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Purpose:Epigenetic alterations play important roles in metastasis and drug resistance through gene regulation. However, the functional features and molecular mechanisms of epigenetic changes remain largely unclear in nasopharyngeal carcinoma (NPC) metastasis.Experimental Design:Gene regulatory network analysis was used to identify metastatic-specific dysregulated genes between normal and NPC tissues and the expression was validated in published Gene-Expression Omnibus data set. The regulatory and functional role of RAB37 downregulation was examined in NPC and was validated in vitro and in vivo, and downstream target of RAB37 was explored. The clinical value of RAB37 methylation was evaluated in NPC metastasis and chemosensitivity.Results:We identified RAB37 as a specific hypermethylated gene that is most commonly downregulated in NPC. Moreover, RAB37 downregulation was attributed to hypermethylation of its promoter and was significantly associated with metastasis- and docetaxel chemoresistance-related features in NPC. Ectopic RAB37 overexpression suppressed NPC cell metastasis and enhanced chemosensitivity to docetaxel. Mechanistically, RAB37 colocalized with TIMP2, regulated TIMP2 secretion, inhibited downstream MMP2 activity, and consequently altered NPC cell metastasis. Furthermore, RAB37 hypermethylation was correlated with poor clinical outcomes in patients with NPC. We developed a prognostic model based on RAB37 methylation and N stage that effectively predicted an increased risk of distant metastasis and a favorable response to docetaxel-containing induction chemotherapy (IC) in NPC patients.Conclusions:This study shows that RAB37 hypermethylation is involved in NPC metastasis and chemoresistance, and that our prognostic model can identify patients who are at a high risk of distant metastasis and might benefit from for docetaxel IC.

Supplementary Data from RAB37 Hypermethylation Regulates Metastasis and Resistance to Docetaxel-Based Induction Chemotherapy in Nasopharyngeal Carcinoma

Purpose: Cisplatin-based chemotherapy effectively improves the distant-metastasis control in nasopharyngeal carcinoma (NPC), but approximately 30% of patients develop treatment failure due to chemoresistance. However, the underlying mechanisms remain poorly understood. Experimental Design: Circular RNA (circRNA) sequencing data were used to identify metastasis-specific circRNAs and the expression of circIPO7 was validated in NPC tissues as well as NPC cell lines by qRT-PCR. The whole transcriptional profile upon circIPO7 knockdown was applied to explore the biological function and regulatory mechanism, which were further confirmed by in vitro and in vivo metastasis/chemosensitivity assays. We also evaluated the value of circIPO7 expression in predicting NPC metastasis and cisplatin chemoresistance by analyzing a cohort of 183 NPC patients. Results: In this study, circIPO7, a novel circRNA, is found to be specifically overexpressed in NPC patients with distant metastasis. Knockdown of circIPO7 in NPC cells suppresses their metastasis and increases sensitivity to cisplatin treatment in vitro and in vivo. Mechanistically, circIPO7 binds to Y-box binding protein-1 (YBX1) protein in the cytoplasm and facilitates its phosphorylation at serine 102 (p-YBX1S102) by the kinase AKT, which further promotes YBX1 nuclear translocation and activates FGFR1, TNC, and NTRK1 transcription. Clinically, higher circIPO7 expression indicates unfavorable distant metastasis-free survival in NPC patients given cisplatin-based chemotherapy. Conclusions: Altogether, this study identifies oncogenic circIPO7 as a prognostic marker after cisplatin-based chemotherapy and as a potential therapeutic target for overcoming metastasis and chemoresistance in NPC.

Metastasis and recurrence account for 95% of deaths from nasopharyngeal carcinoma (NPC). Cancer stem cells (CSCs) are regarded as one of the main reasons for tumor cell resistance to clinical therapy, and cancer metastasis or recurrence, while little is known about CSCs in NPC. The present study uncovers a subpopulation of cells labeled as CD45−EPCAM+PROCR+ in NPC biopsy samples that exhibit stem cell-like characteristics. A relatively low number of these cells initiate xenograft tumors in mice. Functional analysis reveals that protein C receptor (PROCR) not only serves as a stem cell marker in NPC, but also maintains tumor cells’ stemness potential through regulating lipid metabolism and mitochondrial fission. Epistatic studies reveal that cAMP-protein kinase A stimulates Ca2+ release to manipulate lipid metabolism related genes’ expression. Finally, in a cohort of 207 NPC samples, PROCR expression is correlated with tumor metastasis or recurrence, and predicts poor prognosis. These novel findings link PROCR labeled CSCs with lipid metabolism and mitochondrial plasticity, and provides new clinical target against metastatic or recurrent NPC.

