Altered resting-state cerebellar-cerebral functional connectivity in obsessive-compulsive disorder.

BACKGROUND: The role of the cerebellum in obsessive-compulsive disorder (OCD) has drawn increasing attention. However, the functional connectivity between the cerebellum and the cerebral cortex has not been investigated in OCD, nor has the relationship between such functional connectivity and clinical symptoms. METHODS: A total of 27 patients with OCD and 21 healthy controls (HCs) matched on age, sex and education underwent magnetic resonance imaging (MRI). Seed-based connectivity analyses were performed to examine differences in cerebellar-cerebral connectivity in patients with OCD compared with HCs. Associations between functional connectivity and clinical features in OCD were analyzed. RESULTS: Compared with HCs, OCD patients showed significantly decreased cerebellar-cerebral functional connectivity in executive control and emotion processing networks. Within the OCD group, decreased functional connectivity in an executive network spanning the right cerebellar Crus I and the inferior parietal lobule was positively correlated with symptom severity, and decreased connectivity in an emotion processing network spanning the left cerebellar lobule VI and the lingual gyrus was negatively correlated with illness duration. CONCLUSIONS: Altered functional connectivity between the cerebellum and cerebral networks involved in cognitive-affective processing in patients with OCD provides further evidence for the involvement of the cerebellum in the pathophysiology of OCD, and is consistent with impairment in executive control and emotion regulation in this condition.

The right thalamic glutamate level correlates with functional connectivity with right dorsal anterior cingulate cortex/middle occipital gyrus in unmedicated obsessive-compulsive disorder: A combined fMRI and 1H-MRS study.

OBJECTIVE: The imbalance in neurotransmitter and neuronal metabolite concentration within cortico-striato-thalamo-cortical (CSTC) circuit contributes to obsessive-compulsive disorder's (OCD) onset. Previous studies showed that glutamate mediated upregulation of resting-state activity in healthy people. However, there have been few studies investigating the correlational features between functional and neurochemical alterations in OCD. METHODS: We utilize a combined resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy (1H-MRS) approach to investigate the altered functional connectivity (FC) in association with glutamatergic dysfunction in OCD pathophysiology. Three regions of interest are investigated, i.e., medial prefrontal cortex and bilateral thalamus, for seed-based whole-brain FC analysis as well as MRS data acquisition. There are 23 unmedicated adult OCD patients and 23 healthy controls recruited for brain FC analysis. Among them, 12 OCD and 8 controls are performed MRS data acquisition. RESULTS: Besides abnormal FC within CSTC circuit, we also find altered FCs in large-scale networks outside CSTC circuit, including occipital area and limbic and motor systems. The decreased FC between right thalamus and right middle occipital gyrus (MOG) is correlated with glutamatergic signal within right thalamus in OCD patients. Moreover, the FC between right thalamus and right dorsal anterior cingulate cortex (dACC) is associated with glutamate level in right thalamus, specifically in patient's group. Finally, the FC between right thalamus and right MOG is correlated with patient's Yale-Brown Obsessive Compulsive Scale (YBOCS) compulsion and total scores, while the right thalamic glutamatergic signal is associated with YBOCS-compulsion score. CONCLUSION: Our findings showed that the coupled intrinsic functional-biochemical alterations existed both within CSTC circuit and from CSTC to occipital lobe in OCD pathophysiology.

Depression Induced by Total Mastectomy, Breast Conserving Surgery and Breast Reconstruction: A Systematic Review and Meta-analysis.

BACKGROUND: To carry out a systematic review and meta-analysis of the literature to determine whether different type of surgery induces different depression occurrence in female breast cancer at mean time more than 1-year term postoperatively. METHODS: A systematic literature search of PubMed, Web of Science, EMBASE, OvidSP, EBSCO and PsycARTICLES was conducted. Observational clinical studies that compared the depression incidence in different surgery groups and presented empirical findings were selected. RESULTS: Sixteen studies met the inclusion criteria, including 5, 4, 2 and 5 studies compared depression between total mastectomy (TM) and breast conserving therapy (BCS), TM and breast reconstruction (BR), BCS and BR, or among all three groups (TM, BCS and BR), respectively. Only 1 of 5 studies, which subjected to multivariate analysis of depression in female breast cancer, reported a statistically significant effect of type of surgery on depression occurrence. Our meta-analysis showed no significant differences among the three types of surgery, with BCS patients versus TM patients (relative risk [RR] = 0.89, 95% confidence interval [CI] 0.78-1.01; P = 0.06), BR patients versus TM patients (RR = 0.87, 95% CI 0.71-1.06; P = 0.16) and BCS patients versus BR patients (RR = 1.10; 95% CI 0.89-1.35; P = 0.37), respectively. CONCLUSIONS: Our study showed that there were no statistically significant differences concerning the occurrence of depressive symptoms in breast cancer patients as a consequence of TM, BCS or BR at mean time more than 1-year term postoperatively.

