Metabolic abnormalities in fronto-striatal-thalamic white matter tracts in schizophrenia
Abstract The anterior limb of the internal capsule (ALIC) is the major white matter tract providing reciprocal connections between the frontal cortex, striatum and thalamus. Mounting evidence suggests that this tract may be affected in schizophrenia, with brain imaging studies reporting reductions i...
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| Veröffentlicht in: | Schizophrenia research 2009-04, Vol.109 (1), p.159-166 |
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| creator | Beasley, Clare L Dwork, Andrew J Rosoklija, Gorazd Mann, J. John Mancevski, Branislav Jakovski, Zlatko Davceva, Natasa Tait, Andrew R Straus, Suzana K Honer, William G |
| description | Abstract The anterior limb of the internal capsule (ALIC) is the major white matter tract providing reciprocal connections between the frontal cortex, striatum and thalamus. Mounting evidence suggests that this tract may be affected in schizophrenia, with brain imaging studies reporting reductions in white matter volume and density, changes in fractional anisotropy and reduced asymmetry. However, the molecular correlates of these deficits are currently unknown. The aim of this study was to identify alterations in protein and metabolite levels in the ALIC in schizophrenia. Samples were obtained post-mortem from individuals with schizophrenia ( n = 15) and non-psychiatric controls ( n = 13). Immunoreactivity for the myelin-associated protein myelin basic protein (MBP), and the axonal-associated proteins phosphorylated neurofilament and SNAP-25 was measured by enzyme-linked immunoadsorbent assay (ELISA). Metabolite concentrations were quantified by proton nuclear magnetic resonance (1 H NMR) spectroscopy. Levels of myelin- or axonal-associated proteins did not differ between groups. Overall differences in metabolite concentrations were observed between the two groups (MANOVA F = 2.685, p = 0.036), with post-hoc tests revealing lower lactate (19%) and alanine (24%) levels in the schizophrenia group relative to controls. Observed changes in lactate and alanine levels indicate metabolic abnormalities within the ALIC in schizophrenia. |
| doi_str_mv | 10.1016/j.schres.2009.01.017 |
| format | Article |
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John ; Mancevski, Branislav ; Jakovski, Zlatko ; Davceva, Natasa ; Tait, Andrew R ; Straus, Suzana K ; Honer, William G</creator><creatorcontrib>Beasley, Clare L ; Dwork, Andrew J ; Rosoklija, Gorazd ; Mann, J. John ; Mancevski, Branislav ; Jakovski, Zlatko ; Davceva, Natasa ; Tait, Andrew R ; Straus, Suzana K ; Honer, William G</creatorcontrib><description>Abstract The anterior limb of the internal capsule (ALIC) is the major white matter tract providing reciprocal connections between the frontal cortex, striatum and thalamus. Mounting evidence suggests that this tract may be affected in schizophrenia, with brain imaging studies reporting reductions in white matter volume and density, changes in fractional anisotropy and reduced asymmetry. However, the molecular correlates of these deficits are currently unknown. The aim of this study was to identify alterations in protein and metabolite levels in the ALIC in schizophrenia. Samples were obtained post-mortem from individuals with schizophrenia ( n = 15) and non-psychiatric controls ( n = 13). Immunoreactivity for the myelin-associated protein myelin basic protein (MBP), and the axonal-associated proteins phosphorylated neurofilament and SNAP-25 was measured by enzyme-linked immunoadsorbent assay (ELISA). Metabolite concentrations were quantified by proton nuclear magnetic resonance (1 H NMR) spectroscopy. Levels of myelin- or axonal-associated proteins did not differ between groups. Overall differences in metabolite concentrations were observed between the two groups (MANOVA F = 2.685, p = 0.036), with post-hoc tests revealing lower lactate (19%) and alanine (24%) levels in the schizophrenia group relative to controls. Observed changes in lactate and alanine levels indicate metabolic abnormalities within the ALIC in schizophrenia.