The core features of schizophrenia (SCZ) include cognitive deficits and impaired sensory gating represented by P50 inhibition deficits, which appear to be related to the α7 nicotinic acetylcholine receptor (nAChR). An agonist of nAChR receptor may improve these defects. This study aimed to investigate how administering multiple doses of tropisetron, a partial agonist of nAChR, for 1 day would affect cognitive deficits and P50 inhibition deficits in SCZ patients. We randomized 40 SCZ non-smokers into a double-blind clinical trial with four groups: placebo, 5 mg/d, 10 mg/d, and 20 mg/d of oral tropisetron. Their P50 ratios were all more than 0.5 and they took risperidone at 3–6 mg/day for at least a month before participating in the experiment. We measured the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and P50 inhibition before and one day after treatment. After one day of treatment, the total RBANS scores of the 20 mg and 5 mg tropisetron groups, and the immediate memory of the 10 mg group were significantly higher than placebo group. The P50 ratio was smaller in the 5 mg and 10 mg groups than in the placebo group (both p

Additional file 1: Figure S1. Schematic map of circRNA isoforms arising from CRIM1 genome and relative circCRIM1 expression in NPC cells and tissues. Figure S2. Knockdown and overexpression efficiency of circCRIM1 or miR-422a in NPC cells. Figure S3–4. Multiple sequence alignment of two independent siRNAs targeting circCRIM1 and 15 circRNA isoforms derived from CRIM1 gene in S18 cells. Figure S5. Transwell assays for the rescue effects of circCRIM1 with a mutant backsplice junction of circCRIM1. Figure S6. CircCRIM1 induces EMT in NPC cells. Figure S7. FOXQ1 is a downstream target of miR-422a and circCRIM1 involved in metastasis. Figure S8. FOXQ1 downregulation inhibited NPC cell metastasis in vivo. Figure S9. circCRIM1 downregulation enhances the docetaxel efficacy on NPC cell metastasis in vivo. Figure S10. Patients in the combined intermediate and high risk groups did not benefit from docetaxel-containing induction chemotherapy. Figure S11. Full unedited Western blotting gels for all figures. Table S1: List of 15 circRNA isoforms derived from CRIM1 gene in S18 cells. Table S2. Downregulated miRNAs according to miRNA microarray. Table S3. Putative miRNAs predicted to bind circCRIM1 by miRanda and RNAhybrid algorithms. Table S4. Putative miRNAs predicted to bind circCRIM1 by StarBase algorithms. Table S5. Clinical characteristics of NPC patients according to high and low circCRIM1 expression. Table S6. Univariate and multivariable Cox regression analysis of circCRIM1 expression level and survival in NPC patients. Table S7. Primers and RNA sequences used in this study.

Previous studies suggested that serotonergic neurons and platelets share similarities in serotonin (5-HT) uptake by serotonin transporter (SERT), storage, metabolism and release mechanisms, indicating that platelets may be used as a reliable peripheral surrogate to measure central SERT activity in neuropsychiatric research. In this study, platelet 5-HT content and 5-HT uptake capacity of SERT in depression and anxiety patients were measured by ELISA and flow cytometry with IDT307 at baseline and after serotonin reuptake inhibitors (SSRIs) treatment for 4 weeks. Healthy persons matched with age and gender were used as reference. The clinical presentations of the patients were assessed with Hamilton Depression (HAMD) and Anxiety Rating Scales (HAMA) at the same time points. Compared to healthy subjects, anxiety and depression patients showed higher levels of platelet 5-HT and IDT307 fluorescence intensity, but the values were comparable between the patient groups. SSRIs administration for 4 weeks significantly decreased scores of HAMD (29 vs 14) and HAMA (22 vs 14) in depression and anxiety patients, respectively; while it decreased platelet 5-HT content, but did not change the IDT307 fluorescence intensity of platelets. After incubation with fluoxetine in vitro, the IDT307 fluorescence intensity of isolated platelets from both healthy subjects and patients decreased in a dose-dependent manner. These results provide further evidence supporting the employment of platelet 5-HT content and SERT as peripheral surrogates in depression and anxiety patients, and are of help in understanding the several weeks' delay from the initiation of antidepressant medication to their full therapeutic effects in the patients.