Correction to: Depression Induced by Total Mastectomy, Breast Conserving Surgery and Breast Reconstruction: A Systematic Review and Meta-analysis.

The following grant funding information was omitted from the original article.

Blood-based dynamic genomic signature for obsessive-compulsive disorder.

No biologically based diagnostic criteria are in clinical use today for obsessive-compulsive disorder (OCD), schizophrenia, and major depressive disorder (MDD), which are defined with reference to Diagnostic and Statistical Manual clinical symptoms alone. However, these disorders cannot always be well distinguished on clinical grounds and may also be comorbid. A biological blood-based dynamic genomic signature that can differentiate among OCD, MDD, and schizophrenia would therefore be of great utility. This study enrolled 77 patients with OCD, 67 controls with no psychiatric illness, 39 patients with MDD, and 40 with schizophrenia. An OCD-specific gene signature was identified using blood gene expression analysis to construct a predictive model of OCD that can differentiate this disorder from healthy controls, MDD, and schizophrenia using a logistic regression algorithm. To verify that the genes selected were not derived as a result of chance, the algorithm was tested twice. First, the algorithm was used to predict the cohort with true disease/control status and second, the algorithm predicted the cohort with disease/control status randomly reassigned (null set). A six-gene panel (COPS7A, FKBP1A, FIBP, TP73-AS1, SDF4, and GOLGA8A) discriminated patients with OCD from healthy controls, MDD, and schizophrenia in the training set (with an area under the receiver-operating-characteristic curve of 0.938; accuracy, 86%; sensitivity, 88%; and specificity, 85%). Our findings indicate that a blood transcriptomic signature can distinguish OCD from healthy controls, MDD, and schizophrenia. This finding further confirms the feasibility of using dynamic blood-based genomic signatures in psychiatric disorders and may provide a useful tool for clinical staff engaged in OCD diagnosis and decision making.

Clinical factors and incidence of prolonged fever in neurosurgical patients.

AIMS AND OBJECTIVES: To describe the incidence of prolonged fever in patients admitted to the neurosurgery department, and the corresponding risk indicators. BACKGROUND: Prolonged fever was defined as a temperature higher than 38·3°C lasting more than five days. Prolonged fever is a common phenomenon and could lead to worsened outcomes in specific patient groups, especially for those with brain injury. However, the studies on prolonged fever in neurosurgical patients are limited and insufficient. DESIGN: A retrospective observational study. METHODS: Retrospective data were collected from 1 January 2014 to 31 December 2014, at the neurosurgical department of a large teaching hospital. We performed univariate and multivariate analyses to identify independent indicators for prolonged fever vs. short-term fever. RESULTS: Among 2845 patients, prolonged fever occurred in 466 (16%). The older patients were associated with longer duration of mechanical ventilation and hospital stay. It predominantly occurred in patients with subarachnoid haemorrhage (SAH) and traumatic brain injury. Patients receiving antibiotic treatment tended to manifest prolonged fever more frequently. Multivariate analysis revealed that the use of antibiotics, central venous catheter and prolonged mechanical ventilation were independent risk predictors for prolonged fever. Patients diagnosed with brain tumour seemed to be not associated with prolonged fever. CONCLUSIONS: Prolonged fever is the common complication in neurosurgical patients. The risks of prolonged fever in patients are attributed to antibiotic therapy, use of central venous catheter and prolonged mechanical ventilation. Indicators of prolonged fever are helpful for better identification of high-risk patients and fever control. RELEVANCE TO CLINICAL PRACTICE: A better reveal on the epidemiology and predictable factors of prolonged fever in neurosurgical patients will provide a better understanding on those patients who are most at risk, and therefore contribute to fever control and better outcome.

Psychometric Properties of the Chinese Version of the Eating Attitudes Test in Young Female Patients with Eating Disorders in Mainland China.

