Publications by authors named "Chenxiang Li"

11 Publications

  • Page 1 of 1

Effect of citalopram on hippocampal volume in first-episode schizophrenia: Structural MRI results from the DECIFER trial.

Psychiatry Res Neuroimaging 2021 Apr 7;312:111286. Epub 2021 Apr 7.

Department of Psychiatry, NYU Langone Health, 1 Park Avenue, New York, NY 10016, United States of America; Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, United States of America. Electronic address:

Hippocampal volume loss is prominent in first episode schizophrenia (FES) and has been associated with poor clinical outcomes and with BDNF genotype; antidepressants are believed to reverse hippocampal volume loss via release of BDNF. In a 12-month, placebo-controlled add-on trial of the antidepressant, citalopram, during the maintenance phase of FES, negative symptoms were improved with citalopram. We now report results of structural brain imaging at baseline and 6 months in 63 FES patients (34 in citalopram group) from the trial to assess whether protection against hippocampal volume loss contributed to improved negative symptoms with citalopram. Hippocampal volumetric integrity (HVI) did not change significantly in the citalopram or placebo group and did not differ between treatment groups, whereas citalopram was associated with greater volume loss of the right CA1 subfield. Change in cortical thickness was associated with SANS change in 4 regions (left rostral anterior cingulate, right frontal pole, right cuneus, and right transverse temporal) but none differed between treatment groups. Our findings suggest that minimal hippocampal volume loss occurs after stabilization on antipsychotic treatment and that citalopram's potential benefit for negative symptoms is unlikely to result from protection against hippocampal volume loss or cortical thinning.
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http://dx.doi.org/10.1016/j.pscychresns.2021.111286DOI Listing
April 2021

Association of Aripiprazole With Reduced Hippocampal Atrophy During Maintenance Treatment of First-Episode Schizophrenia.

J Clin Psychopharmacol 2021 May-Jun 01;41(3):244-249

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai.

Purpose/background: Hippocampal volume loss in early schizophrenia has been linked with markers of inflammation and oxidative stress, and with less response of negative symptoms. Aripiprazole has been reported to preserve hippocampal volume and to reduce inflammation.

Methods/procedures: Study 1 was a 12-month multicenter randomized placebo-controlled trial of citalopram added to clinician-determined second-generation antipsychotic medication in 95 patients with first-episode schizophrenia (FES), 19 of whom received aripiprazole. We compared participants taking aripiprazole with those on other antipsychotics to determine whether those on aripiprazole had less hippocampal volume loss. We also examined peripheral biomarker data from medication-naive patients with schizophrenia receiving 8 weeks of antipsychotic treatment (n = 24) to see whether markers of inflammation and oxidative stress that previously predicted hippocampal volume differed between aripiprazole (n = 9) and other antipsychotics (study 2).

Findings/results: Aripiprazole was associated with a mean increase in hippocampal volume of 0.35% (SD, 0.80%) compared with a 0.53% decrease (SD, 1.2%) with other antipsychotics during the first year of maintenance treatment in patients with FES. This difference was significant after adjusting for age, sex, citalopram treatment, and baseline Brief Psychiatric Rating Scale score (B = 0.0079, P = 0.03). Aripiprazole was also associated with reduced concentrations of the inflammatory cytokines interleukin-8 and tumor necrosis factor (P < 0.01) during the first 8 weeks of treatment in medication-naive patients with FES.

Implications/conclusions: These results suggest that aripiprazole may protect against hippocampal atrophy via an anti-inflammatory mechanism, but these results require replication in larger, randomized trials, and the clinical relevance of hippocampal volume loss is not established.
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http://dx.doi.org/10.1097/JCP.0000000000001391DOI Listing
April 2021

Corrigendum to 'The impact of social distancing during COVID-19: A conditional process model of negative emotions, alienation, affective disorders, and post-traumatic stress disorder. [Journal of Affective Disorders 281, 15 February 2021, Pages 131-137].

J Affect Disord 2021 Mar 25. Epub 2021 Mar 25.

