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Objectives: This study is to find the correlation among BDNF metabolism, early trauma, and current stress status of OCD patients. As well as to study the BDNF metabolism-stress related pathological mechanism in OCD development., Methods: A total of 140 participants were recruited in this study, including 64 drug-naïve OCD patients (OCDs) and 76 healthy controls (HCs). The clinical data of the subjects were measured using YBOCS, CTQ, and PSS. The plasma mBDNF and proBDNF values were measured by ELISA while the M/P ratio was calculated., Results: The mBDNF, proBDNF plasma levels, and M/P ratio of unmedicated OCD individuals decreased evidently comparing with HCs. Also, positive associations were found between PSS and CTQ and between CTQ and M/P ratio. The negative correlation included proBDNF and PSS as well as proBDNF and CTQ. Intermediary analysis generated by SPSS has showed that the perceived stress played a complete mediating role between early trauma and plasma M/P ratio levels, and the mediating effect was 0.043 in non-medication OCD patients., Conclusions: Findings from this study suggested that early trauma experience and stress state work together in regulating BDNF metabolism level in OCD patients. The nucleus accumbens and reward loop are also pivotal in the pathogenesis of OCD., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: Convergent evidence has demonstrated that trait impulsivity, a key feature in obsessive-compulsive disorder (OCD), involves dysregulated frontal-striatal circuits. The present study aims to explore relationships between frontal-striatal circuits, trait impulsivity, and obsessive-compulsive symptoms., Methods: Thirty-six unmedicated patients with OCD and 50 healthy controls (HCs) matched for age, sex, and years of education underwent a magnetic resonance imaging (MRI) procedure. Voxel-wise statistical parametric analysis was used to investigate the differences in resting-state functional connectivity between brain regions functionally connected to six pairs of a-priori defined striatal seed regions, between patients with OCD and HCs. Associations between frontal-striatal connectivity and both trait impulsivity and symptom severity of OCD were analyzed., Results: The results showed altered striatal functional connectivity in OCD group compared to HCs, including increased connectivity of dorsal caudate (DC)-orbitofrontal cortex (OFC), ventral striatum (VS)-OFC, VS-medial prefrontal cortex, and putamen-sensorimotor area, and decreased functional connectivity of DC-anterior cingulate cortex (ACC), putamen-ACC, and putamen-dorsolateral prefrontal cortex (DLPFC). Furthermore, the putamen-DLPFC connectivity was negatively correlated with attentional impulsivity in the OCD group, but showed a positive correlation in HCs., Conclusions: The present findings suggested that dorsal cognitive circuits could reflect the level of inhibitory control, which is balanced with the impulsive drive in healthy controls, but breakdown in OCD. Our findings supported that DLPFC-putamen connectivity underlying trait impulsivity, which were involved in the pathophysiology of OCD. The findings have provided new insights into the neurobiological mechanisms of OCD., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Emerging evidence suggests that obsessive-compulsive disorder (OCD) is caused by a combination of genetic predisposition and environmental factors. In this regard, abnormity of progranulin (PGRN, a key regulator of brain inflammation) and a history of childhood trauma have both been linked to an increased risk of developing OCD. This study is aimed to investigate the association between PGRN and childhood trauma in the development of OCD., Methods: We genotyped four single nucleotide polymorphisms (SNPs) covering PGRN in 484 OCD patients and 368 healthy controls. Among the OCD patients, 335 of them accepted clinical assessments in details. Generalized multifactor dimensionality reduction (GDMR) analysis and a general linear model were used to identify gene-environment interactions. The Braineac expression Quantitative Trait Loci (eQTL) dataset was used to analyze the differences in PGRN expression in various brain regions among different genotypes., Results: Our linkage disequilibrium analysis revealed that rs3859268-rs2879096-rs3785817 combined OCD and control groups constructed one haplotype block. The haplotype analysis suggested that TCA haplotype frequency was associated with the risk of developing OCD (Padj=0.03). The Braineac eQTL database revealed that rs2879096 and rs3785817 might be associated with PGRN expression in the hippocampus (Padj=0.00085, Padj=0.007). Emotional abuse was positively correlated with the obsession subscale and Y-BOCS total scores. Except for common trauma, physical abuse, emotional abuse and sexual trauma were all positively correlated with the BAI and BDI-II scores of OCD patients (all P<0.05). The interaction between emotional abuse and PGRN haplotype was associated with the development of depression symptoms in OCD patients corrected by age (Padj=0.043)., Conclusions: The PGRN gene and childhood trauma may be closely related to the incidence of OCD, and OCD patients who have experienced more childhood trauma may exhibit a more severe clinical symptom. The interaction between PGRN and the early trauma may play a critical role in the development of depression symptom in OCD patients., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest concerning the research, authorship and/or publication of this article., (Copyright © 2019. Published by Elsevier B.V.)