The study aimed to investigate the reliability and validity of the Chinese version of the eating attitudes test (EAT-26) among female adolescents and young adults in Mainland China. This scale was administered to 396 female eating disorder patients and 406 noneating disorder healthy controls, in addition 35 healthy controls completed a retest after a 4-week intervals. Tests for reliability, convergent validity and receiver operating characteristic analysis were performed to detect the psychometric properties. The EAT-26 demonstrated good internal consistency (Cronbach's alpha = 0.822-0.922), test-retest reliability (interclass correlation coefficient = 0.817) and convergent validity(r = 0.450-0.750). The receiver operating characteristic analysis showed that the cut-off 14 for anorexia nervosa and 15 for bulimia nervosa represented good compromises with approximate sensitivity (0.66-0.68) and specificity (0.85-0.86). Our findings provided evidence that the Chinese version of the EAT-26 was a psychometrically reliable and valid self-rating instrument for identifying people suffering from an eating disorder in Mainland China. A clinical cut-off range between 14 and 15 could be used, but caution should be exercised because of the low sensitivity of the tool. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Altered intrinsic insular activity predicts symptom severity in unmedicated obsessive-compulsive disorder patients: a resting state functional magnetic resonance imaging study.

BACKGROUND: Previous neuroimaging data indicated that the dysfunction in cortico-striato-thalamo-cortical (CSTC) circuit contributed to the neuropathological mechanism of obsessive-compulsive disorder (OCD). Whereas, emerging work has shown that the pathophysiology of OCD might be related to more widely distributed large-scale brain systems including limbic system and the salience network. This study aims to investigate the aberrant spontaneous neuronal activity within the whole brain, and its association with the symptom severity for unmedicated OCD patients. METHOD: Twenty-eight unmedicated OCD adults and twenty-eight matched healthy controls were recruited for a resting state functional magnetic resonance imaging (fMRI) study. The amplitude of low-frequency fluctuation (ALFF) analysis over whole brain was performed to examine the intrinsic cerebral activity of subjects. In addition, we conducted the voxel-based Pearson's correlative analysis to probe into the relationship between ALFF values and symptom severity for OCD patients. RESULTS: Our results showed that OCD patients had increased ALFF measures in the left frontopolar cortex and left orbital frontal cortex (OFC), with decreased ALFF values in the right insula. Moreover, the right insular intrinsic activity was significantly correlated with total YBOCS score (r = 0.611, p = 0.002) and compulsion score (r = 0.640, p = 0.001) for OCD patients. CONCLUSION: The results showed abnormal intrinsic neuronal activity within CSTC circuit and salience network of OCD patients. Our finding of aberrant insular activity advanced the understanding of OCD pathophysiology beyond the traditional CSTC circuit. To the best of our knowledge, it is the first finding about a reduced insular activity at the resting state for unmedicated OCD patients, which might serve as an informative biomarker for OCD pathophysiology.

Differential expression profile of urinary exosomal microRNAs in patients with mesangial proliferative glomerulonephritis.

OBJECTIVE: To investigate the differential expression profile of urinary exosomal microRNA (miRNA) in patients with mesangial proliferative glomerulonephritis (MsPGN) and healthy controls and their potential role in the pathogenesis of MsPGN. METHODS: Urine specimens were collected from five MsPGN patients and five healthy controls, and differentially expressed miRNAs were screened using high-throughput sequencing technology. The sequenced urinary exosomal miRNAs were further investigated by quantitative real-time polymerase chain reaction (qRT-PCR) in a validation cohort (16 MsPGN patients and 16 healthy controls). Correlation and receiver operating characteristic (ROC) curve analyses were used to determine the association between clinical features and miRNA expression in MsPGN. Finally, fluorescence in situ hybridization was performed to detect miRNA expression in the renal tissues of MsPGN patients. RESULTS: Five differentially expressed miRNAs (miR-125b-2-3p, miR-205-5p, let-7b-3p, miR-1262, and miR-548o-3p) were identified by qRT-PCR. The expression of these miRNAs correlated with ACR, 24hUpro, mAlb, UA, and combined yielded a ROC curve area of 0.916 in discriminating MsPGN patients from the controls. In addition, the expression of miR-205-5p, let-7b-3p, miR-1262, and miR-548o-3p was elevated in the MsPGN patient group, and miR-125b-2-3p was decreased in the MsPGN patient group. CONCLUSIONS: Differential expression of urinary exosomal miRNAs may pose a risk of MsPGN and help distinguish MsPGN patients from controls. Certain miRNA expressions may be associated with disease progression, contributing to the epigenetic understanding of the pathophysiology of MsPGN.