Turner's syndrome (TS) is the most common sex chromosome abnormality in females and characterized with short stature and ovarian dysgenesis. Patients with TS may also present many other physical diseases and mental disorders. In this case report, we present a 49-year-old woman with TS, who also met criteria for bipolar disorder, type 2 diabetes mellitus, and autoimmune hypothyroidism. The patient was admitted to the mental health center for depressive symptoms in 1991 and was misdiagnosed as hypopituitarism, which was not corrected until 2005 when her karyotype of 45, X/46, X, i(Xq) was identified. Due to the misdiagnosis and other specific reasons, the patient missed the optimal time for hormone replacement therapy.

Research on the relationship between insight and social cognition, in particular Theory of Mind (ToM), in schizophrenia has yielded mixed findings to date. Very few studies, however, have assessed both clinical insight and cognitive insight when examining their relationships with ToM in schizophrenia. The current study thus investigated the relationship between clinical insight, cognitive insight, and ToM in a sample of 56 patients with schizophrenia and 30 healthy controls. Twenty-seven patients were classified as low in clinical insight according to their scores on the 'insight' item (G12) of the Positive and Negative Syndrome Scale (PANSS). Moreover, cognitive insight and ToM were assessed with the Beck Cognitive Insight Scale (BCIS) and the Yoni task, respectively. The results indicated that patients with poor clinical insight performed worse on taslcs of second-order cognitive and affective ToM, while the ToM performance of patients with high clinical insight was equivalent to that of healthy controls. Furthermore, while clinical insight was correlated with ToM and clinical symptoms, cognitive insight did not correlate with clinical insight, ToM, or clinical symptoms. Clinical insight thus appears to be an important factor related to ToM in schizophrenia. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

This study explored specificity and visual perspective of mental time travel in schizophrenia. Fifteen patients with schizophrenia and 18 controls were recruited. Participants were asked to recall or imagine specific events according to cue words. Results showed that schizophrenia patients generated fewer specific events than controls, the recalled events were more specific than imagined events. Schizophrenia adopted less field perspective and more observer perspective than controls. These results suggested that patients with schizophrenia were impaired in mental time travel both in specificity and visual perspective. Further studies are needed to identify the underlying mechanisms.

Fluoxetine is one of SSRIs commonly used as first-line antidepressants. It also induces adverse effects, including bleeding events. This study clarified the bleeding effect of fluoxetine and explored the action cascade of this drug leading to a longer bleeding time. A total of 48 male adult mice were evenly distributed into four groups and given fluoxetine in saline at 0, 4, 8, or 16 mg/kg, for 14 days. On day 15, tail bleeding time of 6 mice/group was measured, and their blood samples were collected for analyses of relevant platelet functions. The remained mice were allowed to survive for another 14 days without fluoxetine, and subjected to the same analyses on day 29. A significant effect of fluoxetine was reveled on bleeding time (F (3,20) = 16.842, P

Major depressive disorder (MDD), one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide, poses a major challenge to genetic analysis. To date, no robustly replicated genetic loci have been identified, despite analysis of more than 9,000 cases. Here, using low-coverage whole-genome sequencing of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified, and subsequently replicated in an independent sample, two loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene (P = 2.53 × 10(-10)), the other in an intron of the LHPP gene (P = 6.45 × 10(-12)). Analysis of 4,509 cases with a severe subtype of MDD, melancholia, yielded an increased genetic signal at the SIRT1 locus. We attribute our success to the recruitment of relatively homogeneous cases with severe illness.

