Publications by authors named "Renrong Wu"

83 Publications

Drugs Based on NMDAR Hypofunction Hypothesis in Schizophrenia.

Front Neurosci 2021 12;15:641047. Epub 2021 Apr 12.

Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.

Treatments for negative symptoms and cognitive dysfunction in schizophrenia remain issues that psychiatrists around the world are trying to solve. Their mechanisms may be associated with N-methyl-D-aspartate receptors (NMDARs). The NMDAR hypofunction hypothesis for schizophrenia was brought to the fore mainly based on the clinical effects of NMDAR antagonists and anti-NMDAR encephalitis pathology. Drugs targeted at augmenting NMDAR function in the brain seem to be promising in improving negative symptoms and cognitive dysfunction in patients with schizophrenia. In this review, we list NMDAR-targeted drugs and report on related clinical studies. We then summarize their effects on negative symptoms and cognitive dysfunction and analyze the unsatisfactory outcomes of these clinical studies according to the improved glutamate hypothesis that has been revealed in animal models. We aimed to provide perspectives for scientists who sought therapeutic strategies for negative symptoms and cognitive dysfunction in schizophrenia based on the NMDAR hypofunction hypothesis.
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http://dx.doi.org/10.3389/fnins.2021.641047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072017PMC
April 2021

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

Optimizing and Individualizing the Pharmacological Treatment of First-Episode Schizophrenic Patients: Study Protocol for a Multicenter Clinical Trial.

Front Psychiatry 2021 25;12:611070. Epub 2021 Feb 25.

Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.

Affecting ~1% of the world population, schizophrenia is known as one of the costliest and most burdensome diseases worldwide. Antipsychotic medications are the main treatment for schizophrenia to control psychotic symptoms and efficiently prevent new crises. However, due to poor compliance, 74% of patients with schizophrenia discontinue medication within 1.5 years, which severely affects recovery and prognosis. Through research on intra and interindividual variability based on a psychopathology-neuropsychology-neuroimage-genetics-physiology-biochemistry model, our main objective is to investigate an optimized and individualized antipsychotic-treatment regimen and precision treatment for first-episode schizophrenic patients. The study is performed in 20 representative hospitals in China. Three subprojects are included. In subproject 1, 1,800 first-episode patients with schizophrenia are randomized into six different antipsychotic monotherapy groups (olanzapine, risperidone, aripiprazole, ziprasidone, amisulpride, and haloperidol) for an 8-week treatment. By identifying a set of potential biomarkers associated with antipsychotic treatment response, we intend to build a prediction model, which includes neuroimaging, epigenetics, environmental stress, neurocognition, eye movement, electrophysiology, and neurological biochemistry indexes. In subproject 2, apart from verifying the prediction model established in subproject 1 based on an independent cohort of 1,800 first-episode patients with schizophrenia, we recruit patients from a verification cohort who did not get an effective response after an 8-week antipsychotic treatment into a randomized double-blind controlled trial with minocycline (200 mg per day) and sulforaphane (3 tables per day) to explore add-on treatment for patients with schizophrenia. Two hundred forty participants are anticipated to be enrolled for each group. In subproject 3, we tend to carry out one trial to construct an intervention strategy for metabolic syndrome induced by antipsychotic treatment and another one to build a prevention strategy for patients at a high risk of metabolic syndrome, which combines metformin and lifestyle intervention. Two hundred participants are anticipated to be enrolled for each group. The study protocol has been approved by the Medical Ethics committee of the Second Xiangya Hospital of Central South University (No. 2017027). Results will be disseminated in peer-reviewed journals and at international conferences. This trial has been registered on Clinicalrials.gov (NCT03451734). The protocol version is V.1.0 (April 23, 2017).
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http://dx.doi.org/10.3389/fpsyt.2021.611070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947302PMC
February 2021

Dietary fiber and probiotics for the treatment of atypical antipsychotic-induced metabolic side effects: study protocol for a randomized, double-blind, placebo-controlled trial.

Trials 2021 Feb 23;22(1):159. Epub 2021 Feb 23.

National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.

Background: Atypical antipsychotic medications, which are effective for the treatment of schizophrenia and bipolar disorder, are associated with features of metabolic syndrome, such as weight gain, hyperglycemia, dyslipidemia, and insulin resistance. Although there are a few studies on the effects of dietary fiber or probiotics on weight loss in obese people, no published trials have reported the efficacy of dietary fiber and probiotics on reducing atypical antipsychotic-induced weight gain.

Methods: For this 12-week randomized, double-blind, placebo-controlled study, 100 patients with a weight gain of more than 10% after taking atypical antipsychotic medications were recruited. Participants were randomized to four groups as follows: probiotics (840 mg twice daily (bid)) plus dietary fiber (30 g bid), probiotics (840 mg bid) plus placebo, placebo plus dietary fiber (30 g bid), or placebo group. The primary outcome was the change in body weight. Secondary outcomes included changes in metabolic syndrome parameters, appetite score, biomarkers associated with a change in weight, and gut microbiota composition and function.

Discussion: To date, this is the first randomized, placebo-controlled, double-blinded trial investigating the efficacy of dietary fiber and probiotics alone and in combination to reduce metabolic side effects induced by atypical antipsychotic medications. If effective, it is possible to conclude that dietary fiber and probiotics can reduce atypical antipsychotic-induced metabolic side effects.