Prevalence of personality disorders using two diagnostic systems in psychiatric outpatients in Shanghai, China: a comparison of uni-axial and multi-axial formulation.

OBJECTIVE: To compare multi-axial (DSM-IV) with uni-axial diagnostic system (CCMD-3, Chinese Classification and Diagnostic Criteria of Mental Disorders) as diagnostic methods to determine the prevalence of personality disorders (PDs) in Chinese psychiatric outpatients. METHOD: 3,075 outpatients were randomly sampled from clinical settings in China. CCMD-3 PDs were evaluated as per routine psychiatric practice. DSM-IV PDs were assessed using both self-reported questionnaire and structured clinical interview. RESULTS: The prevalence estimate for any type of PD in the total sample is 31.93% as reflected in the DSM-IV. This figure is nearly 110 times as large as the prevalence estimate for the CCMD-3. Only 9 outpatients were diagnosed with PD based on the CCMD-3. Amongst the 10 forms of DSM-IV PDs, avoidant (8.1%), obsessive-compulsive (7.6%), paranoid (6.0%), and borderline (5.8%) PDs were the most prevalent subtypes. This study found that PDs are commonly associated with the following: (i) the younger aged; (ii) single marital status; (iii) those who were not raised by their parents; (iv) introverted personalities; (v) first-time seekers of psycho-counseling treatment; and (vi) patients with co-morbid mood or anxiety disorders. CONCLUSIONS: PDs are easily overlooked when the diagnosis is made based on the CCMD-3 uni-axial diagnostic system. However, it was found that personality pathology is common in the Chinese psychiatric community when using the DSM-IV classification system. Existing evidence suggest, at least indirectly, that there are important benefits of moving towards a multi-axial diagnostic approach in psychiatric practice.

Relative Safety and Efficacy of Two Doses of Tandospirone Citrate for Generalized Anxiety Disorder: A Multicenter Randomized Controlled Trial.

Purpose: To determine the relative safety and efficacy of different doses of tandospirone in treating generalized anxiety disorder (GAD). Patients and Methods: This parallel randomized controlled trial enrolled patients with GAD from eight centers in China. The patients were randomly assigned to 60 mg/day or 30 mg/day tandospirone groups. The primary endpoint was the overall response rate after receiving 6-week treatment. The secondary endpoints included significant response rate, clinical recovery rate, change in the Hamilton Anxiety Scale (HAMA) total score, HAMA subscale score, Hamilton Depression Scale-17 (HAMD-17), Clinical Global Impression-Severity Scale (CGI-S) score, and Impression-Improvement scale (CGI-I) score. Results: No significant difference was found in the overall response rate between the two groups (65.7% vs 58.4%, p = 0.213). A higher significant response rate and change in the HAMA total score were found in the 60 mg/day group. The reduction in the CGI-S score and percentage of patients with a CGI-I score of ≤2 were higher in 60 mg/day group. The reduction in HAMA somatic anxiety factor, cardiovascular symptom factor, gastrointestinal symptom factor, and HAMD-17 score were more significant in the 60 mg/day group. The incidence of total adverse events was higher in the 60 mg/day group than in the 30 mg/day group. No significant difference was found in the proportion of withdrawal due to adverse events. Conclusion: Both 60 mg/day and 30 mg/day tandospirone show good efficacy in treating patients with GAD. High doses of tandospirone may have advantages in relieving the somatic symptoms but also present disadvantages due to their high level. Trial Registration: The trial registration no. was NCT01614041.

Silibinin eliminates mitochondrial ROS and restores autophagy through IL6ST/JAK2/STAT3 signaling pathway to protect cardiomyocytes from doxorubicin-induced injury.

