The impact of childhood trauma on thalamic functional connectivity in patients with obsessive-compulsive disorder.

BACKGROUND: Childhood trauma is a vulnerability factor for the development of obsessive-compulsive disorder (OCD). Empirical findings suggest that trauma-related alterations in brain networks, especially in thalamus-related regions, have been observed in OCD patients. However, the relationship between childhood trauma and thalamic connectivity in patients with OCD remains unclear. The present study aimed to examine the impact of childhood trauma on thalamic functional connectivity in OCD patients. METHODS: Magnetic resonance imaging resting-state scans were acquired in 79 patients with OCD, including 22 patients with a high level of childhood trauma (OCD_HCT), 57 patients with a low level of childhood trauma (OCD_LCT) and 47 healthy controls. Seven thalamic subdivisions were chosen as regions of interest (ROIs) to examine the group difference in thalamic ROIs and whole-brain resting-state functional connectivity (rsFC). RESULTS: We found significantly decreased caudate-thalamic rsFC in OCD patients as a whole group and also in OCD_LCT patients, compared with healthy controls. However, OCD_HCT patients exhibited increased thalamic rsFC with the prefrontal cortex when compared with both OCD_LCT patients and healthy controls. CONCLUSIONS: Taken together, OCD patients with high and low levels of childhood trauma exhibit different pathological alterations in thalamic rsFC, suggesting that childhood trauma may be a predisposing factor for some OCD patients.

QEEG Biomarkers for ECT Treatment Response in Schizophrenia.

Background: Electroconvulsive therapy (ECT) is a clinically effective treatment for schizophrenia (SZD). However, studies have shown that only about 50 to 80% of patients show response to ECT. To identify the most suitable patients for ECT, developing biomarkers predicting ECT response remains an important goal. This study aimed to explore the quantitative electroencephalography (QEEG) biomarkers to predict ECT efficacy. Methods: Thirty patients who met DSM-5 criteria for SZD and had been assigned to ECT were recruited. 32-lead Resting-EEG recordings were collected one hour before the initial ECT treatment. Positive and negative symptoms scale (PANSS) was assessed at baseline and after the eighth ECT session. EEG data were analyzed using mutual information. Results: In the brain network density threshold range of 0.05 to 0.2, the assortativity of the right temporal, right parietal, and right occipital cortex in the response group was significantly higher than that in the non-response group (p < .05) in the beta band. In the theta band, the left frontal, parietal, right occipital cortex, and central area assortativity were higher in the response group than in the non-response group (p < .05). Conclusions: QEEG might be a useful approach to identify the candidate biomarker for ECT in clinical practice.

Resting state functional brain imaging in obsessive-compulsive disorder across genders.

OBJECTIVES: Epidemiological and clinical gender differences in obsessive-compulsive disorder (OCD) have been reported; however, gender differences in brain functional connectivity and the relationship between resting brain functional imaging and clinical symptoms has not been studied in OCD. METHODS: A total of 62 drug-naive patients with OCD (31 males, 31 females) and 60 healthy controls (HCs) (30 males, 30 females) matched for age, sex, and education underwent magnetic resonance imaging. Amplitude of low-frequency fluctuations (ALFF) over the whole brain and seed-based connectivity analyses were evaluated to examine the intrinsic cerebral activity of the subjects. Additionally, associations between functional connectivity and clinical features were analysed. RESULTS: Compared to male OCD (mOCD) patients, female OCD (fOCD) patients showed higher ALFF values in the right parahippocampal gyrus. Compared to HCs, fOCD patients showed significantly decreased functional connectivity between the right parahippocampal gyrus and whole brain to the right posterior central gyrus/precentral gyrus/superior temporal gyrus/barycentric lobule and left anterior cuneus. Abnormal functional connectivity was negatively correlated with the Yale-Brown Obsessive-Compulsive Scale, Beck Depression Inventory-II, and Beck Anxiety Inventory total scores. CONCLUSIONS: Our results suggest that the right parahippocampal gyrus, which is related to executive control and emotional regulation, may show gender differences in OCD.

Intermediation of perceived stress between early trauma and plasma M/P ratio levels in obsessive-compulsive disorder patients.

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.

Impaired cortico-striatal functional connectivity is related to trait impulsivity in unmedicated patients with obsessive-compulsive disorder.

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.

Interaction between PGRN gene and the early trauma on clinical characteristics in patients with obsessive-compulsive disorder.

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.