Search for serum biomarkers in patients with bipolar disorder and major depressive disorder using metabolome analysis.

Objective: Bipolar disorder (BD) and major depressive disorder (MDD) are two common psychiatric disorders. Due to the overlapping clinical symptoms and the lack of objective diagnostic biomarkers, bipolar disorder (BD) is easily misdiagnosed as major depressive disorder (MDD), which in turn affects treatment decisions and prognosis. This study aimed to investigate biomarkers that could be used to differentiate BD from MDD. Methods: Nuclear magnetic resonance (NMR) spectroscopy was performed to assess serum metabolic profiles in depressed patients with BD (n = 59), patients with MDD (n = 14), and healthy controls (n = 10). Data was analyzed using partial least squares discriminant analysis, orthogonal partial least squares discriminant analysis and t-tests. Different metabolites (VIP > 1 and p < 0.05) were identified and further analyzed using Metabo Analyst 5.0 to identify relevant metabolic pathways. Results: The metabolic phenotypes of the BD and MDD groups were significantly different from those of the healthy controls, and there were different metabolite differences between them. In the BD group, the levels of 3-hydroxybutyric acid, n-acetyl glycoprotein, ß-glucose, pantothenic acid, mannose, glycerol, and lipids were significantly higher than those in the healthy control group, and the levels of lactate and acetoacetate were significantly lower than those in the healthy control group. In the MDD group, the levels of 3-hydroxybutyric acid, n-acetyl glycoprotein, pyruvate, choline, acetoacetic acid, and lipids were significantly higher than those of healthy controls, and the levels of acetic acid and glycerol were significantly lower than those of healthy controls. Conclusion: Glycerolipid metabolism is significantly involved in BD and MDD. Pyruvate metabolism is significantly involved in MDD. Pyruvate, choline, and acetate may be potential biomarkers for MDD to distinguish from BD, and pantothenic acid may be a potential biomarker for BD to distinguish from MDD.

Altered Metabolomics in Bipolar Depression With Gastrointestinal Symptoms.

Objective: Although gastrointestinal (GI) symptoms are very common in patients with bipolar disorder (BD), Few studies have researched the pathomechanism behind these symptoms. In the present study, we aim at elucidate the pathomechanism of GI symptoms in BD through metabolomic analysis. Method: BD patients were recruited from Shanxi Bethune Hospital that divided into two groups, each group assessed with the 24-item Hamilton Depression Rating Scale (HAMD-24) according to the presence or absence of GI symptoms. Healthy controls were recruited from the medical examination center of the same hospital. Differential metabolites were identified and further analyzed using Metabo Analyst 3.0 to identify associated metabolic pathways. Results: There were significantly higher HAMD-24 scores in the GI symptoms group than that of non-GI symptoms group (p = 0.007). Based on metabolomic analysis results, we found that the common disturbances metabolic pathway of both two patients groups was ketone body metabolism, and the unique disturbances metabolic pathways of BD with GI symptoms were fatty acid biosynthesis and tyrosine metabolism, and these changes were independent of dietary habits. Conclusion: BD patients with GI symptoms exhibited disturbances in fatty acid and tyrosine metabolism, perhaps suggesting that the GI symptoms in BD patients are related to disturbances of the gut microbiome. Both groups of patients jointly exhibit disturbances of ketone body metabolism, which may serve as a biomarker for the pathogenesis of BD patients.

Altered resting-state functional connectivity of the insula in individuals with clinical high-risk and patients with first-episode schizophrenia.

OBJECTIVES: Abnormalities in insular functional connectivity have been implicated in many clinical features of schizophrenia. The aim of this study was to determine to what degree such abnormalities occur in individuals with clinical high risk for psychosis (CHR), and whether which is associated with symptom severity. METHODS: Resting-state fMRI data were collected from 47 healthy controls, 24 CHR individuals and 19 patients with first-episode schizophrenia. Using the posterior, dorsal and ventral insular subregions as separate seeds, we examined resting-state functional connectivity differences between different groups and the association between concurrent symptom severity and dysconnectivity. RESULTS: Compared with healthy controls, both CHR individuals and schizophrenia patients showed hypoconnectivity between posterior insula (PI) and somatosensory areas, and between dorsal anterior insula (dAI) and putamen. Schizophrenia patients also showed dAI and ventral anterior insula(vAI) hyperconnectivity with visual areas relative to controls and CHR individuals. Correlation analysis revealed that dAI functional connectivity with superior temporal gyrus was positively correlated with positive symptoms of CHR, and vAI connectivity with dorsolateral prefrontal cortex was negatively correlated with the severity of the symptoms of first-episode schizophrenia. CONCLUSIONS: Our findings suggest that insular functional dysconnectivity with the sensory cortex may be a system-level neural substrate preceding the onset of psychosis.

Differential of Frequency and Duration Mismatch Negativity and Theta Power Deficits in First-Episode and Chronic Schizophrenia.

Background: Due to its impairment in patients with schizophrenia, mismatch negativity (MMN) generation has been identified as a potential biomarker for identifying primary impairments in auditory sensory processing. This study aimed to investigate the dysfunctional differences in different MMN deviants and evoked theta power in patients with first-episode schizophrenia (FES) and chronic schizophrenia (CS). Methods: We measured frequency and duration MMN from 40 FES, 40 CS, and 40 healthy controls (HC). Evoked theta power was analyzed by event-related spectral perturbation (ERSP) approaches. Results: Deficits in duration MMN were observed in both FES (p = 0.048, Bonferroni-adjusted) and CS (p < 0.001, Bonferroni-adjusted). However, deficits in frequency MMN were restricted to the CS (p < 0.001, Bonferroni-adjusted). Evoked theta power deficits were observed in both patient groups when compared with the HC (p FES = 0.001, p CS < 0.001, Bonferroni-adjusted), yet no significant differences were found between FES and CS. Frequency MMN was correlated with the MATRICS consensus cognitive battery (MCCB) combined score (r = -0.327, p < 0.05) and MCCB verbal learning (r = -0.328, p < 0.05) in FES. Evoked theta power was correlated with MCCB working memory in both FES (r = 0.347, p < 0.05) and CS (r = 0.408, p < 0.01). Conclusion: These findings suggest that duration MMN and evoked theta power deficits may be more sensitive for detection of schizophrenia during its early stages. Moreover, frequency MMN and theta power could potentially linked to poor cognitive functioning in schizophrenic patients. The findings mentioned above indicated that the neural mechanisms of the three indexes may vary between people.