Xian-Bin Li

Clozapine for Treatment-Resistant Bipolar Disorder: A Systematic Review

To evaluate the efficacy and safety of clozapine for treatment‐resistant bipolar disorder (TRBD).

Adjunctive Aripiprazole Versus Placebo for Antipsychotic-Induced Hyperprolactinemia: Meta-Analysis of Randomized Controlled Trials

Objective To compare the safety and efficacy of adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia. Methods Population: adult patients presenting with antipsychotic-induced hyperprolactinemia diagnosed by prolactin level with or without prolactin-related symptoms. Interventions: adjunctive aripiprazole vs. adjunctive placebo. Outcome measures: adverse events and efficacy of treatment. Studies: randomized controlled trials. Results Five randomized controlled trials with a total of 639 patients (326 adjunctive aripiprazole, 313 adjunctive placebo) met the inclusion criteria. Adjunctive aripiprazole was associated with a 79.11% (125/158) prolactin level normalization rate. Meta-analysis of insomnia, headache, sedation, psychiatric disorder, extrapyramidal symptom, dry mouth, and fatigue showed no significant differences in the adjunctive aripiprazole treatment group compared with the placebo group (risk difference (Mantel-Haenszel, random or fixed) −0.05 to 0.04 (95% confidence interval −0.13 to 0.16); I2 = 0% to 68%, P = 0.20 to 0.70). However, sedation, insomnia, and headache were more frequent when the adjunctive aripiprazole dose was higher than 15 mg/day. Meta-analysis of the prolactin level normalization indicated adjunctive aripiprazole was superior to placebo (risk difference (Mantel-Haenszel, random) 0.76 (95% confidence interval 0.67 to 0.85); I2 = 43%, P<0.00001). The subgroup analysis confirmed that the subjects who received adjunctive aripiprazole 5 mg/day showed a degree of prolactin normalization similar to that of all participants. No significant differences between groups in discontinuation and improvements of psychiatric symptoms. Conclusion Adjunctive aripiprazole is both safe and effective as a reasonable choice treatment for patients with antipsychotic-induced hyperprolactinemia. The appropriate dose of adjunctive aripiprazole may be 5 mg/day.

Childhood trauma associates with clinical features of bipolar disorder in a sample of Chinese patients.

OBJECTIVES Childhood trauma is a major public health problem which has a long-term consequence, a few studies have examined the relationship between childhood trauma and clinical features of bipolar disorder, most in western culture, with no such studies done in Chinese culture. METHODS The CTQ-SF was administered to 132 Chinese patients with DSM-IV bipolar disorder. Participants also completed the Childhood Experience of Care and Abuse Questionnaire (CECA.Q), the Impact of Events Scale-Revised (IES-R), and the State-Trait Anxiety Inventory (STAI). The CTQ-SF cut-off scores for exposure were used to calculate the prevalence of trauma. The relationship between childhood trauma and clinical features of bipolar disorder were examined. RESULTS The internal consistency of CTQ-SF was good (Cronbach׳s α=0.826) and four week test-retest reliability was high (r=0.755). 61.4% of this sample reported physical neglect (PN) in childhood, followed by emotional neglect (EN, 49.6%), sexual abuse (SA, 40.5%), emotional abuse (EA, 26.0%) and physical abuse (PA,13.1%). Significant negative correlations existed between age of onset and EA and EN score (r=-0.178~-0.183, p<0.05). Significant positive correlations were observed between EA, CTQ-SF total score and intrusion and hyper-arousal scores of IES-R (r=0.223~0.309, p<0.05). Similarly, significant positive correlations were found between EN, PN, CTQ-SF total and STAI score (r=0.222~0.425, p<0.05). LIMITATIONS Data on childhood trauma were derived from a retrospective self-report questionnaire without independent corroboration. A number of potential patients (more severe or chronic patients) was excluded because they were either refused to participate or inappropriate to participate in research. CONCLUSIONS Significant number of subjects in patients with BD reported experience of childhood abuse and neglect. Exposure to childhood trauma is associated with age of onset of illness, co morbid PTSD and anxiety symptoms. To study the pathogenesis of childhood trauma on bipolar disorder and explanation the interaction between childhood trauma and susceptibility genes are proposed.

Childhood trauma associates with clinical features of schizophrenia in a sample of Chinese inpatients

This study examined the association between childhood trauma and clinical features, comorbid anxiety and post-traumatic stress disorder (PTSD) symptoms, and suicidal and aggressive behaviors in Chinese patients with schizophrenia. The Childhood Trauma Questionnaire - Short Form (CTQ-SF), the Impact of Events Scale - Revised (IES-R), and the State-Trait Anxiety Inventory (STAI) were administered to 182 Chinese inpatients with schizophrenia. The relationship between the severity and the number of traumic experiences and clinical features were analyzed. Physical neglect (PN) in childhood was reported in 71.7% of this sample, followed by emotional neglect (EN, 58.6%), sexual abuse (SA, 39.9%), emotional abuse (EA, 31.7%) and physical abuse (PA, 22.2%). Significant negative correlations existed between age of onset and the EA scores. Significant positive correlations were found between the subscores of IES-R, STAI and CTQ-SF. Patients with history of suicidal or aggressive behaviors had significantly higher trauma scores than patients without such behaviors. Exposure to childhood trauma is associated with early age of onset, more PTSD and anxiety symptoms, and history of suicidal and aggressive behaviors. A dose-effect may exist between severity, number of trauma experiences, and clinical features.

