Global Brain Gene Expression Analysis Links Glutamatergic and GABAergic Alterations to Suicide and Major Depression
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{"title"=>"Global brain gene expression analysis links Glutamatergic and GABAergic alterations to suicide and major depression", "type"=>"journal", "authors"=>[{"first_name"=>"Adolfo", "last_name"=>"Sequeira", "scopus_author_id"=>"7006133886"}, {"first_name"=>"Firoza", "last_name"=>"Mamdani", "scopus_author_id"=>"6508221761"}, {"first_name"=>"Carl", "last_name"=>"Ernst", "scopus_author_id"=>"7101956889"}, {"first_name"=>"Marquis P.", "last_name"=>"Vawter", "scopus_author_id"=>"7004385870"}, {"first_name"=>"William E.", "last_name"=>"Bunney", "scopus_author_id"=>"7006685206"}, {"first_name"=>"Veronique", "last_name"=>"Lebel", "scopus_author_id"=>"23028456400"}, {"first_name"=>"Sonia", "last_name"=>"Rehal", "scopus_author_id"=>"57188953427"}, {"first_name"=>"Tim", "last_name"=>"Klempan", "scopus_author_id"=>"6603094352"}, {"first_name"=>"Alain", "last_name"=>"Gratton", "scopus_author_id"=>"7004034835"}, {"first_name"=>"Chawki", "last_name"=>"Benkelfat", "scopus_author_id"=>"35460928800"}, {"first_name"=>"Guy A.", "last_name"=>"Rouleau", "scopus_author_id"=>"36042364200"}, {"first_name"=>"Naguib", "last_name"=>"Mechawar", "scopus_author_id"=>"6602902835"}, {"first_name"=>"Gustavo", "last_name"=>"Turecki", "scopus_author_id"=>"7006625367"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-68749087317", "pui"=>"355096248", "doi"=>"10.1371/journal.pone.0006585", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"68749087317", "pmid"=>"19668376"}, "id"=>"99cd3bd3-7e86-3ffb-8cec-adccc45fca72", "abstract"=>"BACKGROUND: Most studies investigating the neurobiology of depression and suicide have focused on the serotonergic system. While it seems clear that serotonergic alterations play a role in the pathogenesis of these major public health problems, dysfunction in additional neurotransmitter systems and other molecular alterations may also be implicated. Microarray expression studies are excellent screening tools to generate hypotheses about additional molecular processes that may be at play. In this study we investigated brain regions that are known to be implicated in the neurobiology of suicide and major depression are likely to represent valid global molecular alterations. METHODOLOGY/PRINCIPAL FINDINGS: We performed gene expression analysis using the HG-U133AB chipset in 17 cortical and subcortical brain regions from suicides with and without major depression and controls. Total mRNA for microarray analysis was obtained from 663 brain samples isolated from 39 male subjects, including 26 suicide cases and 13 controls diagnosed by means of psychological autopsies. Independent brain samples from 34 subjects and animal studies were used to control for the potential confounding effects of comorbidity with alcohol. Using a Gene Ontology analysis as our starting point, we identified molecular pathways that may be involved in depression and suicide, and performed follow-up analyses on these possible targets. Methodology included gene expression measures from microarrays, Gene Score Resampling for global ontological profiling, and semi-quantitative RT-PCR. We observed the highest number of suicide specific alterations in prefrontal cortical areas and hippocampus. Our results revealed alterations of synaptic neurotransmission and intracellular signaling. Among these, Glutamatergic (GLU) and GABAergic related genes were globally altered. Semi-quantitative RT-PCR results investigating expression of GLU and GABA receptor subunit genes were consistent with microarray data. CONCLUSIONS/SIGNIFICANCE: The observed results represent the first overview of global expression changes in brains of suicide victims with and without major depression and suggest a global brain alteration of GLU and GABA receptor subunit genes in these conditions.", "link"=>"http://www.mendeley.com/research/global-brain-gene-expression-analysis-links-glutamatergic-gabaergic-alterations-suicide-major-depres", "reader_count"=>110, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>9, "Researcher"=>18, "Student > Doctoral Student"=>9, "Student > Ph. D. Student"=>26, "Student > Postgraduate"=>8, "Other"=>5, "Student > Master"=>10, "Student > Bachelor"=>13, "Lecturer"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>9, "Researcher"=>18, "Student > Doctoral Student"=>9, "Student > Ph. D. Student"=>26, "Student > Postgraduate"=>8, "Other"=>5, "Student > Master"=>10, "Student > Bachelor"=>13, "Lecturer"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>7, "Biochemistry, Genetics and Molecular Biology"=>6, "Medicine and Dentistry"=>30, "Agricultural and Biological Sciences"=>33, "Neuroscience"=>19, "Sports and Recreations"=>1, "Physics and Astronomy"=>1, "Psychology"=>12, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>30}, "Neuroscience"=>{"Neuroscience"=>19}, "Social Sciences"=>{"Social Sciences"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>12}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>33}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>7}}, "reader_count_by_country"=>{"Canada"=>2, "Venezuela"=>1, "Sweden"=>1, "United States"=>4, "Japan"=>1, "Australia"=>1, "Switzerland"=>1, "Germany"=>1}, "group_count"=>8}

