: Deep brain stimulation for treatment-resistant depression publication-title: Neuron – volume: 66 start-page: 84 year: 2009 end-page: 90 article-title: Gender-specific impact of brain-derived neurotrophic factor signaling on stress-induced depression-like behavior publication-title: Biol Psychiatry – volume: 61 start-page: 187 year: 2007 end-page: 197 article-title: Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors publication-title: Biol Psychiatry – volume: 31 start-page: 727 year: 2011 end-page: 733 article-title: Results from 2 randomized, double-blind, placebo-controlled studies of the novel NK1 receptor antagonist casopitant in patients with major depressive disorder publication-title: J Clin Psychopharmacol – volume: 48 start-page: 830 year: 2000 end-page: 843 article-title: Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response publication-title: Biol Psychiatry – volume: 45 start-page: 995 year: 2011 end-page: 1004 article-title: Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: a systematic review and meta-regression analysis publication-title: J Psychiatr Res – volume: 7 start-page: 314 year: 2008 end-page: 322 article-title: Interaction between BDNF Val66Met and childhood trauma on adult’s violent suicide attempt publication-title: Genes Brain Behav – volume: 92 start-page: 8856 year: 1995 end-page: 8860 article-title: Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor publication-title: Proc Natl Acad Sci USA – volume: 6 start-page: e29610 year: 2011 article-title: Molecular insights into the pathogenesis of Alzheimer’s disease and its relationship to normal aging publication-title: PLoS ONE – volume: 202 start-page: 245 year: 2009 end-page: 251 article-title: Deficit in BDNF does not increase vulnerability to stress but dampens antidepressant-like effects in the unpredictable chronic mild stress publication-title: Behav Brain Res – volume: 65 start-page: 1006 year: 2009 end-page: 1014 article-title: Molecular determinants of dysregulated GABAergic gene expression in the prefrontal cortex of subjects with schizophrenia publication-title: Biol Psychiatry – volume: 25 start-page: 372 year: 2005 end-page: 383 article-title: Relationship of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia publication-title: J Neurosci – volume: 161 start-page: 1957 year: 2004 end-page: 1966 article-title: Hippocampal volume and depression: a meta-analysis of MRI studies publication-title: Am J Psychiatry – volume: 202 start-page: 245 year: 2009 end-page: 251 article-title: Deficit in BDNF does not increase vulnerability to stress but dampens antidepressant-like effects in the unpredictable chronic mild stress publication-title: Behav Brain Res – volume: 61 start-page: 198 year: 2007 end-page: 209 article-title: Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features publication-title: Biol Psychiatry – volume: 161 start-page: 1957 year: 2004 end-page: 1966 article-title: Hippocampal volume and depression: a meta-analysis of MRI studies publication-title: Am J Psychiatry – volume: 22 start-page: 3251 year: 2002 end-page: 3261 article-title: Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression publication-title: J Neurosci – volume: 36 start-page: 195 year: 2011 end-page: 203 article-title: Decreased BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders publication-title: J Psychiatry Neurosci – volume: 45 start-page: 995 year: 2011 end-page: 1004 article-title: Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: a systematic review and meta-regression analysis publication-title: J Psychiatr Res – volume: 66 start-page: 84 year: 2009 end-page: 90 article-title: Gender-specific impact of brain-derived neurotrophic factor signaling on stress-induced depression-like behavior publication-title: Biol Psychiatry – volume: 9 start-page: 712 year: 2010 end-page: 721 article-title: Lack of promoter IV-driven BDNF transcription results in depression-like behavior publication-title: Genes Brain Behav – volume: 4 start-page: 11 year: 2011 article-title: Activity-dependent brain-derived neurotrophic factor expression regulates cortistatin-interneurons and sleep behavior publication-title: Mol Brain – volume: 67 start-page: 258 year: 2010 end-page: 267 article-title: Increased BDNF promoter methylation in