Trial Registration Number: ClinicalTrials.gov NCT03379597 . Registered on 19 November 2017.
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http://dx.doi.org/10.1186/s13063-021-05123-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903643PMC
February 2021

Effect of CYP2D6 polymorphisms on plasma concentration and therapeutic effect of risperidone.

BMC Psychiatry 2021 02 3;21(1):70. Epub 2021 Feb 3.

National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.

Background: This study aimed to investigate the influence of CYP2D6 polymorphisms on risperidone plasma concentrations in patients with schizophrenia. Based on pharmacogenomics, we examined whether plasma concentration of risperidone is associated with clinical response and adverse side-effects.

Methods: We recruited patients with chronic schizophrenia who were then treated with risperidone. The CYP2D6 genotypes were determined using targeted sequencing. All high-frequency mutation sites of the nine exons of the gene were assayed in the present study. Plasma concentrations of risperidone and 9-hydroxyrisperidone (9-OH-RIS) were measured using high-performance liquid chromatography (HPLC). Psychiatric symptoms were monitored using The Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI). Adverse effects were evaluated using the Barnes Akathisia Scale (BAS) and Extrapyramidal Symptom Rating Scale (ESRS). Follow-up visits were scheduled at weeks 2,4, and 8 after treatment initiation.

Results: Among the 76 patients, 100 C > T (rs1065852), 1038 C > T (rs1081003), 1662 G > C (rs1058164), 2851 C > T (rs16947), and 4181G > C (rs1135840) variants were detected. The most common allele was CYP2D6*10 (81.6%), whereas CYP2D6*2 (9.2%) and CYP2D6*5 (17.1%) were relatively rare. Plasma levels of risperidone and the risperidone/9-OH risperidone ratio (R/9-OH) were significantly increased in individuals with CYP2D6*10 (P < 0.05). The change in PANSS score, weight, high-density lipoprotein (HDL) level, prolactin (PRL) level, and ESRS were significantly different from baseline, between the different genotypes (P < 0.01). Moreover, individuals with CYP2D6*10 homozygous (TT) mutations were associated with higher risperidone concentration and R/9-OH ratio than those with heterozygous mutations (CT) (P < 0.01). A change from baseline in BPRS scores was observed only during week 8 and was different between heterozygous and homozygous mutations. As for the C2851T polymorphism, the incidence of adverse metabolic effects was significantly different between the C/C and C/T genotypes (P < 0.01). Regarding the G4181C polymorphisms, the changes from baseline in GLU and TG, were different between the C/C and C/G genotypes (P < 0.01).

Conclusions: The genotype of CYP2D6 significantly influences the plasma concentration of risperidone and may subsequently influence the adverse side-effects following risperidone treatment, while also exerting a slight influence on clinical outcomes.
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http://dx.doi.org/10.1186/s12888-020-03034-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856706PMC
February 2021

New Insight Into Metformin-Induced Cholesterol-Lowering Effect Crosstalk Between Glucose and Cholesterol Homeostasis via ChREBP (Carbohydrate-Responsive Element-Binding Protein)-Mediated PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Regulation.

Arterioscler Thromb Vasc Biol 2021 Apr 4;41(4):e208-e223. Epub 2021 Feb 4.

Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China (D.H., J.L., B.Y., Y.L., D.P.).

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.120.315708DOI Listing
April 2021

Anesthesia, sex and miscarriage history may influence the association between cesarean delivery and autism spectrum disorder.

BMC Pediatr 2021 Feb 1;21(1):62. Epub 2021 Feb 1.

National Clinical Research Center for Mental Disorders, Department of Psychiatry, and China National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.

Background: To explore the association between cesarean section (CS) and risk of autism spectrum disorder (ASD), and evaluate the possible factors influencing this association.

Methods: In total, 950 patients diagnosed with ASD and 764 healthy controls were recruited in this study. Socio-demographic characteristics and prenatal, perinatal, and neonatal characteristics were compared between the two groups. Univariate and multivariable conditional logistic regression analyses were applied to adjust for confounders. Further stratified analyses based on sex and miscarriage history were similarly performed to explore the factors influencing the association between CS and ASD.

Results: CS was evidently associated with an elevated risk of ASD (adjusted odds ratio [aOR] = 1.606, 95% confidence interval (CI) = 1.311-1.969). Unlike regional anesthesia (RA), only CS performed under general anesthesia (GA) consistently elevated the risk of ASD (aOR = 1.887, 95% CI = 1.273-2.798) in females and males in further stratified analysis. The risk of children suffering from ASD following emergency CS was apparently increased in males (aOR = 2.390, 95% CI = 1.392-5.207), whereas a higher risk of ASD was observed among voluntary CS and indicated CS subgroups (aOR = 2.167, 95% CI = 1.094-4.291; aOR = 2.919, 95% CI = 1.789-4.765, respectively) in females. Moreover, the interaction term of CS and past miscarriage history (β = - 0.68, Wald χ2 = 7.5, df = 1, p = 0.006)) was similarly defined as influencing ASD.

