Publications by authors named "Shiping Xie"

45 Publications

Correlation between cognitive deficits and dorsolateral prefrontal cortex functional connectivity in first-episode depression.

J Affect Disord 2022 09 22;312:152-158. Epub 2022 Jun 22.

Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China. Electronic address:

Introduction: Although depression is commonly accompanied by cognitive deficits, the underlying mechanism remains unclear. One possibility is that such deficits are related to abnormal brain network connections. The purpose of this study was thus to investigate changes in brain functional connectivity (FC) in depression and its relationship with cognitive deficits.

Methods: We enrolled 37 first-episode MDD patients and 53 matched healthy controls (HC). All participants completed clinical and neurocognitive assessments and underwent resting-state functional MRI. Seed-based analysis was used to define the dorsolateral prefrontal cortex (DLPFC) and FC analysis was then performed. We used bias correlation to analyze the correlation between FC and clinical and neurocognitive scores.

Results: MDD patients showed increased FC of the right DLPFC with the left inferior temporal gyrus, left cuneus, right inferior frontal gyrus, right anterior cingulate cortex, left BA39, right angular gyrus, right precuneus, left middle frontal gyrus, and right precentral gyrus. MDD patients also showed stronger FC in the left thalamus and reduced FC between the left superior occipital gyrus and left DLPFC seed region. Interestingly, increased FC was related to disease severity (with the right precentral gyrus) and social cognitive dysfunction (with the right angular gyrus) in MDD patients.

Limitations: The sample size was relatively small and it is unclear how age may influence FC changes in patients with depression.

Conclusions: These findings support changes in FC of the DLPFC in early MDD patients related to cognitive function. FC is a potential biomarker for the diagnosis of MDD.
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http://dx.doi.org/10.1016/j.jad.2022.06.024DOI Listing
September 2022

Shared genetics between autism spectrum disorder and attention-deficit/hyperactivity disorder and their association with extraversion.

Psychiatry Res 2022 Aug 13;314:114679. Epub 2022 Jun 13.

Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing 210029, China; Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address:

Background: Deciphering the genetic relationships between autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) may uncover underlining shared pathophysiology as well as inform treatment.

Methods: The summary results of genome-wide association studies on ADHD, ASD, and extraversion were utilized for the analyzes. Genetic correlations between ADHD, ASD, and extraversion were tested using linkage disequilibrium score regression. Causal relationships between ADHD, ASD, and extraversion were investigated using Mendelian randomization (MR) analysis. Novel pleiotropic genomic loci shared by ADHD and ASD were identified using a cross-trait meta-analysis.

Results: Extraversion was positively correlated with ADHD (r = 0.205) and negatively correlated with ASD (r = -0.193). The MR analysis showed that ADHD confers a causal effect on ASD (OR: 1.35, 95% confidence interval (CI):1.20-1.52) and vice versa (1.46, 1.38-1.55). Extraversion exerts a causal effect on ADHD only (1.19, 1.05-1.33). The cross-trait meta-analysis identified three novel pleiotropic genomic loci for ADHD and ASD, involving two pleiotropic genes, LINC00461 and KIZ.

Conclusions: Our study provides new insights into the shared genetics of ADHD and ASD and their connections with extraversion.
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http://dx.doi.org/10.1016/j.psychres.2022.114679DOI Listing
August 2022

Global functioning, cognitive function, psychopathological symptoms in untreated patients with first-episode schizophrenia: A cross-sectional study.

Psychiatry Res 2022 07 9;313:114616. Epub 2022 May 9.

Psychiatry Department, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. Electronic address:

Although many studies have been conducted on the relationship between cognitive functioning, psychopathological symptoms, and global functioning in patients with schizophrenia, these studies frequently suffer from a lack of control for confounding variables, high attrition rates, and a lack of cognitive domains completed at each assessment point. The purpose of this study is to select patients with untreated first-episode schizophrenia to investigate the relationship between psychopathological symptoms, cognitive functioning, and global functioning. A total of 117 untreated first-episode schizophrenia patients were evaluated using the global assessment functions (GAF), the Positive And Negative Syndrome Scale (PANSS), the MATRICS Consensus Cognitive Battery (MCCB), and some social and role functional parameters. The GAF, PANSS, and MCCB scores of 117 patients were significantly lower than normal. Multiple stepwise linear regression analysis revealed that the negative symptom factor, positive symptom factor, excitation-hostility factor, and attention/vigilance were all independent factors influencing global functioning. Our findings show that the negative symptom factor, the positive symptom factor, the excitement hostility factor, and attention/vigilante are all independent risk factors for GAF in first-episode schizophrenia. The negative symptom factor had the most noticeable effect among these influencing factors, followed by the positive symptom factor, the excitement hostility factor, and attention/vigilance in that order.
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http://dx.doi.org/10.1016/j.psychres.2022.114616DOI Listing
July 2022

Aberrant cortical surface and cognition function in drug-naive first-episode schizophrenia.

Ann Gen Psychiatry 2022 Feb 10;21(1). Epub 2022 Feb 10.

Department of Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, 210029, China.

Objective: Impaired cognitive function is a central symptom of schizophrenia and is often correlated with inferior global functional outcomes. However, the role of some neurobiological factors such as cortical structure alterations in the underlying cognitive damages in schizophrenia remains unclear. The present study attempted to explore the neurobiomarkers of cognitive function in drug-naive, first-episode schizophrenia by using structural magnetic resonance imaging (MRI).

Methods: The present study was conducted in patients with drug-naive, first-episode schizophrenia (SZ) and healthy controls (HCs). MRI T1 images were pre-processed using CAT12. Surface-based morphometry (SBM) was utilised to evaluate structural parameters such as cortical thickness and sulcus depth. The positive and negative syndrome scale (PANSS) and Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus cognitive battery (MCCB) were employed to estimate the psychotic symptoms and cognition, respectively.

Results: A total of 117 patients with drug-naive first-episode schizophrenia (SZ) and 98 healthy controls (HCs) were included. Both the cortical thickness and sulcus depth in the frontal lobe were lower in patients with SZ than in the HCs under family-wise error correction (p < 0.05). Attention and visual learning in MCCB were positively correlated with the right lateral orbitofrontal cortical thickness in the patients with SZ (p < 0.01).

