Jianjun Ou

Minocycline supplementation for treatment of negative symptoms in early-phase schizophrenia: A double blind, randomized, controlled trial

BACKGROUND It is difficult to improve negative symptoms and cognitive impairments in schizophrenia. A previous pilot study has shown that minocycline, a semi-synthetic second-generation tetracycline, is effective in treating for negative and/or cognitive symptoms in schizophrenia. OBJECTIVES The present study was designed to examine the efficacy and safety of minocycline for the treatment of negative symptoms and cognitive impairments in patients with schizophrenia. METHODS Ninety-two patients with early stage schizophrenia treated with risperidone entered this 16-week, double blind, randomized, placebo-controlled clinical trial. Subjects were randomly assigned to receive minocycline (200mg per day) or the placebo. The primary outcome was evaluated using the Scale for the Assessment of Negative Symptoms (SANS). Secondary outcomes included the response rate of SANS, the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale (CGI), and cognitive tests. RESULTS Subjects receiving minocycline had greater improvements on SANS total scores and PANSS negative subscale scores (P<0.001) when compared with those receiving the placebo. Rates of treatment response (43.6%) in the minocycline group were significantly higher than those in the placebo group (10.0%) after 16weeks of treatment. There was no significant difference between the seven cognitive domains (P>0.05), except for the attention domain (P=0.044). CONCLUSIONS The addition of minocycline to atypical antipsychotic drugs in early schizophrenia had significant efficacy on negative symptoms but had a slight effect on the attention domains of patients with schizophrenia. It may be considered as a new adjunct treatment for negative symptoms of schizophrenia. Clinical trials.gov identifier: NCT01493622.

Metformin for Treatment of Antipsychotic-Induced Amenorrhea and Weight Gain in Women With First-Episode Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled Study

OBJECTIVE Data on the treatment of antipsychotic-induced amenorrhea, particularly when occurring with weight gain, are limited. The authors investigated the efficacy and safety of metformin in the treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia. METHOD Eighty-four women (ages 18-40 years) with first-episode schizophrenia who suffered from amenorrhea during antipsychotic treatment were randomly assigned, in a double-blind study design, to receive 1000 mg/day of metformin or placebo in addition to their antipsychotic treatment for 6 months. The primary outcome measures were restoration of menstruation and change in body weight and body mass index (BMI). Secondary outcome measures were changes in levels of prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and testosterone; in fasting levels of insulin and glucose; in LH/FSH ratio; and in insulin resistance index. Repeated mixed models with repeated-measures regression analyses and binary logistic regression were used in the analysis. RESULTS A total of 76 patients completed the 6-month trial. Significantly more patients in the metformin group (N=28, 66.7%) than in placebo group (N=2, 4.8%) resumed their menstruation. Among patients treated with metformin, BMI decreased by a mean of 0.93 and the insulin resistance index by 2.04. In contrast, patients who received placebo had a mean increase in BMI of 0.85. The prolactin, LH, and testosterone levels and LH/FSH ratio decreased significantly in the metformin group at months 2, 4, and 6, but these levels did not change in the placebo group. CONCLUSIONS Metformin was effective in reversing antipsychotic-induced adverse events, including restoration of menstruation, promotion of weight loss, and improvement in insulin resistance in female patients with schizophrenia.

Effects of prenatal exposure to atypical antipsychotics on postnatal development and growth of infants: a case-controlled, prospective study

ObjectiveThis study aims to investigate the developmental effects of atypical antipsychotics on infants who were born to mothers taking an atypical antipsychotic throughout pregnancy.MethodThe developmental progress of 76 infants who experienced fetal exposure to atypical antipsychotics was compared to that of 76 matched control infants who had no fetal exposure to any antipsychotics. Planned assessment included Apgar score, body weight, height, and the cognitive, language, motor, social–emotional, and adaptive behavior composite scores of the Bayley Scales of Infant and Toddler Development, third edition (BSID-III). Student’s t test and Chi-square analysis were used as appropriate. Repeated measurements were evaluated by analysis of covariance.ResultsAt 2 months of age, the mean composite scores of cognitive, motor, social–emotional, and adaptive behavior of BSID-III were significantly lower in atypical antipsychotic-exposed infants than the controls. More atypical antipsychotic-exposed infants had delayed development in cognitive, motor, social–emotional, and adaptive behavior domains as defined by the composite score of <85 in these subscales of BSID-III. At 12 months of age, there were no significant differences between the two groups in all mean composite scores of BSID-III. More atypical antipsychotic-exposed infants had low birth weight than the controls (13.2 vs. 2.6 %, P = 0.031), although there were no significant difference in mean birth weight and height between the two groups.ConclusionFetal exposure to atypical antipsychotics may cause short-term delayed development in cognitive, motor, social–emotional, and adaptive behavior, but not in language, body weight, or height.