Conclusions: The exposure of children to GA during CS may explain the possible/emerging association between CS and ASD. In addition, sex and miscarriage history could equally be factors influencing the association between CS and ASD.
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http://dx.doi.org/10.1186/s12887-021-02518-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849114PMC
February 2021

Research advances in add-on treatment for negative symptoms and cognitive dysfunction in schizophrenia.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2020 Dec;45(12):1457-1463

Department of Psychiatry, Second Xiangya Hospital, Central South University, Changsha 410011, China.

Antipsychotic medication is the primary treatment for schizophrenia, which is effective on ameliorating positive symptoms and can reduce the risk of recurrence, but it has limited efficacy for negative symptoms and cognitive dysfunction. The negative symptoms and cognitive dysfunction seriously affects the life quality and social function for the patients with schizophrenia. Currently, there is plenty evidence that antipsychotic drugs combined with adjuvant therapy drugs can effectively improve the negative symptoms and cognitive dysfunction. These drugs include anti-oxidants, nicotinic acetylcholine receptors and neuro-inflammatory drugs (anti-inflammatory drugs, minocycline), which show potential clinical effects.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2020.190556DOI Listing
December 2020

Effects of sulforaphane on cognitive function in patients with frontal brain damage: study protocol for a randomised controlled trial.

BMJ Open 2020 10 16;10(10):e037543. Epub 2020 Oct 16.

Department of Neurosurgery, Central South University (CSU), 410008, Changsha, Hunan, China

Introduction: Many patients with frontal brain damage show serious cognitive function deficits, which hamper their quality of life and result in poor clinical outcomes. Preclinical research has shown that sulforaphane can significantly improve spatial localisation and working memory impairment after brain injury. The primary aim of this double-blind randomised controlled clinical trial is to assess the efficacy of sulforaphane for improving cognitive function in patients with frontal brain damage.

Methods And Analysis: Ninety eligible patients will be randomly allocated to an active treatment or a placebo group in a 2:1 ratio. Participants will undergo a series of cognitive and neuropsychiatric tests at baseline (week 0) and after 12 weeks to determine the effect of sulforaphane on cognition. Magnetic resonance spectrum of the brain will be studied using the 3T MRIs of the brain to detect brain metabolites markers, including N-acetyl aspartate, glutamate (Glu), glutathione (GSH) and γ-aminobutyric acid (GABA). Blood brain-derived neurotrophic factor, Glu, GSH and GABA levels and gut microbiota will also be assessed over this period. This study will also evaluate long-term outcomes of brain trauma, brain tumours and cerebrovascular disease via exploratory analyses. The primary outcome will be the difference in scores of a battery of cognitive tests after 12 weeks of sulforaphane treatment. The secondary outcomes will be changes in the Functional Activities Questionnaire (FAQ), the Patient Health Questionnaire (PHQ-9), the Self-Rating Anxiety Scale, the changes in T1-weighted MRI and resting-state functional MRI findings, and changes in brain and blood metabolic markers and gut microbiota at weeks 0 and 12. We expect that sulforaphane will yield favourable results in treating memory and learning deficits for patients with frontal brain damage. Cognitive functional treatment may also improve brain trauma, brain tumours and cerebrovascular outcomes.

Ethics And Dissemination: The study protocol has been approved by the Medical Ethics committee of the Xiangya Hospital of Central South University (No. 2017121019). The results will be disseminated in peer-reviewed journals and at international conferences.

Trial Registration Number: This trial was registered on Clinicaltrials.gov on 31 January 2020 (NCT04252261). The protocol version is V.1.0 (20 December 2019).
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http://dx.doi.org/10.1136/bmjopen-2020-037543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569949PMC
October 2020

Public Behavior Change, Perceptions, Depression, and Anxiety in Relation to the COVID-19 Outbreak.

Open Forum Infect Dis 2020 Aug 3;7(8):ofaa273. Epub 2020 Jul 3.

Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China.

Background: COVID-19 has spread rapidly and internationally, which has elicited public panic and psychological problems. Public protective behaviors and perception play crucial roles in controlling the spread of illness and psychological status.

Methods: We conducted a cross-sectional online survey in the hardest-hit Hubei province and other areas in China affected by the COVID-19 outbreak. Questions about their basic information, the perception of the COVID-19 outbreak, recent preventive or avoidance behaviors, and self-reported mental health scales including the Patient Health Questionnaire and Self-Rating Anxiety Scale were included. Binary logistic regressions were used to investigate the association between personal variables/perceptions and psychological distress.

Results: A total of 6261 people were included in the analysis, with 3613 (57.7%) in Hubei province (1743 in Wuhan). The majority of people have adopted preventive and avoidance behaviors. People from Hubei, with contact history, and people who were infected or whose family members were infected had a much higher prevalence of depression and anxiety. Providing truthful and sufficient information, informing the public about the severity of the disease, and perceptions that the outbreak can be controlled by protective behaviors were associated with lower prevalence of depression and anxiety.

Conclusions: Assessing the public response, perception, and psychological burden during the outbreak may help improve public health recommendations and deliver timely psychological intervention. Further research may focus on the psychological status of a specialized group to identify methods of delivery of better support based on public response and psychological demand.
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http://dx.doi.org/10.1093/ofid/ofaa273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337830PMC
August 2020

Psychological status and fatigue of frontline staff two months after the COVID-19 pandemic outbreak in China: A cross-sectional study.