This study aimed to examine verbal and visual-spatial working memory (WM) dysfunction in patients with schizophrenia. We compared 60 patients with schizophrenia with 57 healthy controls (matched for age, educational level, and IQ) on three WM tasks. Patients with schizophrenia performed significantly more poorly than healthy controls on verbal, visual, and spatial WM tests. Moreover, WM deficits were inversely associated with both the positive and negative symptoms of the patients. Taken together, these findings suggest that there are pervasive WM impairments in patients with schizophrenia. In addition, clinical features may play a significant role in the expression of WM deficits.

This study aimed to examine the subjective awareness of everyday dysexecutive function and the 'objective' executive function in individuals with schizotypal personality features. Forty-nine individuals with schizotypal personality disorder (SPD) proneness (25 negative schizotypy and 24 non-negative schizotypy were identified using cluster analysis) and 44 non-SPD individuals completed a battery of 'objective' executive function tests and a self-reported Dysexecutive Questionnaire (DEX) on everyday executive problems. The findings showed that individuals with SPD proneness including negative schizotypy and non-negative schizotypy did not have significant worse performance than non-SPD in most of 'objective' executive function tests, but self-reported significantly disproportionate more dysexecutive problems than non-SPD. Furthermore. SPD proneness, especially negative schizotypy was found to give undependable estimation on their everyday dysexecutive function while non-negative schizotypy was not. The current findings suggest that the subjective awareness of dysexecutive function may precede actual 'objective' executive function impairments in a subtype of SPD (non-negative schizotypy) and the subjective complaint of the daily dysexecutive behavior in SPD proneness, especially negative schizotypy might result from their unreliable estimation of executive function. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Executive dysfunctions have been consistently demonstrated in patients with schizophrenia. This study aimed to investigate deficits in specific executive functioning components, namely working memory and inhibition, in schizophrenia. In study 1, a set of neurocognitive function tests was administered to 41 patients with schizophrenia and 25 healthy controls to capture specific components of executive functioning, including semantic inhibition (the Stroop-like paradigm and the Chinese Version of the Hayling Sentence Completion Test (HSC)), working memory (the spatial n-back), and response inhibition (the stop signal task (SST)). Results showed that schizophrenia patients did significantly worse than controls under both working memory and inhibition demands in the Stroop-like paradigm. In particular, patients were impaired when inhibiting a semantically associated response; and performance was correlated with negative symptoms. In study 2, we employed a modified semantic inhibitory error monitoring paradigm to examine whether patients with schizophrenia (n = 11) were impaired in semantic inhibitory error monitoring or not as compared to 11 healthy controls. The results suggested that patients with schizophrenia in this study remained intact in semantic inhibition error monitoring. There was no difference in the semantic inhibitory monitoring performance between healthy controls and patients with schizophrenia. Taken together, these results suggested impaired working memory context maintenance and semantic inhibition in schizophrenia patients, and these impairments were related to clinical symptoms of schizophrenia. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Schizophrenia and normal aging have both been associated with structural and physiological changes in the prefrontal and temporal cortex and impairments in prospective memory (PM). This study aimed to compare PM performance in patients with schizophrenia, healthy older, and healthy younger individuals. Computerized event- and time-based PM tasks were administered to 30 patients with schizophrenia, 30 healthy older adults, and 30 healthy younger adults. The healthy older adults and patients with schizophrenia demonstrated deficits in time-based PM when compared with the healthy younger adults. However, only healthy older adults were found to be impaired in event-based PM when compared with the healthy younger adults. These findings suggest that patients with schizophrenia show a similar pattern of performance on one type but not another type of PM and provide only partial support for the accelerated aging hypothesis of schizophrenia.

