Perturbational Profiling of Metabolites in Patient Fibroblasts Implicates α-Aminoadipate as a Potential Biomarker for Bipolar Disorder.
Many studies suggest the presence of aberrations in cellular metabolism in bipolar disorder. We studied the metabolome in bipolar disorder to gain insight into cellular pathways that may be dysregulated in bipolar disorder and to discover evidence of novel biomarkers. We measured polar and nonpolar metabolites in fibroblasts from subjects with bipolar I disorder and matched healthy control subjects, under normal conditions and with two physiologic perturbations: low-glucose media and exposure to the stress-mediating hormone dexamethasone. Metabolites that were significantly different between bipolar and control subjects showed distinct separation by principal components analysis methods. The most statistically significant findings were observed in the perturbation experiments. The metabolite with the lowest p value in both the low-glucose and dexamethasone experiments was α-aminoadipate, whose intracellular level was consistently lower in bipolar subjects. Our study implicates α-aminoadipate as a possible biomarker in bipolar disorder that manifests under cellular stress. This is an intriguing finding given the known role of α-aminoadipate in the modulation of kynurenic acid in the brain, especially as abnormal kynurenic acid levels have been implicated in bipolar disorder.
Center for Experimental Drugs and Diagnostics, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Harvard Medical School and Massachusetts General Hospital, Boston, Mass., USA; Chemical Biology Program, Broad Institute of Harvard and MIT, Mass., USA.
Joanne H
JH
Huang
Center for Experimental Drugs and Diagnostics, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Harvard Medical School and Massachusetts General Hospital, Boston, Mass., USA; Chemical Biology Program, Broad Institute of Harvard and MIT, Mass., USA.
Shaunna S
SS
Berkovitch
Center for Experimental Drugs and Diagnostics, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Harvard Medical School and Massachusetts General Hospital, Boston, Mass., USA; Chemical Biology Program, Broad Institute of Harvard and MIT, Mass., USA.
Jonathan
J
Iaconelli
Center for Experimental Drugs and Diagnostics, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Harvard Medical School and Massachusetts General Hospital, Boston, Mass., USA; Chemical Biology Program, Broad Institute of Harvard and MIT, Mass., USA.
Bradley
B
Watmuff
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Mass., USA.
Hyoungjun
H
Park
MGH Cancer Center, Boston, Mass., USA; Chemical Biology Program, Broad Institute of Harvard and MIT, Mass., USA.
Shrikanta
S
Chattopadhyay
Schizophrenia and Bipolar Disorder Program, Harvard Medical School and McLean Hospital, Belmont, Mass., USA.
Donna
D
McPhie
Schizophrenia and Bipolar Disorder Program, Harvard Medical School and McLean Hospital, Belmont, Mass., USA.
Dost
D
Öngür
Schizophrenia and Bipolar Disorder Program, Harvard Medical School and McLean Hospital, Belmont, Mass., USA.
Bruce M
BM
Cohen
Chemical Biology Program, Broad Institute of Harvard and MIT, Mass., USA.
Clary B
CB
Clish
Center for Experimental Drugs and Diagnostics, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Harvard Medical School and Massachusetts General Hospital, Boston, Mass., USA; Chemical Biology Program, Broad Institute of Harvard and MIT, Mass., USA; Chemical Biology Program, Broad Institute of Harvard and MIT, Mass., USA.
Rakesh
R
Karmacharya
2-Aminoadipate; 2-Aminoadipic acid; Bipolar disorder; Kynurenic acid; Metabolic profiling; α-Aminoadipate