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  • {"files"=>["https://ndownloader.figshare.com/files/888275"], "description"=>"<p>The 568 unique genes identified in our database of differentially expressed genes were regrouped using DAVID according to their function.</p>", "links"=>[], "tags"=>["568", "genes", "differentially", "regrouped", "david"], "article_id"=>558721, "categories"=>["Genetics", "Neuroscience", "Cell Biology"], "users"=>["Adolfo Sequeira", "Firoza Mamdani", "Carl Ernst", "Marquis P. Vawter", "William E. Bunney", "Veronique Lebel", "Sonia Rehal", "Tim Klempan", "Alain Gratton", "Chawki Benkelfat", "Guy A. Rouleau", "Naguib Mechawar", "Gustavo Turecki"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006585.t003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_568_unique_genes_identified_in_our_database_of_differentially_expressed_genes_were_regrouped_using_DAVID_according_to_their_function_/558721", "title"=>"The 568 unique genes identified in our database of differentially expressed genes were regrouped using DAVID according to their function.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-08-11 02:25:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/440143", "https://ndownloader.figshare.com/files/440186", "https://ndownloader.figshare.com/files/440216", "https://ndownloader.figshare.com/files/440263"], "description"=>"<div><h3>Background</h3><p>Most studies investigating the neurobiology of depression and suicide have focused on the serotonergic system. While it seems clear that serotonergic alterations play a role in the pathogenesis of these major public health problems, dysfunction in additional neurotransmitter systems and other molecular alterations may also be implicated. Microarray expression studies are excellent screening tools to generate hypotheses about additional molecular processes that may be at play. In this study we investigated brain regions that are known to be implicated in the neurobiology of suicide and major depression are likely to represent valid global molecular alterations.</p><h3>Methodology/Principal Findings</h3><p>We performed gene expression analysis using the HG-U133AB chipset in 17 cortical and subcortical brain regions from suicides with and without major depression and controls. Total mRNA for microarray analysis was obtained from 663 brain samples isolated from 39 male subjects, including 26 suicide cases and 13 controls diagnosed by means of psychological autopsies. Independent brain samples from 34 subjects and animal studies were used to control for the potential confounding effects of comorbidity with alcohol. Using a Gene Ontology analysis as our starting point, we identified molecular pathways that may be involved in depression and suicide, and performed follow-up analyses on these possible targets. Methodology included gene expression measures from microarrays, Gene Score Resampling for global ontological profiling, and semi-quantitative RT-PCR. We observed the highest number of suicide specific alterations in prefrontal cortical areas and hippocampus. Our results revealed alterations of synaptic neurotransmission and intracellular signaling. Among these, Glutamatergic (GLU) and GABAergic related genes were globally altered. Semi-quantitative RT-PCR results investigating expression of GLU and GABA receptor subunit genes were consistent with microarray data.</p><h3>Conclusions/Significance</h3><p>The observed results represent the first overview of global expression changes in brains of suicide victims with and without major depression and suggest a global brain alteration of GLU and GABA receptor subunit genes in these conditions.</p></div>", "links"=>[], "tags"=>["links", "glutamatergic", "gabaergic", "alterations"], "article_id"=>146763, "categories"=>["Genetics", "Neuroscience", "Cell Biology"], "users"=>["Adolfo Sequeira", "Firoza Mamdani", "Carl Ernst", "Marquis P. Vawter", "William E. Bunney", "Veronique Lebel", "Sonia Rehal", "Tim Klempan", "Alain Gratton", "Chawki Benkelfat", "Guy A. Rouleau", "Naguib Mechawar", "Gustavo Turecki"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0006585.s001", "https://dx.doi.org/10.1371/journal.pone.0006585.s002", "https://dx.doi.org/10.1371/journal.pone.0006585.s003", "https://dx.doi.org/10.1371/journal.pone.0006585.s004"], "stats"=>{"downloads"=>13, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Global_Brain_Gene_Expression_Analysis_Links_Glutamatergic_and_GABAergic_Alterations_to_Suicide_and_Major_Depression/146763", "title"=>"Global Brain Gene Expression Analysis Links Glutamatergic and GABAergic Alterations to Suicide and Major Depression", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-08-11 01:52:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/888054"], "description"=>"<p>The color and intensity indicate direction and level of change: blue spectrum colors indicate down-regulated expression, while red spectrum colors indicate.