Conclusions: The reduced surface value of multiple cortical structures, particularly the cortical thickness and sulcus depth in the frontal lobe, could be the potential biomarkers for cognitive impairment in SZ.
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http://dx.doi.org/10.1186/s12991-022-00381-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830089PMC
February 2022

Efficacy and safety of aripiprazole once-monthly versus oral aripiprazole in Chinese patients with acute schizophrenia: a multicenter, randomized, double-blind, non-inferiority study.

Psychopharmacology (Berl) 2022 Jan 6;239(1):243-251. Epub 2022 Jan 6.

The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Lane, Dewai Avenue, Xicheng District, Beijing, 100088, China.

Objective: The present study aimed to evaluate the efficacy and safety of aripiprazole once-monthly (AOM) compared to oral aripiprazole in treating acute schizophrenia.

Methods: This randomized, double-blind, non-inferiority study recruited patients from 15 trial sites across China from May 2017 to April 2019. Patients with an acute psychotic episode received AOM at 400 mg or oral aripiprazole at 10-20 mg for 12 weeks. The primary and secondary efficacy endpoints were the difference in scores from baseline to week 10, as assessed on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions-Severity (CGI-S) scores, respectively.

Results: A total of 436 patients were randomized. Among them, 159/218 (72.9%) and 165/218 (75.7%) in the AOM and oral aripiprazole groups completed 10 weeks of treatment, respectively. The least-squares (LS) mean changes from baseline to endpoint (week 10) in PANSS were - 33.6 for the AOM group and - 34.8 in the oral aripiprazole group, respectively, with a difference of - 1.2 (95% CI: - 4.1, 1.7). The non-inferiority margin of AOM to oral aripiprazole was - 4.1, which was above the lower limit of the pre-defined margin. The altered CGI-S score was - 2.2 and - 2.3 in the AOM and oral aripiprazole groups, respectively. The incidence of treatment-emergent adverse events (TEAEs) was similar in both groups. The rate of discontinuation due to TEAEs was 2.3% and 3.2% in the AOM and oral aripiprazole groups, respectively.

Conclusions: This study confirmed the efficacy and safety of AOM for the treatment of Chinese patients with acute schizophrenia. The non-inferiority of AOM to oral aripiprazole was established, with comparable efficacy and tolerability. These findings suggested that AOM could be used as a treatment option for patients experiencing an acute episode of schizophrenia.

Trial Registration: ClinicalTrials.gov identifier: NCT03172871.
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http://dx.doi.org/10.1007/s00213-021-06044-xDOI Listing
January 2022

The Relationship Between Abnormal Resting-State Functional Connectivity of the Left Superior Frontal Gyrus and Cognitive Impairments in Youth-Onset Drug-Naïve Schizophrenia.

Front Psychiatry 2021 13;12:679642. Epub 2021 Oct 13.

Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.

Age of onset is one of the heterogeneous factors in schizophrenia, and an earlier onset of the disease indicated a worse prognosis. The left superior frontal gyrus (SFG) is involved in numerous cognitive and motor control tasks. Hence, we explored the relationship between abnormal changes in SFG resting-state functional connectivity (rsFC) and cognitive function in the peak age of incidence to understand better the pathophysiological mechanism in youth-onset drug-naïve schizophrenia to search for reliable biomarkers. About 66 youth-onset drug-naïve schizophrenia patients and 59 healthy controls (HCs) were included in this study. Abnormal connectivity changes in the left SFG and whole brain were measured using the region of interest (ROI) rsFC analysis method. The cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB), and the severity of the clinical symptoms was evaluated by positive and negative syndrome scale (PANSS). Furthermore, we analyzed the relationships among abnormal FC values, cognition scores, and clinical symptoms. We found decreased FC between left SFG and bilateral precuneus (PCUN), right hippocampus, right parahippocampal gyrus, left thalamus, left caudate, insula, and right superior parietal lobule (SPL), whereas increased FC was seen between the left SFG and right middle frontal gyrus (MFG) in the youth-onset drug-naïve schizophrenia group, compared with HCs. Meanwhile, the -scores were lower in each cognitive domain than HCs. Moreover, in the youth-onset drug-naive schizophrenia group, the insula was negatively correlated with processing speed. No significant correlations were found between the FC-value and PANSS score. Our findings suggest widespread FC network abnormalities in the left SFG and widespread cognitive impairments in the early stages of schizophrenia. The dysfunctional connectivity of the left SFG may be a potential pathophysiological mechanism in youth-onset drug-naïve schizophrenia.
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http://dx.doi.org/10.3389/fpsyt.2021.679642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548582PMC
October 2021

Altered resting-state functional connectivity of the right precuneus and cognition between depressed and non-depressed schizophrenia.

Psychiatry Res Neuroimaging 2021 11 6;317:111387. Epub 2021 Sep 6.

Department of Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, China.

The study investigated the resting-state functional connectivity (FC) and cognitive changes in patients with depressed schizophrenia(DS) and non-depressed schizophrenia(NDS). Eighty patients with first-episode schizophrenia and 50 healthy controls (HC) were included to conduct resting-state fMRI. All participants completed MATRICS Consensus Cognitive Battery (MCCB). The right precuneus was selected as the seed in whole-brain FC analysis. Our results showed the cognitive function (All MCCB dimensions) of all schizophrenia patients were worse than HC, but no differences were found between DS and NDS. The DS had decreased FC than NDS between the right precuneus and left middle cingulate gyrus, left cerebellum, right cerebellum. The DS had increased FC than HC between the right precuneus and temporal lobe, occipital lobe, and decreased FC between the right precuneus and left cerebellum. However, the NDS had increased FC than HC between the right precuneus and left cerebellum, right cerebellum, temporal lobe, occipital lobe, left superior parietal lobule. Correlation analysis showed that FC between the right precuneus and occipital lobe was negatively correlated with visual learning in DS and with social cognition in NDS. Our results suggest DS and NDS patients have different patterns of FC, and their FC changes correlate with different domains of cognition.
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http://dx.doi.org/10.1016/j.pscychresns.2021.111387DOI Listing
November 2021

Regional Homogeneity Brain Alterations in Schizophrenia: An Activation Likelihood Estimation Meta-Analysis.

Psychiatry Investig 2021 Aug 2;18(8):709-717. Epub 2021 Aug 2.

Department of Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.

