High throughput lipidomic profiling of schizophrenia and bipolar disorder brain tissue reveals alterations of free fatty acids, phosphatidylcholines, and ceramides.
A mass spectrometry based high throughput approach was employed to profile white and gray matter lipid levels in the prefrontal cortex (Brodmann area 9) of 45 subjects including 15 schizophrenia and 15 bipolar disorder patients as well as 15 controls samples. We found statistically significant alterations in levels of free fatty acids and phosphatidylcholine in gray and white matter of both schizophrenia and bipolar disorder samples compared to controls. Also, ceramides were identified to be significantly increased in white matter of both neuropsychiatric disorders as compared to control levels. The patient cohort investigated in this study includes a number of drug naive as well as untreated patients, allowing the assessment of drug effects on lipid levels. Our findings indicate that while gray matter phosphatidylcholine levels were influenced by antipsychotic medication, this was not the case for phosphatidylcholine levels in white matter. Changes in free fatty acids or ceramides in either white or gray matter also did not appear to be influenced by antipsychotic treatment. To assess lipid profiles in the living patient, we also profiled lipids of 40 red blood cell samples, including 7 samples from drug naive first onset patients. We found significant alterations in the concentrations of free fatty acids as well as ceramide. Overall, our findings suggest that lipid abnormalities may be a disease intrinsic feature of both schizophrenia and bipolar disorder reflected by significant changes in the central nervous system as well as peripheral tissues.
Schwarz
Emanuel
E
Institute of Biotechnology, University of Cambridge, Cambridge CB2 1QT, United Kingdom.
Prabakaran
Sudhakaran
S
Whitfield
Phil
P
Major
Hilary
H
Leweke
F M
FM
Koethe
Dagmar
D
McKenna
Peter
P
Bahn
Sabine
S
D000328:Adult; D014150:Antipsychotic Agents / Q000737:chemistry / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism*; D001923:Brain Chemistry; D002518:Ceramides / Q000032:analysis*; D005230:Fatty Acids, Nonesterified / Q000032:analysis*; D005260:Female; D006801:Humans; D008055:Lipids / Q000032:analysis*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000032:analysis*; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*
D014150:Antipsychotic Agents; D002518:Ceramides; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D010713:Phosphatidylcholines; D017382:Reactive Oxygen Species