Publications by authors named "Botao Zeng"

14 Publications

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Curcumin prevents obesity by targeting TRAF4-induced ubiquitylation in m A-dependent manner.

EMBO Rep 2021 Apr 20:e52146. Epub 2021 Apr 20.

College of Animal Sciences, Zhejiang University, Hangzhou, China.

Obesity has become a major health problem that has rapidly prevailed over the past several decades worldwide. Curcumin, a natural polyphenolic compound present in turmeric, has been shown to have a protective effect on against obesity and metabolic diseases. However, its underlying mechanism remains largely unknown. Here, we show that the administration of curcumin significantly prevents HFD-induced obesity and decreases the fat mass of the subcutaneous inguinal WAT (iWAT) and visceral epididymal WAT (eWAT) in mice. Mechanistically, curcumin inhibits adipogenesis by reducing the expression of AlkB homolog 5 (ALKHB5), an m A demethylase, which leads to higher m A-modified TNF receptor-associated factor 4 (TRAF4) mRNA. TRAF4 mRNA with higher m A level is recognized and bound by YTHDF1, leading to enhanced translation of TRAF4. TRAF4, acting as an E3 RING ubiquitin ligase, promotes degradation of adipocyte differentiation regulator PPARγ by a ubiquitin-proteasome pathway thereby inhibiting adipogenesis. Thus, m A-dependent TRAF4 expression upregulation by ALKBH5 and YTHDF1 contributes to curcumin-induced obesity prevention. Our findings provide mechanistic insights into how m A is involved in the anti-obesity effect of curcumin.
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http://dx.doi.org/10.15252/embr.202052146DOI Listing
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

Effect of DAOA genetic variation on white matter alteration in corpus callosum in patients with first-episode schizophrenia.

Brain Imaging Behav 2020 Aug 3. Epub 2020 Aug 3.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.

D-amino acid oxidase activator (DAOA) gene, which plays a crucial role in the process of glutamatergic transmission and mitochondrial function, is frequently linked with the liability for schizophrenia. We aimed to investigate whether the variation of DAOA rs2391191 is associated with alterations in white matter integrity of first-episode schizophrenia (FES) patients; and whether it influences the association between white matter integrity, cognitive function and clinical symptoms of schizophrenia. Forty-six patients with FES and forty-nine healthy controls underwent DTI and were genotyped for DAOA rs2391191. Psychopathological assessments were performed by Brief Psychiatric Rating Scale (BPRS) and Scale for Assessment of Negative Symptoms (SANS). Cognitive function was assessed by MATRICS Consensus Cognitive Battery (MCCB). Schizophrenia patients presented lower fractional anisotropy (FA) and higher radial diffusivity (RD), mainly spreading over the corpus callosum and corona radiata compared with healthy controls. Compared with patients carrying G allele, patients with AA showed lower FA in the body of corpus callosum, and higher RD in the genu of corpus callosum, right superior and anterior corona radiata, and left posterior corona radiata. In patients carrying G allele, FA in body of corpus callosum was positively correlated with working memory, RD in genu of corpus callosum was negatively associated with the speed of processing, working memory, and the composite score of MCCB, while no significant correlations were found in AA homozygotes. In our study, patients with FES presented abnormal white matter integrity in corpus callosum and corona radiata. Furthermore, this abnormality was associated with the genetic variation of DAOA rs2391191, with AA homozygotes showing less white matter integrity in the corpus callosum. Our findings possibly provide further support to the evidence that DAOA regulates the process of glutamatergic neurotransmission and mitochondrial function in the pathophysiological mechanism of schizophrenia.
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http://dx.doi.org/10.1007/s11682-020-00368-6DOI Listing
August 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

Parietal memory network and default mode network in first-episode drug-naïve schizophrenia: Associations with auditory hallucination.

Hum Brain Mapp 2020 06 29;41(8):1973-1984. Epub 2020 Feb 29.