Comparison of metabolic effects of ziprasidone versus olanzapine treatment in patients with first-episode schizophrenia

ObjectiveThe objective of the study was to compare metabolic effects of ziprasidone versus olanzapine treatment in patients with first-episode schizophrenia.MethodsIn this 6-week, multicenter, open-label trial, 260 patients were randomly assigned to receive ziprasidone or olanzapine treatment (130 per group). Primary metabolic measures were changes in weight and body mass index (BMI). Secondary metabolic measures were changes in glucose, insulin, lipids, and blood pressure. Efficacy and safety were also measured additionally.ResultsA total number of 230 patients completed the study. The mean daily dosages were 138.2(28.6) mg for ziprasidone and 19.0(2.3) mg for olanzapine. After 6-week treatment, there were significant between-group differences in change scores on weight [4.22(3.49) kg versus −0.84(2.04) kg, p < 0.001] and BMI [1.59(1.37) versus −0.30(0.74), p < 0.001]. In addition, there were significant between-group differences in change scores on fasting plasma glucose, insulin, homeostasis model assessment 2-insulin resistance, low-density lipoprotein, total cholesterol, and triglycerides (p < 0.001); all the changes were clinically in favor of ziprasidone treatment. Both medications were effective in improving schizophrenia symptoms, but the decreases in Positive and Negative Syndrome Scale total scores of the olanzapine group were significantly greater than that of the ziprasidone group (p < 0.05). Compared with olanzapine, ziprasidone also induced more prolonging of corrected QT interval and extrapyramidal side effects (p < 0.05). Both medications were well tolerated, and no serious adverse events were observed in either group.ConclusionsCompared with olanzapine, ziprasidone treatment was associated with less adverse effects on glucose and lipid metabolism in patients with first-episode schizophrenia.

Regional white matter abnormalities in drug-naive, first-episode schizophrenia patients and their healthy unaffected siblings

Objective: Shared neuropathological features between schizophrenia patients and their siblings may represent intermediate phenotypes of schizophrenia and can be used to investigate genetic susceptibility to the illness. This study aimed to discover regional white matter abnormalities in first-episode schizophrenia (FES) patients and their unaffected siblings compared to healthy subjects in the Chinese Han population using optimized Voxel-Based Morphometry (VBM). Method: A total of 51 drug-naive, FES patients, 45 of their unaffected siblings and 59 healthy comparisons were studied with magnetic resonance imaging (MRI). Results: FES patients exhibited significant regional white matter deficits in the left inferior frontal gyrus and left joint of external capsule and internal capsule compared with healthy subjects (corrected FDR, p<0.005). The sibling group also showed significant white matter deficits in these two regions compared with the healthy comparison group (uncorrected, p<0.001). White matter deficits with a less stringent threshold for significance in the left cerebellum anterior lobe, left middle frontal gyrus, left hippocampus, right anterior cingulate and right internal capsule were observed in patients compared to their siblings. Conclusions: Our findings extend those from previous VBM analyses showing that FES patients and their unaffected siblings may share white matter deficits in the left inferior frontal gyrus and the left joint of external capsule and internal capsule. These regional white matter deficits may be related to genetic factors related to schizophrenia susceptibility.

Effects of Clozapine and other Atypical Antipsychotics on Infants Development Who Were Exposed to as Fetus: A Post-Hoc Analysis

Objective To investigate the developmental effects of clozapine and other atypical antipsychotics on infants who were exposed to as fetus. Method The developmental progress of 33 infants who were exposed to clozapine as fetus was compared to 30 infants who were exposed to risperidone, olanzapine or quetiapine as fetus by assessing Apgar scoring, birth weight at birth, body weight, height, and the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at months 2, 6 and 12 of age. Five subscale scores of BSID-III including cognitive, language, motor, social-emotional, and adaptive behavior were also compared. Student’s t test and Chi-square analysis were used as appropriate. Repeated measurements were evaluated by analysis of covariance. Results Of the 63 infants, 58 (92.1%) completed a 12-month study period. At the age of 2 and 6 months, mean adaptive behavior scores of BSID-III were significantly lower in clozapine-exposed infants than infants who exposed to other atypical antipsychotic at 2 and 6 months of age. More clozapine-exposed infants had delayed development (defined as the subscale score of <85) for adaptive behavior at 2 and 6 months of age. There was no difference between the two groups for cognitive, language, motor, social and emotional at 2, 6 and 12 months of age. More infants who were exposed to clozapine as fetus (25 of 33, 75.8%) had disturbed sleep and a labile state than those who were exposed to other atypical antipsychotics (8 of 30, 26.7%) during 2 months of age (P<0.001). Conclusion These results suggest that clozapine has more adaptive behavior effects on infants who were exposed to as a fetus than other atypical antipsychotics at 2 and 6 months of age. Trial Registration ClinicalTrials.gov NCT01479400

