| Abnormalities in the fatty acid composition of the postmortem orbitofrontal cortex of schizophrenic patients: gender differences and partial normalization with antipsychotic medications. | |
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MedLine Citation:
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PMID: 17236749 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previous studies have observed significant abnormalities in the fatty acid composition of peripheral tissues from drug-naïve first-episode schizophrenic (SZ) patients relative to normal controls, including deficits in omega-3 and omega-6 polyunsaturated fatty acids, which are partially normalized following chronic antipsychotic treatment. We hypothesized that postmortem cortical tissue from patients with SZ would also exhibit deficits in cortical docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA; 20:4n-6) relative to normal controls, and that these deficits would be greater in drug-free SZ patients. We determined the total fatty acid composition of postmortem orbitofrontal cortex (OFC) (Brodmann area 10) from drug-free and antipsychotic-treated SZ patients (n=21) and age-matched normal controls (n=26) by gas chromatography. After correction for multiple comparisons, significantly lower DHA (-20%) concentrations, and significantly greater vaccenic acid (VA) (+12.5) concentrations, were found in the OFC of SZ patients relative to normal controls. Relative to age-matched same-gender controls, OFC DHA deficits, and elevated AA:DHA, oleic acid:DHA and docosapentaenoic acid (22:5n-6):DHA ratios, were found in male but not female SZ patients. SZ patients that died of cardiovascular-related disease exhibited lower DHA (-31%) and AA (-19%) concentrations, and greater OA (+20%) and VA (+17%) concentrations, relative to normal controls that also died of cardiovascular-related disease. OFC DHA and AA deficits, and elevations in oleic acid and vaccenic acid, were numerically greater in drug-free SZ patients and were partially normalized in SZ patients treated with antipsychotic medications (atypical>typical). Fatty acid abnormalities could not be wholly attributed to lifestyle or postmortem tissue variables. These findings add to a growing body of evidence implicating omega-3 fatty acid deficiency as well as the OFC in the pathoaetiology of SZ, and suggest that abnormalities in OFC fatty acid composition may be gender-specific and partially normalized by antipsychotic medications. |
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Authors:
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Robert K McNamara; Ronald Jandacek; Therese Rider; Patrick Tso; Chang-Gyu Hahn; Neil M Richtand; Kevin E Stanford |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2007-01-19 |
Journal Detail:
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Title: Schizophrenia research Volume: 91 ISSN: 0920-9964 ISO Abbreviation: Schizophr. Res. Publication Date: 2007 Mar |
Date Detail:
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Created Date: 2007-03-05 Completed Date: 2007-06-12 Revised Date: 2012-04-24 |
Medline Journal Info:
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Nlm Unique ID: 8804207 Medline TA: Schizophr Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 37-50 Citation Subset: IM |
Affiliation:
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Department of Psychiatry, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0559, United States. robert.mcnamara@psychiatry.uc.edu |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Antipsychotic Agents / therapeutic use* Arachidonic Acid / metabolism Benzodiazepines / therapeutic use Brain / metabolism Clozapine / therapeutic use Diagnostic and Statistical Manual of Mental Disorders Docosahexaenoic Acids / metabolism Fatty Acid Desaturases / metabolism Fatty Acids / metabolism* Fatty Acids, Omega-3 / metabolism Female Humans Male Middle Aged Prefrontal Cortex / metabolism*, pathology Risperidone / therapeutic use Schizophrenia / drug therapy*, metabolism*, pathology Sex Factors |
| Grant Support | |
ID/Acronym/Agency:
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MH073704/MH/NIMH NIH HHS; MH074858/MH/NIMH NIH HHS; R21 MH073704/MH/NIMH NIH HHS; R21 MH073704-01A1/MH/NIMH NIH HHS; R21 MH074858/MH/NIMH NIH HHS; R21 MH074858-01A1/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antipsychotic Agents; 0/Fatty Acids; 0/Fatty Acids, Omega-3; 106266-06-2/Risperidone; 12794-10-4/Benzodiazepines; 132539-06-1/olanzapine; 25167-62-8/Docosahexaenoic Acids; 506-32-1/Arachidonic Acid; 5786-21-0/Clozapine; EC 1.14.19.-/Fatty Acid Desaturases; EC 1.14.99.-/delta-12 fatty acid desaturase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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