Influence of More Than 5 Years of Continuous Exposure to Antipsychotics on Cerebral Functional Connectivity of Chronic Schizophrenia.

OBJECTIVE: To explore the effect of long-term antipsychotics use on the strength of functional connectivity (FC) in the brains of patients with chronic schizophrenia. METHOD: We collected resting-state functional magnetic resonance imaging from 15 patients with continuously treated chronic schizophrenia (TCS), 19 patients with minimally TCS (MTCS), and 20 healthy controls (HCs). Then, we evaluated and compared the whole-brain FC strength (FCS; including full-range, short-range, and long-range FCS) among patients with TCS, MTCS, and HCs. RESULTS: Patients with TCS and MTCS showed reduced full-/short-range FC compared with the HCs. No significant differences in the whole-brain FCS (including full-range, short-range, and long-range FCS) or clinical characteristics were identified between patients with TCS and MTCS. Additionally, the FCS in the right fusiform gyrus, right inferior temporal gyrus, and right inferior occipital gyrus negatively correlated with the duration of illness and positively correlated with onset age across all patients with chronic schizophrenia. CONCLUSIONS: Regardless of the long-term use of antipsychotics, patients with chronic schizophrenia show decreased FC compared with healthy individuals. For some patients with chronic schizophrenia, the influence of long-term and minimal/short-term antipsychotic exposure on resting-state FC was similar. The decreased full- and short-range FCS in the right fusiform gyrus, right inferior temporal gyrus, and right inferior occipital gyrus may be an ongoing pathological process that is not altered by antipsychotic interventions in patients with chronic schizophrenia. Large-sample, long-term follow-up studies are still needed for further exploration.

Neurocognitive effects of atypical antipsychotics in patients with first-episode schizophrenia.

Introduction: Cognitive impairment is a core feature of schizophrenia. The effects of atypical antipsychotics on the cognitive functions of patients with first-episode schizophrenia have not been comprehensively investigated so far. This study aims to compare neurocognitive effects of risperidone, olanzapine, and aripiprazole for first-episode schizophrenia.Methods: The study was a multicenter, randomized, open-label clinical trial. 546 patients were randomly divided into three medication groups, and followed up for 1 year. Cognitive performance was evaluated with a neuropsychological test battery. The Clinical trials.gov ID of the study is NCT01057849.Results: At 6 months, treatment resulted in significant improvements in all three groups in most cognitive domains except verbal learning and memory. At 12 months, three treatment groups had further improvements in three cognitive domains, but visual learning and memory performance dropped back to baseline.Conclusion: All three atypical antipsychotics tested in the study can potentially improve cognitive performance in first-episode schizophrenia, but no significant difference in the degree of improvement was found between drugs.

Trajectories of social function in patients with first-episode schizophrenia: Analysis of data from a 10-year follow-up study.

BACKGROUND: Patients with schizophrenia may have diverse functional outcomes. However, the long-term functional trajectories of patients with first-episode schizophrenia (FES) are unclear. METHODS: We extracted data from the Chinese First-Episode Schizophrenia Trial, a 10-year prospective study of antipsychotic-naïve patients with FES. We applied K means cluster modelling to longitudinal data on the social function of patients with FES and examined associations of the empirically derived trajectories with baseline clinical characteristics of the 10-year follow-up. OUTCOMES: Three distinct functional trajectories emerged: improving-favorable (39·3%), improving-poor (17·8%) and improving-stable (42·9%). All three trajectories demonstrated Personal and Social Performance (PSP) score improvement in the first six months. The improving-poor trajectory demonstrated PSP score decline during the second six months and thereafter, while PSP scores in the other two trajectories were mainly stable during the same period. Patients in the improving-favorable trajectory had higher baseline PSP scores than those in the improving-poor trajectory (OR=0·904 [0·852, 0·961], p < 0·05) and the improving-stable trajectory (OR=0·870 [0·825, 0·918], p < 0·001) and were more likely to be female than those in the improving-stable trajectory (OR=2·699 [1·030, 7·074], p < 0·05). CONCLUSIONS: Patients with FES demonstrated varied long-term functional recovery profiles. The first year, especially the second half of the first year, is a key period for social function interventions that improve long-term functional outcomes. Male patients and patients with poor baseline function may particularly benefit from such interventions.

