Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression
The etiology of major depression (MDD), a common and complex disorder, remains obscure. Gene expression profiling was conducted on post-mortem brain tissue samples from Brodmann Area 10 (BA10) in the prefrontal cortex from psychotropic drug-free persons with a history of MDD and age, gender, and pos...
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| Veröffentlicht in: | Molecular psychiatry 2011-07, Vol.16 (7), p.751-762 |
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| creator | Shelton, R C Claiborne, J Sidoryk-Wegrzynowicz, M Reddy, R Aschner, M Lewis, D A Mirnics, K |
| description | The etiology of major depression (MDD), a common and complex disorder, remains obscure. Gene expression profiling was conducted on post-mortem brain tissue samples from Brodmann Area 10 (BA10) in the prefrontal cortex from psychotropic drug-free persons with a history of MDD and age, gender, and post-mortem interval-matched normal controls (
n
=14 pairs of subjects). Microarray analysis was conducted using the Affymetrix Exon 1.0 ST arrays. A set of differential expression changes was determined by dual-fold change-probability criteria (∣average log ratios∣>0.585 [equivalent to a 1.5-fold difference in either direction],
P |
| doi_str_mv | 10.1038/mp.2010.52 |
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n
=14 pairs of subjects). Microarray analysis was conducted using the Affymetrix Exon 1.0 ST arrays. A set of differential expression changes was determined by dual-fold change-probability criteria (∣average log ratios∣>0.585 [equivalent to a 1.5-fold difference in either direction],
P
<0.01), whereas molecular pathways of interest were evaluated using Gene Set Enrichment Analysis software. The results strongly implicate increased apoptotic stress in the samples from the MDD group. Three anti-apoptotic factors, Y-box-binding protein 1, caspase-1 dominant-negative inhibitor pseudo-ICE, and the putative apoptosis inhibitor FKGS2, were over-expressed. Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1α (IL-1α), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNγ), and lymphotoxin α (TNF superfamily member 1). The genes showing reduced expression included metallothionein 1M (MT1M), a zinc-binding protein with a significant function in the modulation of oxidative stress. The results of this study indicate that post-mortem brain tissue samples from BA10, a region that is involved in reward-related behavior, show evidence of local inflammatory, apoptotic, and oxidative stress in MDD.</description><identifier>ISSN: 1359-4184</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/mp.2010.52</identifier><identifier>PMID: 20479761</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208/191/2018 ; 631/80/82/23 ; 692/420/256 ; 692/699/476/1414 ; Adult ; Adult and adolescent clinical studies ; Aged ; Amphetamines ; Apoptosis ; Apoptosis - physiology ; Behavioral Sciences ; Biological and medical sciences ; Biological Psychology ; Brain ; Brain research ; Brodmann's area ; Caspase-1 ; Cluster Analysis ; Computer programs ; Cortex (frontal) ; Cortex (prefrontal) ; Cytokines ; Cytokines - genetics ; Cytokines - metabolism ; Depression ; Depression, Mental ; Depressive Disorder, Major - pathology ; DNA microarrays ; Etiology ; Female ; Frontal Lobe - metabolism ; Frontal Lobe - physiopathology ; gamma -Interferon ; Gene expression ; Gene Expression Profiling ; Genetic aspects ; Humans ; Inflammation ; Interleukin 10 ; Interleukin 13 ; Interleukin 15 ; Interleukin 18 ; Interleukin 2 ; Interleukin 3 ; Interleukin 5 ; Interleukin 8 ; Interleukin 9 ; Lymphotoxin ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Mental depression ; Metallothionein ; Middle Aged ; Mood disorders ; Neurosciences ; Oligonucleotide Array Sequence Analysis ; original-article ; Oxidative stress ; Pharmacotherapy ; Physiological aspects ; Prefrontal cortex ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychotropic drugs ; Reinforcement ; Review boards ; software ; Statistics as Topic ; Tomography ; Tumor necrosis factor ; Zinc-binding protein ; γ-Interferon</subject><ispartof>Molecular psychiatry, 2011-07, Vol.16 (7), p.751-762</ispartof><rights>Macmillan Publishers Limited 2011</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2011 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2011.</rights><rights>Copyright Nature Publishing Group Jul 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c638t-8877b0c5af64e171288b6ef2a750cb2b2ab715534f1e80f2f768449def7a5aac3</citedby><cites>FETCH-LOGICAL-c638t-8877b0c5af64e171288b6ef2a750cb2b2ab715534f1e80f2f768449def7a5aac3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/mp.2010.52$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/mp.2010.52$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24336115$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20479761$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shelton, R C</creatorcontrib><creatorcontrib>Claiborne, J</creatorcontrib><creatorcontrib>Sidoryk-Wegrzynowicz, M</creatorcontrib><creatorcontrib>Reddy, R</creatorcontrib><creatorcontrib>Aschner, M</creatorcontrib><creatorcontrib>Lewis, D A</creatorcontrib><creatorcontrib>Mirnics, K</creatorcontrib><title>Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><addtitle>Mol Psychiatry</addtitle><description>The etiology of major depression (MDD), a common and complex disorder, remains obscure. Gene expression profiling was conducted on post-mortem brain tissue samples from Brodmann Area 10 (BA10) in the prefrontal cortex from psychotropic drug-free persons with a history of MDD and age, gender, and post-mortem interval-matched normal controls (
