Neuron Number and Size in Prefrontal Cortex of Children With Autism
CONTEXT Autism often involves early brain overgrowth, including the prefrontal cortex (PFC). Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown. OBJECTIVE To investigate whether early brain overgro...
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| Veröffentlicht in: | JAMA : the journal of the American Medical Association 2011-11, Vol.306 (18), p.2001-2010 |
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| creator | Courchesne, Eric Mouton, Peter R Calhoun, Michael E Semendeferi, Katerina Ahrens-Barbeau, Clelia Hallet, Melodie J Barnes, Cynthia Carter Pierce, Karen |
| description | CONTEXT Autism often involves early brain overgrowth, including the prefrontal cortex (PFC). Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown. OBJECTIVE To investigate whether early brain overgrowth in children with autism involves excess neuron numbers in the PFC. DESIGN, SETTING, AND CASES Postmortem prefrontal tissue from 7 autistic and 6 control male children aged 2 to 16 years was examined by expert anatomists who were blinded to diagnostic status. Number and size of neurons were quantified using stereological methods within the dorsolateral (DL-PFC) and mesial (M-PFC) subdivisions of the PFC. Cases were from the eastern and southeastern United States and died between 2000 and 2006. MAIN OUTCOME MEASURES Mean neuron number and size in the DL-PFC and M-PFC were compared between autistic and control postmortem cases. Correlations of neuron number with deviation in brain weight from normative values for age were also performed. RESULTS Children with autism had 67% more neurons in the PFC (mean, 1.94 billion; 95% CI, 1.57-2.31) compared with control children (1.16 billion; 95% CI, 0.90-1.42; P = .002), including 79% more in DL-PFC (1.57 billion; 95% CI, 1.20-1.94 in autism cases vs 0.88 billion; 95% CI, 0.66-1.10 in controls; P = .003) and 29% more in M-PFC (0.36 billion; 95% CI, 0.33-0.40 in autism cases vs 0.28 billion; 95% CI, 0.23-0.34 in controls; P = .009). Brain weight in the autistic cases differed from normative mean weight for age by a mean of 17.6% (95% CI, 10.2%-25.0%; P = .001), while brains in controls differed by a mean of 0.2% (95% CI, −8.7% to 9.1%; P = .96). Plots of counts by weight showed autistic children had both greater total prefrontal neuron counts and brain weight for age than control children. CONCLUSION In this small preliminary study, brain overgrowth in males with autism involved an abnormal excess number of neurons in the PFC. |
| doi_str_mv | 10.1001/jama.2011.1638 |
| format | Article |
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Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown. OBJECTIVE To investigate whether early brain overgrowth in children with autism involves excess neuron numbers in the PFC. DESIGN, SETTING, AND CASES Postmortem prefrontal tissue from 7 autistic and 6 control male children aged 2 to 16 years was examined by expert anatomists who were blinded to diagnostic status. Number and size of neurons were quantified using stereological methods within the dorsolateral (DL-PFC) and mesial (M-PFC) subdivisions of the PFC. Cases were from the eastern and southeastern United States and died between 2000 and 2006. MAIN OUTCOME MEASURES Mean neuron number and size in the DL-PFC and M-PFC were compared between autistic and control postmortem cases. Correlations of neuron number with deviation in brain weight from normative values for age were also performed. RESULTS Children with autism had 67% more neurons in the PFC (mean, 1.94 billion; 95% CI, 1.57-2.31) compared with control children (1.16 billion; 95% CI, 0.90-1.42; P = .002), including 79% more in DL-PFC (1.57 billion; 95% CI, 1.20-1.94 in autism cases vs 0.88 billion; 95% CI, 0.66-1.10 in controls; P = .003) and 29% more in M-PFC (0.36 billion; 95% CI, 0.33-0.40 in autism cases vs 0.28 billion; 95% CI, 0.23-0.34 in controls; P = .009). Brain weight in the autistic cases differed from normative mean weight for age by a mean of 17.6% (95% CI, 10.2%-25.0%; P = .001), while brains in controls differed by a mean of 0.2% (95% CI, −8.7% to 9.1%; P = .96). Plots of counts by weight showed autistic children had both greater total prefrontal neuron counts and brain weight for age than control children. CONCLUSION In this small preliminary study, brain overgrowth in males with autism involved an abnormal excess number of neurons in the PFC.