J Affect Disord 2020 10 2;275:247-252. Epub 2020 Jul 2.

National Clinical Research Center for Mental Disorders, and Department of Psychaitry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China. Electronic address:

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http://dx.doi.org/10.1016/j.jad.2020.06.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330556PMC
October 2020

Reduced Hippocampal Volume and Its Relationship With Verbal Memory and Negative Symptoms in Treatment-Naive First-Episode Adolescent-Onset Schizophrenia.

Schizophr Bull 2021 01;47(1):64-74

MOE Key Lab for Neuroinformation, The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China, Chengdu, PR China.

Accumulating neuroimaging evidence has shown remarkable volume reductions in the hippocampi of patients with schizophrenia. However, the relationship among hippocampal morphometry, clinical symptoms, and cognitive impairments in schizophrenia is still unclear. In this study, high-resolution structural magnetic resonance imaging data were acquired in 36 patients with adolescent-onset schizophrenia (AOS, age range: 13-18 years) and 30 age-, gender-, and education-matched typically developing controls (TDCs). Hippocampal volume was assessed automatically through volumetric segmentation and measurement. After adjusting for total intracranial volume, we found reduced hippocampal volume in individuals with AOS compared with TDCs, and the hippocampal volume was positively correlated with verbal memory and negatively correlated with negative symptoms in AOS. In addition, mediation analysis revealed the indirect effect of hippocampal volume on negative symptoms via verbal memory impairment. When the negative symptoms were represented by 2 dimensions of deficits in emotional expression (EXP) and deficits in motivation and pleasure (MAP), the indirect effect was significant for EXP but not for MAP. Our findings provide further evidence of hippocampal volume reduction in AOS and highlight verbal memory impairment as a mediator to influence the relationship between hippocampal morphometry and negative symptoms, especially the EXP dimension of negative symptoms, in individuals with AOS.
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http://dx.doi.org/10.1093/schbul/sbaa092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825026PMC
January 2021

Autism spectrum disorder and severe social impairment associated with elevated plasma interleukin-8.

Pediatr Res 2021 Feb 24;89(3):591-597. Epub 2020 Apr 24.

Department of Psychiatry and 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, Hunan, 410011, China.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unclear etiology and pathophysiology. Previous studies have indicated that the dysregulation of cytokines may be involved in the pathogenesis of ASD and that the levels of cytokines may serve as potential biomarkers of this disorder.

Methods: The current study employed a family triad-based case-control design to study the levels of plasma cytokines in families with ASD (n = 45 triads) and controls (n = 38 triads) with a Human Cytokine Twenty-Five-Plex Kit. The Social Responsiveness Scale (SRS) was used to measure social impairment of ASD children.

Results: After controlling for the levels of parental cytokines, we identified that interferon-α (IFN-α), interleukin-7 (IL-7), IL-8, IFN-γ-inducible protein-10, and macrophage inflammatory protein-1β were associated with ASD, and IL-8 was the only cytokine also associated with the levels of both parental cytokines in the offspring-parents regression analysis and three subdomains of SRS (social awareness, cognition, and motivations) in the children with ASD. The receiver operating characteristic curve showed that the log-transformed IL-8 level discriminated children with autism from controls with an area under the curve of 0.858 (95% confidence interval: 0.777-0.939).

Conclusions: Our study suggests that IL-8 is a potential biomarker for ASD and may be involved in the pathogenesis of ASD.

Impact: The study suggests that IL-8 is a promising biomarker for ASD and may be involved in the pathogenesis of ASD. Only a very few studies have reported the parental cytokine levels. The significant strength of this article is that we applied the family triad-based approach to explore cytokine levels in families with autism and controls. There are no objective biomarkers, making the accurate diagnosis, prognostic prediction and effective treatment difficult, and our study provides promising results.
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http://dx.doi.org/10.1038/s41390-020-0910-xDOI Listing
February 2021

Care for the Psychological Status of Frontline Medical Staff Fighting Against Coronavirus Disease 2019 (COVID-19).

Clin Infect Dis 2020 12;71(12):3268-3269

Psychiatry Department and Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

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http://dx.doi.org/10.1093/cid/ciaa385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184370PMC
December 2020

Air pollution and hippocampal atrophy in first episode schizophrenia.

Schizophr Res 2020 04 10;218:63-69. Epub 2020 Mar 10.