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

Atypical spontaneous activities in resting-state networks may play a role in auditory hallucinations (AHs), but networks relevant to AHs are not apparent. Given the debating role of the default mode network (DMN) in AHs, a parietal memory network (PMN) may better echo cognitive theories of AHs in schizophrenia, because PMN is spatially adjacent to the DMN and more relevant to memory processing or information integration. To examine whether PMN is more relevant to AHs than DMN, we characterized these intrinsic networks in AHs with 59 first-episode, drug-naïve schizophrenics (26 AH+ and 33 AH-) and 60 healthy participants in resting-state fMRI. We separated the PMN, DMN, and auditory network (AN) using independent component analysis, and compared their functional connectivity across the three groups. We found that only AH+ patients displayed dysconnectivity in PMN, both AH+ and AH- patients exhibited dysfunctions of AN, but neither patient group showed abnormal connectivity within DMN. The connectivity of PMN significantly correlated with memory performance of the patients. Further region-of-interest analyses confirmed that the connectivity between the core regions of PMN, the left posterior cingulate gyrus and the left precuneus, was significantly lower only in the AH+ group. In exploratory correlation analysis, this functional connectivity metric significantly correlated with the severity of AH symptoms. The results implicate that compared to the DMN, the PMN is more relevant to the AH symptoms in schizophrenia, and further provides a more precise potential brain modulation target for the intervention of AH symptoms.
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http://dx.doi.org/10.1002/hbm.24923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267906PMC
June 2020

Anterior Hippocampal-Cortical Functional Connectivity Distinguishes Antipsychotic Naïve First-Episode Psychosis Patients From Controls and May Predict Response to Second-Generation Antipsychotic Treatment.

Schizophr Bull 2020 04;46(3):680-689

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

Background: Converging evidence implicates the anterior hippocampus in the proximal pathophysiology of schizophrenia. Although resting state functional connectivity (FC) holds promise for characterizing anterior hippocampal circuit abnormalities and their relationship to treatment response, this technique has not yet been used in first-episode psychosis (FEP) patients in a manner that distinguishes the anterior from posterior hippocampus.

Methods: We used masked-hippocampal-group-independent component analysis with dual regression to contrast subregional hippocampal-whole brain FC between healthy controls (HCs) and antipsychotic naïve FEP patients (N = 61, 36 female). In a subsample of FEP patients (N = 27, 15 female), we repeated this analysis following 8 weeks of second-generation antipsychotic treatment and explored whether baseline FC predicted treatment response using random forest.

Results: Relative to HC, untreated FEP subjects displayed reproducibly lower FC between the left anteromedial hippocampus and cortical regions including the anterior cingulate and insular cortex (P < .05, corrected). Anteromedial hippocampal FC increased in FEP patients following treatment (P < .005), and no longer differed from HC. Random forest analysis showed baseline anteromedial hippocampal FC with four brain regions, namely the insular-opercular cortex, superior frontal gyrus, precentral gyrus, and postcentral gyrus predicted treatment response (area under the curve = 0.95).

Conclusions: Antipsychotic naïve FEP is associated with lower FC between the anterior hippocampus and cortical regions previously implicated in schizophrenia. Preliminary analysis suggests that random forest models based on hippocampal FC may predict treatment response in FEP patients, and hence could be a useful biomarker for treatment development.
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http://dx.doi.org/10.1093/schbul/sbz076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147586PMC
April 2020

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

Aberrant resting-state functional connectivity of salience network in first-episode schizophrenia.

Brain Imaging Behav 2020 Oct;14(5):1350-1360

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200030, China.

