Serum Metabolomics Analysis of the At-risk Mental State (ARMS) Group

～ Discovery of several biological substances in the ARMS subjects whose concentrations differ from those in the healthy subjects

A group including Prof. Takeshi Fukushima (Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University), Dr. Naohisa Tsujino (Lecturer, Department of Neuropsychiatry, Faculty of Medicine, Toho University), and Dr. Hiromi Tagata (Assistant Professor, Department of Neuropsychiatry, Toho University) collected 30 μL of serum from each of the 24 subjects in the at-risk mental state (ARMS) group and 23 subjects in the healthy control group who had given written consent to participate in this study. The group then performed serum metabolomics analysis of the collected serum using high-performance liquid chromatography-high-resolution mass spectrometry and found that the serum of the subjects in the ARMS group had different concentrations of several biological substances compared to the serum of the subjects in the healthy control group. This finding is expected to lead to new research into the pathogenesis of ARMS and schizophrenia. These results were published in the journal Early Intervention in Psychiatry on March 28, 2021.

Key Points

Metabolomics analysis revealed that the serum concentrations of inosine and glutamate were increased in the ARMS subjects, whereas those of taurine and lactate were decreased.
This is the first study to perform the serum metabolomics analysis of ARMS subjects.
In the future, the results of this study may be useful for the development of preventive interventions with few side effects for the treatment of patients at the pre-onset stage of schizophrenia.

（スマホで崩れるようなら使用する。）

Dr. Taro Toho, Professor, Department of Environmental Science

Key Pointsテキスト

Figure 1
Volcano plot (ARMS vs HC: Positive mode (a), negative mode (b)). Black: adjusted p-value >.05, |log2FC| .05, |log2FC| > 1. Red: adjusted p-value <.05, |log2FC| < 1. Green: adjusted p-value 1. Point size: variable importance in projection (OPLS-DA model). (a) 1: Glutamate, 2: Taurine, 3: Methylthioribose, 4: Inosine, 5: Ornithine. (b) 1: Lactate, 2: 2,3-Dihydroxypropanoate, 3: Inosine, 4: Citramalate, 5: 2-Isopropyl-3-oxosuccinate. ARMS: at-risk mental state; OPLS-DA, orthogonal partial least-squares discriminant analysis; HC, healthy control

Summary
Schizophrenia is characterized by symptoms, including hallucinations and delusions (positive symptoms), emotional stupor and withdrawal (negative symptoms), and cognitive dysfunction, which occur at the onset of the disease. The prognosis of schizophrenia can be improved by taking the appropriate interventions at the at-risk mental state (ARMS) stage before the onset of psychosis or as early as possible after the onset of the disease.

As psychiatric disorders are mainly diagnosed by the symptoms, there is no objective index that can be expressed in numerical values as can be done for other disease, like hypertension or diabetes, thus making it difficult to detect and intervene in the treatment of the patients who do not present any severe symptoms.

Therefore, this research group aimed at clarifying the specific serum concentrations of substances in the subjects at the ARMS stage, which might aid in the development of improved early interventions strategies for the effective treatment of the patients. Using 30 μL of serum from every subject in the ARMS and the healthy control groups, serum metabolomics analysis was performed using high-performance liquid chromatography-high-resolution mass spectrometry. The group found that the concentrations of several endogenous substances in the serum of the subjects in the ARMS group differed from those in the serum of the subjects in the healthy control group. The results of this study are expected to accelerate the research on the elucidation of the pathogenesis of ARMS, which is largely unknown.

The results of this study will aid in the future development of effective methods of intervention with few side effects for the treatment of patients in the ARMS stage before the onset of schizophrenia.

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