</description><identifier>ISSN: 0098-7484</identifier><identifier>EISSN: 1538-3598</identifier><identifier>DOI: 10.1001/jama.2011.1638</identifier><identifier>PMID: 22068992</identifier><identifier>CODEN: JAMAAP</identifier><language>eng</language><publisher>Chicago, IL: American Medical Association</publisher><subject>Adolescent ; Autism ; Autistic Disorder - pathology ; Autopsy ; Biological and medical sciences ; Brain research ; Case-Control Studies ; Cell Count ; Cell Size ; Child ; Child clinical studies ; Child development ; Child, Preschool ; Developmental disorders ; General aspects ; Health risk assessment ; Humans ; Infant ; Infantile autism ; Male ; Medical sciences ; Neurons ; Neurons - cytology ; Organ Size ; Prefrontal Cortex - cytology ; Prefrontal Cortex - growth & development ; Prefrontal Cortex - pathology ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry</subject><ispartof>JAMA : the journal of the American Medical Association, 2011-11, Vol.306 (18), p.2001-2010</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright American Medical Association Nov 9, 2011</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a403t-5808f882ec20b4c99bd02dedeac276db01b8dce1d4073bf82e8681f1e2f71623</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jama/articlepdf/10.1001/jama.2011.1638$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2011.1638$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,314,776,780,3327,27901,27902,76232,76235</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24750055$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22068992$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Courchesne, Eric</creatorcontrib><creatorcontrib>Mouton, Peter R</creatorcontrib><creatorcontrib>Calhoun, Michael E</creatorcontrib><creatorcontrib>Semendeferi, Katerina</creatorcontrib><creatorcontrib>Ahrens-Barbeau, Clelia</creatorcontrib><creatorcontrib>Hallet, Melodie J</creatorcontrib><creatorcontrib>Barnes, Cynthia Carter</creatorcontrib><creatorcontrib>Pierce, Karen</creatorcontrib><title>Neuron Number and Size in Prefrontal Cortex of Children With Autism</title><title>JAMA : the journal of the American Medical Association</title><addtitle>JAMA</addtitle><description>CONTEXT Autism often involves early brain overgrowth, including the prefrontal cortex (PFC). Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown. OBJECTIVE To investigate whether early brain overgrowth in children with autism involves excess neuron numbers in the PFC. DESIGN, SETTING, AND CASES Postmortem prefrontal tissue from 7 autistic and 6 control male children aged 2 to 16 years was examined by expert anatomists who were blinded to diagnostic status. Number and size of neurons were quantified using stereological methods within the dorsolateral (DL-PFC) and mesial (M-PFC) subdivisions of the PFC. Cases were from the eastern and southeastern United States and died between 2000 and 2006. MAIN OUTCOME MEASURES Mean neuron number and size in the DL-PFC and M-PFC were compared between autistic and control postmortem cases. Correlations of neuron number with deviation in brain weight from normative values for age were also performed. RESULTS Children with autism had 67% more neurons in the PFC (mean, 1.94 billion; 95% CI, 1.57-2.31) compared with control children (1.16 billion; 95% CI, 0.90-1.42; P = .002), including 79% more in DL-PFC (1.57 billion; 95% CI, 1.20-1.94 in autism cases vs 0.88 billion; 95% CI, 0.66-1.10 in controls; P = .003) and 29% more in M-PFC (0.36 