The disruption of salience network (SN) has been consistently found in patients with schizophrenia and thought to give rise to specific symptoms. However, the functional dysconnectivity pattern of SN remains unclear in first-episode schizophrenia (FES). Sixty-five patients with FES and sixty-six health controls (HC) were enrolled in this study and underwent resting-state functional magnetic resonance imaging (rs-fMRI). The eleven regions of interest (ROIs) within SN were derived from the peaks of the group independent component analysis (gICA). Seed-based whole-brain functional connectivity (FC) analyses were performed with all SN ROIs as the seeds. Both hyper- and hypo-connectivity of SN were found in the FES. Specifically, the increased FC mainly existed between the SN and cortico-cerebellar sub-circuit and prefrontal cortex, while the reduced FC mainly existed within cortico-striatal-thalamic-cortical (CSTC) sub-circuit. Our findings suggest that FES is associated with pronounced dysregulation of SN, characterized prominently by hyperconnectivity of SN-prefrontal cortex and cerebellum, as well as hypoconnectivity of CSTC sub-circuit of the SN.
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http://dx.doi.org/10.1007/s11682-019-00040-8DOI Listing
October 2020

Association between catechol-O-methyltransferase genetic variation and functional connectivity in patients with first-episode schizophrenia.

Schizophr Res 2018 09 3;199:214-220. Epub 2018 May 3.

Department of Psychiatry, New York University Langone Medical Center, New York 10116, United States.

Dopamine in the prefrontal cortex (PFC) plays an important role in cognitive performance and regulates by catechol-O-methyltransferase (COMT) expression. To clarify the effect of COMT genotype on cognitive function in patients with schizophrenia, we performed DNA genotyping, cognitive evaluations, and functional magnetic resonance imaging (fMRI) in antipsychotic-naïve patients with first-episode schizophrenia (FES) and matched healthy control subjects. We found that all cognitive domains were impaired in patients with FES compared with healthy subjects. Moreover, COMT genotype influenced the verbal learning performance in healthy subjects, but not in patients with FES. Resting-state fMRI data revealed that patients with FES exhibited higher functional connectivity degree centrality in the medial PFC and lower degree centrality in the parietal-occipital junction than healthy subjects. Furthermore, patients with FES who were COMT Met allele carriers had higher degree centrality in the medial PFC than those with the Val/Val genotype. In contrast, in healthy controls, Met allele carriers exhibited higher degree centrality than healthy controls with the Val/Val genotype in the left hippocampus and left amygdala. There was a negative correlation between the degree centrality value in medial PFC and score of the Hopkins Verbal Learning Test-Revised (HVLT-R) in FES patients with the Met allele. Our findings suggest that COMT genotype differentially influences pathways related to cognitive performance in patients with FES versus healthy individuals, providing an important insight into schizophrenia pathophysiology.
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http://dx.doi.org/10.1016/j.schres.2018.04.023DOI Listing
September 2018

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

Reduced -Aminobutyric Acid and Glutamate+Glutamine Levels in Drug-Naïve Patients with First-Episode Schizophrenia but Not in Those at Ultrahigh Risk.

Neural Plast 2016 28;2016:3915703. Epub 2016 Nov 28.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiaotong University, Shanghai 200030, China.

Altered -aminobutyric acid (GABA), glutamate (Glu) levels, and an imbalance between GABAergic and glutamatergic neurotransmissions have been involved in the pathophysiology of schizophrenia. However, it remains unclear how these abnormalities impact the onset and course of psychosis. In the present study, 21 drug-naïve subjects at ultrahigh risk for psychosis (UHR), 16 drug-naïve patients with first-episode schizophrenia (FES), and 23 healthy controls (HC) were enrolled. In vivo GABA and glutamate+glutamine (Glx) levels in the medial prefrontal cortex were measured using proton magnetic resonance spectroscopy. Medial prefrontal GABA and Glx levels in FES patients were significantly lower than those in HC and UHR, respectively. GABA and Glx levels in UHR were comparable with those in HC. In each group, there was a positive correlation between GABA and Glx levels. Reduced medial prefrontal GABA and Glx levels thus may play an important role in the early stages of schizophrenia.
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http://dx.doi.org/10.1155/2016/3915703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5149697PMC
October 2017

Abnormal white matter microstructure in drug-naive first episode schizophrenia patients before and after eight weeks of antipsychotic treatment.