Objective: Resting state functional magnetic resonance imaging (rsfMRI) provides a lot of evidence for local abnormal brain activity in schizophrenia, but the results are not consistent. Our aim is to find out the consistent abnormal brain regions of the patients with schizophrenia by using regional homogeneity (ReHo), and indirectly understand the degree of brain damage of the patients with drug-naive first episode schizophrenia (Dn-FES) and chronic schizophrenia.

Methods: We performed the experiment by activation likelihood estimation (ALE) software to analysis the differences between people with schizophrenia group (all schizophrenia group and chronic schizophrenia group) and healthy controls.

Results: Thirteen functional imaging studies were included in quantitative meta-analysis. All schizophrenia group showed decreased ReHo in bilateral precentral gyrus (PreCG) and left middle occipital gyrus (MOG), and increased ReHo in bilateral superior frontal gyrus (SFG) and right insula. Chronic schizophrenia group showed decreased ReHo in bilateral MOG, right fusiform gyrus, left PreCG, left cerebellum, right precuneus, left medial frontal gyrus and left anterior cingulate cortex (ACC). No significant increased brain areas were found in patients with chronic schizophrenia.

Conclusion: Our findings suggest that patients with chronic schizophrenia have more extensive brain damage than FES, which may contribute to our understanding of the progressive pathophysiology of schizophrenia.
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http://dx.doi.org/10.30773/pi.2021.0062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390947PMC
August 2021

Screening of the college students at clinical high risk for psychosis in China: a multicenter epidemiological study.

BMC Psychiatry 2021 05 17;21(1):253. Epub 2021 May 17.

Department of Psychiatry, Tongji Hospital of Tongji University, Tongji University School of Medicine, 389 Xincun Road, Shanghai, 200065, PR China.

Background: To investigate a 3-stage screening procedure and explore the clinical features of subjects at Clinical High Risk (CHR) for psychosis in a representative sample of Chinese college students.

Methods: An epidemiological survey of the prevalence of the CHR syndrome in Chinese college students that was selected by stratified random sampling from Shanghai, Nanjing and Nanchang cities was done following a 3-stage procedure. Participants were initially screened with the Prodromal Questionnaire-brief version (PQ-B), and whose distress score of PQ-B exceeded 24 would be invited to a telephone assessment using the subscale for positive symptoms of the Scale of Prodromal Symptoms (SOPS)/Structured Interview for Prodromal Syndromes (SIPS). Lastly, participants who scored 3 or higher in any item of the subscale would be administered with the SIPS interview conducted by trained researchers to confirm the diagnosis of CHR syndrome.

Results: Twenty-three thousand sixty-three college students completed the survey during September 2017 to October 2018. Seventy-two students were diagnosed as CHR subjects, and the detection rate in the total sample was 0.3%. The peak age range for the first diagnosis of CHR was 17 to 20 years. Thirteen and forty-six were set as the cutoff points of PQ-B total score and distress score to balance the greatest sensitivity and specificity. Binary logistic regression revealed that 8 items in PQ-B showed significant distinction for detecting CHR subjects.

Conclusions: The 3-stage screening method can be utilized in the detection of CHR subjects for psychosis in the general population, during which delusional ideas, perceptual abnormalities and suspiciousness deserve great attention.
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http://dx.doi.org/10.1186/s12888-021-03229-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127262PMC
May 2021

Preparation of Methyltriazolo[1,4]benzodiazepine via Oxidative Activation of a Thiolactam for the Synthesis of BET Inhibitor Molibresib.

J Org Chem 2022 02 20;87(4):1961-1970. Epub 2021 Apr 20.

Product Development and Supply, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, United States.

A novel oxidative activation of a thiolactam was developed for the preparation of methyltriazolo[1,4]benzodiazepine in a single step. A sulfenic acid (R-SOH) was proposed as the activated intermediate with the concurrent formation of acetylhydrazone from acethydrazide and cyclocondensation to the triazole. A version of the method with 35% peracetic acid was scaled up to 40 kg as a part of the new route for the synthesis of BET inhibitor molibresib (GSK525762). The thiolactam was prepared from commercially available (2-amino-5-methoxyphenyl)(4-chlorophenyl)methanone in two steps in 66% yield. The concise four-step synthesis delivered 52 kg of molibresib of >99.9% ee in an overall 41% yield from the ketone. The condition for the methyltriazole was mild and free of racemization of the sensitive stereocenter. The oxidative method, with several advantages to the known methods, should be applicable to the synthesis of alkyltriazoles from other thiolactams and acylhydrazines.
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http://dx.doi.org/10.1021/acs.joc.1c00563DOI Listing
February 2022

Abnormal regional homogeneity (ReHo) and fractional amplitude of low frequency fluctuations (fALFF) in first-episode drug-naïve schizophrenia patients comorbid with depression.

Brain Imaging Behav 2021 Oct 31;15(5):2627-2636. Epub 2021 Mar 31.

Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China.

The current study aimed to characterize the regional homogeneity (ReHo) or fractional amplitude of low frequency fluctuations (fALFF) alterations in first-episode drug-naïve schizophrenia comorbid with depression. Sixty-nine first-episode drug-naïve schizophrenia patients and 34 healthy controls (HC) were included in the final analysis. Schizophrenia patients were divided into depressive patients (DP) and non-depressive patients (NDP), with 35 and 34 patients respectively, using the Hamilton Rating Scale for Depression -17(HRSD-17). All participants underwent resting-state fMRI (rs-fMRI), the fALFF (slow-4 and slow-5 bands) and ReHo were used to process the data. The results revealed eleven brain regions with altered slow-5 fALFF, eleven brain regions with altered slow-4 fALFF and ten brain regions with altered ReHo among DP, NDP and HC groups. Compared to NDP, the DP group had increased slow-5 fALFF in the Right Inferior Temporal Gyrus, increased ReHo in the Right Superior and Inferior Frontal Gyrus. The altered slow-5 fALFF in the Right Inferior Temporal Gyrus, altered ReHo in the Right Inferior Frontal Gyrus and Superior Frontal Gyrus were all positively correlated with the depressive symptoms in patients. However, there were no significant differences in slow-4 fALFF between DP and NDP groups. Our results indicate that the increased slow-5 fALFF in the Right Inferior Temporal Gyrus, increased ReHo in the Right Superior and Inferior Frontal Gyrus were associated with depressive symptoms in schizophrenia, which may provide preliminary evidence in better understanding the neural mechanisms underlying depressive symptoms in schizophrenia.
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http://dx.doi.org/10.1007/s11682-021-00465-0DOI Listing
October 2021

Quality of Life and Its Correlates in Alcohol Use Disorder Patients With and Without Depression in China.