Effect of Subanesthetic Dose of Esketamine on Perioperative Neurocognitive Disorders in Elderly Undergoing Gastrointestinal Surgery: A Randomized Controlled Trial.

Background: Perioperative neurocognitive disorders (PND), including delayed neurocognitive recovery (dNCR) and postoperative cognitive dysfunction (POCD), are common postoperative complications in elderly patients and adversely affect their prognosis. The study was designed to explore the effects of esketamine on postoperative cognitive function in elderly patients who underwent gastrointestinal surgery under general anesthesia and its potential mechanism. Methods: Eighty-four patients aged 65 and above undergoing gastrointestinal surgery were randomly divided into 2 groups: the esketamine group (group S) and the control group (group C). Group S received intravenous sub-anesthetic doses of esketamine (0.15 mg/kg) 5 minutes before the initiation of surgery, while group C received the same volume of saline. A battery of neuropsychological tests was used to assess cognitive function before surgery, 7 days, and 3 months after surgery. The primary outcome was the incidence of dNCR at 7 days postoperatively and POCD at 3 months postoperatively in both groups. The secondary outcome measures included changes in the levels of serum interleukin-6 (IL-6) and calcium-binding protein ß (S100ß) before and 1 day after surgery. Results: The incidence of dNCR in group S was lower than that of group C (18.15% vs 38.24% P=0.033). Contrarily, there was no difference in both groups regarding POCD 3 months postoperatively (6.06% vs 14.37% P=0.247). Plasma IL-6 and S100ß levels were significantly elevated in both groups on postoperative day 1 (p<0.05), but esketamine pretreatment reduced these levels to some extent compared with group C (p<0.05). Conclusion: Sub-anesthetic doses of esketamine might reduce the incidence of dNCR and improve early postoperative cognitive function in elderly patients undergoing gastrointestinal surgery, which might be related to the anti-neuroinflammation effects of esketamine.

Study of a possible role of the monoamine oxidase A (MAOA) gene in paranoid schizophrenia among a Chinese population.

Monoamine oxidase A (MAOA) is the enzyme responsible for degradation of several monoamines, such as dopamine and serotonin that are considered as being two of the most important neurotransmitters involved in the pathophysiology of schizophrenia. To study a possible role of the MAOA gene in conferring susceptibility to schizophrenia, the present study genotyped the variable number of tandem repeat (VNTR) polymorphism and 41 SNPs across this gene among 555 unrelated patients with paranoid schizophrenia and 567 unrelated healthy controls. Quantitative real-time PCR analysis was employed to quantify expression of MAOA mRNA in 73 drug-free patients. While none of these genotyped DNA markers showed allelic association with paranoid schizophrenia, haplotypic association was found for the VNTR-rs6323, VNTR-rs1137070, and VNTR-rs6323-rs1137070 haplotypes in female subjects. Nevertheless, no significant change of the expression of MAOA mRNA was detected in either female or male patients with paranoid schizophrenia. Our study suggests that the interaction between genetic variants within the MAOA gene may contribute to an increased risk of paranoid schizophrenia, but the precise mechanism needs further investigation.

[Three methods with functions of modification on aluminum borate whisker and with influence on flexural properties of dental composite resins].

