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Background: Human brain is a topologically complex network embedded in anatomical space, and anatomical distance may affect functional connectivity (FC) in schizophrenia. However, little is known if and how this effect occurs in adolescent-onset schizophrenia (AOS)., Methods: We explored long- and short-range FC through resting-state functional magnetic resonance imaging in 48 first-episode, drug-naive AOS patients and 31 healthy controls, and we examined if these abnormalities could be utilized to separate patients from controls using receiver operating characteristic curves and support vector machines (SVM)., Results: Patients had increased long-range positive FC (lpFC) and short-range positive FC (spFC) in the right middle frontal gyrus and right superior medial prefrontal cortex within the anterior default mode network (DMN), decreased lpFC and spFC in several regions of the posterior DMN, and decreased lpFC within the important hubs of salience network (SN). The decreased lpFC in the left superior temporal gyrus was positively correlated with cognitive impairment. We found that SVM has high accuracy (up to 92.4%) in classifying patients and control., Conclusion: Disrupted anatomical distance would underlie network-level dysconnectivity, highlighting the importance of the DMN and SN in the neurodevelopment of schizophrenia. Abnormalities of long- and short-range FC in brain regions could discriminate patients from controls with high accuracy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Structural and functional abnormalities have been reported in the brain of patients with adolescent-onset schizophrenia (AOS). The brain regional functional synchronization in patients with AOS remains unclear., Methods: We analyzed resting-state functional magnetic resonance scans in 48 drug-naive patients with AOS and 31 healthy controls by using regional homogeneity (ReHo), a measurement that reflects brain local functional connectivity or synchronization and indicates regional integration of information processing. Then, receiver operating characteristic curves and support vector machines were used to evaluate the effect of abnormal regional homogeneity in differentiating patients from controls., Results: Patients with AOS showed significantly increased ReHo values in the bilateral superior medial prefrontal cortex (MPFC) and significantly decreased ReHo values in the left superior temporal gyrus (STG), right precentral lobule, right inferior parietal lobule (IPL), and left paracentral lobule when compared with controls. A combination of the ReHo values in bilateral superior MPFC, left STG, and right IPL was able to discriminate patients from controls with the sensitivity of 88.24%, specificity of 91.89%, and accuracy of 90.14%., Conclusion: The brain regional functional synchronization abnormalities exist in drug-naive patients with AOS. A combination of ReHo values in these abnormal regions might serve as potential imaging biomarker to identify patients with AOS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Patients with adolescent-onset schizophrenia (AOS) hold the same but severe form of symptoms with adult-onset schizophrenia, and with worse outcome and poor treatment response to antipsychotics. Several dominant brain regions of schizophrenia patients show significantly abnormal structural and functional connectivity during resting-state scans. However, coherence regional homogeneity (Cohe-ReHo) in drug-naive first-episode patients with AOS remains unclear., Method: A total of 48 drug-naive first-episode AOS outpatients and 31 healthy controls underwent resting-state functional magnetic resonance scans. Cohe-ReHo and support vector machine analyses were used to analyze the data., Results: Compared with the healthy controls, the AOS group showed significantly decreased Cohe-ReHo values distributed over brain regions, including the left postcentral gyrus, left superior temporal gyrus, left paracentral lobule, right precentral gyrus, right inferior parietal lobule (IPL), right middle frontal gyrus, and bilateral precuneus. No region with increased Cohe-ReHo values was observed in the AOS group compared with healthy controls. In addition, the right IPL was correlated with fluency (r=-0.324, p=0.030). However, the correlation was not significant after the Bonferroni correction at p<0.0083 (0.05/6). A combination of the Cohe-ReHo values in the bilateral precuneus and right IPL discriminated the patients from controls with the sensitivity, specificity, and accuracy of 91.67%, 87.10%, and 89.87%, respectively., Conclusion: Our findings suggested that the AOS patients exhibited diminished Cohe-ReHo values in some regions within the DMN network and sensorimotor network. The abnormalities in particular brain regions (bilateral precuneus and right IPL) may serve as potential biomarkers for AOS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Abnormal default-mode network (DMN) homogeneity has been involved in the neurophysiology of major depressive disorder (MDD) with inconsistent findings. The inconsistency may be due to clinical and methodological variability, and the reproducibility of the findings is limited. The present study aimed to examine alterations of the DMN homogeneity in two independent samples of patients with first-episode, drug-naive MDD., Methods: The samples included 59 patients with MDD and 31 comparison subjects from Sample 1 and 29 patients with MDD and 24 comparison subjects from Sample 2. Network homogeneity (NH) was computed with an overlapping technique, which