Behavioral features and disorganization of oscillatory activity in C57BL/6J mice after acute low dose MK-801 administration.

Low dose acute administration of N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 is widely used to model cognition impairments associated with schizophrenia (CIAS) in rodents. However, due to no unified standards for animal strain, dose, route of drug delivery, and the duration of administration, how different doses of MK-801 influence behavior and fundamental frequency bands of the local field potential (LFP) in cortical and subcortical brain regions without consistent conclusions. The optimal dose of MK-801 as a valid cognition impairers to model CIAS in C57BL/6J mice remains unclear. The current study characterizes the behavior and neural oscillation alterations induced by different low doses of MK-801 in medial prefrontal cortex (mPFC) and hippocampus CA1 of C57BL/6J mice. The results reveal that mice treated with 0.1 and 0.3 mg/kg MK-801 demonstrate increased locomotion and diminished prepulse inhibition (PPI), while not when treated with 0.05 mg/kg MK-801. We also find that MK-801 dose as low as 0.05 mg/kg can significantly diminishes spontaneous alteration during the Y-maze test. Additionally, the oscillation power in delta, theta, alpha, gamma and HFO bands of the LFP in mPFC and CA1 was potentiated by different dose levels of MK-801 administration. The current findings revealed that the observed sensitivity against spontaneous alteration impairment and neural oscillation at 0.05 mg/kg MK-801 suggest that 0.05 mg/kg will produce changes in CIAS-relevant behavior without overt changes in locomotion and sensorimotor processing in C57BL/6J mice.

Clinical characteristics of familial schizophrenia.

INTRODUCTION: A family history of psychiatric disorders is one of the strongest risk factors for schizophrenia. The characteristics of patients with a family history of psychiatric disorders have not been systematically evaluated. METHODS: This multicenter study (26 centers, 2425 cases) was performed in a Chinese population to examine the sociodemographic and clinical characteristics of schizophrenia patients with a family history of psychotic disorders in comparison with those of patients with sporadic schizophrenia. RESULTS: Nineteen percent of patients had a family history of mental disease. Multiple logistic regression analysis revealed that ≥4 hospitalizations (OR = 1.78, P = .004), tobacco dependence (OR = 1.48, P = .006), alcohol dependence (OR = 1.74, P = .013), and physical illness (OR = 1.89, P = .001) were independently and significantly associated with a family history of mental disease. CONCLUSION: Patients with a family history of mental disorders present different demographics and clinical features than patients without a family history of psychiatric disorders.

Multiomics Study of Gut Bacteria and Host Metabolism in Irritable Bowel Syndrome and Depression Patients.

Background and Aims: Irritable bowel syndrome (IBS) and depression have high tendencies of comorbidity. In particular, diarrhea-predominant IBS (IBS-D) and depression exhibit similar fecal microbiota signatures, yet little is known about their pathogenic mechanism. Here, we propose that the differences in structure and composition of IBS-D and depression gut microbiota give rise to different downstream functions, which lead to distinct clinical phenotypes via host metabolism and further influence the interaction of brain-gut axis. Methods: We performed multiomics study, including fecal metagenome-wide sequencing and serum metabolomics profiling in 65 individuals with IBS-D (n=22), depression (n=15), comorbid patients (n=13), and healthy controls (n=15). We analyzed functional genes contributed by the primary genus and evaluated their correlations with clinical indices and host metabolites. Results: Metagenomic analysis revealed 26 clusters of orthologous groups of protein (COG) categories consisting of a total of 4,631 functional genes. Trehalose and maltose hydrolase (COG1554) and fucose permease (COG0738) were the most relevant and enriched functional genes in the IBS-D patients; urease accessory proteins UreE (COG2371) was that in the depression patients. Context based genome annotation suggest that an alteration of Escherichia coli and Enterobacter cloacae in IBS-D and depression respectively may be responsible for the enrichment described above. Correlation with host metabolites, such as maltotriose and isomaltose in carbohydrate metabolism and anandamide in neuroactive metabolism, drew further connections between these findings. Conclusions: These changes led us to propose a connection between genomic signatures and clinical differences observed in IBS-D and depression. Our findings provide further insights into the involvement of gut microbiota in diseases related to brain-gut disorder.

Who will benefit from computerized cognitive remediation therapy? Evidence from a multisite randomized controlled study in schizophrenia.