The present paper is aimed to discuss the influence of three different ways on modification of aluminum borate whiskers (AlBw) and on flexural properties of dental composite resins. In Group A, AlBw and silicon dioxide (SiO2) nanoparticles were thermally fused directly under certain processes. In Group B, Si-O network was formed on the surface of AlBw via the sol-gel process of tetraethoxysilane, then thermally fused with SiO2 nanoparticles to form AlBw-SiO2 compound as inorganic fillers. In Group C, SiO2 nanoparticles were repaired by sol-gel method of tetraethoxysilane under certain processes, and were deposited in the surface of AlBw. The mixtures were fused with high temperature sintering method. The effects of the surface morphology of AlBw with different ways were characterized by TEM and SEM. Then the mixtures were polymerized with resin matrix after surface siliconization and their flexural strength and Young's modulus were determined. SEM was used to examine specimen fracture surfaces. The results showed that the flexural properties of dental composite resins were significantly improved after whiskers were modified. Different methods produce different effects. Flexural strength of the Group A is (95.28 +/- 4.53) MPa. The results of TEM and SEM revealed that the aggregation was obvious between AlBw and SiO2 nanoparticles. Flexural strength of the Group B was (123.14 +/- 17.37) MPa. The results of TEM and SEM revealed that the dispersity was improved but SiO2 nanoparticles also reunited. AlBw were modified with nanometer-size SiO2 particles which were prepared by sol-gel method based on tetraethyl orthosioate (TEOS), the flexural properties of a new type of dental composite resins was (130.29 +/- 8.38) MPa. The results of TEM and SEM revealed that better dispersion between AlBw and SiO2 nanoparticles occurred. The SiO2 nanoparticles were fused and attached onto the surface of AlBw uniformly.

Lipid storage myopathy due to late-onset multiple Acyl-CoA dehydrogenase deficiency with novel mutations in ETFDH: A case report.

Background: Lipid storage myopathy (LSM) is an autosomal recessive inherited lipid and amino metabolic disorder with great clinical heterogeneity. Variations in the electron transfer flavoprotein dehydrogenase (ETFDH) gene cause multiple acyl-CoA dehydrogenase deficiency (MADD), and have a manifestation of LSM. Muscle biopsy helps clarify the diagnosis of LSM, and next-generation sequencing (NGS) can be useful in identifying genomic mutation sites. The diagnosis of MADD contributes to targeted therapy. Case presentation: We report on a teenager who appeared to have muscle weakness and exercise intolerance at the onset. Before the referral to our hospital, he was unsuccessfully treated with glucocorticoid for suspected polymyositis. The next-generation sequencing of the proband and his parents revealed heterozygous variations, c.365G>A (p.G122D) inherited from the father, c.176-194_176-193del, and c.832-316C>T inherited from the mother in the ETFDH gene. The tandem mass spectrometry identified the mutations to be pathogenic. However, his parents and his younger sister who were detected with a mutation of c.365G>A presented no clinical symptoms. This indicates that the combination of the three compound heterozygous mutations in ETFDH is significant. After MADD was diagnosed, a dramatic clinical recovery and biochemical improvement presented as riboflavin was given to the patient across a week, which further confirmed the diagnosis of MADD. Conclusion: Our observations extend the spectrum of ETFDH variants in Chinese the population and reinforce the role of NGS in diagnosis of MADD. Early diagnosis and appropriate treatment of LSM lead to great clinical efficacy and avoid some lethal complications.

[Neurocognitive performance in the patients with first-episode schizophrenia and their independent first-degree relatives: a cross-sectional study].

OBJECTIVE: To evaluate neurocognitive performance in first-episode schizophrenic patients and unaffected first-degree relatives of different patients samples. METHODS: A total of 42 patients with first-episode schizophrenia, 24 unaffected first-degree relatives and 40 healthy individuals, matched with age, gender and years of education, were recruited from both outpatients and inpatients after being diagnosed with structured tool (SCID-I/P). Subjects' cognitive performance was evaluated by a set of neuropsychological test battery, which assessed four cognitive domains including learning and memory, motor skills, speed of processing and executive function. RESULTS: Healthy individuals performed better than first-episode schizophrenic patients in nearly all cognitive domains (ES=0.63-1.54) with exception of inhibition sub-domain. first-degree relatives showed moderate impairment in verbal learning (ES=0.62), digital symbol (ES=1.05), symbol search (ES=1.18), animal category (ES=0.80) and WCST perseverate errors (ES=0.68). Degree of impairment in first-degree relatives was less than that in the patients. CONCLUSION: Patients with first-episode schizophrenia have global neurocognitive deficits. Independent first-degree relatives also have deficits in some neurocognitive domains, with a moderate degree between patients and normal controls. Our results indicate that neurocognitive performance may be viewed as a biomarker for candidates reflecting genetic liability for schizophrenia.

