title: Lipidomics reveals early metabolic changes in subjects with schizophrenia: effects of atypical antipsychotics.
abstract: There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease.
authors.affiliation: Duke University Medical Center, Department of Psychiatry and Behavioral Sciences, Durham, North Carolina, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: McEvoy
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Baillie
authors.forename: Hongjie
authors.initials: H
authors.lastname: Zhu
authors.forename: Peter
authors.initials: P
authors.lastname: Buckley
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
authors.forename: Henry A
authors.initials: HA
authors.lastname: Nasrallah
authors.forename: George G
authors.initials: GG
authors.lastname: Dougherty
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Yao
authors.forename: Rima
authors.initials: R
authors.lastname: Kaddurah-Daouk
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005260:Female; D005997:Glycerylphosphorylcholine / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D005997:Glycerylphosphorylcholine
references.citation: Acta Psychiatr Scand. 2008 May;117(5):342-7
references.pmid: 18307585
references.citation: Mol Psychiatry. 2007 Oct;12(10):934-45
references.pmid: 17440431
references.citation: Compr Psychiatry. 1996 Jan-Feb;37(1):68-73
references.pmid: 8770530
references.citation: Arch Gen Psychiatry. 2010 Feb;67(2):146-54
references.pmid: 20124114
references.citation: Neuroscience. 2006;139(4):1397-403
references.pmid: 16600514
references.citation: Schizophr Res. 1998 Apr 10;30(3):193-208
references.pmid: 9589514
references.citation: J Psychopharmacol. 2012 May;26(5 Suppl):33-41
references.pmid: 22472311
references.citation: Psychopharmacol Bull. 1988;24(1):101-4
references.pmid: 3290934
references.citation: J Lipid Res. 2002 Nov;43(11):1809-17
references.pmid: 12401879
references.citation: J Clin Psychiatry. 2007;68 Suppl 14:4-7
references.pmid: 18284271
references.citation: Schizophr Res. 2012 Nov;141(2-3):153-61
references.pmid: 22981812
references.citation: J Clin Psychiatry. 2004;65 Suppl 18:47-56
references.pmid: 15600384
references.citation: J Clin Psychiatry. 2011 Feb;72(2):194-204
references.pmid: 20673553
references.citation: Schizophr Res. 2008 Jul;102(1-3):329-36
references.pmid: 18396386
references.citation: Schizophr Bull. 2009 May;35(3):528-48
references.pmid: 19223657
references.citation: Schizophr Res. 2005 Jul 15;76(2-3):343-51
references.pmid: 15949667
references.citation: Biol Psychiatry. 2003 Jan 1;53(1):56-64
references.pmid: 12513945
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2004 Sep;71(3):171-6
references.pmid: 15253886
references.citation: Neuro Endocrinol Lett. 2012;33(8):736-48
references.pmid: 23391975
references.citation: PLoS One. 2011;6(12):e29662
references.pmid: 22216341
references.citation: Biol Psychiatry. 1998 Aug 15;44(4):243-9
references.pmid: 9715355
references.citation: J Psychiatr Res. 1995 May-Jun;29(3):227-32
references.pmid: 7473298
references.citation: Schizophr Res. 2000 Mar 16;42(1):7-17
references.pmid: 10706981
references.citation: Eur Neuropsychopharmacol. 2006 Apr;16(3):187-94
references.pmid: 16263247
references.citation: Behav Brain Funct. 2012 Dec 10;8:56
references.pmid: 23228189
references.citation: Biol Psychiatry. 1999 Mar 15;45(6):687-93
references.pmid: 10187998
references.citation: Nat Rev Mol Cell Biol. 2008 Feb;9(2):139-50
references.pmid: 18216770
references.citation: Cell Mol Immunol. 2008 Feb;5(1):1-7
references.pmid: 18318989
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30;31(2):469-74
references.pmid: 17184889
references.citation: Lipids. 2001 Mar;36(3):247-54
references.pmid: 11337979
references.citation: Psychiatry Res. 2011 Mar 30;186(1):23-7
references.pmid: 20800904
references.citation: Psychiatry Res. 1993 Oct;49(1):89-95
references.pmid: 8140184
references.citation: Psychiatry Res. 2013 May 15;207(1-2):1-12
references.pmid: 23068078
references.citation: J Clin Psychiatry. 2004 Feb;65(2):267-72
references.pmid: 15003083
references.citation: Psychiatr Clin North Am. 2003 Mar;26(1):85-102
references.pmid: 12683261
references.citation: Psychiatry Res. 2012 Aug 15;198(3):347-52
references.pmid: 22513041
references.citation: J Psychiatr Res. 1994 May-Jun;28(3):239-65
references.pmid: 7932285
references.citation: Med Hypotheses. 1983 Mar;10(3):329-36
references.pmid: 6348496
references.citation: Prostaglandins Leukot Essent Fatty Acids. 1996 Aug;55(1-2):9-15
references.pmid: 8888117
references.citation: Psychiatry Res. 2010 May 30;182(2):180-2
references.pmid: 20413278
references.citation: Mol Psychiatry. 2003 Mar;8(3):316-23, 251
references.pmid: 12660804
references.citation: J Neurochem. 2007 May;101(3):577-99
references.pmid: 17257165
references.citation: J Clin Psychiatry. 1999;60 Suppl 1:4-6; discussion 28-30
references.pmid: 10037163