BACKGROUND: Computerized cognitive remediation therapy (CCRT) is generally effective for the cognitive deficits of schizophrenia. However, there is much uncertainty about what factors mediate or moderate effectiveness and are therefore important to personalize treatment and boost its effects. METHOD: In total, 311 Chinese inpatients with Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia were randomized to receive CCRT or Active control for 12 weeks with four to five sessions per week. All participants were assessed at baseline, post-treatment and 3-month follow-up. The outcomes were cognition, clinical symptoms and functional outcomes. RESULTS: There was a significant benefit in the MATRICS Consensus Cognitive Battery (MCCB) total score for CCRT (F1,258 = 5.62; p = 0.02; effect size was 0.27, 95% confidence interval 0.04-0.49). There were no specific moderators of CCRT improvements. However, across both groups, Wisconsin Card Sort Test improvement mediated a positive effect on functional capacity and Digit Span benefit mediated decreases in positive symptoms. In exploratory analyses younger and older participants showed cognitive improvements but on different tests (younger on Symbol Coding Test, while older on the Spatial Span Test). Only the older age group showed MSCEIT benefits at post-treatment. In addition, cognition at baseline negatively correlated with cognitive improvement and those whose MCCB baseline total score was around 31 seem to derive the most benefit. CONCLUSIONS: CCRT can improve the cognitive function of patients with schizophrenia. Changes in cognitive outcomes also contributed to improvements in functional outcomes either directly or solely in the context of CCRT. Age and the basic cognitive level of the participants seem to affect the cognitive benefits from CCRT.

Can acupuncture combined with SSRIs improve clinical symptoms and quality of life in patients with depression? Secondary outcomes of a pragmatic randomized controlled trial.

OBJECTIVES: To explore the effects of acupuncture (manual acupuncture or electroacupuncture) combined with SSRIs for moderate to severe depression improving major clinical symptoms and life quality of the patients on secondary outcomes. DESIGN: Pragmatic, parallel, randomized controlled trial. SETTING: 6 hospitals in China. INTERVENTIONS: 6 weeks of manual acupuncture (MA)+selective serotonin reuptake inhibitors (SSRIs), electroacupuncture (EA)+SSRIs, and SSRIs alone. MAIN OUTCOME MEASURES: The primary outcome was response rate of 17-item Hamilton Depression Scale (HAMD-17) total score at 6th week. The secondary outcomes reported in this analysis were HAMD-17 factor scores at 1st, 2nd, 4th, 6th, 10th week and WHO Quality of Life-BREF (WHOQOL-BREF) scores at 6th week. RESULTS: 477 patients were randomly assigned into MA + SSRIs (n = 161), EA + SSRIs (n = 160), or SSRIs alone (n = 156) groups. For HAMD-17 (at 6th week), the MA + SSRIs group was significantly better than the SSRIs alone group in retardation factor (p = 0.008), while the EA+SSRIs group was significantly better than the SSRIs alone group in anxiety/somatization factor (p<0.001) and sleep disturbance factor (p = 0.002). For WHOQOL-BREF (at 6th week), the EA + SSRIs group, compared with the SSRIs alone group, produced a more significant improvement in the overall quality of life, general health, physical health, and psychological health (p<0.05). While, the MA + SSRIs group, compared to the SSRIs alone group, showed significant advantage only in psychological health (p = 0.023). CONCLUSIONS: Either MA or EA combined SSRIs treatment could improve symptoms and quality of life for patients with moderate to severe depression. The main limitation of this trial was not using a sham control therefore the placebo effect could not be excluded.

Manual or electroacupuncture as an add-on therapy to SSRIs for depression: A randomized controlled trial.

Selective serotonin reuptake inhibitors (SSRIs) are first-line antidepressants, however, only around 60% of patients could benefit from them. Acupuncture is supported by insufficient evidence to help with symptom relieving and SSRIs tolerance. This pragmatic randomized controlled trial compared SSRIs alone versus SSRIs together with manual acupuncture (MA) or electroacupuncture (EA) in moderate to severe depressed patients. Patients were randomly allocated to receive MA + SSRIs (161), EA + SSRIs (160), or SSRIs alone (156) for six weeks, and then followed up for another four weeks. The primary outcome was response rate of the 17-item Hamilton Depression Scale (HAMD-17) at 6th week. The secondary outcomes were HAMD-17 (remission rate, early onset rate, total score), Self-Rating Depression Scale (SDS: total score), Clinical Global Impression (CGI), Rating Scale for Side Effects (SERS: total and domain scores), number of patients with adjusted dosage of SSRIs and adverse events (AEs). Both MA + SSRIs and EA + SSRIs were significantly better than SSRIs at 6th week on HAMD-17 response rate (RR = 1.21, 95% CI 1.04, 1.42, P = 0.013; RR = 1.27, 95% CI 1.09, 1.48, P = 0.0014), HAMD-17 early onset rate (P < 0.0001), HAMD-17 and SDS total scores (P < 0.05), CGI (P < 0.01), SERS total score (P < 0.01), number of patients with increased dosage of SSRIs (P < 0.01). For HAMD-17 remission rate, EA + SSRIs was significantly higher than SSRIs (P = 0.0083), while MA + SSRIs showed no significant difference at 6th week (P = 0.092). No unintended acupuncture-related severe AE was observed. This study identified that both MA and EA showed beneficial effects in addition to SSRIs alone in patients with moderate to severe depression, and were well tolerated. Clinical trials registration: ChiCTR-TRC-08000297.