Growing evidence indicates that silibinin (SLB), a main component extracted from Chinese herb Silybum marianum, can effectively antagonize doxorubicin (DOX) induced myocardial injury (DIMI), but the specific molecular mechanism is still unelucidated. Herein, DOX induced human AC16 cardiomyocyte injury model and Network Pharmacology are used to predict and verify the potential mechanism. The analysis results of the core PPI network of SLB against DIMI show that JAK/STAT signaling pathway and autophagy are significantly enriched. Molecular docking results indicate that SLB has stronger binding ability to signaling key proteins IL6ST, JAK2 and STAT3 (affinity ≤ -7.0 kcal/mol). The detection results of pathway activation and autophagy level demonstrate that SLB significantly alleviates DOX induced IL6ST/JAK2/STAT3 signaling pathway inhibition and autophagy inhibition, reduces the death rate of cardiomyocytes. This protective effect of SLB is eliminated when key pathway proteins (IL6ST, JAK2, STAT3) are knocked down or autophagy is inhibited (3-MA or Beclin1 knockdown). These results suggest that the regulation of IL6ST/JAK2/STAT3 signaling pathway and autophagy may be important mechanism for SLB's protective effect on DOX injured cardiomyocytes. Further experimental results prove that knockdown of IL6ST, JAK2 and STAT3 eliminate the mitochondrial ROS scavenging effect and autophagy promoting effect of SLB. In sum, SLB can decrease the mitochondrial ROS and restore autophagy to antagonize DOX-induced cardiomyocyte injury by activating IL6ST/JAK2/STAT3 signaling pathway.

Discordance between family report and clinical assessment of suicide attempts: a prospective study from the emergency department.

BACKGROUND: Developing accurate identification methods for individuals with suicide attempts and providing them with follow-up care and supports can be a vital component of all comprehensive suicide prevention strategies. However, because of the difficulties concerning one's intentions behind injurious behaviour, identifying suicide attempts is a challenge for families and clinicians. AIMS: The aim of this study was to investigate the differences between family report and clinical assessment for suicide attempts in the emergency department (ED). METHODS: A total of 148 patients with suspected suicide attempts (SSAs) and 148 family caregivers in the ED were enrolled. The suicide risk module of the Chinese version of the MINI International Neuropsychiatric Interview and the self-report measure were used to assess those with SSA's suicidal behaviours. The Family Adaptability and Cohesion Evaluation Scales and semi-structured interviews were used to investigate the characteristics of suicide risk and demographics of patients with SSA, as well as the rate and influencing factors of omitted suicide attempts reported by family caregivers. RESULTS: The underreporting rate for family reported suicide attempts in the ED was 69.0%. The suicide attempts group indicated lower mean scores on perceptions of family resources, adaptability and cohesion. Patients' suicide risk rating (OR =-1.81, 95% CI: -3.87 to -0.33, p=0.036), family satisfaction (OR =-1.11, 95% CI: -2.29 to -0.06, p=0.048), and caregiver's age (OR =-1.68, 95% CI: -3.10 to -0.48, p=0.010) might be associated with underreporting by families. If patients committed suicide attempts through a falling injury or medication overdose, their families may have misreported the suicide attempt. CONCLUSIONS: The discordance of suicide attempt records between family report and clinical assessment reveals the limitations of family self-reports when identifying suicide attempts. Interviews and observations, together with information from certain diagnoses, should be combined to accurately identify suicide attempters in the ED.

circRNA expression profiling of colon tissue from mesalazine-treated mouse of inflammatory bowel disease reveals an important circRNA-miRNA-mRNA pathway.

Mesalazine (5-aminosalicylic acid, 5-ASA) has been widely used to treat inflammatory bowel disease (IBD). However, it remains unclear about the underlying biological mechanisms of IBD pathogenesis and mesalazine treatment, which could be partially clarified by exploring the profiling of circular RNAs (circRNAs) using RNA-seq. A total of 15 mice (C57BL/6) were randomly assigned to three equally sized groups: control, dextran sulfate sodium (DSS, using DSS to induce IBD), and DSS+5-ASA (using mesalazine to treat IBD). We randomly selected three mice of each group to collect colon tissues for RNA-seq and then performed bioinformatic analysis for two comparisons: DSS vs. control and DSS+5-ASA vs. DSS. Comparisons of a series of indicators (e.g., body weight) verified the establishment of DSS-induced IBD mouse model and the effectiveness of mesalazine in treating IBD. We identified 182 differentially expressed circRNAs, including 55 up-regulated and 47 down-regulated circRNAs when comparing the DSS+5-ASA with the DSS group. These 102 circRNA-associated genes were significantly involved in the N-Glycan biosynthesis and lysine degradation. The network analysis of circRNA-miRNA-mRNAs identified an important pathway, i.e., chr10:115386962-115390436+/mmu-miR-6914-5p/Atg7, which is related to autophagy. The findings provide new insights into the biological mechanisms of IBD pathogenesis and mesalazine treatment, particularly highlighting the circRNA-miRNA-mRNA pathway.