was employed to define brain regions with abnormal NH common to the MDD samples., Results: Compared with comparison subjects, patients with MDD exhibited increased NH in an overlapped brain region of the left superior medial prefrontal cortex (MPFC). No correlations were found between abnormal NH and HAMD total/subscale scores in the patients of each sample and in the combined patients from both samples., Conclusions: This study is the first to examine alterations of DMN homogeneity in first-episode, drug-naive patients with MDD in two independent samples by using an overlapping technique. Patients with MDD exhibit increased NH in an overlapped region in the anterior DMN. The present study thus highlights the importance of the DMN in the neurophysiology of MDD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Brain structural and functional alterations in the cortical-subcortical circuits have been observed in somatization disorder (SD). However, whether and how anatomical distance affects the cortical-subcortical connectivity in SD remain unclear. This study aims to examine whether anatomical distance affects the cortical-subcortical in first-episode, drug-naive SD., Methods: Twenty-five first-episode, drug-naive patients with SD and twenty-eight healthy controls were recruited for a resting-state scan. Regional functional connectivity strength (FCS) was calculated for each voxel in the brain, which was further divided into short- and long-range FCSs. Correlation analyses were conducted between abnormal FCS and clinical/cognitive variables in the patients., Results: Compared with the controls, the patients showed increased short-range positive FCS (spFCS) in the right superior frontal gyrus (SFG) and decreased spFCS in the left pallidum, and increased long-range positive FCS (lpFCS) in the left middle frontal gyrus and right inferior temporal gyrus (ITG). Positive correlations were observed between the spFCS values in the right SFG and Eysenck Personality Questionnaire psychoticism scores (r=0.441, p=0.027, uncorrected) and between the lpFCS values in the right ITG and scores of digit symbol-coding of Wechsler Adult Intelligence Scale (r=0.416, p=0.039, uncorrected) in the patients CONCLUSIONS: The patients exhibited increased spFCS/lpFCS in the cortical regions and decreased spFCS in the subcortical regions. The left pallidum is first reported here to show decreased spFCS in SD. The present results suggest that abnormal cortical-subcortical circuits may play an important role in SD neurobiology., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Abnormal short-range and long-range functional connectivities (FCs) have been implicated in the neurophysiology of schizophrenia. This study was conducted to examine the potential of short-range and long-range FCs for differentiating the patients from the controls with a family-based case-control design. Twenty-eight first-episode, drug-naive patients with schizophrenia, 28 unaffected siblings of the patients (family-based controls, FBCs), and 40 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (fMRI) scans. The data were analyzed by short-range and long-range FC analyses, receiver operating characteristic curve (ROC) and support vector machine (SVM). Compared with the FBCs/HCs, the patients exhibit increased short-range positive FC strength (spFCS) and/or long-range positive FC strength (lpFCS) in the default-mode network (DMN) and decreased spFCS and lpFCS in the sensorimotor circuits. Furthermore, a combination of the spFCS values in the right superior parietal lobule and the lpFCS values in the left fusiform gyrus/cerebellum VI can differentiate the patients from the FBCs with high sensitivity and specificity. The findings highlight the importance of the DMN and sensorimotor circuits in the pathogenesis of schizophrenia. Combining with family-based case-control design may be a viable option to limit the confounding effects of environmental risk factors in neuroimaging studies of schizophrenia., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Treatment effects of antipsychotic drugs on cerebral function are seldom examined. Exploring functional connectivity (FC) in drug-free schizophrenia patients before and after antipsychotic treatment can improve the understanding of antipsychotic drug mechanisms. A total of 17 drug-free patients with recurrent schizophrenia and 24 healthy controls underwent resting-state functional magnetic resonance imaging scans. Long- and short-range FC strengths (FCS) were calculated for each participant. Compared with the controls, the patients at baseline exhibited increased long-range positive FCS (lpFCS) in the bilateral inferior parietal lobule (IPL) and decreased lpFCS in the brain regions of the default-mode network (DMN) regions and sensorimotor circuits of the brain. By contrast, increased short-range positive FCS was observed in the right IPL of the patients at baseline compared with the controls. After treatment with olanzapine, increased FC in the DMN and sensorimotor circuits of the brain was noted, whereas decreased FC was observed in the left superior temporal gyrus (STG). Moreover, the alterations of the FCS values and the reductions in symptom severity among the patients after treatment were correlated. The present study provides evidence that olanzapine normalizes the abnormalities of long- and short-range FCs in schizophrenia. FC reductions in the right IPL may be associated with early treatment response, whereas those in the left STG may be related to poor treatment outcome., (Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.)