Which Subgroup of First-Episode Schizophrenia Patients Can Remit During the First Year of Antipsychotic Treatment?

OBJECTIVE: To investigate the persistent remission rate (PRR) and its predictors within the first year of antipsychotic treatment in first-episode schizophrenia (FES) patients. METHODS: In a sample of 301 FES patients who remained in antipsychotic treatment for 1 year, we assessed symptoms with the Positive and Negative Syndrome Scale (PANSS), cognition in six domains and functioning with the Personal and Social Performance Scale (PSP). RESULTS: In total, 75.4% (227/301) of FES patients remaining in antipsychotic treatment reached persistent remission (PR) in one year. The PSP score was higher in remitters than non-remitters at the endpoint of the 1-year follow-up (P <0.0001). The PANSS negative score-but not the PANSS total score, positive score or general psychopathological score; PSP score; or cognitive performance at baseline-was negatively associated with PR. Lower scores for "abstract thinking" and "stereotyped thinking" were independent predictors of PR. CONCLUSIONS: In FES, nearly 3/4 patients could achieve PR with 1 year of antipsychotic treatment, and having fewer negative symptoms, especially thinking and volition symptoms, can predict PR. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT01057849.

Sustained attention deficit along the psychosis proneness continuum: a study on the Sustained Attention to Response Task (SART).

BACKGROUND: Sustained attention deficits have been associated with schizophrenia. However, these findings were limited to patients with schizophrenia and cannot be generalized to a wider nonclinical sample with schizotypal personality features. OBJECTIVES: This study aimed to examine the sensitivity of a theory-driven test, the Sustained Attention Response to Task (SART), in individuals with schizotypal personality features. We also investigated the relationships between different parameters of SART and different dimensions of schizotypal features. METHODS: One hundred and ninety-nine participants (74 individuals with schizophrenia, 69 individuals with psychometrically determined schizotypal features, and 56 healthy controls) took part in this study. Participants scoring in the top 10% of the Schizotypal Personality Questionnaire (SPQ) score were identified as having schizotypal features, and those scoring in the bottom 10% were recruited as healthy controls. All participants were administered the SART in an experimental cubicle. RESULTS: The findings indicated that: (1) significant differences were found in SART commission error and sensitivity between the 3 experimental groups, with patients with schizophrenia and individuals with schizotypal features performing worse than healthy controls; (2) there was a trend toward statistical significance for SART efficiency score and d', with controls performing better than patients with schizophrenia and individuals with schizotypal features; (3) some associations between some SART indices and schizotypal traits were found; and (4) there was no significant relationship between SART indices and clinical symptoms in patients with schizophrenia in this study. CONCLUSIONS: : This investigation demonstrated the potential value of a relatively new sustained attention paradigm for research in schizophrenia spectrum disorders.

[Progress in the studies of methods for testing cytotoxicity of dental biomaterial].

The favorable biocompatibility of dental biomaterial is very important, which guarantees the safety and effectiveness of its clinical application. The cytotoxicity test, as one of the biological evaluation screening tests, is known to be an important and frequently used method to evaluate biocompatibility of biomaterials. This text is devoted to an overview of the cytotoxicity test for dental materials.

Preoperative anxiety induces chronic postoperative pain by activating astrocytes in the anterior cingulate cortex region.

OBJECTIVE: The study aims to explore the relationship between preoperative anxiety and chronic postoperative pain. METHODS: A total of forty rats were divided into four groups, control, single-prolonged stress alone, Hysterectomy alone, and SPS+ Hysterectomy. The paw withdrawal mechanical thresholds (PWMT) were examined. qRT-PCR and western blotting assay were performed to detect the GFAP expression in astrocytes isolated from the anterior cingulate cortex (ACC) region. In addition, the long-term potentiation (LTP) in ACC was examined. RESULTS: Rats in the SPS group or the Hysterectomy alone group had no significant effect on chronic pain formation, but SPS can significantly induce chronic pain after surgery. Astrocytes were still active, and the LTP was significantly increased three days after modeling in the SPS+Hysterectomy group. CONCLUSIONS: anxiety can induce chronic pain by activating astrocytes in the ACC region.