Efficacy and Safety of Adjunctive Aripiprazole in Schizophrenia: Meta-Analysis of Randomized Controlled Trials.

Abstract This meta-analysis of randomized controlled trials (RCTs) evaluated the efficacy and safety of adding aripiprazole to other antipsychotics in schizophrenia. A systematic computer search identified 55 RCTs including 4457 patients who were randomized to aripiprazole (14.0 ± 7.0 mg/d) versus placebo (18 RCTs) or open antipsychotic treatment (37 RCTs). Aripiprazole significantly outperformed the comparison interventions based on psychiatric scales: (1) total score in 43 RCTs (N = 3351) with a standardized mean difference (SMD) of −0.48 (95% confidence interval [CI], −0.68 to −0.28; P < 0.00001; I2 = 88%), (2) negative symptom score in 30 RCTs (N = 2294) with an SMD of −0.61(95% CI, −0.91 to −0.31; P < 0.00001; I2 = 91%), and (3) general psychopathology score in 13 RCTs (N = 1138) with a weighted mean difference (WMD) of −4.02 (95% CI, −7.23 to −0.81; P = 0.01; I2 = 99%), but not in positive symptoms in 29 RCTs (N = 2223) with a SMD of −0.01 (95% CI, 0.26 to 0.25; P = 0.95; I2 = 88%). Differences in total score based on psychiatric scales may be explained by the use of an antipsychotic for comparison rather than placebo in 31 RCTs with a nonblind design. Aripiprazole outperformed the comparison interventions for body weight in 9 RCTs (N = 505) with a WMD of −5.08 kg (95% CI, −7.14 to −3.02; P < 0.00001; I2 = 35%) and for body mass index (BMI) in 14 RCTs (N = 809) with a WMD of −1.78 (CI: −2.25 to −1.31; P < 0.00001; I2 = 54%). The BMI meta-regression analysis indicated aripiprazoles association with lower BMI was stronger in females. Adjunctive aripiprazole appears safe but better RCTs are needed to demonstrate efficacy. Chinese journals and scientific societies should encourage the publication of high-quality RCTs and require registration in a centralized Chinese database.

QT Interval Prolongation Associated with Intramuscular Ziprasidone in Chinese Patients: A Case Report and a Comprehensive Literature Review with Meta-Analysis

Intramuscular (IM) ziprasidone has been associated with QTc interval prolongations in patients with preexisting risk factors. A 23-year-old male Chinese schizophrenia patient experienced an increase of QTc interval of 83 milliseconds (ms) after receiving 20 mg IM ziprasidone (baseline and increased QT/QTc were, respectively, 384/418 and 450/501). This was rated as a probable adverse drug reaction (ADR) by the Liverpool ADR causality assessment tool. A systematic review including all types of trials reporting the effect of IM ziprasidone on the QTc interval prolongation identified 19 trials with a total of 1428 patients. Mean QTc change from baseline to end of each study was −3.7 to 12.8 ms after IM ziprasidone. Four randomized trials (3 of 4 published in Chinese) were used to calculate a meta-analysis of QTc interval prolongation which showed no significant differences between IM ziprasidone and IM haloperidol groups (risk ratio 0.49 to 4.31, 95% confidence interval 0.09 to 19.68, P = 0.06 to 0.41). However, our review included two cases of patients who experienced symptoms probably related to QTc prolongation after IM ziprasidone. Thus, careful screening and close monitoring, including baseline ECG, should be considered in patients receiving IM ziprasidone for the first time.

Extrapyramidal Symptoms During Risperidone Maintenance Treatment in Schizophrenia: A Prospective, Multicenter Study.

Abstract The risperidone maintenance treatment in schizophrenia study was designed to identify the duration of maintenance treatment required with an initial therapeutic dose in contrast to reducing the dose over time. This study investigated extrapyramidal symptoms (EPSs) in different risperidone maintenance treatment paradigms over 1 year. Clinically stabilized patients with schizophrenia (n = 374) were randomized to a no-dose-reduction group and 4-week and 26-week reduction groups, in which the dose was gradually reduced by 50% over 8 weeks and maintained. Extrapyramidal symptoms were assessed at baseline and monthly for 6 months, followed by every 2 months. The Simpson-Angus Scale of Extrapyramidal Symptoms–Chinese version assessed EPS severity. Data were analyzed by a generalized linear mixed model (GLMM). The frequency of EPS at baseline was 23.2%, 20.0%, and 21.3% in the 4-week, 26-week, and no-dose-reduction groups, respectively. Risperidone dosage, positive symptoms, and disorganized thoughts at baseline predicted development of EPS. The GLMM indicated that a significant decrease in EPS was maintained, and different trajectories occurred over time across groups. In the 235 patients who continued treatment after 1 year, the incidence of EPS decreased to 4.1%, 2.8%, and 10.0% in the 4-week, 26-week, and no-dose-reduction groups, respectively, whereas the numbers of dropouts because of intolerable EPS were not significantly different (4.8%, 6.7%, and 6.2%, respectively). These novel findings indicate EPSs were tolerable and differentially decreased depending on the dose paradigm during the 1-year treatment period. Future studies should implement a GLMM to investigate antipsychotic adverse effects during long-term treatment.