n
=14 pairs of subjects). Microarray analysis was conducted using the Affymetrix Exon 1.0 ST arrays. A set of differential expression changes was determined by dual-fold change-probability criteria (∣average log ratios∣>0.585 [equivalent to a 1.5-fold difference in either direction],
P
<0.01), whereas molecular pathways of interest were evaluated using Gene Set Enrichment Analysis software. The results strongly implicate increased apoptotic stress in the samples from the MDD group. Three anti-apoptotic factors, Y-box-binding protein 1, caspase-1 dominant-negative inhibitor pseudo-ICE, and the putative apoptosis inhibitor FKGS2, were over-expressed. Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1α (IL-1α), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNγ), and lymphotoxin α (TNF superfamily member 1). The genes showing reduced expression included metallothionein 1M (MT1M), a zinc-binding protein with a significant function in the modulation of oxidative stress. The results of this study indicate that post-mortem brain tissue samples from BA10, a region that is involved in reward-related behavior, show evidence of local inflammatory, apoptotic, and oxidative stress in MDD.</description><subject>631/208/191/2018</subject><subject>631/80/82/23</subject><subject>692/420/256</subject><subject>692/699/476/1414</subject><subject>Adult</subject><subject>Adult and adolescent clinical studies</subject><subject>Aged</subject><subject>Amphetamines</subject><subject>Apoptosis</subject><subject>Apoptosis - physiology</subject><subject>Behavioral Sciences</subject><subject>Biological and medical sciences</subject><subject>Biological Psychology</subject><subject>Brain</subject><subject>Brain research</subject><subject>Brodmann's area</subject><subject>Caspase-1</subject><subject>Cluster Analysis</subject><subject>Computer programs</subject><subject>Cortex (frontal)</subject><subject>Cortex (prefrontal)</subject><subject>Cytokines</subject><subject>Cytokines - genetics</subject><subject>Cytokines - metabolism</subject><subject>Depression</subject><subject>Depression, Mental</subject><subject>Depressive Disorder, Major - pathology</subject><subject>DNA microarrays</subject><subject>Etiology</subject><subject>Female</subject><subject>Frontal Lobe - metabolism</subject><subject>Frontal Lobe - physiopathology</subject><subject>gamma -Interferon</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Genetic aspects</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Interleukin 10</subject><subject>Interleukin 13</subject><subject>Interleukin 15</subject><subject>Interleukin 18</subject><subject>Interleukin 2</subject><subject>Interleukin 3</subject><subject>Interleukin 5</subject><subject>Interleukin 8</subject><subject>Interleukin 9</subject><subject>Lymphotoxin</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mental depression</subject><subject>Metallothionein</subject><subject>Middle Aged</subject><subject>Mood disorders</subject><subject>Neurosciences</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>original-article</subject><subject>Oxidative stress</subject><subject>Pharmacotherapy</subject><subject>Physiological aspects</subject><subject>Prefrontal cortex</subject><subject>Psychiatry</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychotropic drugs</subject><subject>Reinforcement</subject><subject>Review boards</subject><subject>software</subject><subject>Statistics as Topic</subject><subject>Tomography</subject><subject>Tumor necrosis factor</subject><subject>Zinc-binding protein</subject><subject>γ-Interferon</subject><issn>1359-4184</issn><issn>1476-5578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqF0luL1DAUAOAiinvRF3-AFGURlBlzbdIXYVi8wYIv-hzS9GQ2Q5vUpDOs_96Emd1xZcW20Dbny0lzeqrqBUZLjKh8P05LgvILJ4-qU8xEs-BcyMf5mfJ2wbBkJ9VZShuESpA_rU4IYqIVDT6trlfDDBH6Gm6mCCm54Otg6zV4SLXzuzDsctD5fNlBj6Oei9C-r_UUpjkkV1htY_CzHmoT4gw3ZWTUmxDrHm6zPqueWD0keH64n1c_Pn38fvllcfXt89fL1dXCNFTOCymF6JDh2jYMsMBEyq4BS7TgyHSkI7oTmHPKLAaJLLGikYy1PVihudaGnlcf9nmnbTdCb8DPUQ9qim7U8ZcK2qn7Ee-u1TrsFGmJZEjkBG8OCWL4uYU0q9ElA8OgPYRtUlJSRDnh6P9SUIG4pCzLV3_JTdhGn-tQUD4wKej1vxBpGBe8FRwf1VoPoPJfCXkXpiysVqRBmMpWlE9bPqDy2cPoTPBgXR6_N-HtfoKJIaUI9q5iGKnSZWqcVOkyxUnGL_-s8R29basMLg5AJ6MHG7U3Lh0do7TBmGf3bu9SDvk1xOOWH1j2N3TT55s</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>Shelton, R C</creator><creator>Claiborne, J</creator><creator>Sidoryk-Wegrzynowicz, M</creator><creator>Reddy, R</creator><creator>Aschner, M</creator><creator>Lewis, D A</creator><creator>Mirnics, K</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20110701</creationdate><title>Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression</title><author>Shelton, R