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

Air pollution has recently been linked to central nervous system (CNS) diseases, possibly mediated by inflammation and oxidative stress. Hippocampal atrophy in individuals with first episode schizophrenia (FES) has also been associated with biomarkers of inflammation and oxidative stress, whereas hippocampal atrophy was not observed in matched healthy controls with similar biomarker levels of inflammation and oxidative stress. Fine particulate matter (PM2.5), one component of air pollution, is most strongly implicated in CNS disease. The present study examined the association between PM2.5 and hippocampal volume in individuals with FES who participated in a 52-week placebo-controlled clinical trial of citalopram added to clinician-determined antipsychotic treatment at four sites in the US and China. Left hippocampal volumetric integrity (LHVI; inversely related to atrophy) was measured at baseline and week 52 using an automated highly-reliable algorithm. Mean annual PM2.5 concentrations were obtained from records compiled by the World Health Organization. The relationships between baseline LHVI and PM2.5 and change in LHVI and PM2.5 were evaluated using regression analyses. 89 participants completed imaging at baseline and 46 participants completed imaging at week 52. Mean annual PM2.5 was significantly associated with both baseline LHVI and change in LHVI after controlling for age, sex, baseline LHVI, duration of untreated psychosis and baseline antipsychotic medication dose. Air pollution may contribute to the progression of hippocampal atrophy after a first episode of illness, but these findings should be considered preliminary since other unmeasured factors may have differed between cities and contributed to the observed effect.
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http://dx.doi.org/10.1016/j.schres.2020.03.001DOI Listing
April 2020

[Metformin treatment of antipsychotic-induced dyslipidemia: analysis of two randomized, placebo-controlled trials].

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2019 Oct;44(10):1128-1136

Mental Health Institute, Second Xiangya Hospital, Central South University, Changsha 410011, China.

Objective: To examine the efficacy and safety for metformin in treating antipsychotic-induced dyslipidemia.
 Methods: Two randomized placebo-controlled trials were included in the analysis. A total of 201 schizophrenia patients with dyslipidemia after treatment with an antipsychotic were collected, and the patients were divided into two groups: a 1 000 mg/d metformin group (n=103) and a placebo group (n=98). The clinical symptoms and metabolic indicators such as body weight, blood glucose, and blood lipids were assessed at baseline, the 12th week and the 24th week after treatment respectively.
 Results: After metformin treatment, the mean difference in the low-density lipoprotein cholesterol (LDL-C) value between the metformin group and the placebo group was from 0.16 mmol/L at baseline to -0.86 mmol/L at the end of the 24th week, which was decreased by 1.02 mmol/L 
(P<0.01). At the 24th week, the LDL-C was more than 3.37 mmol/L in 25.3% patients in the metformin group, which was significantly lower than that in the placebo group (64.8%) (P<0.01). Compared with the placebo group, there were significant changes in the weight, body mass index (BMI), insulin, insulin resistance index, total cholesterol and triglyceride, and high-density lipoprotein cholesterol (HDL-C) in the metformin group (all P<0.05). The treatment effects on weight and insulin resistance appeared at the 12th week and further improved at the 24th week, but the effects on improving dyslipidemia only significantly occurred at the end of the 24th week.
 Conclusion: The metformin treatment is effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effect to reduce the antipsychotic-induced insulin resistance appears earlier than the effect to improve dyslipidemia.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2019.180379DOI Listing
October 2019

Reduced Brain Activity in the Right Putamen as an Early Predictor for Treatment Response in Drug-Naive, First-Episode Schizophrenia.

Front Psychiatry 2019 8;10:741. Epub 2019 Oct 8.

University of Massachusetts Medical School, UMass Memorial Medical Center, One Biotech, Worcester, MA, United States.

Antipsychotic medications can have a significant effect on brain function after only several days of treatment. It is unclear whether such an acute effect can serve as an early predictor for treatment response in schizophrenia. Thirty-two patients with drug-naive, first-episode schizophrenia and 32 healthy controls underwent resting-state functional magnetic resonance imaging. Patients were treated with olanzapine and were scanned at baseline and 1 week of treatment. Healthy controls were scanned once at baseline. Symptom severity was assessed within the patient group using the Positive and Negative Syndrome Scale (PANSS) at three time points (baseline, 1 week of treatment, and 8 weeks of treatment). The fractional amplitude of low frequency fluctuation (fALFF) and support vector regression (SVR) methods were used to analyze the data. Compared with the control group, the patient group showed increased levels of fALFF in the bilateral putamen at baseline. After 1week of olanzapine treatment, the patient group showed decreased levels of fALFF in the right putamen relative to those at baseline. The SVR analysis found a significantly positive relationship between the reduction in fALFF after 1 week of treatment and the improvement in positive symptoms after 8 weeks of treatment ( = 0.431, = 0.014). The present study provides evidence that early reduction and normalization of fALFF in the right putamen may serve as a predictor for treatment response in patients with schizophrenia.
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http://dx.doi.org/10.3389/fpsyt.2019.00741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791918PMC
October 2019

[Role of sulforaphane in improving negative symptoms and cognitive symptoms of schizophrenia and the underlying mechanism].

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2019 Jun;44(6):701-705

Department of Psychiatry, Second Xiangya Hospital, Central South University, Changsha 410011, China.

The negative symptoms and cognitive symptoms of schizophrenia patients are still clinical problems to be solved. Schizophrenia patients are abnormal in oxidative stress, immune regulation, and anti-histone deacetylase (HDAC), while sulforaphane plays a role in anti-oxidative stress, anti-inflammation, and anti-HDAC. Therefore, the sulforaphane could improve the negative symptoms and cognitive deficits of schizophrenia.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2019.06.014DOI Listing
June 2019

Resting-state functional hypoconnectivity of amygdala in clinical high risk state and first-episode schizophrenia.

