Association between human blood metabolome and the risk of psychiatric disorders

Schizophrenia BulletinScott Cunningham MD PhD, et al. | September 21, 2022



Identification of biomarkers for psychiatric disorders will make diagnosis more objective than at the present, which often is based on the subjective interpretation of clinical symptoms.

In the current study, 8 such metabolic biomarkers were identified that could serve as treatment targets, 4 of which had no predicted side effects.

Ninety-two blood metabolites from 3 genome-wide association studies involving 147,827 patients were evaluated.

Mendelian randomization analyses were used to determine the association of blood metabolites with bipolar disorder, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, major depressive disorder, schizophrenia, panic disorder, autistic spectrum disorder, and anorexia nervosa based on data from 1,143,340 participants in the Psychiatric Genomics Consortium.

Phenome-wide Mendelian randomization was used to predict side effects of metabolite targeted therapy.

Five known and 3 novel metabolites were shown to be associated with psychiatric disorders.

Specifically, among the known metabolites, N-acetylornithine was associated bipolar disorder and schizophrenia, glycine was associated with bipolar disorder, docosahexaenoic acid was associated with major depressive disorder, 3-lhydroxybutyrate was associated with major depressive disorder, and butyrylcarnitine was associated with schizophrenia.

Among the novel metabolites, 1-arachidonoylglycerophosphocholine was associated with bipolar disorder, glycoproteins were associated with bipolar disorder, and sphingomyelins were associated with anorexia nervosa.

Targeting glycine, 3-hydroxybutyrate, N-acetylornithine, and butyrylcarnitine for treatment had no predicted side effects.