</p>", "links"=>[], "tags"=>["hierarchical", "glutamatergic", "differentially", "genes", "17", "regions"], "article_id"=>558501, "categories"=>["Genetics", "Neuroscience", "Cell Biology"], "users"=>["Adolfo Sequeira", "Firoza Mamdani", "Carl Ernst", "Marquis P. Vawter", "William E. Bunney", "Veronique Lebel", "Sonia Rehal", "Tim Klempan", "Alain Gratton", "Chawki Benkelfat", "Guy A. Rouleau", "Naguib Mechawar", "Gustavo Turecki"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006585.g004", "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clustered_image_map_CIM_of_the_hierarchical_cluster_analysis_of_the_glutamatergic_system_differentially_expressed_genes_across_the_17_regions_investigated_/558501", "title"=>"Clustered image map (CIM) of the hierarchical cluster analysis of the glutamatergic system differentially expressed genes across the 17 regions investigated.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-11 02:21:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/888314"], "description"=>"<p>C = control, S = suicide, SMD = suicide with major depression, MDD = major depressive disorder, SSRI = Selective serotonin reuptake inhibitor.</p>", "links"=>[], "tags"=>["toxicological", "characteristics", "subjects", "included"], "article_id"=>558758, "categories"=>["Genetics", "Neuroscience", "Cell Biology"], "users"=>["Adolfo Sequeira", "Firoza Mamdani", "Carl Ernst", "Marquis P. Vawter", "William E. Bunney", "Veronique Lebel", "Sonia Rehal", "Tim Klempan", "Alain Gratton", "Chawki Benkelfat", "Guy A. Rouleau", "Naguib Mechawar", "Gustavo Turecki"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006585.t001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographic_clinical_and_toxicological_characteristics_of_the_subjects_included_in_the_study_/558758", "title"=>"Demographic, clinical and toxicological characteristics of the subjects included in the study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-08-11 02:25:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/887686"], "description"=>"<p>The number of chips per group that passed quality control assessment is also given.</p>", "links"=>[], "tags"=>["charts", "differentially", "genes", "prefrontal", "cortical", "areas", "subcortical"], "article_id"=>558123, "categories"=>["Genetics", "Neuroscience", "Cell Biology"], "users"=>["Adolfo Sequeira", "Firoza Mamdani", "Carl Ernst", "Marquis P. Vawter", "William E. Bunney", "Veronique Lebel", "Sonia Rehal", "Tim Klempan", "Alain Gratton", "Chawki Benkelfat", "Guy A. Rouleau", "Naguib Mechawar", "Gustavo Turecki"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006585.g001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pie_charts_representing_the_distribution_of_the_total_number_of_differentially_expressed_genes_in_A_prefrontal_cortical_areas_and_in_B_other_cortical_and_subcortical_brain_areas_/558123", "title"=>"Pie charts representing the distribution of the total number of differentially expressed genes in (A) prefrontal cortical areas and in (B) other cortical and subcortical brain areas.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-11 02:15:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/888130"], "description"=>"<p>Differentially expressed genes directly implicated in synaptic transmission as determined using DAVID (2006).</p>", "links"=>[], "tags"=>["genes", "implicated", "synaptic", "david"], "article_id"=>558575, "categories"=>["Genetics", "Neuroscience", "Cell Biology"], "users"=>["Adolfo Sequeira", "Firoza Mamdani", "Carl Ernst", "Marquis P. Vawter", "William E. Bunney", "Veronique Lebel", "Sonia Rehal", "Tim Klempan", "Alain Gratton", "Chawki Benkelfat", "Guy A. Rouleau", "Naguib Mechawar", "Gustavo Turecki"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006585.t004", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differentially_expressed_genes_directly_implicated_in_synaptic_transmission_as_determined_using_DAVID_2006_/558575", "title"=>"Differentially expressed genes directly implicated in synaptic transmission as determined using DAVID (2006).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-08-11 02:22:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/887947"], "description"=>"<p>The color and intensity indicate direction and level of change: blue spectrum colors indicate down-regulated expression, while red spectrum colors indicate up-regulated expression.</p>", "links"=>[], "tags"=>["hierarchical", "gabaergic", "differentially", "subunit", "genes", "17", "regions"], "article_id"=>558385, "categories"=>["Genetics", "Neuroscience", "Cell Biology"], "users"=>["Adolfo Sequeira", "Firoza Mamdani", "Carl Ernst", "Marquis P. Vawter", "William E. Bunney", "Veronique Lebel", "Sonia Rehal", "Tim Klempan", "Alain Gratton", "Chawki Benkelfat", "Guy A. Rouleau", "Naguib Mechawar", "Gustavo Turecki"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006585.g003", "stats"=>{"downloads"=>3, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clustered_image_map_CIM_of_the_hierarchical_cluster_analysis_of_the_GABAergic_differentially_expressed_subunit_genes_across_the_17_regions_investigated_/558385", "title"=>"Clustered image map (CIM) of the hierarchical cluster analysis of the GABAergic differentially expressed subunit genes across the 17 regions investigated.