Brain Imaging Behav 2020 Oct;14(5):1840-1849

Department of Psychiatry, The Second Xiangya Hospital, Central South University, No. 139, Middle Renmin Road, Changsha, 410011, China.

Resting-state functional hypoconnectivity of the amygdala with several brain regions has been identified in patients with schizophrenia. However, little is known about it in individuals at clinical high risk state. Treatment-seeking, drug-naive young adults were recruited for the study. The participants included 33 adults at Clinical High Risk (CHRs), 31 adults with first-episode schizophrenia (FSZs), and 37 age-, gender-, and education-matched healthy controls. All the participants were subjected to resting-state functional magnetic resonance imaging scans. Seed-based voxel-wise amygdala/whole-brain functional connectivity (FC) was calculated and compared. In the CHR group, the right amygdala showed decreased FC with clusters located in the left orbital, right temporal, insular, and bilateral frontal and cingulate areas. In the FSZ group, the right amygdala showed decreased FC with clusters located in the right temporal, insular, cingulate, and frontal areas. Exactly 30% of the voxels showing decreased FC in the FSZ group coincided with those in the CHR group. No difference in FC was identified between the CHR and FSZ groups. Voxel-wise FC values with the left or right amygdala in the bilateral occipital cortex were negatively correlated with the PANSS total score in the FSZ group. Resting-state functional hypoconnectivity of the amygdala is a valuable risk phenotype of schizophrenia, and its distribution, rather than degree, distinguishes CHR state from schizophrenia. This particular hypoconnectivity in CHRs and FSZs is relatively independent of the symptomatology and may reflect a dysfunctional dopamine system.
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http://dx.doi.org/10.1007/s11682-019-00124-5DOI Listing
October 2020

Childhood trauma as a mediator between emotional intelligence and recidivism in male offenders.

Child Abuse Negl 2019 07 17;93:162-169. Epub 2019 May 17.

Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha 410011, China. Electronic address:

Background: Prior researches have implicated a relationship of recidivism with childhood trauma (CT) and emotional intelligence (EI). However, the internal mechanism by which CT and EI influence the recidivism has not been examined.

Objective: This study aimed to map the road from CT and EI to recidivism in Chinese male offenders.

Participants And Setting: Three thousand one hundred and eighty-one Chinese adult male offenders participated in this study and completed Childhood Trauma Questionnaire (CTQ) and Wong Law Emotional Intelligence Scale (WLEIS). Recidivism was quantified by the number of convictions according to official records.

Methods: After controlling for age, education levels, family criminal history, and nature of offence, logistic regression sanalysis was performed to examine the effects of CT and EI on severity of recidivism. Structural Equation Modeling (SEM) was applied to explore the mediation model between CT, EI and recidivism.

Results: Logistic regression model shows a significant effect of CT (OR = 1.008, p < 0.01), rather than EI, on recidivism. SEM supported a full mediating effect of CT in the relationship between EI and severity of recidivism.

Conclusions: Our findings suggest that EI has no direct effect on the recidivism, but exerts indirect influence on the recidivism through the mediating role of childhood trauma.
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http://dx.doi.org/10.1016/j.chiabu.2019.04.015DOI Listing
July 2019

Brain-derived neurotrophic factor is associated with cognitive impairments in first-episode and chronic schizophrenia.

Psychiatry Res 2019 03 18;273:528-536. Epub 2019 Jan 18.

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

Brain-derived neurotrophic factor (BDNF) may be related to the pathophysiology of schizophrenia. This study aims to examine the relation between plasma BDNF levels and the cognition of patients with schizophrenia. We recruited 31 patients with chronic schizophrenia, 34 first-episode patients, and 35 healthy control subjects. We examined the MATRICS Consensus Cognitive Battery (MCCB) and the plasma BDNF levels in all groups. The schizophrenic symptoms were assessed using the positive and negative syndrome scale. The BDNF levels of schizophrenic patients were remarkably lower than those of the controls. The cognitive MCCB global composite scores and part index scores of schizophrenic patients were remarkably lower than those of the controls. Moreover, remarkable correlations were observed between BDNF levels and partial cognitive dimensions, such as visual learning, memory, and processing speed. Therefore, BDNF may be involved in the pathophysiology and cognitive impairment of schizophrenia.
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http://dx.doi.org/10.1016/j.psychres.2019.01.051DOI Listing
March 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

Effect of Betahistine and Metformin on Antipsychotic-Induced Weight Gain: An Analysis of Two Clinical Trials.

Front Psychiatry 2018 27;9:620. Epub 2018 Nov 27.

Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, China.