Faculty of Psychology, Southwest University, Chongqing 400715, China; Key Lab of Cognition and Personality (Ministry of Education), Southwest University, Chongqing 400715, China. Electronic address:

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http://dx.doi.org/10.1016/j.jad.2021.03.004DOI Listing
March 2021

Association of Psychiatric Disorders With Mortality Among Patients With COVID-19.

JAMA Psychiatry 2021 04;78(4):380-386

Department of Psychiatry, New York University Langone Medical Center, New York, New York.

Importance: To date, the association of psychiatric diagnoses with mortality in patients infected with coronavirus disease 2019 (COVID-19) has not been evaluated.

Objective: To assess whether a diagnosis of a schizophrenia spectrum disorder, mood disorder, or anxiety disorder is associated with mortality in patients with COVID-19.

Design, Setting, And Participants: This retrospective cohort study assessed 7348 consecutive adult patients for 45 days following laboratory-confirmed COVID-19 between March 3 and May 31, 2020, in a large academic medical system in New York. The final date of follow-up was July 15, 2020. Patients without available medical records before testing were excluded.

Exposures: Patients were categorized based on the following International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnoses before their testing date: (1) schizophrenia spectrum disorders, (2) mood disorders, and (3) anxiety disorders. Patients with these diagnoses were compared with a reference group without psychiatric disorders.

Main Outcomes And Measures: Mortality, defined as death or discharge to hospice within 45 days following a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result.

Results: Of the 26 540 patients tested, 7348 tested positive for SARS-CoV-2 (mean [SD] age, 54 [18.6] years; 3891 [53.0%] women). Of eligible patients with positive test results, 75 patients (1.0%) had a history of a schizophrenia spectrum illness, 564 (7.7%) had a history of a mood disorder, and 360 (4.9%) had a history of an anxiety disorder. After adjusting for demographic and medical risk factors, a premorbid diagnosis of a schizophrenia spectrum disorder was significantly associated with mortality (odds ratio [OR], 2.67; 95% CI, 1.48-4.80). Diagnoses of mood disorders (OR, 1.14; 95% CI, 0.87-1.49) and anxiety disorders (OR, 0.96; 95% CI, 0.65-1.41) were not associated with mortality after adjustment. In comparison with other risk factors, a diagnosis of schizophrenia ranked behind only age in strength of an association with mortality.

Conclusions And Relevance: In this cohort study of adults with SARS-CoV-2-positive test results in a large New York medical system, adults with a schizophrenia spectrum disorder diagnosis were associated with an increased risk for mortality, but those with mood and anxiety disorders were not associated with a risk of mortality. These results suggest that schizophrenia spectrum disorders may be a risk factor for mortality in patients with COVID-19.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.4442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841576PMC
April 2021

The impact of social distancing during COVID-19: A conditional process model of negative emotions, alienation, affective disorders, and post-traumatic stress disorder.

J Affect Disord 2021 02 8;281:131-137. Epub 2020 Dec 8.

Faculty of Psychology, Southwest University, Chongqing 400715, China; Key Lab of Cognition and Personality (Ministry of Education), Southwest University, Chongqing 400715, China. Electronic address:

Background The social distancing during COVID-19 is likely to cause a feeling of alienation, which may pose a threat to the public's mental health. Our research aims to examine the relationship between negative emotions and Post-Traumatic Stress Disorder (PTSD), considering the mediation effect of alienation and how it is moderated by anxiety and depression. Methods For this, the current study conducted a cross-sectional survey on 7145 participants during the outbreak of COVID-19, via online questionnaires comprised of a self-designed Negative emotions questionnaire, Symptom Check List 90 (SCL-90), PTSD Checklist-civilian version (PCL-C), and Adolescent Students Alienation Scale (ASAS). Results A total of 6666 pieces of data from the general population were included in the statistical analysis. The descriptive statistics showed a relatively mild level of mental disorders. Besides, results of Conditional Process Model analysis supported our hypotheses that negative emotions and alienation were both predictors for PTSD symptoms, and their direct and indirect effects were all moderated by the level of anxiety. Limitations This study was limited by the generality and causality of the conclusion. The moderating effect of depression was left for further study due to the collinearity problem of variables. Conclusions Social distancing may have an impact on individuals' mental health by the feeling of alienation, which was moderated by affective disorders. Clinical psychologists should identify individuals' particular cognition and mental disorders to provide a more accurate and adequate intervention for them.
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http://dx.doi.org/10.1016/j.jad.2020.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723399PMC
February 2021