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-11 02:19:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/888180"], "description"=>"<p>Mean values per group are shown for the SemiQ RT-PCR experiment as well as for the MAS 5.1 normalized Affymetrix gene expression experiment.</p>", "links"=>[], "tags"=>["microarray", "involving", "gabaergic", "glutamatergic", "genes", "adjacent", "samples", "semi-quantitative", "rt-pcr"], "article_id"=>558614, "categories"=>["Genetics", "Neuroscience", "Cell Biology"], "users"=>["Adolfo Sequeira", "Firoza Mamdani", "Carl Ernst", "Marquis P. Vawter", "William E. Bunney", "Veronique Lebel", "Sonia Rehal", "Tim Klempan", "Alain Gratton", "Chawki Benkelfat", "Guy A. Rouleau", "Naguib Mechawar", "Gustavo Turecki"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006585.t005", "stats"=>{"downloads"=>16, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Confirmation_of_the_microarray_results_involving_critical_GABAergic_and_glutamatergic_genes_in_major_depression_and_suicide_using_independent_adjacent_samples_from_the_same_subjects_areas_by_semi_quantitative_RT_PCR_SemiQ_RT_PCR_/558614", "title"=>"Confirmation of the microarray results involving critical GABAergic and glutamatergic genes in major depression and suicide using independent adjacent samples from the same subjects/areas by semi-quantitative RT-PCR (SemiQ RT-PCR).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-08-11 02:23:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/888229"], "description"=>"<p>C = control, S = suicide, SMD = suicide with major depression, Amy = amygdala, Hippo = hippocampus, NAcc = nucleus accumbens. Information on Brodmann areas is provided elsewhere<sup>93–94</sup>. The number of genes analyzed corresponds to the number of genes considered as “Present” by the detection algorithm (MAS 5.1) in at least 75% of subjects in at least one of the groups. The number of genes reported as significant is that obtained in an ANCOVA model which included substance abuse/dependence as a covariate.</p>", "links"=>[], "tags"=>["differential", "17", "areas", "controls", "suicides"], "article_id"=>558671, "categories"=>["Genetics", "Neuroscience", "Cell Biology"], "users"=>["Adolfo Sequeira", "Firoza Mamdani", "Carl Ernst", "Marquis P. Vawter", "William E. Bunney", "Veronique Lebel", "Sonia Rehal", "Tim Klempan", "Alain Gratton", "Chawki Benkelfat", "Guy A. Rouleau", "Naguib Mechawar", "Gustavo Turecki"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006585.t002", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_the_differential_expression_analysis_in_17_brain_areas_of_controls_and_suicides_with_and_without_major_depression_/558671", "title"=>"Summary of the differential expression analysis in 17 brain areas of controls and suicides with and without major depression.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-08-11 02:24:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/887833"], "description"=>"<p>Both ontological categories and the regions were clustered. The color and intensity indicate level of significance: red spectrum colors indicate very highly significant gene ontologies (0.001), yellow colors indicate highly significant gene ontologies (0.01) and white colors represent no significance.</p>", "links"=>[], "tags"=>["hierarchical", "erminej", "calculated", "20", "overrepresented", "ontologies", "regions"], "article_id"=>558271, "categories"=>["Genetics", "Neuroscience", "Cell Biology"], "users"=>["Adolfo Sequeira", "Firoza Mamdani", "Carl Ernst", "Marquis P. Vawter", "William E. Bunney", "Veronique Lebel", "Sonia Rehal", "Tim Klempan", "Alain Gratton", "Chawki Benkelfat", "Guy A. Rouleau", "Naguib Mechawar", "Gustavo Turecki"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0006585.g002", "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clustered_image_map_CIM_of_the_hierarchical_cluster_analysis_of_the_distribution_pattern_of_ErmineJ_calculated_P_values_of_the_20_top_overrepresented_ontologies_across_all_the_regions_studied_/558271", "title"=>"Clustered image map (CIM) of the hierarchical cluster analysis of the distribution pattern of ErmineJ calculated <i>P</i>-values of the 20 top overrepresented ontologies across all the regions studied.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-08-11 02:17:51"}

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  • {"unique-ip"=>"18", "full-text"=>"19", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"21", "full-text"=>"26", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}

Relative Metric

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