Biomarkers for Differentiating Bipolar Disorder From Schizophrenia

In Brazil, researchers assessed blood serum identified with the use of proton nuclear magnetic resonance spectroscopy in an effort to differentiate individuals with psychiatric disorders, including schizophrenia and bipolar disorder.

Blood serum metabolomics identified with the use of proton nuclear magnetic resonance (NMR) spectroscopy has enabled the discrimination of individuals with psychiatric disorders, including schizophrenia and bipolar disorder, according to the Brazilian cross-sectional study results published in the Journal of Psychiatric Research.

Recognizing that the underlying pathophysiology of schizophrenia and bipolar disorder remains largely unknown, the investigators sought to verify whether the metabolomics approach, according to proton NMR (1H NMR) analysis of patients’ blood serum samples, would have the ability to allow the correct, precise discrimination of individuals into 3 distinct groups: (1) schizophrenia, (2) bipolar disorder, and (3) healthy controls. In the study, researchers used 1H NMR data treated by chemometrics, principal component analysis, and supervised partial least-squares discriminant analysis to identify those metabolites that are present only in patients with schizophrenia or only in patients with bipolar disorder.

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A total of 54 patients with schizophrenia and 68 patients with bipolar disorder type 1 were enrolled in the study. The patients were between age 18 and 65 years. For psychiatric diagnosis assessment, all patients underwent a clinical interview in which trained psychiatrists applied the Structured Clinical Interview for Axis-1 (SCID-1), according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition. In addition, investigators evaluated patients with schizophrenia using the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale. For inclusion in the schizophrenia group, the researchers required severe symptoms to be maintained for a minimum time of 6 months. Moreover, they assessed manic and depressive symptom severities via the use of the Young Mania Rating Scale and the Hamilton Depression Rating Scale-17, respectively. All patients from both the schizophrenia and the bipolar disorder groups were being treated with a stable medication regimen (ie, taking the same medication at the same dose for a minimum of 2 months before inclusion in the analysis).

Included in the control group were 60 healthy volunteers with no current or lifelong history of mental disorders according to the SCID-1, no history of prescribed psychotropic medications, and a negative family history of a major psychiatric disorder.

Investigators identified the presence of 2,3-diphospho-D-glyceric acid, N-acetyl aspartyl-glutamic acid, and monoethyl malonate only in patients with bipolar disorder. In contrast, they observed the presence of isovaleryl carnitine, pantothenate, mannitol, glycine, and gamma aminobutyric acid only in patients with schizophrenia.

Study limitations include the fact that the small sample size prevented subgroup analysis, including for ethnicity influence. Furthermore, all patients with schizophrenia and bipolar disorder were taking medication, which may be a potential confounder: Though the influence of the medications in the Principal Component

Analysis demonstrated only a statistically nonsignificant tendency toward clustering.

The investigators concluded that the biomarkers that were identified in this study will contribute strongly to supporting the diagnosis of these psychiatric disorders in the future.


Tasic L, Larcerda ALT, Pontes JGM, et al. Peripheral biomarkers allow differential diagnosis between schizophrenia and bipolar disorder. J Psychiatr Res. 2019;119:67-75.