title: Endocannabinoid metabolism in the prefrontal cortex in schizophrenia.
abstract: Adolescent cannabis use is associated with greater relative risk, increased symptom severity, and earlier age of onset of schizophrenia. We investigated whether this interaction may be partly attributable to disease-related disturbances in metabolism of the major cortical endocannabinoid 2-arachidonoylglycerol (2-AG). Transcript levels for the recently discovered 2-AG metabolizing enzyme, α-β-hydrolase domain 6 (ABHD6), were assessed using quantitative PCR in the prefrontal cortex of schizophrenia and healthy subjects (n=84) and antipsychotic- or tetrahydrocannabinol-exposed monkeys. ABHD6 mRNA levels were elevated in schizophrenia subjects who were younger and had a shorter illness duration but not in antipsychotic- or tetrahydrocannabinol-exposed monkeys. Higher ABHD6 mRNA levels may increase 2-AG metabolism which may influence susceptibility to cannabis in the earlier stages of schizophrenia.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, United States. Electronic address: volkdw@upmc.edu.
authors.forename: David W
authors.initials: DW
authors.lastname: Volk
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: Benjamin I
authors.initials: BI
authors.lastname: Siegel
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, United States; Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX 77030, United States.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Verrico
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, United States; Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D001599:Berberine / Q000031:analogs & derivatives / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D063388:Endocannabinoids / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D008875:Middle Aged; D008994:Monoacylglycerol Lipases / Q000378:metabolism; D000077152:Olanzapine; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000473:pathology*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D002121:Calcium Channel Blockers; D063388:Endocannabinoids; D001599:Berberine; D001569:Benzodiazepines; C540878:ABHD6 protein, human; D008994:Monoacylglycerol Lipases; D006220:Haloperidol; D000077152:Olanzapine; C004645:canadine
references.citation: Mol Psychiatry. 2007 Jul;12(7):620-9
references.pmid: 17440437
references.citation: Am J Psychiatry. 2011 Sep;168(9):921-9
references.pmid: 21632647
references.citation: Science. 2007 May 25;316(5828):1212-6
references.pmid: 17525344
references.citation: Neuroscience. 2010 Sep 15;169(4):1651-61
references.pmid: 20542094
references.citation: Arch Gen Psychiatry. 2008 Jul;65(7):772-84
references.pmid: 18606950
references.citation: Arch Gen Psychiatry. 2000 Mar;57(3):237-45
references.pmid: 10711910
references.citation: Arch Gen Psychiatry. 1995 Apr;52(4):258-66
references.pmid: 7702443
references.citation: Neurosci Biobehav Rev. 2011 Aug;35(8):1779-87
references.pmid: 21530584
references.citation: J Neurosci. 2010 Oct 20;30(42):13992-4007
references.pmid: 20962221
references.citation: J Neurosci. 2006 May 3;26(18):4740-51
references.pmid: 16672646
references.citation: Am J Psychiatry. 2010 Aug;167(8):987-93
references.pmid: 20478874
references.citation: Neuropsychopharmacology. 2012 May;37(6):1357-66
references.pmid: 22218091
references.citation: Neuroscience. 2011 Feb 3;174:50-63
references.pmid: 21035522
references.citation: Psychol Med. 2012 Jun;42(6):1321-8
references.pmid: 21999906
references.citation: Am J Psychiatry. 2008 Apr;165(4):479-89
references.pmid: 18281411
references.citation: Neuroscience. 2008 Apr 9;152(4):1032-9
references.pmid: 18343585
references.citation: Biol Psychiatry. 2005 Mar 15;57(6):594-608
references.pmid: 15780846
references.citation: Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
references.pmid: 12184808
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19115-20
references.pmid: 16357196
references.citation: Cereb Cortex. 2012 May;22(5):1215-23
references.pmid: 21810780
references.citation: Am J Psychiatry. 2010 Dec;167(12):1479-88
references.pmid: 21041246
references.citation: J Physiol. 2011 Oct 15;589(Pt 20):4857-84
references.pmid: 21807615
references.citation: Mol Psychiatry. 2007 Sep;12(9):854-69
references.pmid: 17767149
references.citation: J Biol Chem. 2010 Jan 8;285(2):1358-70
references.pmid: 19861414
references.citation: J Lipid Res. 2012 Nov;53(11):2413-24
references.pmid: 22969151
references.citation: Prog Neurobiol. 2011 Jun;94(1):77-90
references.pmid: 21515336
references.citation: Am J Psychiatry. 2010 Dec;167(12):1489-98
references.pmid: 20889653
references.citation: Am J Psychiatry. 2012 Oct;169(10):1082-91
references.pmid: 22983435
references.citation: Neuropsychopharmacology. 2005 Sep;30(9):1649-61
references.pmid: 15756305
references.citation: Nat Neurosci. 2010 Aug;13(8):951-7
references.pmid: 20657592
references.citation: Arch Gen Psychiatry. 2000 Nov;57(11):1061-9
references.pmid: 11074872
references.citation: Am J Psychiatry. 2009 Nov;166(11):1251-7
references.pmid: 19797432
references.citation: J Biol Chem. 2011 Aug 19;286(33):28723-28728
references.pmid: 21665953
references.citation: Schizophr Res. 2012 Aug;139(1-3):157-60
references.pmid: 22727454