Antipsychotic-induced weight gain is one of the most common adverse effects of antipsychotic treatment. However, there are no well-established interventions for the weight gain yet. In this study, we pooled the data from two clinical trials, which were originally examining the efficacy of betahistine and the efficacy of metformin in treating antipsychotic-induced weight gain and insulin resistance. A total of 67 people with schizophrenia or bipolar disorder treated with antipsychotics were assigned to 36 mg day betahistine ( = 13) or 1,000 mg day metformin ( = 25) or placebo ( = 29) treatment for 12 weeks, with evaluation at baseline and week 12. The primary outcome was the body mass index (BMI). After treatment, metformin group had a mean decrease in BMI of 1.46 ± 0.14 ( < 0.001) and insulin resistance index (IRI) of 4.30 ± 2.02 ( < 0.001). The betahistine group had no significant alteration in BMI or IRI. However, placebo group had a mean increase in BMI of 1.27 ± 0.77 ( < 0.001) and IRI of 0.45 ± 0.86 ( < 0.001). Between the two treatment groups, metformin significantly decreased weight, BMI, fasting glucose, insulin level, and IRI but not waist circumference when compared with betahistine. Moreover, metformin significantly decreased weight, BMI, waist circumference, fasting glucose, insulin level, and IRI when compared with placebo, whereas betahistine significantly decreased body weight, waist circumference, BMI, insulin level, and IRI but not fasting glucose when compared with placebo. In this study, we found that both metformin treatment and betahistine treatment were efficacious in improving antipsychotic-induced weight gain and insulin resistance, and metformin was more efficacious in preventing and revising the weight gain induced by antipsychotics. www.ClinicalTrials.gov, NCT00451399(Study 1), NCT00709202(Study 2).
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http://dx.doi.org/10.3389/fpsyt.2018.00620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277778PMC
November 2018

Betahistine effects on weight-related measures in patients treated with antipsychotic medications: a double-blind placebo-controlled study.

Psychopharmacology (Berl) 2018 Dec 31;235(12):3545-3558. Epub 2018 Oct 31.

Psychiatric Institute University of Illinois, Chicago, Illinois and John Hopkins University Medical School, Baltimore, USA.

Rationale: Weight gain during treatment with antipsychotics is a prominent side-effect, especially with some second-generation antipsychotics, such as olanzapine and clozapine, and pharmacological treatments which ameliorate this side-effect are important to investigate. Decreases in histaminergic transmission in the brain induced by antipsychotics may be one of the mechanisms contributing to weight gain. Since betahistine is a histaminergic agonist, it may potentially counteract the weight gain effects of antipsychotics.

Method: We conducted a double-blind placebo-controlled study to evaluate the effects of 12 weeks of treatment with betahistine (N = 29) or placebo (N = 22) in adolescents and adults on anthropomorphically measured weight-related parameters, appetite, and fasting glucose-lipid and leptin levels in 51 patients treated with first and/or second-generation antipsychotics who had gained weight during treatment or had high body-mass-index (BMI). Psychopathology and side-effects were also assessed with relevant scales.

Results: In a sub-group of patients being treated with olanzapine or clozapine (n = 26), betahistine was significantly (P < .05) better than placebo in preventing increases in weight (3.1 kg less weight gain than placebo), BMI, and waist circumference. Betahistine did not decrease weight or BMI in patients treated with other antipsychotics. There was also no effect of betahistine on preventing weight or BMI gain in the total combined sample of all subjects. Betahistine did not significantly improve appetite or glucose-lipid measures in either subgroup. There were no significant differences in side-effects or psychopathology changes in the betahistine- vs. placebo-treated patients.

Conclusions: These results suggest that betahistine may potentially be a useful adjunctive drug for decreasing weight gain in patients treated with antipsychotics that are potent histamine antagonists, such as olanzapine or clozapine, but may not be useful for this purpose in patients on other antipsychotic medications. The results justify larger placebo-controlled studies to further confirm these effects before specific recommendations can be made for routine use.
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http://dx.doi.org/10.1007/s00213-018-5079-1DOI Listing
December 2018

Regional white matter volume abnormalities in first-episode somatization disorder.

Int J Psychophysiol 2018 11 15;133:12-16. Epub 2018 Sep 15.

Department of Psychiatry, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China. Electronic address:

Background: Alterations of white matter integrity have been implicated in patients with somatization disorder (SD). However, changes of white matter volume (WMV) remain unclear. This study is designed to examine regional WMV in patients with SD and to investigate the potential relationships between WMV abnormalities and personality traits, cognitive function, and symptom severity.

Methods: We recruited 25 first-episode, drug-naive patients with SD and 28 sex-, age-, and education-matched healthy controls for the study. Personality traits, cognitive function, and symptom severity were assessed for all participants. Data were analyzed with the computational anatomy toolbox (CAT12) methods.

Results: Patients with SD exhibited a significantly increased WMV in the right inferior frontal gyrus (IFG) (t = 4.4009) and a significantly decreased WMV in the left inferior longitudinal fasciculus (ILF) (t = -3.4292) relative to healthy controls. No correlation was found between abnormal WMV and clinical/cognitive variables in the patients.

Conclusions: Our findings suggest the presence of significant regional WMV abnormalities in first-episode, drug-naive patients with SD, which might improve understanding the pathophysiology of SD.
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http://dx.doi.org/10.1016/j.ijpsycho.2018.09.003DOI Listing
November 2018

Altered Serum Tumor Necrosis Factor and Interleukin-1β in First-Episode Drug-Naive and Chronic Schizophrenia.

Front Neurosci 2018 11;12:296. Epub 2018 May 11.