Although there is a consensus that patients with schizophrenia have certain deficits in perceiving and expressing facial emotions, previous studies of facial emotion perception in schizophrenia do not present consistent results. The objective of this study was to explore facial emotion perception deficits in Chinese patients with schizophrenia and their non-psychotic first-degree relatives. Sixty-nine patients with schizophrenia, 56 of their first-degree relatives (33 parents and 23 siblings), and 92 healthy controls (67 younger healthy controls matched to the patients and siblings, and 25 older healthy controls matched to the parents) completed a set of facial emotion perception tasks, including facial emotion discrimination, identification, intensity, valence, and corresponding face identification tasks. The results demonstrated that patients with schizophrenia performed significantly worse than their siblings and younger healthy controls in accuracy in a variety of facial emotion perception tasks, whereas the siblings of the patients performed as well as the corresponding younger healthy controls in all of the facial emotion perception tasks. Patients with schizophrenia also showed significantly reduced speed than younger healthy controls, while siblings of patients did not demonstrate significant differences with both patients and younger healthy controls in speed. Meanwhile, we also found that parents of the schizophrenia patients performed significantly worse than the corresponding older healthy controls in accuracy in terms of facial emotion identification, valence, and the composite index of the facial discrimination, identification, intensity and valence tasks. Moreover, no significant differences were found between the parents of patients and older healthy controls in speed after controlling the years of education and IQ. Taken together, the results suggest that facial emotion perception deficits may serve as potential endophenotypes for schizophrenia.

Sensory gating deficit, as reflected by P50 suppression, has been demonstrated in schizophrenia. Despite extensive evidence of the irreversible effects of typical neuroleptics on this deficit, recent studies of atypical neuroleptics have produced inconsistent findings on the reversibility of P50 suppression in schizophrenia. As the majority of these studies were limited by either their cross-sectional design or the recruitment of patients on multiple medications, the current study was designed to examine the effects of different neuroleptic medications on the P50 sensory gating index in patients with first-episode, never-medicated schizophrenia. P50-evoked potential recordings were obtained from 62 normal controls when they entered the study and from 65 patients with first-episode, never-medicated schizophrenia at baseline and after six weeks of different neuroleptic treatments (sulpiride [n=24], risperidone [n=24] and clozapine [n=17]). The first-episode, never-medicated schizophrenia patients had impaired sensory gating relative to the normal controls (mean=94.19% [SD=61.31%] versus mean=41.22% [SD=33.82%]). The test amplitude S2 was significantly higher in the schizophrenia patients than in the normal controls. The conditioning amplitude S1 and the positive symptom scores were related to the P50 gating ratios in schizophrenia at baseline. There was no change in P50 sensory gating (P>0.10) and a significant improvement in the clinical ratings (P>0.10) after six-week neuroleptic treatment for schizophrenia. P50 sensory gating was not significant for the patients who received sulpiride, risperidone or clozapine at baseline (F=1.074, df=2, 62, P=0.348) or at endpoint (F=0.441, df=2, 62, p=0.646). Our findings indicate that there is P50 sensory gating impairment in first-episode, never-medicated schizophrenia and that treatment with typical and atypical antipsychotics has no significant impact on such gating in this illness.

While a number of studies have shown that individuals with schizophrenia are impaired on various types of prospective memory, few studies have examined the relationship between subjective and objective measures of this construct in this clinical group. The purpose of the current study was to explore the relationship between computer-based prospective memory tasks and the corresponding subjective complaints in patients with schizophrenia, individuals with schizotypal personality features, and healthy volunteers. The findings showed that patients with schizophrenia demonstrated significantly poorer performance in all domains of memory function except visual memory than individuals with schizotypal personality disorder and healthy controls. More importantly, there was a significant interaction effect of prospective memory type and group. Although patients with schizophrenia were found to show significantly poorer performance on computer-based measures of prospective memory than controls, their level of subjective complaint was not found to be significantly higher. While subjective complaints of prospective memory were found to associate significantly with self-reported executive dysfunctions, significant relationships were not found between these complaints and performance on a computer-based task of prospective memory and other objective measures of memory. Taken together, these findings suggest that subjective and objective measures of prospective memory are two distinct domains that might need to be assessed and addressed separately.