Mindfulness-Based Cognitive Therapy for Unmedicated Obsessive-Compulsive Disorder: A Randomized Controlled Trial With 6-Month Follow-Up.

Background: This was the first randomized controlled trial (RCT) designed to compare the efficacy of mindfulness-based cognitive therapy (MBCT) on unmedicated obsessive-compulsive disorder with that of the first-line treatment for OCD (SSRIs) or a placebo, as well as to analyze the treatment acceptability and safety of MBCT. Methods: A total of 123 unmedicated OCD patients with mild to moderate symptoms were randomly assigned into selective serotonin reuptake inhibitors group (SSRIs group), MBCT group or psycho-education group (PE group), respectively. They were intervened for 10 weeks. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) grade was the primary outcome, and Hamilton Depression Scale-24 (HAMD-24) and Hamilton Anxiety Scale (HAMA) grades were secondary outcomes to be measured at baseline, mid-intervention, post-intervention and 14, 22, and 34 weeks of follow-up. The Five Facet Mindfulness Questionnaire (FFMQ) and Sheehan Disability Scale (SDS) were used to assess mindfulness and social functions, respectively. In addition, treatment acceptability (dropout rate and frequency of occurrence) and safety [adverse event (AE)] of MBCT were investigated. Results: Significant differences were detected in the treatment responses among SSRIs group, MBCT group and PE group. Notably, treatment responses were significantly better in the former two groups than that of PE group (χ2 = 6.448, p = 0.04), although we did not identify significant differences between SSRIs group and MBCT group (χ2 = 1.220, p = 0.543). Observed until 6 months of follow-up, there were no significant differences in treatment response among three groups. No AE was recorded in MBCT group. Conclusion: MBCT is effective in the treatment of unmedicated OCD with mild to moderate symptoms comparable to that of SSRIs, which contributes to maintain the treatment outcomes at follow-up. Besides, MBCT is safe with a good clinical compliance.

Neuroendocrine abnormalities associated with untreated first episode patients of major depressive disorder with comorbid obstructive sleep apnea.

There are few studies that explore the relationship of neuroendocrine hormones of the HPA, HPT and HPG axes with major depressive disorder (MDD) with comorbid obstructive sleep apnea (OSA). The aim of this study is to examine neuroendocrine abnormalities and the relationship in untreated first episode patients of MDD comorbided with OSA. Polysomnography, neuroendocrine hormones were determined for 111 patients. After excluding the influences of age and BMI, phase I in non-REM sleep (N1)% increased significantly in MDD with OSA when compared with non-OSA. In the OSA group, cortisol increased and exceeded the normal standard, and for the numbers of patients exceeding the normal range, there were significant difference between two groups. In MDD with OSA, adrenocorticotropic hormone was significantly negatively correlated with slow wave sleep (SWS)%, while thyroxine was significantly correlated with phase II in non-REM sleep (N2)%, and prolactin was significantly negatively correlated with N1%. This study revealed that for untreated first episode MDD patients with OSA, the HPA axis was hyperfunctional. Cortisol and adrenocorticotropic hormone may be increased along with disturbed sleep structure and less slow-wave sleep time. Concurrently prolactin was decreased and thyroxine increased during the N1 and N2 phase of sleep.

Mindfulness-based cognitive therapy for obsessive-compulsive disorder: Study protocol for a randomized controlled trial with functional magnetic resonance imaging and a 6-month follow-up.

This article presents a study protocol for a single-blind randomized controlled trial to test the efficacy and feasibility of mindfulness-based cognitive therapy. A total of 120 un-medicated Chinese obsessive-compulsive disorder patients will be randomized to the mindfulness-based cognitive therapy group, the selective serotonin reuptake inhibitor group or the psycho-education group for 11 sessions in 10 weeks. A range of scales for clinical symptoms and functional magnetic resonance imaging will be completed at baseline (week 0), mid-intervention (week 4), post-intervention (week 10) and the 6-month follow-up (weeks 14, 22 and 34). The study will have relevance to decisions about treatment options for un-medicated obsessive-compulsive disorder patients.

Stereotactic treatment of refractory obsessive compulsive disorder by bilateral capsulotomy with 3 years follow-up.