Front Psychiatry 2020 22;11:627338. Epub 2021 Jan 22.

Key Laboratory of Psychiatry and Mental Health of Hunan Province, The China National Clinical Research Center for Mental Health Disorders, National Technology Institute of Psychiatry, Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China.

Alcohol use disorder (AUD) is a serious issue worldwide and frequently co-occurs with depression. However, the quality of life (QOL) of AUD patients with and without depression is not well studied in the Chinese Han population. The aim of this study was to investigate QOL and its correlates in AUD patients with and without depression in China. Five hundred and fifteen psychiatric patients diagnosed with AUD were recruited. All these patients completed the Beck Depression Inventory (BDI) to assess depression, the Medical Outcome Study 36-Item Short Form Health Survey (SF-36) to evaluate QOL and the Alcohol Use Disorders Identification Test (AUDIT) to measure the severity of drinking. Compared with AUD patients without depression, those with depression had a lower QOL in all eight domains of the SF-36 (all < 0.001), but were more willing to have alcohol-related treatment ( < 0.05). Negative correlations were noted between (i) the BDI total score and all eight domains of the SF-36 (all < 0.001); and (ii) between the AUDIT total score and six domains of the SF-36 (all < 0.05). Depression impairs QOL in patients with AUD in China. Early intervention in comorbid depression to improve QOL is needed.
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http://dx.doi.org/10.3389/fpsyt.2020.627338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862321PMC
January 2021

Altered Patterns of the Fractional Amplitude of Low-Frequency Fluctuation in Drug-Naive First-Episode Unipolar and Bipolar Depression.

Front Psychiatry 2020 17;11:587803. Epub 2020 Nov 17.

Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.

An early and correct diagnosis is crucial for treatment of unipolar depression (UD) and bipolar disorder (BD). The fractional amplitude of low-frequency fluctuations (fALFFs) has been widely used in the study of neuropsychiatric diseases, as it can detect spontaneous brain activities. This study was conducted to survey changes of fALFF within various frequency bands of the UD and BD patients, as well as to explore the effects on changes in fALFF on cognitive function. In total, 58 drug-naive first-episode patients, including 32 UD and 26 BD, were enrolled in the study. The fALFF values were calculated under slow-5 band (0.01-0.027 Hz) and slow-4 band (0.027-0.073 Hz) among UD patients, BD patients, and healthy control (HC). Additionally, we conducted correlation analyses to examine the association between altered fALFF values and cognitive function. Under the slow-5 band, compared to the HC group, the UD group showed increased fALFF values in the right cerebellum posterior lobe, whereas the BD group showed increased fALFF values in the left middle temporal gyrus (MTG). Under the slow-4 band, in comparison to HC, the UD group showed increased fALFF values in the left superior temporal gyrus, whereas the right inferior parietal lobule (IPL) and BD group showed increased fALFF values in the bilateral postcentral gyrus. Notably, compared to BD, the UD group showed increased fALFF values in the right IPL under the slow-4 band. Furthermore, altered fALFF values in the left MTG and the right IPL were significantly positively correlated with Verbal Fluency Test scores. This current study indicated that there were changes in brain activities in the early UD and BD groups, and changes were related to executive function. The fALFF values can serve as potential biomarker to diagnose and differentiate UD and BD patients.
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http://dx.doi.org/10.3389/fpsyt.2020.587803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704435PMC
November 2020

Reduced white matter integrity associated with cognitive deficits in patients with drug-naive first-episode schizophrenia revealed by diffusion tensor imaging.

Am J Transl Res 2020 15;12(8):4410-4421. Epub 2020 Aug 15.

Department of Psychiatry, Affiliated Brain Hospital of Nanjing Medical University Nanjing 210029, China.

Patients with schizophrenia have shown widespread white matter microstructural abnormalities and cognitive deficits, but the definitive relationship between white matter and cognitive performance remains unclear. In this study, we investigated the possible associations between white matter integrity and cognitive deficits in drug-naive first-episode schizophrenia (dn-FES) using diffusion tensor imaging (DTI). A total of 96 participants, including 46 dn-FES patients and 50 healthy individuals, underwent 3.0 T magnetic resonance diffusion-weighted imaging and cognitive assessments using the Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). Group differences were tested using tract-based spatial statistics (TBSS). Compared with the control group, the dn-FES group exhibited reduced white matter integrity, as indexed using fractional anisotropy (FA) metrics, in the right-hemispheric cluster comprising the posterior thalamic radiation, posterior corona radiata, superior longitudinal fasciculus, retrolenticular part of the internal capsule, tapetum, splenium of the corpus callosum, sagittal stratum, and inferior longitudinal fasciculus. We found that social cognitive deficit is significantly correlated with reduced FA in these white matter regions, except the sagittal stratum and inferior longitudinal fasciculus. Furthermore, we found that speed of processing is positively correlated with reduced FA in the right superior longitudinal fasciculus of dn-FES patients. In summary, white matter deficits were validated in dn-FES patients and could be associated with speed of processing and social cognition, providing clues about a neural basis of schizophrenia and a potential biomarker for clinical studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476109PMC
August 2020

Prevalence, Demographic, and Clinical Correlates of Comorbid Depressive Symptoms in Chinese Psychiatric Patients With Alcohol Dependence.

Front Psychiatry 2020 3;11:499. Epub 2020 Jun 3.

Mental Health Institute of the Second Xiangya Hospital, Central South University, The China National Clinical Research Center for Mental Health Disorders, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Changsha, China.

Background: Depressive symptoms are common among psychiatric patients with alcohol dependence (AD). However, the prevalence and clinical correlates of comorbid depressive symptoms are less well studied in Chinese Han patients.

Methods: In this hospital-based survey, we recruited 378 psychiatric patients diagnosed with AD according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV). All patients completed the Beck Depression Inventory (BDI) to evaluate depressive symptoms and the Alcohol Use Disorders Identification Test (AUDIT) to assess the severity of drinking.