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

Abnormality of the immune system might play a significant role in the pathogenesis of schizophrenia. We want to identity whether the serum TNF-α and IL-1β levels were changed in FEDN patients and CP and to investigate the relationship between both cytokines and psychopathological symptoms. We recruited 69 FEDN patients, 87 CP and 61 healthy controls. Schizophrenia symptomatology was evaluated with the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS) and Clinical Global Impression Scale (CGI). Serum TNF-α and IL-1β levels were examined using sandwich enzyme-linked immunosorbent assay (ELISA). TNF-α and IL-1β levels in CP were significantly higher compared to healthy controls, but TNF-α and IL-1β levels in FEDN patients were significantly lower than in both CP and healthy controls. A moderate correlation between serum TNF-α or IL-1β levels and PANSS negative subscore was found in CP. But there was no correlation between altered cytokines and clinical symptoms in FEDN patients. Increased TNF-α and IL-1β levels in chronic patients may be associated with the progression, psychotropic drugs or other factors occur during chronic stage. Immune modulating treatments may become a new strategy of therapy for this subgroup of patients.
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http://dx.doi.org/10.3389/fnins.2018.00296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958184PMC
May 2018

Bidirectional Causal Connectivity in the Cortico-Limbic-Cerebellar Circuit Related to Structural Alterations in First-Episode, Drug-Naive Somatization Disorder.

Front Psychiatry 2018 26;9:162. Epub 2018 Apr 26.

Department of Psychiatry, Second Xiangya Hospital of Central South University, Changsha, China.

Anatomical and functional deficits in the cortico-limbic-cerebellar circuit are involved in the neurobiology of somatization disorder (SD). The present study was performed to examine causal connectivity of the cortico-limbic-cerebellar circuit related to structural deficits in first-episode, drug-naive patients with SD at rest. A total of 25 first-episode, drug-naive patients with SD and 28 healthy controls underwent structural and resting-state functional magnetic resonance imaging. Voxel-based morphometry and Granger causality analysis (GCA) were used to analyze the data. Results showed that patients with SD exhibited decreased gray matter volume (GMV) in the right cerebellum Crus I, and increased GMV in the left anterior cingulate cortex (ACC), right middle frontal gyrus (MFG), and left angular gyrus. Causal connectivity of the cortico-limbic-cerebellar circuit was partly affected by structural alterations in the patients. Patients with SD showed bidirectional cortico-limbic connectivity abnormalities and bidirectional cortico-cerebellar and limbic-cerebellar connectivity abnormalities. The mean GMV of the right MFG was negatively correlated with the scores of the somatization subscale of the symptom checklist-90 and persistent error response of the Wisconsin Card Sorting Test (WCST) in the patients. A negative correlation was observed between increased driving connectivity from the right MFG to the right fusiform gyrus/cerebellum IV, V and the scores of the Eysenck Personality Questionnaire extraversion subscale. The mean GMV of the left ACC was negatively correlated with the WCST number of errors and persistent error response. Negative correlation was found between the causal effect from the left ACC to the right middle temporal gyrus and the scores of WCST number of categories achieved. Our findings show the partial effects of structural alterations on the cortico-limbic-cerebellar circuit in first-episode, drug-naive patients with SD. Correlations are observed between anatomical alterations or causal effects and clinical variables in patients with SD, and bear clinical significance. The present study emphasizes the importance of the cortico-limbic-cerebellar circuit in the neurobiology of SD.
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http://dx.doi.org/10.3389/fpsyt.2018.00162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932337PMC
April 2018

The Wnt Signaling Pathway Effector TCF7L2 Mediates Olanzapine-Induced Weight Gain and Insulin Resistance.

Front Pharmacol 2018 16;9:379. Epub 2018 Apr 16.

Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China.

Olanzapine is a widely used atypical antipsychotic medication for treatment of schizophrenia and is often associated with serious metabolic abnormalities including weight gain and impaired glucose tolerance. These metabolic side effects are severe clinical problems but the underpinning mechanism remains poorly understood. Recently, growing evidence suggests that Wnt signaling pathway has a critical role in the pathogenesis of schizophrenia and molecular cascades of antipsychotics action, of which Wnt signaling pathway key effector TCF7L2 is strongly associated with glucose homeostasis. In this study, we aim to explore the characteristics of metabolic disturbance induced by olanzapine and to elucidate the role of TCF7L2 in this process. C57BL/6 mice were subject to olanzapine (4 mg/kg/day), or olanzapine plus metformin (150 mg/kg/day), or saline, respectively, for 8 weeks. Metabolic indices and TCF7L2 expression levels in liver, skeletal muscle, adipose, and pancreatic tissues were closely monitored. Olanzapine challenge induced remarkably increased body weight, fasting insulin, homeostasis model assessment-insulin resistance index, and TCF7L2 protein expression in liver, skeletal muscle, and adipose tissues. Notably, these effects could be effectively ameliorated by metformin. In addition, we found that olanzapine-induced body weight gain and insulin resistance actively influence the expression of TCF7L2 in liver and skeletal muscle, and elevated level of insulin determines the increased expression of TCF7L2 in adipose tissue. Our results demonstrate that TCF7L2 participates in olanzapine-induced metabolic disturbance, which presents a novel mechanism for olanzapine-induced metabolic disturbance and a potential therapeutic target to prevent the associated metabolic side effects.
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http://dx.doi.org/10.3389/fphar.2018.00379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911481PMC
April 2018