An open-label randomised comparison of aripiprazole, olanzapine and risperidone for the acute treatment of first-episode schizophrenia: Eight-week outcomes.

PURPOSE: This study aimed to investigate the efficacy and tolerability of aripiprazole, olanzapine and risperidone in first-episode schizophrenia (FES). METHODS: The eight-week, open, randomised study was conducted in six Chinese medical centres. Altogether, 498 FES subjects were randomised to aripiprazole (n = 165), olanzapine (n = 168) or risperidone (n = 165). Efficacy was measured with the Positive and Negative Syndrome Scale (PANSS), tolerability with the Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU) and functioning with the Personal and Social Performance Scale (PSP). RESULTS: All three antipsychotics significantly improved the baseline to end-point PANSS total and each of the sub-scale scores (p < 0.001). Risperidone was superior to olanzapine and aripiprazole regarding PANSS total end-point scores (p < 0.05). Cumulative response (PANSS total score reduction ⩾30%) was similar between risperidone, olanzapine and aripiprazole (74.8%, 73.5% and 70.1%; p = 0.707), but risperidone was superior to aripiprazole regarding PANSS total score reduction ⩾50% (37.8% vs. 26.6%; p < 0.05). Olanzapine was associated with the largest weight gain at week 4 and 8 (p < 0.01), weight gain ⩾7% (olanzapine = 49.0% vs. risperidone = 32.5% vs. aripiprazole = 17.0%; p < 0.01), more psychic side effects at week 8 (p < 0.01 each) and more 'other' side effects at week 4 (p < 0.001) and week 8 (p < 0.05) but fewer neurological side effects at week 4 (p < 0.05) and week 8 (p < 0.01). PSP improved more with risperidone than with aripiprazole at week 4 and 8 (p < 0.05). CONCLUSIONS: For FES, risperidone might be a better choice than aripiprazole due to improved efficacy and functional improvement, without inferior tolerability. Aripiprazole is a better choice to avoid relevant short-term weight gain. Olanzapine could be chosen to avoid neurological adverse effects.

Rates and predictors of one-year antipsychotic treatment discontinuation in first-episode schizophrenia: Results from an open-label, randomized, "real world" clinical trial.

Antipsychotic treatment discontinuation is a major challenge in the treatment of first-episode schizophrenia (FES) patients. However, the rate and predictors remain unclear. Five hundred and sixty-nine FES patients were randomized to risperidone (n = 190), olanzapine (n = 185) or aripiprazole (n = 194) in a six-site study in China with 1-year follow-up. Patients failing the initially assigned antipsychotic were switched to one of the other 2 antipsychotics. By 52 weeks, 47.1% of FES patients discontinued all antipsychotics. In the 8-week acute phase, an antipsychotic switch was protective against antipsychotic discontinuation, whereas higher positive symptoms at the endpoint predicted discontinuation. In the maintenance phase, discontinuation was predicted by male gender and higher CGI-S score at the endpoint. The findings indicate that in China nearly half of patients with FES discontinued antipsychotic treatment during one year treatment. Clinicians should employ strategies other than medication choice to keep them from discontinuing.

Prospective memory in schizophrenia: further clarification of nature of impairment.

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.

Objective measures of prospective memory do not correlate with subjective complaints in schizophrenia.

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.

Preparation of rapamycin-loaded chitosan/PLA nanoparticles for immunosuppression in corneal transplantation.

Rapamycin-loaded chitosan/polylactic acid nanoparticles with size of about 300 nm in diameter were prepared through nanoprecipitation method using cholesterol-modified chitosan as a stabilizer. The surface coating of chitosan, which was demonstrated by zeta potential measurement, endowed the nanoparticles good retention ability at the procorneal area, facilitating the sustained release of rapamycin on the corneal. The immunosuppression in corneal transplantation of the nanoparticles was investigated using rabbit as animal model, the median survival time of the corneal allografts treated with nanoparticles was 27.2+/-1.03 days and 50% grafts still remained surviving by the end of the observation, while the group treated with 0.5% rapamycin suspension was 23.7+/-3.20 days. The median survival time of drug-free nanoparticles group and untreated groups were 10.9+/-1.45 and 10.6+/-1.26 days, respectively. The results demonstrated the excellent immunosuppression of rapamycin-loaded chitosan/polylactic acid nanoparticles in corneal transplantation.