Results: Compared to patients without depressive symptoms, 48.9% (185/378) of the patients with comorbid depressive symptoms were younger, had a more unstable marital status, had a higher AUDIT total score, and had a higher adverse consequences subscore (all < 0.05). Further logistic regression analysis showed that unstable marital status (Odds ratios [OR] = 2.20, 95% confidence interval [CI] 1.21-3.99) and AUDIT total score (OR=1.07, 95% CI 1.03-1.11) were significantly associated with depressive symptoms.

Conclusions: Our findings indicate high comorbidity between AD and depressive symptoms in Chinese psychiatric patients. Moreover, some variables are correlates of comorbid depressive symptoms. Particular attention should be paid to the early detection and intervention for this comorbid condition and its risk factors.
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http://dx.doi.org/10.3389/fpsyt.2020.00499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283605PMC
June 2020

Relationships between abnormal neural activities and cognitive impairments in patients with drug-naive first-episode schizophrenia.

BMC Psychiatry 2020 06 5;20(1):283. Epub 2020 Jun 5.

Department of Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, 210029, China.

Background: Prior resting state functional Magnetic Resonance Imaging studies (rs-fMRI) via the regional homogeneity (ReHo) method have demonstrated inconsistent and conflicting results because of several confounding factors, such as small sample size, medicinal influence, and illness duration. Relationships between ReHo measures and cognitive impairments in patients with drug-naive First-Episode Schizophrenia (dn-FES) are rarely reported. This study was conducted to explore the correlations between ReHo measures and cognitive deficits and clinical symptoms in patients with dn-FES.

Methods: A total of 69 patients with dn-FES and 74 healthy controls were recruited. MATRICS Consensus Cognitive Battery (MCCB), Wechsler Adult Intelligence Scale (WAIS), and Positive And Negative Syndrome Scale (PANSS) were used to assess cognitive function, Intelligence Quotient (IQ), and clinical symptoms, respectively. The correlations between ReHo maps and cognitive deficits and the severity of symptoms were examined using strict correlation analysis.

Results: ReHo values in right Middle Frontal Gyrus (MFG) and Superior Frontal Gyrus (SFG) increased in dn-FES group, whereas ReHo values in right cuneus decreased. Correlation analysis showed that the ReHo values in right MFG positively correlated with attention/vigilance impairments, social cognition deficits, and the severity of clinical manifestations.

Conclusions: These findings suggested that abnormal spontaneous activities in right MFG reflect illness severity and cognitive deficits, which also serve as a basis for establishing objective diagnostic markers and might be a clinical intervention target for treating patients with schizophrenia.
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http://dx.doi.org/10.1186/s12888-020-02692-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275517PMC
June 2020

Randomized, double-blind, 6-week non-inferiority study of lurasidone and risperidone for the treatment of schizophrenia.

Psychiatry Clin Neurosci 2020 Jun 8;74(6):336-343. Epub 2020 Jan 8.

Department of Psychiatry, Beijing Anding Hospital, National Clinical Research Center for Mental Disorders, Capital Medical University, Beijing, China.

Aim: The aim of the present study was to evaluate the efficacy and safety of lurasidone for the treatment of Chinese schizophrenic patients.

Methods: Hospitalized schizophrenia patients aged 18-65 were randomized to 6 weeks of double-blind, double-dummy, flexible-dose treatment with lurasidone (40 or 80 mg/day) or risperidone (2, 4 or 6 mg/day). Efficacy was evaluated using a non-inferiority comparison of lurasidone relative to risperidone based on week 6 change in the Positive and Negative Syndrome Scale (PANSS) total score. Safety assessments included adverse events, clinical laboratory measures, and electrocardiograms.

Results: Four hundred and forty-four patients were screened to obtain an intent-to-treat sample of 384 patients, of whom 54 patients discontinued treatment prior to 6 weeks. Lurasidone met the criteria for non-inferiority versus risperidone on the PANSS total score. Adjusted mean (SE) change at week 6 on the PANSS total score was -31.2 (1.0) and -34.9 (1.0) in the lurasidone and risperidone group, respectively. The mean difference score was 3.7, and the upper boundary of the 95%-confidence interval (1.0-6.3) was less than the prespecified margin of 7.0. No clinically meaningful between-treatment group differences were evident on secondary efficacy measures, including PANSS positive, PANSS negative, Clinical Global Impression scale - Severity, and Calgary Depression Scale for Schizophrenia scales. The incidence of adverse events was lower for lurasidone vs risperidone for extrapyramidal symptoms (17.0% vs 38.2%), akathisia (7.2% vs 13.6%), prolactin increase (3.1% vs 14.1%), and weight increase (0.5% vs 5.2%).

Conclusion: Lurasidone was found to be non-inferior to risperidone on the primary endpoint with minimal effects on weight, metabolic parameters, or prolactin levels.
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http://dx.doi.org/10.1111/pcn.12965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317929PMC
June 2020

Convergent Synthesis of the NS5B Inhibitor GSK8175 Enabled by Transition Metal Catalysis.

J Org Chem 2019 04 29;84(8):4680-4694. Epub 2018 Oct 29.

API Chemistry , GlaxoSmithKline , King of Prussia , Pennsylvania 19406 , United States.

A convergent eight-stage synthesis of the boron-containing NS5B inhibitor GSK8175 is described. The previous route involves 13 steps in a completely linear sequence, with an overall 10% yield. Key issues include a multiday SAr arylation of a secondary sulfonamide using HMPA as solvent, multiple functional group interconversions after all of the carbon atoms are installed (including a Sandmeyer halogenation), use of carcinogenic chloromethyl methyl ether to install a protecting group late in the synthesis, and an unreliable Pd-catalyzed Miyaura borylation as the penultimate step. We have devised an orthogonal approach using a Chan-Lam coupling between a halogenated aryl pinacol boronate ester and an aryl methanesulfonamide. This reaction is performed using a cationic Cu(I) precatalyst, which can be easily generated in situ using KPF as a halide abstractor. High-throughput screening revealed a new Pd catalyst system to effect the penultimate borylation chemistry using simple monodentate phosphine ligands, with PCyPh identified as optimal. Reaction progress analysis of this borylation indicated likely mass-transfer rate limitations under standard conditions using KOAc as the base. We have devised a KCO/pivalic acid system as an alternative, which dramatically outperforms the standard conditions. This new synthesis proceeds in eight stages with a 20% overall yield.
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http://dx.doi.org/10.1021/acs.joc.8b02269DOI Listing
April 2019

A 6-week, multicenter, double-blind, double-dummy, chlorpromazine-controlled non-inferiorityrandomized phase iiitrial to evaluate the efficacy and safety of quetiapine fumarate (SEROQUEL) extended-release (XR) in the treatment of patients with schizophrenia and acute episodes.