In this study, a new method for fabricating 3-D polyacrylamide gel microarrays was presented. In the method, a 3-D gel microarray was successfully fabricated by directly heating the slides with arrayed prepolymer at 80 degrees C for 2 min. The prepolymer on the microarray only contained 40% v/v raw/unpurified PCR products, 1.4% ammonium persulfate (APS), 6% acrylamide, and 20% glycerol and the balance H2O but no TEMED. The heat could induce the free radicals from APS to initiate polymerization of the 3-D gel and allow the incorporation of raw PCR products into the 3-D gel. The immobilized DNA on the gel microarray had the specificity of hybridization and the ability to distinguish base mismatch. It has been demonstrated that SNP genotyping of both the 194072 loci and the 252944 loci in the beta2 subunit gene of gamma-aminobutyric acid A receptor (GABRB2) gene was successfully performed by using the 3-D gel microarray. This method is efficient, simple, rapid, and easy to control in preparing a 3-D gel microarray, which would be widely used for various purposes in laboratory research and clinic application.

Although emerging evidence has suggested an association between the Val66Met (rs6265) polymorphisms in brain-derived neurotrophic factor (BDNF) gene and the panic disorder, the conclusion is inclusive given the mixed results. This meta-analysis reviewed and analyzed the recent studies addressing the potential association between the Val66Met polymorphisms and panic disorder susceptibility. Related case-control studies were retrieved by database searching and selected according to established inclusion criteria. Six articles were identified, which explored the association between the BDNF Val66Met polymorphism and panic disorder. Statistical analyses revealed no association for the allele contrast and the dominant model. However, the recessive model showed a significant association between the BDNF Val66Met polymorphism and panic disorder (odds ratio = 1.26, 95% confidence interval = 1.04-1.52, z = 2.39, P = 0.02). Despite of some limitations, this meta-analysis suggests that the Val66Met polymorphism of BDNF gene is a susceptibility factor for panic disorder.

Background We sought to investigate the clinical features of and risk factors for recurrent major depression (MD) with history of postpartum episodes (PPD) in Han Chinese women and the differences between first-onset postpartum MD (MD that has its first lifetime depressive episode in the postpartum period) and first-onset non-postpartum MD (MD with history of PPD and has its first lifetime depressive episode in a period other than postpartum). Methods Data were derived from the China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology (CONVERGE) study (N=6017 cases) and analyzed in two steps. We first examined the clinical features of and risk factors for MD patients with (N=981) or without (N=4410) a history of PPD. We then compared the differences between first-onset postpartum MD (N=583) and first-onset non-postpartum MD (N=398) in those with a history of PPD. Linear, logistic and multinomial logistic models were employed to measure the associations. Results A history of PPD was associated with more guilt feelings, greater psychiatric comorbidity, higher neuroticism, earlier onset and more chronicity (OR 0.2–2.8). Severe premenstrual symptoms (PMS) and more childbirths increased the risk of PPD, as did a family history of MD, childhood sexual abuse, stressful life events and lack of social support (OR 1.1–1.3). In the MD with history of PPD subsample, first-onset postpartum MD was associated with fewer recurrent major depressive episodes, less psychiatric comorbidity, lower neuroticism, less severe PMS and fewer disagreements with their husbands (OR 0.5–0.8), but more childbirths (OR 1.2). Limitations Data were obtained retrospectively through interview and recall bias may have affected the results. Conclusions MD with history of PPD in Han Chinese women is typically chronic and severe, with particular risk factors including severe PMS and more childbirths. First-onset postpartum MD and first-onset non-postpartum MD can be partly differentiated by their clinical features and risk factors, but are not clearly distinctive.

Very few studies have examined physical and social anhedonia across the spectrum of schizophrenia. In the present study, we recruited three groups of participants (n=84 in each group): patients with schizophrenia, schizotypy and non-schizotypy as assessed by the Schizotypal Personality Questionnaire (SPQ). All participants completed the self-reported trait anhedonia scales (the Revised Physical Anhedonia Scale and the Social Anhedonia Scale). The clinical symptoms of schizophrenia patients were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Scale for Assessment of Negative Symptoms (SANS). We found that the three groups differed in both physical and social anhedonia. The schizotypy group reported higher levels of physical anhedonia than the non-schizotypy group, and the patient group reported higher levels of physical anhedonia than the schizotypy group. For social anhedonia, the non-schizotypy group differed significantly from both the schizotypy and the patient group, while no significant difference was found between the last two groups. Our findings show that individuals with schizotypy exhibits similar social but not physical anhedonia compared with patients with schizophrenia, which further suggests that decreased pleasure experiences in the social environment may be a valuable target for identification and early intervention in high-risk populations.