miR­200b­3p inhibits proliferation and induces apoptosis in colorectal cancer by targeting Wnt1.

MicroRNA (miR)­200b­3p is downregulated in multiple human cancer types. Wnt signaling serves a role in human colorectal cancer (CRC). The present study aimed to examine the effect of miR­200b­3p on human CRC and its potential association with Wnt signaling. The Cell Counting Kit­8 (CCK­8) was employed to assess cell viability. A flow cytometric assay was conducted to examine cell proliferation and apoptosis. The regulation model of miR­200b­3p and Wnt1 was assessed by a luciferase reporter assay. A commercial kit was used to evaluate the activity of caspase­3 following treatment of the cells by miR­200b­3p or Wnt1. The expression of target factors was determined by a quantitative real­time polymerase chain reaction and western blot analysis. The expression of miR­200b­3p was decreased in human CRC tissues and in cell lines. The bioinformatics analysis and the luciferase reporter assay revealed that Wnt1 may be a direct target of miR­200b­3p. Moreover, the viability and proliferation of CRC cells was suppressed by miR­200b­3p. miR­200b­3p additionally induced apoptosis in CRC cells. Furthermore, the caspase­3 activity was enhanced in the miR­200b­3p mimics group. The expression of antigen Ki­67 (additionally termed KI­67) and ß­catenin was decreased, while the expression of cleaved caspase­3 was increased by miR­200b­3p. In conclusion, miR­200b­3p inhibited proliferation and induced apoptosis in CRC cells by inactivating Wnt/ß­catenin signaling. The present study provided potential biomarkers and candidate modalities for the management of CRC.

Similar Fecal Microbiota Signatures in Patients With Diarrhea-Predominant Irritable Bowel Syndrome and Patients With Depression.

BACKGROUND & AIMS: Patients with irritable bowel syndrome (IBS) often have psychiatric comorbidities. Alterations in the intestinal microbiota have been associated with IBS and depression, but it is not clear if there is a microbial relationship between these disorders. We studied the profiles of fecal microbiota samples from patients with IBS, depression, or comorbidities of IBS and depression; we determined the relationships among these profiles and clinical and pathophysiological features of these disorders. METHODS: We used 454 pyrosequencing to analyze fecal microbiota samples from 100 subjects (40 with diarrhea-predominant IBS [IBS-D], 15 with depression, 25 with comorbidities of IBS and depression, and 20 healthy individuals [controls]), recruited at Peking University. Abdominal and psychological symptoms were evaluated with validated questionnaires. Visceral sensitivity was evaluated using a barostat. Colonic mucosal inflammation was assayed by immunohistochemical analyses of sigmoid tissue biopsy specimens. RESULTS: Fecal microbiota signatures were similar between patients with IBS-D and depression in that they were less diverse than samples from controls and had similar abundances of alterations. They were characterized by high proportions of Bacteroides (type I), Prevotella (type II), or nondominant microbiota (type III). Most patients with IBS-D or depression had type I or type II profiles (IBS-D had 85% type I and type II profiles, depression had 80% type I and type II profiles). Colon tissues from patients with type I or type II profiles had higher levels of inflammatory markers than colon tissues from patients with type III profiles. The level of colon inflammation correlated with the severity of IBS symptoms. CONCLUSIONS: Patients with IBS-D and depression have similar alterations in fecal microbiota; these might be related to the pathogenesis of these disorders. We identified 3 microbial profiles in patients that could indicate different subtypes of IBS and depression or be used as diagnostic biomarkers.

Impairments in Negative Facial Emotion Recognition in Chinese Schizophrenia Patients Detected With a Newly Designed Task.