Psychiatry Res 2018 01 22;259:117-124. Epub 2017 Jul 22.

Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. Electronic address:

This study aimed to evaluate the efficacy and safety of quetiapine fumarate extended-release (XR) in the treatment of Chinese patients with acute schizophrenia. Multicenter, double-blind, double-dummy, active-controlled non-inferiority randomized study in Chinese patients (n = 388) with schizophrenia randomly assigned to quetiapine XR or chlorpromazine for 6 weeks. Primary outcome was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at the end of treatment. Safety objectives included adverse event (AE) monitoring, laboratory test results, and electrocardiograms. Changes in PANSS total score were -33.4 for quetiapine XR and -35.9 for chlorpromazine (P > 0.05). Least squares mean changes were: positive subscale, -9.9 ± 0.53 and -11.1 ± 0.51; negative subscale, -5.9 ± 0.50 and -6.7 ± 0.48; general psychopathology subscale, -12.9 ± 0.74 and -13.9 ± 0.71; aggression and hostility cluster scores, -4.8 ± 0.33 and -5.4 ± 0.32; and depression cluster scores, -1.8 ± 0.18 and -1.7 ± 0.18, for quetiapine XR and chlorpromazine, respectively. For quetiapine XR, AEs were constipation, dizziness, insomnia, and agitation, and nine patients (4.6%) discontinued due to AEs. For chlorpromazine, AEs were extrapyramidal symptoms, constipation, insomnia, dizziness, and agitation, and 17 patients (8.9%) discontinued due to AEs; two patients reported serious AEs. Quetiapine XR monotherapy was not inferior to chlorpromazine for treating acute schizophrenia in Chinese patients and was well tolerated.
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http://dx.doi.org/10.1016/j.psychres.2017.07.006DOI Listing
January 2018

Effects of haloperidol, olanzapine, ziprasidone, and PHA-543613 on spatial learning and memory in the Morris water maze test in naïve and MK-801-treated mice.

Brain Behav 2017 08 11;7(8):e00764. Epub 2017 Jul 11.

Department of Psychiatry Nanjing Medical University Nanjing China.

Introduction: Cognitive impairment is the core symptom of schizophrenia, significantly impacting the functional outcome. Improvement of cognitive function has been an important aspect of the treatment of schizophrenia. Therefore, this study is to demonstrate the effects of first-generation antipsychotic haloperidol, second-generation antipsychotic olanzapine and ziprasidone, and alpha-7 nicotinic acetylcholine receptor agonist PHA-543613 on spatial learning and memory.

Material And Methods: C57BL/6 mice received intraperitoneal injections of haloperidol (2 mg/kg), olanzapine (2.5 mg/kg), ziprasidone (2 mg/kg), and PHA-543613 (1 mg/kg), and cognitive dysfunctions were induced by MK-801 (0.1 mg/kg). Morris water maze was used for investigating the effects of all agents.

Results: Mk-801 significantly increased the mean escape latency to the platform and decreased the number of platform area crossings. Ziprasidone had no effect on the mean escape latency to platform and the number of platform area crossings in naïve mice, but haloperidol, olanzapine, and PHA-543613 did not. Haloperidol and olanzapine significantly increased the mean escape latency to platform and decreased the number of platform area crossings, while ziprasidone and PHA-543613 did not. All the agents had no effect on swimming speed.

Conclusions: Ziprasidone and alpha-7 nicotinic acetylcholine receptor agonist PHA-543613 might be helpful in the treatment of CIAS.
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http://dx.doi.org/10.1002/brb3.764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561323PMC
August 2017

Prevalence and risk factors of agitation in newly hospitalized schizophrenia patients in China: An observational survey.

Psychiatry Res 2017 07 2;253:401-406. Epub 2017 Mar 2.

Peking University Sixth Hospital, Peking University Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), 51, Huayuan Bei Road, Beijing 100191, China. Electronic address:

This multi-center observational study investigated the prevalence of agitation in newly hospitalized schizophrenia patients in China and its potential risk factors. It was performed in 2014 and covered 14 hospitals. Newly hospitalized patients with schizophrenia or suspected schizophrenia who met the diagnostic criteria of the International Statistical Classification of Diseases and Related Health Problems, 10th revision, were recruited. Agitation and related risk factors were evaluated by a questionnaire designed for the survey. General demographic data, disease characteristics, scores on schizophrenia rating scales and agitation rating scales (e.g., Positive and Negative Syndrome Scale-Excited Component [PANSS-EC] and Behavioral Activity Rating Scale [BARS]) were collected. Among the 1512 patients screened in the study, 1400 (92.59%) were eligible. According to the PANSS-EC and BARS, the prevalence of agitation was 60.92% (853 of 1400) and 59.00% (826 of 1400), respectively. The overall prevalence of agitation was 47.50% (665 of 1400). The most important risk factor of agitation was being aggressive at baseline (Modified Overt Aggression Scale score ≥4, odds ratio=6.54; 95% confidence interval=4.93-8.69). Other risk factors included a history of aggressive behavior, northern region of residence, involuntary hospitalization, disease severity, low level of education, living alone, being unemployed or retired.
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http://dx.doi.org/10.1016/j.psychres.2017.02.065DOI Listing
July 2017

Prevalence, correlates and treatment status of alcohol use disorders in psychiatric patients in China.

Gen Hosp Psychiatry 2017 Mar - Apr;45:70-75. Epub 2017 Jan 9.

Mental Health Institute of the Second Xiangya Hospital, Central South University, The China National Clinical Research Center for Mental Health Disorders, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Changsha, PR China. Electronic address:

Objective: To determine the prevalence, associated factors and treatment status of alcohol use disorders (AUDs) in psychiatric patients in China.