[Effects of body-shade resin layer thickness on the color of polyetheretherketone-Crea.lign restorations].

OBJECTIVE: This study aims to assess the effects of the different thicknesses of body-shade resin layers on the color of polyetheretherketone (PEEK)-Crea.lign restorations. METHODS: Five PEEK specimens with the thickness of 0.6 mm were prepared. The color values of PEEK specimens were measured. Afterward, opaque-shade resin layers (0.1 mm) and body-shade resin layers (1.5 mm) were stacked with mold. The five specimens were evenly ground to a thickness of 1.4, 1.2, 1.0, 0.8, 0.6, 0.4, 0.2, and 0.0 mm in sequence. After grinding and ultrasonic cleaning, the color value was measured. RESULTS: With the constant thickness of PEEK and 0.1 mm thickness of opaque-shade resin layer, the L*, a*, and b* values all showed downward trend with the increased thickness of the body-shade resin layer (1.0-1.4 mm). With the constant thickness of PEEK and 0.1 mm thickness of opaque-shade resin layer, the color difference between the adjacent groups was less than 1.5 NBS. This difference between nonadjacent groups was more than 1.5 NBS when the thickness of the body-shade resin layer reached 0.6 mm. Color difference between PEEK-Crea.lign restoration and PEEK was more than 1.5 NBS. CONCLUSIONS: The thickness change in the body-shade resin layers influence the color of the PEEK-Crea.lign restorations. Using A2 shade Crea.lign, opaque-shade resin layer thickness is 0.1 and 0.6 mm thickness of body-shade resin layer can produce color which clinically acceptable.

An association study between polymorphisms in five genes in glutamate and GABA pathway and paranoid schizophrenia.

Dysfunctions of glutamatergic and GABAergic neurotransmission are two important hypotheses for the pathogenesis of schizophrenia. Thus, genes in the pathway are candidates for schizophrenia susceptibility. Phosphate-activated glutaminase (GLS), glutamine synthetase (GLUL), glutamic acid decarboxylase (GAD), GABA transaminase (ABAT) and succinic semialdehyde dehydrogenase (ALDH5A1) are five primary enzymes in glutamate and GABA synthetic and degradative pathway. In order to investigate the possible involvement of these genes in the development of paranoid schizophrenia, we genotyped 80 paranoid schizophrenics from northern China and 108 matched controls by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) methods or directly sequencing of PCR product. Seven SNPs were found to be polymorphic in the population investigated. No significant differences in the genotype distributions or allele frequencies between patients and controls were found. Therefore, we conclude the polymorphisms studied in the five genes do not play major roles in pathogenesis of paranoid schizophrenia in the population investigated.

Detection of circulating miRNA levels in schizophrenia.

OBJECTIVE: Diagnosis of schizophrenia is currently dependent on symptom-based criteria and lacks objective indicators. In this study, the authors investigated whether circulating miRNA can serve as a diagnostic biomarker for schizophrenia. METHODS: Global plasma miRNAs were profiled in a test cohort of 164 schizophrenia patients and 187 control subjects, using Solexa sequencing, TaqMan Low Density Array, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. The captured miRNAs were then validated by qRT-PCR assays in an independent cohort of 400 schizophrenia patients, 213 control subjects, and 162 patients with nonschizophrenia psychiatric disorders; the 400 schizophrenia patients underwent a 12-month follow up study of regular treatment with an atypical antipsychotic (risperidone and aripiprazole). RESULTS: The global plasma miRNA screening revealed eight miRNAs that were up-regulated in schizophrenia, as revealed by both assay platforms. The qRT-PCR analysis showed the up-regulation of miR-130b and miR-193a-3p in schizophrenia but not in nonschizophrenia disorders. CONCLUSIONS: The up-regulation of miR-130b and miR-193a-3p is a state-independent biomarker for schizophrenia, and these two miRNAs could be used to develop a diagnostic tool for schizophrenia.