Methods of diagnosing bipolar disorders and screening for therapeutic compounds

A method of treating a bipolar disorder in a subject, the method comprising:

• collecting, from the subject, a cerebrospinal fluid sample, a serum sample, or both a cerebrospinal fluid sample and a serum sample, wherein the cerebrospinal fluid sample comprises at least one biomarker selected from the group consisting of isocitric acid and cis-aconitic acid, and wherein the serum sample comprises at least one biomarker selected from the group consisting of N-acetylglutamic acid, 2-oxoglutaric acid, and serine;
• measuring an amount of the at least one biomarker in one or both of the cerebrospinal fluid sample and the serum sample collected from the subject;
• comparing the amount of the at least one biomarker in one or both of the cerebrospinal fluid sample and the serum sample collected from the subject with a control amount of the at least one biomarker in a corresponding sample collected from a subject without the bipolar disorder, wherein an increase in the amount of isocitric acid, an increase in the amount of cis-aconitic acid, an increase in the amount of N-acetylglutamic acid, an increase in the amount of 2-oxoglutaric acid, and a decrease in the amount of serine, in comparison to the control amount of the at least one biomarker are indicative that the subject has the bipolar disorder or a predisposition for the bipolar disorder;
• and
• administering at least one bipolar medication selected from the group consisting of lithium, valproic acid, carbamazepine, oxcarbazepine, lamotrigine, lurasidone, divalproex, and a salt of lurasidone to the subject, and
• wherein:
• the at least one biomarker of the serum sample further comprises at least one further biomarker selected from the group consisting of pyruvic acid, β-alanine, arginine, uric acid, and citric acid, and
• wherein the method further comprises:
• measuring an amount of at least one further biomarker in the serum sample collected from the subject;
• and
• comparing the amount of the at least one further biomarker with a control amount of the at least one further biomarker in a corresponding sample collected from a subject without the bipolar disorder,
• wherein an increase in the amount of pyruvic acid, a decrease in the amount of β-alanine, a decrease in the amount of arginine, an increase in the amount of uric acid, and a decrease in the amount of citric acid, in comparison to the control amount of the at least one biomarker are indicative that the subject has the bipolar disorder or a predisposition for the bipolar disorder and wherein a) both the cerebrospinal fluid sample and the serum sample are collected from the subject, and wherein the following biomarkers are measured in combination:
• isocitric acid;
• cis-aconitic acid;
• serine;
• uric acid;
• and
• citric acid;
• or b) wherein the serum sample is collected from the subject, and wherein the following biomarkers are measured in combination:
• pyruvic acid;
• N-acetylglutamic acid;
• 2-oxoglutaric acid;
• β-alanine;
• arginine;
• and
• serine.