Objectives: To pilot efficacy and safety data of quetiapine-XR monotherapy or adjunctive therapy to antidepressant(s) in the acute treatment of MDD with current generalized anxiety disorder (GAD)., Methods: The Mini International Neuropsychiatric Interview was used to ascertain the diagnosis of DSM-IV Axis I disorders. Eligible patients were randomly assigned to quetiapine-XR or placebo for up to 8 weeks. Changes from baseline to endpoint in Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impression-Severity (CGI-S), Quick Inventory of Depression Symptomatology-16 items Self-Report (QIDS-16-SR) total scores, and other outcome measures were analyzed with the last observation carried forward strategy and/or mixed-effects modeling for repeated measures., Results: Of the 34 patients screened, 23 patients were randomized to receive quetiapine-XR (n = 11) or placebo (n = 12), with 5 and 4 completing the study, respectively. The mean dose of quetiapine-XR was 154 ± 91 mg/d. The change from baseline to endpoint in the total scores of HAMD-17, HAM-A, QIDS-16-SR, and CGI-S were significant in the quetiapine-XR group, but only the change in HAM-A total score was significant in the placebo group. The differences in these changes between the two groups were only significant in CGI-S scores, with the rest of numerical larger in the quetiapine-XR group. The most common side effects from quetiapine-XR were dry mouth, somnolence/sedation, and fatigue., Conclusions: In this pilot study, quetiapine-XR was numerically superior to placebo in reducing depressive and anxiety symptoms in patients with MDD and current GAD. Large sample studies are warranted to support or refute these preliminary findings.

Background: Previous meta-analyses have compared paliperidone extended-release (ER) tablets with other antipsychotics, but none have involved Chinese patients or studies from People's Republic of China. Further, the results of these meta-analyses may not be applicable to Chinese patients. In the present study, we evaluated the efficacy, safety, and acceptability of paliperidone ER compared with other second-generation antipsychotics (SGAs) for Chinese patients with schizophrenia., Methods: Randomized controlled studies of paliperidone ER and other SGAs as oral monotherapy in the acute phase treatment of schizophrenia were retrieved from Medline, Embase, and the Cochrane Library (CENTRAL), as well as from Chinese databases including the China National Knowledge Infrastructure, Wanfang, and VIP Information/Chinese Scientific Journals Database. We pooled data on response rates, chance of withdrawal due to adverse events, probability of adverse events, and odds of withdrawal for any reason., Results: Fifty randomized controlled trials were identified. The response rate for paliperidone ER was significantly higher than that of other pooled SGAs (risk ratio [RR] 0.83, 95% confidence interval [CI] 0.72-0.96) and ziprasidone (RR 0.57, 95% CI 0.39-0.82). Paliperidone ER significantly reduced the chance of withdrawal due to adverse events and the chance of any adverse events compared with other pooled SGAs (RR 0.32, 95% CI 0.17-0.58 and RR 0.88, 95% CI 0.79-0.97) and risperidone (RR 0.31, 95% CI 0.14-0.67 and RR 0.70, 95% CI 0.57-0.86). The incidence of extrapyramidal symptoms on paliperidone ER was comparable with other pooled SGAs (RR 0.94, 95% CI 0.66-1.35) and significantly lower than that of risperidone (RR 0.56, 0.41-0.77) but higher than that of olanzapine (RR 1.88, 95% CI 1.05-3.36). Paliperidone ER was superior to other pooled SGAs (RR 0.32, 95% CI 0.21-0.49 and RR 0.50, 95% CI 0.35-0.72) and olanzapine (RR 0.23, 95% CI 0.15-0.33 and RR 0.33, 95% CI 0.23-0.47) as far as weight gain and somnolence were concerned. Further, prolactin-related adverse events caused by paliperidone ER were comparable with other pooled SGAs (RR 1.30, 95% CI 0.73-2.33), but outnumbered those caused by olanzapine (RR 7.53, 95% CI 2.05-27.71)., Conclusion: Paliperidone ER is efficacious, safe, and well accepted when compared with other pooled SGAs for the treatment of Chinese patients with schizophrenia.