the Wernicke area of suicide subjects publication-title: Arch Gen Psychiatry – volume: 61 start-page: 198 year: 2007 end-page: 209 article-title: Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features publication-title: Biol Psychiatry – volume: 60 start-page: 804 year: 2003 end-page: 815 article-title: Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects publication-title: Arch Gen Psychiatry – volume: 441 start-page: 288 year: 2001 end-page: 301 article-title: Substance P and nitric oxide signaling in cerebral cortex: anatomical evidence for reciprocal signaling between two classes 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Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response publication-title: Biol Psychiatry – volume: 43 start-page: 1175 year: 2009 end-page: 1184 article-title: Expression of hippocampal brain-derived neurotrophic factor and its receptors in Stanley consortium brains publication-title: J Psychiatr Res – volume: 4 start-page: 11 year: 2011 article-title: Activity-dependent brain-derived neurotrophic factor expression regulates cortistatin-interneurons and sleep behavior publication-title: Mol Brain – volume: 7 start-page: 314 year: 2008 end-page: 322 article-title: Interaction between BDNF Val66Met and childhood trauma on adult’s violent suicide attempt publication-title: Genes Brain Behav – volume: 156 start-page: 675 year: 1999 end-page: 682 article-title: Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness publication-title: Am J Psychiatry – volume: 67 start-page: 258 year: 2010 end-page: 267 article-title: Increased BDNF promoter methylation in the Wernicke area of suicide subjects publication-title: Arch Gen Psychiatry – volume: 128 start-page: 287 year: 2011 end-page: 290 article-title: The association between brain-derived neurotrophic factor polymorphism (BDNF Val66Met) and suicide publication-title: J Affect Disord – volume: 156 start-page: 675 year: 1999 end-page: 682 article-title: Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness publication-title: Am J Psychiatry – volume: 67 start-page: 258 year: 2010 end-page: 267 article-title: Increased BDNF promoter methylation in the Wernicke area of suicide subjects publication-title: Arch Gen Psychiatry – volume: 45 start-page: 995 year: 2011 end-page: 1004 article-title: Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: a systematic review and meta-regression analysis publication-title: J 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| Snippet | ObjectiveThe subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of... The subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived... Objective: The subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of... |
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| SubjectTerms | Adult and adolescent clinical studies Animals Biological and medical sciences Brain Brain-Derived Neurotrophic Factor - genetics Brain-Derived Neurotrophic Factor - physiology Case-Control Studies Depression Depressive Disorder, Major - genetics Depressive Disorder, Major - pathology Depressive Disorder, Major - physiopathology Dominance, Cerebral - genetics Down-Regulation - genetics Down-Regulation - physiology Exons - genetics Female gamma-Aminobutyric Acid - physiology Gene Expression - genetics Gene Expression - physiology Genetic Carrier Screening Glutamate Decarboxylase - genetics Glutamate Decarboxylase - physiology Gyrus Cinguli - pathology Gyrus Cinguli - physiopathology Humans Male Medical sciences Mental depression Mice Mice, Inbred C57BL Mice, Knockout Mood disorders Neuropsychology Polymerase Chain Reaction Proteins Psychology. Psychoanalysis. Psychiatry Psychopathology Psychopathology. Psychiatry Receptor, trkB - genetics Receptor, trkB - physiology RNA, Messenger - genetics Sex Factors Signal transduction Signal Transduction - physiology |
| Title | Brain-Derived Neurotrophic Factor Signaling and Subgenual Anterior Cingulate Cortex Dysfunction in Major Depressive Disorder |
| URI | http://dx.doi.org/10.1176/appi.ajp.2012.12020248 https://www.ncbi.nlm.nih.gov/pubmed/23128924 https://www.proquest.com/docview/1316094563 https://www.proquest.com/docview/1141529625 https://pubmed.ncbi.nlm.nih.gov/PMC3638149 |
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