D-cycloserine augmentation of cognitive behavioral therapy for delusions: A randomized clinical trial.

Schizophr Res 2020 08 23;222:145-152. Epub 2020 Jun 23.

Department of Psychiatry, NYU Langone Health, New York, NY, United States of America; Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States of America. Electronic address:

Objective: D-cycloserine (DCS) promotes consolidation of extinction learning. This study extends earlier work by examining whether DCS can enhance cognitive behavioral therapy (CBT) for delusions.

Methods: Adults reporting moderate or greater delusions were randomly assigned to receive 50 mg of DCS or placebo prior to 10 weekly CBT sessions. The primary outcome was change in severity of delusions measured with the Psychotic Symptom Rating Scale delusion subscale (PSYRATS-D). Secondary outcomes included persistence of response at 3 and 6 month follow-up and the effects of DCS on memory consolidation and cognitive flexibility. Fifty-eight participants were randomized and 44 completed the trial.

Results: The DCS and placebo groups did not differ in change from baseline to end of CBT on PSYRATS-D, nor did DCS improve memory consolidation or cognitive flexibility compared to placebo. However, at the 3 month follow-up visit (week 24), 47% of participants who completed treatment with DCS reported a 20% or greater decrease on PSYRATS-D compared to 15% in the placebo group (p = .04). Change in distress across CBT sessions interacted with treatment group to predict change from baseline to week 24 in PSYRATS-D total score (p = .03) such that response at week 24 was greatest in DCS-treated participants who experienced a decrease in distress during CBT sessions.

Conclusions: DCS augmentation of CBT did not improve delusions compared to placebo during treatment; however, DCS was associated with a higher response rate at 3-month follow-up. DCS may produce a delayed therapeutic effect, associated with successful CBT sessions, but this finding requires replication.
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http://dx.doi.org/10.1016/j.schres.2020.06.015DOI Listing
August 2020

Does Early Intervention Improve the Long-Term Course of Schizophrenia?

Am J Psychiatry 2020 04 4;177(4):288-290. Epub 2020 Mar 4.

Department of Psychiatry (Goff), Department of Population Health, Division of Statistics (Li), and Department of Population Health, Division of Epidemiology (Thorpe), New York University Grossman School of Medicine, New York University Langone Health, New York; Nathan Kline Institute for Psychiatric Research, Orangeburg, N.Y. (Goff).

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http://dx.doi.org/10.1176/appi.ajp.2020.20020111DOI Listing
April 2020

Probucol promotes high glucose-induced proliferation and inhibits apoptosis by reducing reactive oxygen species generation in Müller cells.

Int Ophthalmol 2019 Dec 29;39(12):2833-2842. Epub 2019 May 29.

AIER School of Ophthalmology, Central South University, Changsha, 410015, Hunan Province, China.

Purpose: To explore the protective effect of probucol on human retinal Müller cells cultured in high glucose.

Methods: Primary Müller cells from human retinas were cultured in complete DMEM. Third-generation Müller cells were identified using glutamine synthetase (GS) antibody and randomly divided into three groups: normoglycemia (NG, 5.5 mmol/L); hyperglycemia (HG, 30 mmol/L); and hyperglycemia (30 mmol/L) with probucol (10 μmol/L; HGPB). After a 24-h intervention, cell proliferation, apoptosis, and cellular reactive oxygen species (ROS) were measured with a CCK-8 kit, flow cytometry, and DCFH-DA probe, respectively. Kelch-like ECH-associated protein 1 (Keap1), NF-E2-related factor 2 (Nrf2), and glutamate cysteine ligase catalytic subunit (GCLC) protein expression were detected by immunofluorescence staining.