The purpose of the current study was to explore the association of auditory P50 sensory gating (P50) and prepulse inhibition (PPI) of schizophrenia with polymorphisms in the CHRNA7 and COMT genes. One hundred and fourty patients with schizophrenia participated in this study. They were administered the tests P50 and PPI. Moreover, three single nucleotide polymorphisms (SNPs) (rs2337980, rs1909884 and rs883473) in CHRNA7 and three SNPs (rs4680, rs737865 and rs165599) in COMT were selected to be genotyped by polyacrylamide gel microarray techniques. P50 index showed significant reduction in S2 amplitude between wild-type and mutation groups in the COMT rs4680. S1 amplitude of mutation group in the COMT rs737865 was also lower compared to wild-type group. PPI index revealed a shorter pulse latency of mutation group in the rs4680. The suppression ratio of mutation group was lower in COMT rs165599. Negative findings were shown between comparisons in all the CHRNA7 SNPs. We find that P50 and PPI may be influenced by COMT rs4680 polymorphisms in schizophrenia; more excitingly, we find that P50 might be influenced by COMT rs737865 polymorphisms and PPI may be influenced by COMT rs165599 polymorphisms in schizophrenia, and their mutations are associated with the reduction of the risk of P50 or PPI defects in schizophrenia. Futher studies with a larger number of subjects are needed to verify the present findings.

The α7 nicotinic acetylcholine receptor (nAChR) is associated with cognitive and P50 auditory gating deficits in schizophrenia, and α7 nAChR agonists can potentially reverse these deficits. The authors examined multiple dosages of tropisetron, a partial agonist at the nAChR, for short-term effects on cognition and P50 deficits in schizophrenia.In a randomized double-blind design, 40 nonsmoking patients with schizophrenia who had P50 ratios greater than 0.5 and were stabilized on 3-6 mg/day of risperidone were randomly assigned to receive placebo (N=10) or oral tropisetron at 5 mg/day (N=10), 10 mg/day (N=10), or 20 mg/day (N=10). The authors measured P50 inhibitory gating and administered the Chinese-language version of the Repeatable Battery for the Assessment of Neuropsychological Status at baseline and after 10 days of treatment.After 10 days of treatment, all three daily doses of tropisetron significantly improved overall cognitive deficits, with 10 mg showing the greatest improvement for the immediate memory index score and 20 mg for the delayed memory index score on the cognitive battery. The P50 deficits were also improved, and that improvement was significantly correlated with cognitive improvement. Two patients in the 20 mg/day group dropped out because of adverse effects, but the other dosages were well tolerated.The improvement of cognition with tropisetron appeared to be associated with normalization in P50 deficits. Thus, α7 nAChR agonists appear to be a promising therapeutic approach for the treatment of cognitive deficits that are related to abnormal P50 suppression in schizophrenia.

Sensory gating deficits have been found in patients with schizophrenia and their unaffected relatives. However, the underlying neurobiological mechanism of this deficit remains unclear. Pre-clinical studies have implicated adenosine in sensory gating deficits in schizophrenia. Therefore, the current study investigated a possible relationship between peripheral adenosine A2A receptor (ADORA2A) and sensory gating indices (P50 measures) in medication-free schizophrenia (n = 31) and healthy (n = 21) groups. The effects of six-week antipsychotic treatment were examined. At baseline, schizophrenia patients showed impaired sensory gating compared to healthy controls. However, there was no significant difference in ADORA2A gene expression among groups. In addition, ADORA2A expression was not correlated with sensory gating at any time point. Following treatment, we found a significant upregulation of ADORA2A expression. Intriguingly, we observed a significant positive association between ADORA2A upregulation and baseline P50 amplitudes in the schizophrenia group. A main finding of the current pilot study is the upregulation of ADORA2A expression following treatment with antipsychotics. In addition, this upregulation was predicted by baseline P50 amplitude, an observation that awaits replication in an expanded sample.

