Methods of diagnosing, confirming a diagnosis of, and determining a predisposition for a bipolar disorder in a subject are provided. An amount of at least one of biomarker from the cerebrospinal fluid and/or serum of a subject is measured, for example, isocitric acid. The amount of the at least one biomarker can be compared with a control amount of the at least one biomarker in a corresponding sample collected from a subject without the bipolar disorder. An increase or decrease in the amount of the particular biomarker or biomarkers measured can be indicative that the subject has the bipolar disorder or a predisposition for the bipolar disorder. Methods of identifying a compound for preventing and/or treating a bipolar disorder are also provided based on the expression level of an isocitric acid dehydrogenase 3 alpha and/or beta-subunit gene, and/or based on one or more metabolite biomarker.