Results: For NG, HG, and HGPB, optical density (OD) values for cell proliferation were 0.98 ± 0.23, 0.58 ± 0.11, and 0.73 ± 0.11; apoptotic rates were 2.79 ± 0.52%, 7.70 ± 0.44%, and 4.00 ± 0.95%; and intracellular ROS were 20.89 ± 5.14, 55.17 ± 14.07, and 26.28 ± 4.73, respectively. Compared to NG, OD was markedly decreased (P < 0.01), apoptosis was increased (P < 0.001), and intracellular ROS level was significantly higher than in HG (P < 0.01). Compared to HG, OD was markedly increased (P < 0.01), apoptosis was meaningfully decreased (P < 0.01), and intracellular ROS level was significantly lower than in HGPB (P < 0.01). GS, Keap1, Nrf2, and GCLC had positive expression.

Conclusions: Probucol could inhibit intracellular ROS generation, promote proliferation, and decrease apoptosis of human retinal Müller cells cultured in high glucose. This might also be associated with Keap1/Nrf2/ARE oxidative stress signaling pathway activation.
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http://dx.doi.org/10.1007/s10792-019-01130-8DOI Listing
December 2019

Citalopram in first episode schizophrenia: The DECIFER trial.

Schizophr Res 2019 06 30;208:331-337. Epub 2019 Jan 30.

National Clinical Research Center for Mental Disorders, Mental Health Institute, The Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, Hunan, China.

Antidepressants are frequently prescribed in first episode schizophrenia (FES) patients for negative symptoms or for subsyndromal depressive symptoms, but therapeutic benefit has not been established, despite evidence of efficacy in later-stage schizophrenia. We conducted a 52 week, placebo-controlled add-on trial of citalopram in patients with FES who did not meet criteria for major depression to determine whether maintenance therapy with citalopram would improve outcomes by preventing or improving negative and depressive symptoms. Primary outcomes were negative symptoms measured by the Scale for Assessment of Negative Symptoms and depressive symptoms measured by the Calgary Depression Scale for Schizophrenia; both were analyzed by an intent-to-treat, mixed effects, area-under-the-curve analysis to assess the cumulative effects of symptom improvement and symptom prevention over a one-year period. Ninety-five patients were randomized and 52 (54%) completed the trial. Negative symptoms were reduced with citalopram compared to placebo (p = .04); the effect size of citalopram versus placebo was 0.32 for participants with a duration of untreated psychosis (DUP) of <18 weeks (median split) and 0.52 with a DUP >18 weeks. Rates of new-onset depression did not differ between groups; improvement in depressive symptoms was greater with placebo than citalopram (p = .02). Sexual side effects were more common with citalopram, but overall treatment-emergent side effects were not increased compared to placebo. In conclusion, citalopram may reduce levels of negative symptoms, particularly in patients with longer DUP, but we found no evidence of benefit for subsyndromal depressive symptoms.
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http://dx.doi.org/10.1016/j.schres.2019.01.028DOI Listing
June 2019

Association of Hippocampal Atrophy With Duration of Untreated Psychosis and Molecular Biomarkers During Initial Antipsychotic Treatment of First-Episode Psychosis.

JAMA Psychiatry 2018 04;75(4):370-378

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Importance: Duration of untreated psychosis (DUP) has been associated with poor outcomes in schizophrenia, but the mechanism responsible for this association is not known.

Objectives: To determine whether hippocampal volume loss occurs during the initial 8 weeks of antipsychotic treatment and whether it is associated with DUP, and to examine molecular biomarkers in association with hippocampal volume loss and DUP.