Use of the MATRICS consensus cognitive battery (MCCB) to evaluate cognitive deficits in bipolar disorder: A systematic review and meta-analysis

Background The Measurement and Treatment Research to Improve Cognition Schizophrenia Consensus Cognitive Battery (MCCB) has also been proposed for use in clinical trials to assess cognitive deficits in patients with bipolar disorder (BD). The aim of this study was to evaluate cognitive function assessed by the MCCB in BD. Methods A literature search of the PubMed, Embase, PsycINFO, SCI, Cochrane Library databases and the Cochrane Controlled Trials Register was conducted. Case reports, reviews and meta-analyses were excluded and a systematic review of the remaining studies of cognitive function in BD was carried out. The cognitive outcome measure was the MCCB, including 7 domains and overall cognition. A random-effects model was applied. Results Eighty eight studies were initially identified. Seven clinical studies comprising a total of 487 patients and 570 healthy controls (HC) were included in the meta-analysis. Patients with BD performed worse than HC in overall cognition and processing speed with a large effect size of >0.8; with a medium effect size (0.5–0.8) in attention, working memory, verbal learning and visual learning; and with a small effect size (0.2–0.5) in reasoning and problem solving and social cognition. Conclusion Patients with BD performed worse than HC in overall cognition and all cognitive domains of the MCCB. Cognitive deficits in domains of processing speed and working memory are prominent in patients with BD. Our findings suggest that MCCB can be usefully applied in BD.

The dynamic characteristics of the anterior cingulate cortex in resting-state fMRI of patients with depression

BACKGROUND The anterior cingulate cortex (ACC) is part of the limbic system of the brain. It is a bridge between attentional and emotional processing, which is responsible for the integration of visceral, attentional, and affective information. Lesioning of the ACC, which produces striking changes, is used to treat major depression disorder (MDD). Moreover, the brain dynamically integrates and coordinates functions of its different subparts to realize its cognitive capability. Hence, the spatio-temporal community distribution of the ACC is necessary to completely understand MDD. METHODS First, community structure detection was used to reveal the community distribution of brain regions. Thereafter, the flexibility, i.e., the frequency of community assignment changes of the ACC in such a community, and the module allegiance matrix (MAM) between the ACC and other brain regions, were analyzed. RESULTS Our analysis demonstrated significant differences in the distribution of community assignment and flexibility of the ACC in MDD, compared to healthy controls (HC). The results also showed that the pairwise values of the MAMs between the ACC and the amygdala, insula, precuneus, and thalamus were significantly lower in patients with MDD compared to those in HC. LIMITATIONS The data collected is subject to patient-specific noise because (1) the medication effect varies from patient to patient, and (2) with most fMRI studies, the thoughts of the participants during imaging are difficult to control. CONCLUSION ACC exhibits abnormal flexibility in community structures in MDD. The pairwise abnormal entries in the MAM for the ACC with four other brain regions, i.e., amygdala, insula, precuneus, and thalamus, quantified the role played by the ACC in MDD.

S15. ABNORMAL EYE TRACKING IN PATIENTS WITH SCHIZOPHRENIA UNDER THE SOCIAL SCENE

Abstract Background To investigate whether the eye movement pattern is different between facial emotion recognition and real social scene emotion recognition, and which can better reflect the social function and the clinical symptoms using a novel theme identification task. Methods Total 29 patients with schizophrenia and 31 healthy controls completed the theme identification task, in which subjects selected which word, out of positive, neutral and negative, described the theme of a picture under facial emotion recognition and real social scene emotion recognition. Positive and negative syndrome scale (PANSS) and social function in psychosis inpatients (SSPI) were used to assess the symptom and social function. Results The schizophrenia’s eye movement paradigms under both facial emotion and social scene show decreased number of fixation (t=-3.49, P=0.00; t=-3.62, P=0.00), decreased number of saccades (t=-3.15, P=0.00; t=-3.72, P=0.00), decreased scan path length (t=-2.23, P=0.03; t=-4.18, P=0.03), decreased fixation number in interest area (t=3.01, P=0.00; t=-3.24, P=0.00). Different from facial emotion cognition, the eye movement under social scene cognition showed lower percentage of fixation number in interest area than that in healthy subjects (P=0.01), furthermore, the length of scan path under the negative social scene pictures was associated with the total score of SSPI (r=-0.38, P=0.04), the PANSS total score (r=-0.46, P=0.01), the positive symptoms score (r=-0.39, P=0.04), the general score (r=-0.50, P=0.01). Discussion The patients showed more abnormal eye tracking indicators under social scene than facial emotion. Under negative emotion social scene, the length of scan path related to social function and clinical symptoms, it may be a potential indicator to evaluate social function and degree of disease.