Facial emotion recognition has been found to be impaired in schizophrenia, although overall results have been inconclusive. A new set of facial emotion stimuli with Chinese faces was developed, using static and dynamic avatars, the identification of which were subsequently validated in 562 healthy control subjects. This test was then used to identify facial emotion recognition accuracy in 44 patients with schizophrenia and 41 healthy controls. Overall, patients identified facial emotions significantly worse than healthy controls (p = 0.018) with a significant main effect for type of emotion (p = 0.016). Patients performed significantly worse in fear (p = 0.029) and sadness (p = 0.037), and marginally worse in anger (p = 0.052). No significant differences were evident in contempt (p = 0.254) or happiness (p = 0.943). Regarding error rates of misattribution, patients overidentified contempt (p = 0.035) and sadness (p = 0.01), but not anger, fear, or happiness. Conclusion, patients of Chinese ethnicity with schizophrenia may have significantly greater difficulties identifying negative, but not positive emotions.

[Survey of suicidal ideation and suicide attempts in outpatients at 50 general hospitals in Beijing].

OBJECTIVE: Describe the prevalence and risk factors for suicidal ideation and suicide attempt among outpatients at general hospitals in Beijing. METHODS: Trained psychiatric nurses obtained data about the characteristics of suicidal thoughts and suicide attempts from 2877 persons 15 years of age or older who were consecutive outpatients at 35 level-1, 8 level-2 and 7 level-3 general hospitals selected from all hospitals in Beijing by stratified random sampling. Logistic regression analysis was used to identify risk factors for suicidal ideation and suicide attempt. RESULTS: The lifetime prevalence of suicidal ideation and suicide attempt were 6.08% (95% CI: 5.25% - 7.25%) and 1.18% (0.82% - 1.65%), respectively. Mutivariate logistic analysis found that the most important risk factors for suicidal ideation were hopelessness in the prior year (OR = 7.96), current depression (OR = 3.41), younger age (OR for < 35 = 2.83; OR for 35 - 55 = 2.08), having a blood relative with prior suicidal behavior (OR = 2.58), and so forth; the most important risk factors for suicide attempt were younger age (OR for < 35 = 4.96; OR for 35 - 55 = 4.40), hopelessness in the prior year (OR = 4.02), self-report of health status in last weeks as poor (OR = 2.81), not currently married (never married, divorced, widowed, etc) (OR = 2.80), and so forth. Four variables were independent risk factors for both suicidal ideation and suicide attempt: hopelessness in the last year, younger age, having associates with prior suicidal behavior and female gender. CONCLUSIONS: Many patients treated at medical, surgical and other outpatient departments of general hospitals in Beijing are depressed and at risk for suicide; this is particularly true of young female patients who feel hopeless about their future. Outpatient clinicians need to be trained to identify such patients, to assess the severity of their psychological problems and, if necessary, to provide appropriate treatment or refer them for psychiatric evaluation.

Multi-dimension aspiration control mode in phacoemulsification.

PURPOSE: Multi-dimension aspiration control mode was put forward in this study. Accuracy of multi-dimension aspiration control model was compared to simple traditional pedal control model. METHODS: Induced by high aspiration pressure (200-250 mmHg), hard nucleus (> OR = Grade III ) of senile cataract was chopped before phacoemulsification in 170 patients (174 eyes). Ninety-one patients (94 eyes) accepted multi-dimension aspiration control model in which aspiration direction, distance and targets prevention were adjusted by phaco-tip besides traditional pedal control. Another 79 patients (80 eyes) were compared as reviewed group, aspiration of which was controlled simply by traditional pedal control. Postcapsular rupture rates (PCRR) were compared between two groups. RESULTS: Multi-dimension control model could make the terminal effects cooperate with phacoemulsification more precisely and protect post capsular from damage (chi(2) =5.41, P < 0.02). CONCLUSION: Multi-dimension control model could improve the accuracy of aspiration effects and protect postcapsular from damage.

[Clinical significance of accumulated energy complex parameter in phacoemulsification].

OBJECTIVE: The accumulated energy complex parameter [AECP, AECP = actual power (AP) x time (T)] was put forward and used to analyze the correlation between phacoemulsification energy and postoperative complication. METHODS: Ninety-two cases with senile cataract who underwent phacoemulsification were observed. The correlation between AECP and postoperative corneal edema rate (CER) was analyzed. The difference of AECP between the method of divided-conque and that of epi-capsular rotated-chipping was compared for the same hard nucleus (IV) cataract extraction. RESULTS: The positive correlation was observed between AECP and CER (r = 0.974, t = 5.643, P < 0.05). The difference of the average AECP values existed between the two methods (t = 2.947, P < 0.01). The AECP and CER were lower in the method of divided-conque than that in epi-capsular rotated-chipping. CONCLUSION: AECP can be used as a dynamic index to control the phacoemulsification energy in order to decrease CER predictably. Our study suggests that AECP provide an important integrated energy index to evaluate phacoemulsification.