Association between human blood metabolome and the risk of psychiatric disorders

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

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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.

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