C ; Claiborne, J ; Sidoryk-Wegrzynowicz, M ; Reddy, R ; Aschner, M ; Lewis, D A ; Mirnics, K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c638t-8877b0c5af64e171288b6ef2a750cb2b2ab715534f1e80f2f768449def7a5aac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>631/208/191/2018</topic><topic>631/80/82/23</topic><topic>692/420/256</topic><topic>692/699/476/1414</topic><topic>Adult</topic><topic>Adult and adolescent clinical studies</topic><topic>Aged</topic><topic>Amphetamines</topic><topic>Apoptosis</topic><topic>Apoptosis - physiology</topic><topic>Behavioral Sciences</topic><topic>Biological and medical sciences</topic><topic>Biological Psychology</topic><topic>Brain</topic><topic>Brain research</topic><topic>Brodmann's area</topic><topic>Caspase-1</topic><topic>Cluster Analysis</topic><topic>Computer programs</topic><topic>Cortex (frontal)</topic><topic>Cortex (prefrontal)</topic><topic>Cytokines</topic><topic>Cytokines - genetics</topic><topic>Cytokines - metabolism</topic><topic>Depression</topic><topic>Depression, Mental</topic><topic>Depressive Disorder, Major - pathology</topic><topic>DNA microarrays</topic><topic>Etiology</topic><topic>Female</topic><topic>Frontal Lobe - metabolism</topic><topic>Frontal Lobe - physiopathology</topic><topic>gamma -Interferon</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Genetic aspects</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Interleukin 10</topic><topic>Interleukin 13</topic><topic>Interleukin 15</topic><topic>Interleukin 18</topic><topic>Interleukin 2</topic><topic>Interleukin 3</topic><topic>Interleukin 5</topic><topic>Interleukin 8</topic><topic>Interleukin 9</topic><topic>Lymphotoxin</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mental depression</topic><topic>Metallothionein</topic><topic>Middle Aged</topic><topic>Mood disorders</topic><topic>Neurosciences</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>original-article</topic><topic>Oxidative stress</topic><topic>Pharmacotherapy</topic><topic>Physiological aspects</topic><topic>Prefrontal cortex</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. 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Gene expression profiling was conducted on post-mortem brain tissue samples from Brodmann Area 10 (BA10) in the prefrontal cortex from psychotropic drug-free persons with a history of MDD and age, gender, and post-mortem interval-matched normal controls (
n
=14 pairs of subjects). Microarray analysis was conducted using the Affymetrix Exon 1.0 ST arrays. A set of differential expression changes was determined by dual-fold change-probability criteria (∣average log ratios∣>0.585 [equivalent to a 1.5-fold difference in either direction],
P
<0.01), whereas molecular pathways of interest were evaluated using Gene Set Enrichment Analysis software. The results strongly implicate increased apoptotic stress in the samples from the MDD group. Three anti-apoptotic factors, Y-box-binding protein 1, caspase-1 dominant-negative inhibitor pseudo-ICE, and the putative apoptosis inhibitor FKGS2, were over-expressed. Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1α (IL-1α), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNγ), and lymphotoxin α (TNF superfamily member 1). The genes showing reduced expression included metallothionein 1M (MT1M), a zinc-binding protein with a significant function in the modulation of oxidative stress. The results of this study indicate that post-mortem brain tissue samples from BA10, a region that is involved in reward-related behavior, show evidence of local inflammatory, apoptotic, and oxidative stress in MDD.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>20479761</pmid><doi>10.1038/mp.2010.52</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/208/191/2018 631/80/82/23 692/420/256 692/699/476/1414 Adult Adult and adolescent clinical studies Aged Amphetamines Apoptosis Apoptosis - physiology Behavioral Sciences Biological and medical sciences Biological Psychology Brain Brain research Brodmann's area Caspase-1 Cluster Analysis Computer programs Cortex (frontal) Cortex (prefrontal) Cytokines Cytokines - genetics Cytokines - metabolism Depression Depression, Mental Depressive Disorder, Major - pathology DNA microarrays Etiology Female Frontal Lobe - metabolism Frontal Lobe - physiopathology gamma -Interferon Gene expression Gene Expression Profiling Genetic aspects Humans Inflammation Interleukin 10 Interleukin 13 Interleukin 15 Interleukin 18 Interleukin 2 Interleukin 3 Interleukin 5 Interleukin 8 Interleukin 9 Lymphotoxin Male Medical sciences Medicine Medicine & Public Health Mental depression Metallothionein Middle Aged Mood disorders Neurosciences Oligonucleotide Array Sequence Analysis original-article Oxidative stress Pharmacotherapy Physiological aspects Prefrontal cortex Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychotropic drugs Reinforcement Review boards software Statistics as Topic Tomography Tumor necrosis factor Zinc-binding protein γ-Interferon |
| title | Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression |
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