Prospective memory (PM) is the ability to remember to carry out an intended action in the future and it is an important function for everyday living. Studies have found that the neural basis of PM is located mainly in the prefrontal lobes (particularly in Brodmann Area 10) and patients with schizophrenia have functional deficits in this area. The present study provided a meta-analytic review of PM performances in patients with schizophrenia in 11 studies. A total of 485 patients with schizophrenia and 409 controls were included. Results showed that patients with schizophrenia exhibited impairments in all time- (d=-1.33), event- (d=-0.827), and activity-based (d=-0.729) PM, with time-based PM more impaired than event-based PM. In addition, PM was found to be significantly correlated with negative symptoms (r=-0.18), general psychopathology (r=-0.168), medication dosage (r=-0.119), duration of illness (r=-0.131), age (r=-0.23), education (r=0.249), IQ (r=0.439) and premorbid IQ (r=0.356). It has theoretical and clinical implications. Theoretically, the results indicate time-based PM involves more initiation than event-based PM. Clinically, the results indicate patients on high dose of antipsychotic medication and with long duration of illness need special attention from care givers for PM problems.

Although a number of studies have found prospective memory (PM) impairment in patients with schizophrenia, very little is known about the PM performance in non-psychotic relatives of these patients. The current study aimed to explore the PM performance in non-psychotic first-degree relatives of these patients. Two groups of participants (26 non-psychotic first-degree relatives of schizophrenia patients and 26 healthy comparison participants) were administered three PM tasks (time-, event-, and activity-based) and a set of neurocognitive tests. Results showed that the relatives performed significantly worse than the comparisons on most indices of the PM tasks, with a similar pattern of impairment found in other neurocognitive measures. Together with findings from previous studies, results of the current study suggest that PM may be a potential endophenotype for schizophrenia.

This study examined anticipatory and consummatory pleasure in schizophrenia patients with and without negative symptoms. Negative symptom patients experienced less anticipatory pleasure than non-negative symptom patients; only one facet of consummatory pleasure was unaffected in negative schizophrenia. Greater pleasure deficits were correlated with more severe positive and negative symptoms.

Prospective memory (PM) refers to the ability to execute a delayed intention and is different from retrospective memory (RM) in its nature and underlying mechanism (e.g., intention formation, maintenance, detection of PM cue and intention execution). Although preliminary studies have found PM impairment in patients with schizophrenia, the nature and magnitude of this problem in this clinical group is not yet fully known. The current study aimed to further clarify the nature of this impairment in schizophrenia. Fifty-four patients with schizophrenia and fifty-four healthy volunteers matched on demographic variables, IQ and executive functions took part in the study. Time-, event-, and activity-based PM tasks and a set of neurocognitive tests were administered to the participants. Results showed that patients with schizophrenia performed significantly worse on all sub-types of PM tasks, even after controlling for neurocognitive functions such as working memory, verbal memory, visual memory, and executive function. These findings suggest PM deficit is a primary deficit rather than a secondary consequence of neurocognitive impairments in schizophrenia. Analysis found that PM deficits may be mainly due to the impairment of the cue detection and intention retrieval stage.

Although emerging evidence has suggested an association between the Val66Met (rs6265) polymorphisms in brain-derived neurotrophic factor (BDNF) gene and the panic disorder, the conclusion is inclusive given the mixed results. This meta-analysis reviewed and analyzed the recent studies addressing the potential association between the Val66Met polymorphisms and panic disorder susceptibility. Related case-control studies were retrieved by database searching and selected according to established inclusion criteria. Six articles were identified, which explored the association between the BDNF Val66Met polymorphism and panic disorder. Statistical analyses revealed no association for the allele contrast and the dominant model. However, the recessive model showed a significant association between the BDNF Val66Met polymorphism and panic disorder (odds ratio = 1.26, 95% confidence interval = 1.04-1.52, z = 2.39, P = 0.02). Despite of some limitations, this meta-analysis suggests that the Val66Met polymorphism of BDNF gene is a susceptibility factor for panic disorder.