Methods: We asked 24,379 consecutive patients aged ≥18years who presented at the psychiatric departments in eight hospitals in 2013 whether they had consumed alcoholic beverages in the previous month. Of the 2964 (12.2%) patients who answered yes and were then screened with the Alcohol Use Disorders Identification Test (AUDIT), 1304 (5.3%) screened positive (AUDIT≥7) and, based on DSM-IV criteria, were diagnosed with AUDs by psychiatrists. The treatments prescribed for them were also recorded. Logistic regression was used to identify AUDs associated factors.

Results: The prevalence of AUDs was 2.4% (95% CI: 2.2-2.6%). None of the patients diagnosed with AUDs had got medical treatment for preventing relapse. The risk factors for AUDs were middle-aged or elderly (OR=1.86, 95% CI: 1.23-2.80), and consuming beverages with high degree of alcohol content (OR=2.92, 95% CI: 2.11-4.06).

Conclusions: The prevalence of AUDs in psychiatric patients in China was not high, but the rate of treatment was dramatically low, indicating the serious neglect of AUDs. Our study suggests an urgent need to improve the situation of unmet need for treatment of psychiatric patients with AUDs.
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http://dx.doi.org/10.1016/j.genhosppsych.2017.01.002DOI Listing
December 2017

Gene Expression Profiles of HIV/AIDS Patients with Qi-Yin Deficiency and Dampness-Heat Retention.

J Altern Complement Med 2016 Nov 19;22(11):865-879. Epub 2016 Oct 19.

8 Department of Internal Medicine of TCM, People's Hospital of Zhongmou County , Zhongmou, China .

Objectives: Traditional Chinese Medicine (TCM) applied in the clinic as a complementary and alternative therapy has helped improve immunity and reduce side effects and symptomatic treatment in patients with HIV/AIDS. However, the mechanisms of TCM syndromes are not clear. Transcriptomics enables the study of such TCM syndromes.

Design: This study compared the messenger RNA (mRNA) expressions of healthy persons and patients with HIV/AIDS who had two common TCM syndromes, qi-yin deficiency and dampness-heat retention, to find the difference in HIV/AIDS with TCM syndromes.

Results: Comparison with healthy persons identified 113 mRNAs-41 enhanced and 72 decreased-in the qi-yin deficiency group. Additionally, 76 mRNAs were found in the dampness-heat retention group: 14 increased and 62 decreased. Functional genetic analysis of the mRNAs indicated that two TCM syndromes were correlated with cell apoptosis, immunoinflammatory responses, and lymphocyte activation. Differentially expressed mRNAs in the qi-yin deficiency group were obviously associated with cellular activity, communication, protein localization, cellular ion homeostasis, and regulation of cell motion, whereas mRNAs in the dampness-heat retention group were associated with sequence-specific DNA binding, cellular response to stress, and hemopoietic or lymphoid organ development.

Conclusions: These results suggest that the formation of different TCM syndromes in patients with HIV/AIDS were founded on biological transcriptomics, which reveal mechanisms of the formation of these syndromes in HIV/AIDS. Differentially expressed mRNAs in two TCM syndrome groups tended to normalize after TCM intervention, which indicates that TCM might remit symptoms by changing genetic expression.
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http://dx.doi.org/10.1089/acm.2015.0350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116685PMC
November 2016

The effectiveness and safety of amisulpride in Chinese patients with schizophrenia: An 8-week, prospective, open-label, multicenter, single-arm study.

Asia Pac Psychiatry 2016 Sep 28;8(3):241-4. Epub 2016 Mar 28.

National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Institute of Mental Health, and the Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China.

Introduction: This study evaluated the effectiveness and safety of amisulpride in Chinese schizophrenia patients.

Methods: A multicenter, single-arm Phase IV study (NCT01795183). Chinese patients with schizophrenia received amisulpride for 8 weeks. The primary endpoint was ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8.

Results: A total of 316 patients were enrolled; 295 were included in the effectiveness analysis; 66.8% (197/295) achieved ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Nine patients discontinued treatment because of adverse events.

Discussion: Amisulpride had clinical effectiveness and was relatively well tolerated in Chinese patients with schizophrenia.
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http://dx.doi.org/10.1111/appy.12238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5071681PMC
September 2016

Efficacy and safety of quetiapine extended release monotherapy in bipolar depression: a multi-center, randomized, double-blind, placebo-controlled trial.

Psychopharmacology (Berl) 2016 Apr 25;233(7):1289-97. Epub 2016 Feb 25.

Peking University Sixth Hospital, No.51 North Huayuan Rd., Haidian District, Beijing, 100191, China.

Rationale: Quetiapine extended release (XR) has been used to treat various psychiatric disorders, including depressive episodes associated with bipolar I and II disorders. Quetiapine XR is the first approved drug in China for the treatment of bipolar disorder.

Objectives: The study evaluated the efficacy and safety of short-term quetiapine XR monotherapy in the treatment of depressive episodes of bipolar I and II disorders.

Methods: This was an 8-week multi-center, randomized, double-blind, placebo-controlled, fixed-dose phase 3 study. The primary endpoint was the mean change of the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary endpoints included Clinical Global Impressions-Bipolar (CGI-BP) and remission rates.

Results: The study recruited 279 adult bipolar I or II patients currently experiencing depression from 11 Chinese provinces. Of these, 139 received quetiapine XR (300 mg/day) and 140 received placebo for 8 weeks. The mean change in the MADRS total score was significantly greater in the quetiapine XR group than in the placebo group (-19.00 ± 7.88 vs. -16.20 ± 9.32; p = 0.004). Adverse events occurred in 96 patients (65.3 %) in the quetiapine XR group and 72 (49.0 %) in the placebo group. The incidence of serious adverse events did not differ significantly between the groups (p = 0.247).

Conclusions: This study, which is the first to evaluate 300 mg/day quetiapine XR monotherapy for depression in Chinese patients with bipolar disorders, found that this drug was superior to the placebo. Quetiapine XR was generally safe and well tolerated (ClinicalTrials.gov number, NCT01256177).
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http://dx.doi.org/10.1007/s00213-016-4215-zDOI Listing
April 2016

Safety and efficacy of paliperidone extended-release in Chinese patients with schizophrenia: a 24-week, open-label extension of a randomized, double-blind, placebo-controlled study.

Neuropsychiatr Dis Treat 2016 8;12:69-77. Epub 2016 Jan 8.

Janssen Research & Development, LLC, Titusville, NJ, USA.