In order to study the clinical effect of bilateral capsulotomy in patients with refractory obsessive compulsive disorder (OCD), 35 patients with refractory obsessive compulsive disorder for whom anti-OCD medications and psychological/behavior therapy had failed, underwent MRI-guided stereotactic bilateral anterior capsulotomy. Pre- and post-operative Yale-Brown obsessive compulsive scale (Y-BOCS), Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) scores were determined by psychiatrists. All patients underwent fluorodeoxyglucose positron emission tomography evaluation before and 6 months after the operation. Twenty patients became OCD symptom-free (57%), 10 experienced significant improvement (29%) and five experienced no significant improvement (14%). There were significant decreases in Y-BOCS, HAMD and HAMA scores. Our results show that MRI-guided stereotactic bilateral capsulotomy is a precise, safe and effective therapy for refractory obsessive compulsive disorder. This promising technique may also improve anxiety and depression in addition to OCD. OCD patients who have not responded to medication, psychotherapy or behavioral therapy might benefit from MRI-guided stereotactic bilateral capsulotomy.

Hematopoietic stem/progenitor cell senescence is associated with altered expression profiles of cellular memory-involved gene.

To evaluate the contributions of cellular memory mechanisms to hematopoietic stem/progenitor cell (HSPC) senescence. HSPCs (Lin-CD117+, hereafter referred to as HSPC) were separated from young (6-week-old) and aged (18-month-old) mice using Magnetic Activated Cell Sorting (MACS). Cell cycle distribution of HSPCs was determined using flow cytometry. The mixed colony forming unit (CFU-Mix) assay was used to study the HSPCs' ability to proliferate. The mRNA expression levels of cellular memory-implicated PCG family (enhancer of zeste homolog 2 (Ezh2), B lymphoma mo-MLV insertion region 1 (Bmi-1), embryonic ectoderm development (Eed), melanoma nuclear protein 18 (Mel18), Mph1/polyhomeotic-like protein 1 (Rae-28)) and Trithorax group (TrxG) family (mixed lineage leukemia (Mll), thioredoxin (Trx)) were determined by quantitative real-time PCR. We obtained highly purified populations of mouse HSPCs (Lin-CD117+) (92.2 ± 4.5% CD117+). The percentage of HSPCs was significantly higher in older mice compared with younger control mice and the percentage of SA-ß-galactosidase positive cells was significantly higher in HSPCs isolated from older mice (P<0.05). The percentage of HSPCs in G0/G1 was significantly higher in older mice compared with younger control mice (52.0 compared with 47.1%), indicating increased cell cycle arrest in senescent HSPCs. The amount of CFU-Mix was significantly decreased in aged group (13.8 compared with 40.0), indicating a diminished ability to proliferate in senescent HSPCs. Ezh1, Bmi-1, Eed, Rae-28 gene mRNA expression was significantly lower in HSPCs from older mice compared to younger controls, while Mel18 mRNA expression was significantly higher in HSPCs from older mice (P<0.05). The expression of genes associated with cellular memory is altered in senescent (Lin- CD117+) HSPCs, which may affect the potential plasticity of aged hematopoietic stem cells (HSCs) and thereby contribute to senescence-associated disease processes.

Intrinsic functional connectivity alteration of dorsal and rostral anterior cingulate cortex in obsessive-compulsive disorder: A resting fMRI study.

Cortico-striato-thalamo-cortical (CSTC) circuit has been implicated in OCD pathophysiology by converging neuroimaging findings. The anterior cingulate cortex (ACC), as an important part within CSTC circuit, plays a critical role in OCD etiology. The ACC can be divided into dorsal and rostral parts anatomically, which are involved in cognitive process and emotional function, respectively. However, the diverse function of intrinsic signals from dorsal and rostral ACC regions remains unclear in OCD study. In this work, we applied resting-state functional magnetic resonance imaging (rs-fMRI) technology to investigate and differentiate the functional connectivity (FC) characteristics between dACC and rACC in unmedicated OCD patients. Also, the correlation between the altered FC and clinical symptom severity was analyzed. Decreased FC of rACC-DLPFC and increased FC between dACC and caudate were found. Moreover, the altered dACC-caudate FC was positively correlated with total Y-BOCS and compulsion score in OCD patients. Our findings implied the crossed function of dorsal and rostral circuits in the pathophysiologic mechanism of OCD. The dorsal cingulate-striatum functional pathway served as a potential biomarker for OCD symptomatology and merits further investigations.