Schizophr Res 2016 Apr 3;172(1-3):1-8. Epub 2016 Feb 3.

Shanghai Key Laboratory of Psychotic Disorders (No.13dz2260500), Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, PR China; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiaotong University, Shanghai, 200030, PR China. Electronic address:

Background: Abnormal white matter integrity has been reported among first episode schizophrenia patients. However, findings on whether it can be reversed by short-term antipsychotic medications are inconsistent.

Method: Diffusion tensor imaging (DTI) was obtained from 55 drug-naive first episode schizophrenia patients and 61 healthy controls, and was repeated among 25 patients and 31 controls after 8 weeks during which patients were medicated with antipsychotics. White matter integrity is measured using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). These measures showing a group difference by Tract-based spatial statistics (TBSS) at baseline were extracted for longitudinal comparisons.

Results: At baseline, patients exhibited lower FA, higher MD and higher RD versus controls in forceps, left superior longitudinal fasciculus, inferior fronto-occipital fasciculus, left corticospinal tract, left uncinate fasciculus, left anterior thalamic radiation, and bilateral inferior longitudinal fasciculi. FA values of schizophrenia patients correlated with their negative symptoms (r=-0.412, P=0.002), working memory (r=0.377, P=0.005) and visual learning (r=0.281, P=0.038). The longitudinal changes in DTI indices in these tracts did not differ between patients and controls. However, among the patients the longitudinal changes in FA values in left superior longitudinal fasciculus correlated with the change of positive symptoms (r=-0.560, p=0.004), and the change of processing speed (r=0.469, p=0.018).

Conclusions: White matter deficits were validated in the present study by a relatively large sample of medication naïve and first episode schizophrenia patients. They could be associated with negative symptoms and cognitive impairment, whereas improvement in white matter integrity of left superior longitudinal fasciculus correlated with improvement in psychosis and processing speed. Further examination of treatment-related changes in white matter integrity may provide clues to the mechanism of antipsychotic response and provide a biomarker for clinical studies.
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http://dx.doi.org/10.1016/j.schres.2016.01.051DOI Listing
April 2016

Prolonged cortical silent period among drug-naive subjects at ultra-high risk of psychosis.

Schizophr Res 2014 Dec 31;160(1-3):124-30. Epub 2014 Oct 31.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China; Department of EEG and Imaging, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China. Electronic address:

Background: Deficits in gamma-aminobutyric acid (GABA) inhibitory neurotransmission have been associated with pathophysiological mechanisms underlying schizophrenia. However, little is known about whether these deficits occur before or after the onset of psychosis.

Method: We recruited 16 drug-naive subjects at ultra-high risk of psychosis (UHR), 17 schizophrenia patients and 28 healthy controls. Cortical inhibition was determined using transcranial magnetic stimulation (TMS) over the left primary motor cortex. TMS markers such as short-interval cortical inhibition (SICI), cortical silent period (CSP) and intracortical facilitation (ICF) were obtained from each subject. While SICI can reflect GABA type A (GABAA) mediated inhibition, CSP is thought to indicate GABA type B (GABAB) mediated inhibitory circuits.

Results: As compared with healthy controls, UHR subjects showed a prolonged CSP with no change in SICI, whereas schizophrenia patients demonstrated both a prolonged CSP and a reduced SICI. No group differences were found for ICF. CSP in schizophrenia patients also had a positive correlation with positive symptom score of the positive and negative symptom scale (PANSS).

Conclusions: Cortical inhibitory deficits among UHR subjects were relatively limited compared to those among schizophrenia patients. Alterations might occur in some subgroup of GABA-mediated neurotransmitter systems before the onset of psychosis, while alterations in both GABAA and GABAB networks might contribute to full-blown psychosis.
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http://dx.doi.org/10.1016/j.schres.2014.10.004DOI Listing
December 2014