Objectives: The long-term safety, tolerability, and efficacy of paliperidone extended-release (ER) were evaluated in Chinese patients with schizophrenia.

Methods: Patients (aged ≥18 years) with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria) who had completed run-in (8-week), stabilization (6-week), and double-blind (DB) phases (variable) of a phase-3, placebo-controlled study entered this 24-week, open-label extension (OLE) study. These patients, who had either experienced a relapse or remained relapse-free through DB phase of the study, were treated with flexible-dose paliperidone-ER (3-12 mg/day) during the OLE phase. Major safety evaluations included treatment-emergent adverse events (TEAEs) and extrapyramidal symptoms. Efficacy endpoints included changes in Positive and Negative Syndrome Scale total score, Clinical Global Impression-Severity scale, and Personal and Social Performance scale from OLE baseline to OLE endpoint.

Results: Out of 106 patients who entered the OLE phase (placebo: 59, paliperidone-ER: 47), a total of 85 (80%) completed it. Thirty-five (33%) patients experienced at least one TEAE; most common were akathisia, somnolence, nasopharyngitis, and constipation (3.8% each). Serious TEAEs were noted in two patients (completed suicide; schizophrenia worsening). No TEAEs with an onset during the OLE phase led to discontinuation. Extrapyramidal symptoms related-TEAEs were reported in eight (7.5%) patients. Mean (standard deviation) changes in Positive and Negative Syndrome Scale total scores (-10.4 [13.2]), Clinical Global Impression-Severity scores (-0.6 [0.96]) and Personal and Social Performance scores (7.4 [13.2]) from OLE baseline to OLE endpoint showed patients who had been treated with placebo during the DB phase experienced more pronounced improvements.

Conclusion: In this OLE study, flexibly dosed paliperidone-ER (3-12 mg/day) was tolerable and efficacious in Chinese patients with schizophrenia.
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http://dx.doi.org/10.2147/NDT.S88875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712970PMC
January 2016

Hexanucleotide Repeat Expansion in C9ORF72 Is Not Detected in the Treatment-Resistant Schizophrenia Patients of Chinese Han.

PLoS One 2015 21;10(12):e0145347. Epub 2015 Dec 21.

Department of Psychiatry, Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, 210029, China.

Hexanucleotide (GGGGCC) repeat expansion in C9ORF72 (HRE) causes frontotemporal lobar degeneration, frontotemporal dementia-amyotrophic lateral sclerosis, and amyotrophic lateral sclerosis. HRE was also seen in the genomes of patients suffering from several other degenerative diseases. However, whether it is present in the treatment-resistant schizophrenia patients remains unknown. Genotyping 386 patients suffering from treatment-resistant schizophrenia using the method of Repeat-Primed PCR, we reported here that no HRE was detected in the patients of Chinese Han.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145347PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687052PMC
July 2016

Treatment of major depressive disorders with generic duloxetine and paroxetine: a multi-centered, double-blind, double-dummy, randomized controlled clinical trial.

Shanghai Arch Psychiatry 2015 Aug;27(4):228-36

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: This study is a pre-registration trial of generic duloxetine that was approved by the China Food and Drug Administration (approval number: 2006L01603).

Aims: Compare the treatment efficacy and safety of generic duloxetine to that of paroxetine in patients with major depressive disorders (MDD).

Methods: This was a double-dummy, double-blind, multicenter, positive drug (paroxetine), parallel randomized controlled clinical trial. The 299 patients with MDD recruited for the study were randomly assigned to use duloxetine (n=149; 40-60 mg/d) or paroxetine (n=150; 20 mg/d) for 8 weeks. The Hamilton Depression rating scale (HAMD-17) was administered at baseline and 1, 2, 4, 6, and 8 weeks after starting treatment. Remission was defined as a HAMD-17 score below 8 at the end of the trial, and treatment effectiveness was defined as a decrease in baseline HAMD-17 score of at least 50% by the end of the trial. Safety was assessed based on the reported prevalence and severity of side effects and changes in laboratory and electrocardiographic findings. Three patients in the duloxetine group dropped out before starting medication, so results were analyzed using a modified intention-to-treat (ITT) method with 146 in the experimental group and 150 in the control group.

Results: Both groups experienced 29 dropouts during the 8-week trial. HAMD-17 scores decreased significantly from baseline throughout the trial in both groups. Based on the ITT analysis, at the end of the trial there was no significant difference between the duloxetine group and the paroxetine group in effectiveness (67.1% v. 71.3%, X(2)=0.62 p=0.433), remission rate (41.1% v. 51.3%, X(2)=3.12, p=0.077), or in the incidence of side effects (56.8% v. 54.7%, X(2)=0.14, p=0.705).

Conclusions: Generic duloxetine is as effective and safe as paroxetine in the acute treatment of patients with MDD who seek care at psychiatric outpatient departments in China.
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http://dx.doi.org/10.11919/j.issn.1002-0829.215064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621288PMC
August 2015

Conversion of a Benzofuran Ester to an Amide through an Enamine Lactone Pathway: Synthesis of HCV Polymerase Inhibitor GSK852A.

J Org Chem 2015 Oct 30;80(19):9610-9. Epub 2015 Sep 30.

Product Development, GlaxoSmithKline , 709 Swedeland Road, King of Prussia, Pennsylvania 19406, United States.

HCV NS5B polymerase inhibitor GSK852A (1) was synthesized in only five steps from ethyl 4-fluorobenzoylacetate (3) in 46% overall yield. Key to the efficient route was the synthesis of the highly functionalized benzofuran core 15 from the β-keto ester in one pot and the efficient conversion of ester 6 to amide 19 via enamine lactone 22. Serendipitous events led to identification of the isolable enamine lactone intermediate 22. Single crystal X-ray diffraction and NMR studies supported the intramolecular hydrogen bond shown in enamine lactone 22. The hydrogen bond was considered an enabler in the proposed pathway from ester 6 to enamine lactone 22 and its rearrangement to amide 19. GSK852A (1) was obtained after reductive amination and mesylation with conditions amenable to the presence of the boronic acid moiety which was considered important for the desirable pharmacokinetics of 1. The overall yield of 46% in five steps was a significant improvement to the previous synthesis from the same β-keto ester in 5% yield over 13 steps.
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http://dx.doi.org/10.1021/acs.joc.5b01598DOI Listing
October 2015
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