</description><identifier>ISSN: 0920-9964</identifier><identifier>EISSN: 1573-2509</identifier><identifier>DOI: 10.1016/j.schres.2009.01.017</identifier><identifier>PMID: 19272755</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Adult ; Adult and adolescent clinical studies ; Aged ; Aged, 80 and over ; Alanine - metabolism ; Anisotropy ; Autopsy ; Axon ; Biological and medical sciences ; Brain - metabolism ; Corpus Striatum - metabolism ; Diffusion Magnetic Resonance Imaging ; Female ; Frontal Lobe - metabolism ; Functional Laterality - physiology ; Humans ; Internal capsule ; Internal Capsule - metabolism ; Lactate ; Lactic Acid - metabolism ; Magnetic Resonance Imaging ; Male ; Medical sciences ; Metabolite ; Middle Aged ; Myelin ; Myelin Basic Protein - metabolism ; Neural Pathways - metabolism ; Psychiatry ; Psychology. 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Psychiatry ; Psychoses ; Schizophrenia ; Schizophrenia - diagnosis ; Schizophrenia - metabolism ; Synaptosomal-Associated Protein 25 - metabolism ; Thalamus - metabolism</subject><ispartof>Schizophrenia research, 2009-04, Vol.109 (1), p.159-166</ispartof><rights>Elsevier B.V.</rights><rights>2009 Elsevier B.V.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c612t-1b51a13c5be854408f72a293b2bfeed8c0aab637d49fb9aad9196cd37337af893</citedby><cites>FETCH-LOGICAL-c612t-1b51a13c5be854408f72a293b2bfeed8c0aab637d49fb9aad9196cd37337af893</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.schres.2009.01.017$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21391919$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19272755$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Beasley, Clare L</creatorcontrib><creatorcontrib>Dwork, Andrew J</creatorcontrib><creatorcontrib>Rosoklija, Gorazd</creatorcontrib><creatorcontrib>Mann, J. John</creatorcontrib><creatorcontrib>Mancevski, Branislav</creatorcontrib><creatorcontrib>Jakovski, Zlatko</creatorcontrib><creatorcontrib>Davceva, Natasa</creatorcontrib><creatorcontrib>Tait, Andrew R</creatorcontrib><creatorcontrib>Straus, Suzana K</creatorcontrib><creatorcontrib>Honer, William G</creatorcontrib><title>Metabolic abnormalities in fronto-striatal-thalamic white matter tracts in schizophrenia</title><title>Schizophrenia research</title><addtitle>Schizophr Res</addtitle><description>Abstract The anterior limb of the internal capsule (ALIC) is the major white matter tract providing reciprocal connections between the frontal cortex, striatum and thalamus. Mounting evidence suggests that this tract may be affected in schizophrenia, with brain imaging studies reporting reductions in white matter volume and density, changes in fractional anisotropy and reduced asymmetry. However, the molecular correlates of these deficits are currently unknown. The aim of this study was to identify alterations in protein and metabolite levels in the ALIC in schizophrenia. Samples were obtained post-mortem from individuals with schizophrenia ( n = 15) and non-psychiatric controls ( n = 13). Immunoreactivity for the myelin-associated protein myelin basic protein (MBP), and the axonal-associated proteins phosphorylated neurofilament and SNAP-25 was measured by enzyme-linked immunoadsorbent assay (ELISA). Metabolite concentrations were quantified by proton nuclear magnetic resonance (1 H NMR) spectroscopy. Levels of myelin- or axonal-associated proteins did not differ between groups. Overall differences in metabolite concentrations were observed between the two groups (MANOVA F = 2.685, p = 0.036), with post-hoc tests revealing lower lactate (19%) and alanine (24%) levels in the schizophrenia group relative to controls. Observed changes in lactate and alanine levels indicate metabolic abnormalities within the ALIC in schizophrenia.