billion; 95% CI, 0.33-0.40 in autism cases vs 0.28 billion; 95% CI, 0.23-0.34 in controls; P = .009). Brain weight in the autistic cases differed from normative mean weight for age by a mean of 17.6% (95% CI, 10.2%-25.0%; P = .001), while brains in controls differed by a mean of 0.2% (95% CI, −8.7% to 9.1%; P = .96). Plots of counts by weight showed autistic children had both greater total prefrontal neuron counts and brain weight for age than control children. CONCLUSION In this small preliminary study, brain overgrowth in males with autism involved an abnormal excess number of neurons in the PFC.</description><subject>Adolescent</subject><subject>Autism</subject><subject>Autistic Disorder - pathology</subject><subject>Autopsy</subject><subject>Biological and medical sciences</subject><subject>Brain research</subject><subject>Case-Control Studies</subject><subject>Cell Count</subject><subject>Cell Size</subject><subject>Child</subject><subject>Child clinical studies</subject><subject>Child development</subject><subject>Child, Preschool</subject><subject>Developmental disorders</subject><subject>General aspects</subject><subject>Health risk assessment</subject><subject>Humans</subject><subject>Infant</subject><subject>Infantile autism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neurons</subject><subject>Neurons - cytology</subject><subject>Organ Size</subject><subject>Prefrontal Cortex - cytology</subject><subject>Prefrontal Cortex - growth & development</subject><subject>Prefrontal Cortex - pathology</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><issn>0098-7484</issn><issn>1538-3598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90b1r3DAYBnARUnKXtGuGDEEESrr4-r6SLEvjYZq0cKSFBjoa2ZKJD39cJBvS_PWVuUsCGapFg356xKuHkHOEFQLg163pzIoB4golV0dkiSlXCU-1OiZLAK2STCixIKchbCEu5NkJWTAGUmnNliS_c5Mfeno3daXz1PSW_m6eHW16-su7Oh6NpqX54Ef3RIea5g9Na73r6Z9mfKDraWxC95F8qE0b3KfDfkbub77d59-Tzc_bH_l6kxgBfExSBapWirmKQSkqrUsLzDrrTMUyaUvAUtnKoRWQ8bKOUEmFNTpWZygZPyPX-9idHx4nF8aia0Ll2tb0bphCoYGjkFqqKL_8VyJoLiRPpYz06h3dDpPv4xgxT_JMoswiWu1R5YcQ4rcUO990xv-NScVcQzHXUMw1FHMN8cLlIXUqO2df-cu_R_D5AEyoTFt701dNeHMiSwHSNLqLvZvzXx9FEDKO8A_3yZZ0</recordid><startdate>20111109</startdate><enddate>20111109</enddate><creator>Courchesne, Eric</creator><creator>Mouton, Peter R</creator><creator>Calhoun, Michael E</creator><creator>Semendeferi, Katerina</creator><creator>Ahrens-Barbeau, Clelia</creator><creator>Hallet, Melodie J</creator><creator>Barnes, Cynthia Carter</creator><creator>Pierce, Karen</creator><general>American Medical Association</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>7QL</scope><scope>7QP</scope><scope>7TK</scope><scope>7TS</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20111109</creationdate><title>Neuron Number and Size in Prefrontal Cortex of Children With Autism</title><author>Courchesne, Eric ; Mouton, Peter R ; Calhoun, Michael E ; Semendeferi, Katerina ; Ahrens-Barbeau, Clelia ; Hallet, Melodie J ; Barnes, Cynthia Carter ; Pierce, Karen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a403t-5808f882ec20b4c99bd02dedeac276db01b8dce1d4073bf82e8681f1e2f71623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adolescent</topic><topic>Autism</topic><topic>Autistic Disorder - pathology</topic><topic>Autopsy</topic><topic>Biological and medical sciences</topic><topic>Brain research</topic><topic>Case-Control Studies</topic><topic>Cell Count</topic><topic>Cell Size</topic><topic>Child</topic><topic>Child clinical studies</topic><topic>Child development</topic><topic>Child, Preschool</topic><topic>Developmental disorders</topic><topic>General aspects</topic><topic>Health risk assessment</topic><topic>Humans</topic><topic>Infant</topic><topic>Infantile autism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neurons</topic><topic>Neurons - cytology</topic><topic>Organ Size</topic><topic>Prefrontal Cortex - cytology</topic><topic>Prefrontal Cortex - growth & development</topic><topic>Prefrontal Cortex - pathology</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Courchesne, Eric</creatorcontrib><creatorcontrib>Mouton, Peter R</creatorcontrib><creatorcontrib>Calhoun, Michael E</creatorcontrib><creatorcontrib>Semendeferi, Katerina</creatorcontrib><creatorcontrib>Ahrens-Barbeau, Clelia</creatorcontrib><creatorcontrib>Hallet, Melodie J</creatorcontrib><creatorcontrib>Barnes, Cynthia Carter</creatorcontrib><creatorcontrib>Pierce, Karen</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>JAMA : the journal of the American Medical Association</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Courchesne, Eric</au><au>Mouton, Peter R</au><au>Calhoun, Michael E</au><au>Semendeferi, Katerina</au><au>Ahrens-Barbeau, Clelia</au><au>Hallet, Melodie J</au><au>Barnes, Cynthia Carter</au><au>Pierce, Karen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuron Number and Size in Prefrontal Cortex of Children With Autism</atitle><jtitle>JAMA : the journal of the American Medical Association</jtitle><addtitle>JAMA</addtitle><date>2011-11-09</date><risdate>2011</risdate><volume>306</volume><issue>18</issue><spage>2001</spage><epage>2010</epage><pages>2001-2010</pages><issn>0098-7484</issn><eissn>1538-3598</eissn><coden>JAMAAP</coden><abstract>CONTEXT Autism often involves early brain overgrowth, including the prefrontal cortex (PFC). Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown. OBJECTIVE To investigate whether early brain overgrowth in children with autism involves excess neuron numbers in the PFC. DESIGN, SETTING, AND CASES Postmortem prefrontal tissue from 7 autistic and 6 control male children aged 2 to 16 years was examined by expert anatomists who were blinded to diagnostic status. Number and size of neurons were quantified using stereological methods within the dorsolateral (DL-PFC) and mesial (M-PFC) subdivisions of the PFC. Cases were from the eastern and southeastern United States and died between 2000 and 2006. MAIN OUTCOME MEASURES Mean neuron number and size in the DL-PFC and M-PFC were compared between autistic and control postmortem cases. Correlations of neuron number with deviation in brain weight from normative values for age were also performed. RESULTS Children with autism had 67% more neurons in the PFC (mean, 1.94 billion; 95% CI, 1.57-2.31) compared with control children (1.16 billion; 95% CI, 0.90-1.42; P = .002), including 79% more in DL-PFC (1.57 billion; 95% CI, 1.20-1.94 in autism cases vs 0.88 billion; 95% CI, 0.66-1.10 in controls; P = .003) and 29% more in M-PFC (0.36 billion; 95% CI, 0.33-0.40 in autism cases vs 0.28 billion; 95% CI, 0.23-0.34 in controls; P = .009). Brain weight in the autistic cases differed from normative mean weight for age by a mean of 17.6% (95% CI, 10.2%-25.0%; P = .001), while brains in controls differed by a mean of 0.2% (95% CI, −8.7% to 9.1%; P = .96). Plots of counts by weight showed autistic children had both greater total prefrontal neuron counts and brain weight for age than control children. CONCLUSION In this small preliminary study, brain overgrowth in males with autism involved an abnormal excess number of neurons in the PFC.</abstract><cop>Chicago, IL</cop><pub>American Medical Association</pub><pmid>22068992</pmid><doi>10.1001/jama.2011.1638</doi><tpages>10</tpages></addata></record> |
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| subjects | Adolescent Autism Autistic Disorder - pathology Autopsy Biological and medical sciences Brain research Case-Control Studies Cell Count Cell Size Child Child clinical studies Child development Child, Preschool Developmental disorders General aspects Health risk assessment Humans Infant Infantile autism Male Medical sciences Neurons Neurons - cytology Organ Size Prefrontal Cortex - cytology Prefrontal Cortex - growth & development Prefrontal Cortex - pathology Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry |
| title | Neuron Number and Size in Prefrontal Cortex of Children With Autism |
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