Objective: To investigate the effect of ziprasidone and olanzapine on glucose and lipid metabolism in first-episode schizophrenia., Methods: A total of 260 schizophrenics were assigned randomly to receive ziprasidone or olanzapine for 6 weeks. The weight was measured at baseline, week 2, 4 and 6. Fasting blood glucose (FBS), fasting insulin, high-density lipoprotein (HDL), total-cholesterol (TC) and triglycerides (TG) were measured at baseline and the end of 6-week treatment. Low-density lipoprotein (LDL) was measured in some patients at baseline and the end of 6-week treatment. Body mass index (BMI) and insulin resistance index (IRI) were counted., Results: A total of 245 patients completed the trial, including 121 ziprasidone patients and 124 olanzapine patients. The average dose was 137.5 mg/d for ziprasidone and 19.5 mg/d for olanzapine. Patients treated with olanzapine had higher weight gain than those treated with ziprasidone [(4.55±3.37) kg vs (-0.83±2.05) kg, P<0.001]. After the treatment, FBS, fasting insulin, HDL, TC, TG, LDL and IRI levels were significantly increased in the olanzapine group (all P values<0.001 ). However, in the ziprasidone group, FBS decreased significantly and HDL and TG levels increased significantly after the 6-week treatment (all P values<0.05). The mean changes of FBS, fasting insulin, TC, TG, LDL and IRI were significantly different in the two groups (all P values<0.001)., Conclusion: Ziprasidone has less glucose and lipid metabolic effect for first-episode schizophrenia patients in short-term treatment. However, olanzapine induces weight gain and dysfunction of glucose and lipid metabolism significantly, which is associated with increased risk of complications. When the doctors choose antipsychotics in the clinic, they should consider the side effects of the medication.

Objective: To determine associations between weight gain induced by antipsychotic and the polymorphisms of HTR2C gene -759C/T and -697G/C, histamine-1 receptor gene, leptine gene -2548G/A, and adiponectin gene +276G/T and +45T/G., Methods: In the case-matched study, 85 patients who gained more than 7% of their pre-drug body weight served as the study group and another 85 patients who gained less than 7% of their pre-drug body weight served as the control group. The ligation diction reaction technique was used to analyze the frequencies of the -759C/T and -697G/C polymorphism of the HTR2C gene, -2548A/G polymorphism of leptin gene, +276G/T and +45T/G polymorphism of adiponectin gene and glu349asp polymorphism of H1 receptor gene., Results: The presence of the -759C allele, -697G allele, -2548A allele and +276G allele was significantly higher in the study group than that in the control group (P<0.05)., Conclusion: The -759C/T and -697G/C polymorphisms of the promoter region of 5HT(2)C receptor gene, -2548A/G polymorphisms of leptin gene and +276G/T polymorphisms of adiponectin gene may be associated with the antipsychotic induced weight gain. The glu349asp polymorphisms of histamine-1 receptor gene is not associated with antipsychotic induced weight gain.

Objective: To investigate whether antipsychotic-induced weight gain was associated with adiponectin gene +45T/G and +276G/T polymorphism., Methods: A case-matched study was done: 85 patients who gained more than 7% of their pre-drug body weight were designed to the study group and 85 patients who gained less than 7% of their pre-drug body weight served as the control group. Ligation diction reaction technique was used to analyze the frequencies of the +276G/T and +45T/G polymorphism of adiponectin gene., Results: The presence of +276G allele was significantly higher in the study group as compared with the control group., Conclusion: Subjects with the +276G variant alleles may have a greater risk for weight gain after antipsychotic treatment.