</description><subject>Adult</subject><subject>Adult and adolescent clinical studies</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alanine - metabolism</subject><subject>Anisotropy</subject><subject>Autopsy</subject><subject>Axon</subject><subject>Biological and medical sciences</subject><subject>Brain - metabolism</subject><subject>Corpus Striatum - metabolism</subject><subject>Diffusion Magnetic Resonance Imaging</subject><subject>Female</subject><subject>Frontal Lobe - metabolism</subject><subject>Functional Laterality - physiology</subject><subject>Humans</subject><subject>Internal capsule</subject><subject>Internal Capsule - metabolism</subject><subject>Lactate</subject><subject>Lactic Acid - metabolism</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolite</subject><subject>Middle Aged</subject><subject>Myelin</subject><subject>Myelin Basic Protein - metabolism</subject><subject>Neural Pathways - metabolism</subject><subject>Psychiatry</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychoses</subject><subject>Schizophrenia</subject><subject>Schizophrenia - diagnosis</subject><subject>Schizophrenia - metabolism</subject><subject>Synaptosomal-Associated Protein 25 - metabolism</subject><subject>Thalamus - metabolism</subject><issn>0920-9964</issn><issn>1573-2509</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk2LFDEQhhtR3HH1H4jMRW89VqU_0rkIsvgFKx5U8Baq09VOxu5kTDIr66837Qzr6kUI5JCn3norbxXFY4QNArbPd5totoHjRgCoDWA-8k6xwkZWpWhA3S1WoASUSrX1WfEgxh0AYAPyfnGGSkghm2ZVfHnPiXo_WbOm3vkw02ST5bi2bj0G75IvYwqWEk1l2tJEcyZ_bG3i9UwpcVinQCb95rMf-9Pvsyln6WFxb6Qp8qPTfV58fv3q08Xb8vLDm3cXLy9L06JIJfYNElam6blr6hq6UQoSqupFPzIPnQGivq3kUKuxV0SDQtWaoZJVJWnsVHVevDjq7g_9zINhlw1Neh_sTOFae7L67xdnt_qrv9I1tgpxEXh2Egj--4Fj0rONhqeJHPtD1K2ETjVQZ7A-gib4GAOPN00Q9BKJ3uljJHqJRAPmI3PZk9sG_xSdMsjA0xNA0dA0BnLGxhtOYJVnxluTcv7OK8shd7PsDA82sEl68PZ_Tv4VMJN1Nvf8xtccd_4QXI5Ko45Cg_64rM-yPaDy5tSA1S91jMQ7</recordid><startdate>20090401</startdate><enddate>20090401</enddate><creator>Beasley, Clare L</creator><creator>Dwork, Andrew J</creator><creator>Rosoklija, Gorazd</creator><creator>Mann, J. John</creator><creator>Mancevski, Branislav</creator><creator>Jakovski, Zlatko</creator><creator>Davceva, Natasa</creator><creator>Tait, Andrew R</creator><creator>Straus, Suzana K</creator><creator>Honer, William G</creator><general>Elsevier B.V</general><general>Elsevier</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090401</creationdate><title>Metabolic abnormalities in fronto-striatal-thalamic white matter tracts in schizophrenia</title><author>Beasley, Clare L ; Dwork, Andrew J ; Rosoklija, Gorazd ; Mann, J. John ; Mancevski, Branislav ; Jakovski, Zlatko ; Davceva, Natasa ; Tait, Andrew R ; Straus, Suzana K ; Honer, William G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c612t-1b51a13c5be854408f72a293b2bfeed8c0aab637d49fb9aad9196cd37337af893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Adult and adolescent clinical studies</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alanine - metabolism</topic><topic>Anisotropy</topic><topic>Autopsy</topic><topic>Axon</topic><topic>Biological and medical sciences</topic><topic>Brain - metabolism</topic><topic>Corpus Striatum - metabolism</topic><topic>Diffusion Magnetic Resonance Imaging</topic><topic>Female</topic><topic>Frontal Lobe - metabolism</topic><topic>Functional Laterality - physiology</topic><topic>Humans</topic><topic>Internal capsule</topic><topic>Internal Capsule - metabolism</topic><topic>Lactate</topic><topic>Lactic Acid - metabolism</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolite</topic><topic>Middle Aged</topic><topic>Myelin</topic><topic>Myelin Basic Protein - metabolism</topic><topic>Neural Pathways - metabolism</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Psychoses</topic><topic>Schizophrenia</topic><topic>Schizophrenia - diagnosis</topic><topic>Schizophrenia - metabolism</topic><topic>Synaptosomal-Associated Protein 25 - metabolism</topic><topic>Thalamus - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Beasley, Clare L</creatorcontrib><creatorcontrib>Dwork, Andrew J</creatorcontrib><creatorcontrib>Rosoklija, Gorazd</creatorcontrib><creatorcontrib>Mann, J. John</creatorcontrib><creatorcontrib>Mancevski, Branislav</creatorcontrib><creatorcontrib>Jakovski, Zlatko</creatorcontrib><creatorcontrib>Davceva, Natasa</creatorcontrib><creatorcontrib>Tait, Andrew R</creatorcontrib><creatorcontrib>Straus, Suzana K</creatorcontrib><creatorcontrib>Honer, William G</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Schizophrenia research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Beasley, Clare L</au><au>Dwork, Andrew J</au><au>Rosoklija, Gorazd</au><au>Mann, J. John</au><au>Mancevski, Branislav</au><au>Jakovski, Zlatko</au><au>Davceva, Natasa</au><au>Tait, Andrew R</au><au>Straus, Suzana K</au><au>Honer, William G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolic abnormalities in fronto-striatal-thalamic white matter tracts in schizophrenia</atitle><jtitle>Schizophrenia research</jtitle><addtitle>Schizophr Res</addtitle><date>2009-04-01</date><risdate>2009</risdate><volume>109</volume><issue>1</issue><spage>159</spage><epage>166</epage><pages>159-166</pages><issn>0920-9964</issn><eissn>1573-2509</eissn><abstract>Abstract The anterior limb of the internal capsule (ALIC) is the major white matter tract providing reciprocal connections between the frontal cortex, striatum and thalamus. Mounting evidence suggests that this tract may be affected in schizophrenia, with brain imaging studies reporting reductions in white matter volume and density, changes in fractional anisotropy and reduced asymmetry. However, the molecular correlates of these deficits are currently unknown. The aim of this study was to identify alterations in protein and metabolite levels in the ALIC in schizophrenia. Samples were obtained post-mortem from individuals with schizophrenia ( n = 15) and non-psychiatric controls ( n = 13). Immunoreactivity for the myelin-associated protein myelin basic protein (MBP), and the axonal-associated proteins phosphorylated neurofilament and SNAP-25 was measured by enzyme-linked immunoadsorbent assay (ELISA). Metabolite concentrations were quantified by proton nuclear magnetic resonance (1 H NMR) spectroscopy. Levels of myelin- or axonal-associated proteins did not differ between groups. Overall differences in metabolite concentrations were observed between the two groups (MANOVA F = 2.685, p = 0.036), with post-hoc tests revealing lower lactate (19%) and alanine (24%) levels in the schizophrenia group relative to controls. Observed changes in lactate and alanine levels indicate metabolic abnormalities within the ALIC in schizophrenia.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>19272755</pmid><doi>10.1016/j.schres.2009.01.017</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Adult and adolescent clinical studies Aged Aged, 80 and over Alanine - metabolism Anisotropy Autopsy Axon Biological and medical sciences Brain - metabolism Corpus Striatum - metabolism Diffusion Magnetic Resonance Imaging Female Frontal Lobe - metabolism Functional Laterality - physiology Humans Internal capsule Internal Capsule - metabolism Lactate Lactic Acid - metabolism Magnetic Resonance Imaging Male Medical sciences Metabolite Middle Aged Myelin Myelin Basic Protein - metabolism Neural Pathways - metabolism Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychoses Schizophrenia Schizophrenia - diagnosis Schizophrenia - metabolism Synaptosomal-Associated Protein 25 - metabolism Thalamus - metabolism |
| title | Metabolic abnormalities in fronto-striatal-thalamic white matter tracts in schizophrenia |
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