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The objective of the study was to explore the potential value of plasma indicators for identifying amnesic mild cognitive impairment (aMCI) and determine whether levels of plasma indicators are related to the performance of cognitive function and brain tissue volumes. In total, 155 participants (68 aMCI patients and 87 health controls) were recruited in the present cross-sectional study. The levels of plasma amyloid-β (Aβ) 40, Aβ42, total tau (t-tau), and neurofilament light (NFL) were measured using an ultrasensitive quantitative method. Machine learning algorithms were performed for establishing an optimal model of identifying aMCI. Compared with healthy controls, Aβ40 and Aβ42 levels were lower and NFL levels were higher in plasma of aMCI patients with an exception of t-tau levels. In aMCI patients, the higher plasma Aβ40 levels were correlated with the impaired episodic memory and negative correlations were observed between plasma t-tau levels and global cognitive function and gray matter (GM) volume. In addition, the higher plasma NFL levels were correlated with reduced hippocampus volume and total GM volume of the left inferior and middle temporal gyrus. An integrated model included clinical features, hippocampus volume, and plasma Aβ42 and NFL and had the highest accuracy for detecting aMCI patients (accuracy, 74.2%). We demonstrated that plasma Aβ40, Aβ42, t-tau, and NFL may be useful to identify aMCI and correlate with cognitive decline and brain atrophy. Among these plasma indicators, Aβ42 and NFL are more valuable as key members of a peripheral biomarker panel to detect aMCI.

Background circular RNAs (circRNAs) are expressed abundantly in the brain and are implicated in the pathophysiology of neuropsychiatric disease. However, the potential clinical value of circRNAs in major depressive disorder (MDD) remains unclear. Methods RNA sequencing was conducted in whole-blood samples in a discovery set (7 highly homogeneous MDD patients and 7 matched healthy controls [HCs]). The differential expression of circRNAs was verified in an independent validation set. The interventional study was conducted to assess the potential effect of the antidepressive treatment on the circRNA expression. Findings in the validation set, compared with 52 HCs, significantly decreased circFKBP8 levels (Diff: -0.24; [95% CI -0.39 ~ -0.09]) and significantly elevated circMBNL1 levels (Diff: 0.37; [95% CI 0.09 ~ 0.64]) were observed in 53 MDD patients. The expression of circMBNL1 was negatively correlated with 24-item Hamilton Depression Scale (HAMD-24) scores in 53 MDD patients. A mediation model indicated that circMBNL1 affected HAMD-24 scores through a mediator, serum brain-derived neurotrophic factor. In 53 MDD patients, the amplitude of low-frequency fluctuations in the right orbital part middle frontal gyrus was positively correlated with circFKBP8 and circMBNL1 expression. Furthermore, the interventional study of 53 MDD patients demonstrated that antidepressive treatment partly increased circFKBP8 expression and the change in expression of circFKBP8 was predictive of further reduced HAMD-24 scores. Interpretation whole-blood circFKBP8 and circMBNL1 may be potential biomarkers for the diagnosis of MDD, respectively, and circFKBP8 may show great potential for the antidepressive treatment.

Background: Altered resting-state functional connectivity of the cerebellum in obsessive-compulsive disorder (OCD) has been previously reported. However, the previous study investigating cerebellar–cerebral functional connectivity relied on a priori –defined seeds from specific networks. In this study, we aimed to explore the connectivity alterations of the cerebellum in OCD under resting-state conditions with a hypothesis-free approach. Methods: Thirty patients with OCD and 26 healthy controls (HCs) underwent functional magnetic resonance imaging (fMRI) scanning at resting state. Regional cerebral function was evaluated by measuring the fraction of amplitude of low-frequency fluctuation (fALFF). Regions with mean fALFF (mfALFF) alterations were used as seeds in seed correlation analysis (SCA). An independent samples t test was used to compare the differences in mfALFF and functional connection (FC) between the two groups. Pearson correlation analysis was performed to identify the association between functional neural correlates and OCD symptom severity evaluated using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Results: Compared with the HC group, the OCD group showed significantly increased mfALFF values in bilateral cerebellar. The results of FC analysis showed weakened connectivity among the left Crus II, lobule VIII, and right striatum and between the right lobule VIII and the right striatum, and cingulate in the OCD group compared with the HC group. Some of the abovementioned results were associated with symptom severity. Conclusions: OCD patients showed abnormal spontaneous cerebellar activity and weakened functional connectivity between the cerebellum and the cortico-striato-thalamo-cortical (CSTC) circuit (striatum and cingulate), suggesting that the cerebellum may play an essential role in the pathophysiology of OCD.

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