Different Visual Preference Patterns in Response to Simple and Complex Dynamic Social Stimuli in Preschool-Aged Children with Autism Spectrum Disorders

Eye-tracking studies in young children with autism spectrum disorder (ASD) have shown a visual attention preference for geometric patterns when viewing paired dynamic social images (DSIs) and dynamic geometric images (DGIs). In the present study, eye-tracking of two different paired presentations of DSIs and DGIs was monitored in a group of 13 children aged 4 to 6 years with ASD and 20 chronologically age-matched typically developing children (TDC). The results indicated that compared with the control group, children with ASD attended significantly less to DSIs showing two or more children playing than to similar DSIs showing a single child. Visual attention preference in 4- to 6-year-old children with ASDs, therefore, appears to be modulated by the type of visual stimuli.

Association and gene–gene interactions study of reelin signaling pathway related genes with autism in the Han Chinese population

Autism is a neurodevelopmental disorder with unclear etiology. Reelin had been proposed to participate in the etiology of autism due to its important role in brain development. The goal of this study was to explore the association and gene–gene interactions of reelin signaling pathway related genes (RELN, VLDLR, LRP8, DAB1, FYN, and CDK5) with autism in Han Chinese population. Genotyping data of the six genes were obtained from a recent genome‐wide association study performed in 430 autistic children who fulfilled the DSM‐IV‐TR criteria for autistic disorder, and 1,074 healthy controls. Single marker case‐control association analysis and haplotype case‐control association analysis were conducted after the data was screened. Multifactor dimensionality reduction (MDR) was applied to further test gene–gene interactions. Neither the single marker nor the haplotype association tests found any significant difference between the autistic group and the control group after permutation test of 1,000 rounds. The 4‐locus MDR model (comprising rs6143734, rs1858782, rs634500, and rs1924267 which belong to RELN and DAB1) was determined to be the model with the highest cross‐validation consistency (CVC) and testing balanced accuracy. The results indicate that an interaction between RELN and DAB1 may increase the risk of autism in the Han Chinese population. Furthermore, it can also be inferred that the involvement of RELN in the etiology of autism would occur through interaction with DAB1. Autism Res 2016, 9: 436–442.

Aggressive behaviors and treatable risk factors of preschool children with autism spectrum disorder

Aggressive behaviors of children with autism spectrum disorder (ASD) are common. We conducted this study to describe the aggressive mode of preschool children with ASD and examine the associations between specific aggressive behaviors and two treatable factors: sleep problems and attention deficit hyperactivity disorder (ADHD) symptoms. In total, 577 typically developing (TD) children and 490 children with ASD were investigated in this study. The Institute for Basic Research – Modified Overt Aggression Scale (IBR‐MOAS) was used to assess aggressive behaviors. Childrens social impairments, sleep problems and ADHD symptoms were also measured with specific scales. The total IBR‐MOAS score was significantly higher (worse) in the TD group [4.47 (5.36)] than in the ASD group [3.47 (5.63), P = 0.004]. The aggressive modes differed between groups: when compared with each other, the TD group received higher scores on Verbal and Physical Aggression Toward Others (all P < 0.01), while the ASD group had higher scores on Physical Aggression Against Self (P = 0.006). The linear regression model demonstrated that the aggressive behaviors of children with ASD were significantly associated with two treatable factors: sleep problems and ADHD symptoms. These findings have substantial clinical implications: treatment of these two risk factors may be helpful in managing aggressive behavior in children with ASD. Autism Res 2017.

Associations among maternal pre-pregnancy body mass index, gestational weight gain and risk of autism in the Han Chinese population

BackgroundAutism is a neurodevelopmental disorder with an unclear etiology. Pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) have been suggested to play a role in the etiology of autism. The current study explores the associations among maternal pre-pregnancy BMI, GWG and the risk of autism in the Han Chinese population.MethodsDemographic information, a basic medical history and information regarding maternal pre-pregnancy and pregnancy conditions were collected from the parents of 705 Han Chinese children with autism and 2236 unrelated typically developing children. Binary logistic regressions were conducted to calculate the odds ratio (OR) for the relationship among pre-pregnancy BMI, GWG and the occurrence of autism. The interaction between pre-pregnancy BMI and GWG was analyzed by performing stratification analyses using a logistic model.ResultsAfter adjusting for the children’s gender, parental age and family annual income, excessive GWG was associated with autism risk in the entire sample (OR = 1.327, 95% CI: 1.021–1.725), whereas the relationship between maternal pre-pregnancy BMI and autism was not significant. According to the stratification analyses, excessive GWG increased the risk of autism in overweight/obese mothers (OR = 2.468, 95% CI: 1.102–5.526) but not in underweight or normal weight mothers.ConclusionsThe maternal pre-pregnancy BMI might not be independently associated with autism risk. However, excessive GWG might increase the autism risk of offspring of overweight and obese mothers.