Design, Setting, And Participants: A naturalistic longitudinal study with matched healthy controls was conducted at Shanghai Mental Health Center. Between March 5, 2013, and October 8, 2014, 71 medication-naive individuals with nonaffective first-episode psychosis (FEP) and 73 age- and sex-matched healthy controls were recruited. After approximately 8 weeks, 31 participants with FEP and 32 controls were reassessed.

Exposures: The participants with FEP were treated according to standard clinical practice with second-generation antipsychotics.

Main Outcomes And Measures: Hippocampal volumetric integrity (HVI) (an automated estimate of the parenchymal fraction in a standardized hippocampal volume of interest), DUP, 13 peripheral molecular biomarkers, and 14 single-nucleotide polymorphisms from 12 candidate genes were determined.

Results: The full sample consisted of 71 individuals with FEP (39 women and 32 men; mean [SD] age, 25.2 [7.7] years) and 73 healthy controls (40 women and 33 men; mean [SD] age, 23.9 [6.4] years). Baseline median left HVI was lower in the FEP group (n = 57) compared with the controls (n = 54) (0.9275 vs 0.9512; difference in point estimate, -0.020 [95% CI, -0.029 to -0.010]; P = .001). During approximately 8 weeks of antipsychotic treatment, left HVI decreased in 24 participants with FEP at a median annualized rate of -.03791 (-4.1% annualized change from baseline) compared with an increase of 0.00115 (0.13% annualized change from baseline) in 31 controls (difference in point estimate, -0.0424 [95% CI, -0.0707 to -0.0164]; P = .001). The change in left HVI was inversely associated with DUP (r = -0.61; P = .002). Similar results were found for right HVI, although the association between change in right HVI and DUP did not achieve statistical significance (r = -0.35; P = .10). Exploratory analyses restricted to the left HVI revealed an association between left HVI and markers of inflammation, oxidative stress, brain-derived neurotrophic factor, glial injury, and markers reflecting dopaminergic and glutamatergic transmission.

Conclusions And Relevance: An association between longer DUP and accelerated hippocampal atrophy during initial treatment suggests that psychosis may have persistent, possibly deleterious, effects on brain structure. Additional studies are needed to replicate these exploratory findings of molecular mechanisms by which untreated psychosis may affect hippocampal volume and to determine whether these effects account for the known association between longer DUP and poor outcome.
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http://dx.doi.org/10.1001/jamapsychiatry.2017.4595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875378PMC
April 2018

Laparoscopic anti-reflux surgery for idiopathic pulmonary fibrosis at a single centre.

Eur Respir J 2016 09 4;48(3):826-32. Epub 2016 Aug 4.

Dept of Surgery, University of Washington Medical Center, Seattle, WA, USA.

We sought to assess whether laparoscopic anti-reflux surgery (LARS) is associated with decreased rates of disease progression in patients with idiopathic pulmonary fibrosis (IPF).The study was a retrospective single-centre study of IPF patients with worsening symptoms and pulmonary function despite antacid treatment for abnormal acid gastro-oesophageal reflux. The period of exposure to LARS was September 1998 to December 2012. The primary end-point was a longitudinal change in forced vital capacity (FVC) % predicted in the pre- versus post-surgery periods.27 patients with progressive IPF underwent LARS. At time of surgery, the mean age was 65 years and mean FVC was 71.7% pred. Using a regression model, the estimated benefit of surgery in FVC % pred over 1 year was 5.7% (95% CI -0.9-12.2%, p=0.088) with estimated benefit in FVC of 0.22 L (95% CI -0.06-0.49 L, p=0.12). Mean DeMeester scores decreased from 42 to 4 (p<0.01). There were no deaths in the 90 days following surgery and 81.5% of participants were alive 2 years after surgery.Patients with IPF tolerated the LARS well. There were no statistically significant differences in rates of FVC decline pre- and post-LARS over 1 year; a possible trend toward stabilisation in observed FVC warrants prospective studies. The ongoing prospective randomised controlled trial will hopefully provide further insights regarding the safety and potential efficacy of LARS in IPF.
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http://dx.doi.org/10.1183/13993003.00488-2016DOI Listing
September 2016