Qinling Wei

Disrupted brain anatomical connectivity in medication-naïve patients with first-episode schizophrenia

Previous studies suggested that the topological properties of brain anatomical networks may be aberrant in schizophrenia (SCZ), and most of them focused on the chronic and antipsychotic-medicated SCZ patients which may introduce various confounding factors due to antipsychotic medication and duration of illness. To avoid those potential confounders, a desirable approach is to select medication-naïve, first-episode schizophrenia (FE-SCZ) patients. In this study, we acquired diffusion tensor imaging datasets from 30 FE-SCZ patients and 34 age- and gender-matched healthy controls. Taking a distinct gray matter region as a node, inter-regional connectivity as edge and the corresponding streamline counts as edge weight, we constructed whole-brain anatomical networks for both groups, calculated their topological parameters using graph theory, and compared their between-group differences using nonparametric permutation tests. In addition, network-based statistic method was utilized to identify inter-regional connections which were impaired in the FE-SCZ patients. We detected only significantly decreased inter-regional connections in the FE-SCZ patients compared to the controls. These connections were primarily located in the frontal, parietal, occipital, and subcortical regions. Although small-worldness was conserved in the FE-SCZ patients, we found that the network strength and global efficiency as well as the degree were significantly decreased, and shortest path length was significantly increased in the FE-SCZ patients compared to the controls. Most of the regions that showed significantly decreased nodal parameters belonged to the top–down control, sensorimotor, basal ganglia, and limbic-visual system systems. Correlation analysis indicated that the nodal efficiency in the sensorimotor system was negatively correlated with the severity of psychosis symptoms in the FE-SCZ patients. Our results suggest that the network organization is changed in the early stages of the SCZ disease process. Our findings provide useful information for further understanding the brain white matter dysconnectivity of schizophrenia.

The comparison of glycometabolism parameters and lipid profiles between drug-naïve, first-episode schizophrenia patients and healthy controls.

To compare the difference in body mass index (BMI), waist-to-hip ratio (WHR), and glucose and lipid metabolism parameters between drug-naïve, first-episode schizophrenia patients and healthy controls matched for age, ethnicity and gender, we conducted a test including BMI, WHR, and fasting glucose and lipid metabolism parameters in both 70 drug-naïve, first-episode schizophrenia patients, having not a single day of cumulative exposure to antipsychotic medications and 44 normal healthy controls at baseline. Students t tests (two tailed) were conducted to examine between group differences. We found that drug-naïve first-episode schizophrenia patients had higher insulin, insulin resistance and C-peptide levels, and had lower total cholesterol (TC), high density lipoprotein cholesterol (HDL-c) and apolipoproteinA1 levels. Simultaneously, drug-naïve, first-episode schizophrenia patients show a potential tendency of WHR enlargement, although there were no statistically significant differences between groups (mean=0.82, SD=0.06, for the patients versus mean=0.79, SD=0.06, for the health subjects). These results suggest that drug-naïve, first-episode schizophrenia patients do differ from healthy controls in their fasting glycometabolism parameters and lipid profiles, including fasting plasma levels of insulin, C-peptide, TC, HDL-c, and apolipoproteinA1, and patients are more insulin resistant before the onset of antipsychotic medication treatment.

Association of the ZNF804A gene polymorphism rs1344706 with white matter density changes in Chinese schizophrenia

BACKGROUND ZNF804A gene polymorphism rs1344706, the first genetic risk variant to achieve genome wide significance for schizophrenia, has been linked to neural functional connectivity. Dysconnectivity of WM may be the primary pathological mechanism of schizophrenia. Association of this variant with regional WM density has not been investigated in schizophrenic patients. METHODS 69 healthy controls and 80 patients with schizophrenia underwent genotyping of rs1344706 SNPs, and were examined for WM density (T1-weighted MRI). The association of rs1344706 with WM changes in schizophrenia patients and healthy controls was analyzed using a full-factorial 2×2 analysis of variance. RESULTS 1. There was an interaction on WM density in the left prefrontal lobe between the rs1344706 genotype and schizophrenic diagnosis, where the risk T allele carriers presented higher WM density in the schizophrenia patients and lower WM density in healthy controls in comparison with the non-risk allele carriers. 2. The risk allele was associated with an increased WM density of the bilateral hippocampus in both the patients and the healthy group. LIMITATION The influence of antipsychotics to the white matter in schizophrenic patients was not fully eliminated. CONCLUSIONS The ZNF804A variant may confer risk for schizophrenia by exerting its effects on the WM in the left prefrontal lobe together with other risk factors for schizophrenia.

No association of ZNF804A rs1344706 with white matter integrity in schizophrenia: a tract-based spatial statistics study.

Altered brain connectivity has been widely considered as a genetic risk mechanism for schizophrenia. Of the many susceptibility genes identified so far, ZNF804A (rs1344706) is the first common genetic variant associated with schizophrenia on a genome-wide level. Previous fMRI studies have found that carriers of rs1344706 exhibit altered functional connectivity. However, the relationship between ZNF804A and white matter structural connectivity in patients of schizophrenia remains unknown. In this study, 100 patients with schizophrenia and 69 healthy controls were genotyped at the single nucleotide polymorphism rs1344706. Diffusion tensor imaging (DTI) was conducted and analyzed with tract-based spatial statistics. Systematic statistical analysis was conducted on multiple diffusion indices, including fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity. Unpaired two-sample t-test revealed significant differences in fractional anisotropy and diffusivity between schizophrenia and control groups. A two-way ANOVA analysis was conducted to assess the main effects of and the interaction between schizophrenia and ZNF804A. Although significant main effects of the diagnosis of schizophrenia were found on radial diffusivity, no association between the ZNF804A (rs1344706) and white matter connectivity was found in the entire group of subjects or in a selected subgroup of age-matched subjects (n=72).

The impact of educational status on the clinical features of major depressive disorder among Chinese women

Background Years of education are inversely related to the prevalence of major depressive disorder (MDD), but the relationship between the clinical features of MDD and educational status is poorly understood. We investigated this in 1970 Chinese women with recurrent MDD identified in a clinical setting. Methods Clinical and demographic features were obtained from 1970 Han Chinese women with DSM-IV major depression between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models were used to determine the association between educational level and clinical features of MDD. Results Subjects with more years of education are more likely to have MDD, with an odds ratio of 1.14 for those with more than ten years. Low educational status is not associated with an increase in the number of episodes, nor with increased rates of co-morbidity with anxiety disorders. Education impacts differentially on the symptoms of depression: lower educational attainment is associated with more biological symptoms and increased suicidal ideation and plans to commit suicide. Limitations Findings may not generalize to males or to other patient populations. Since the threshold for treatment seeking differs as a function of education there may an ascertainment bias in the sample. Conclusions The relationship between symptoms of MDD and educational status in Chinese women is unexpectedly complex. Our findings are inconsistent with the simple hypothesis from European and US reports that low levels of educational attainment increase the risk and severity of MDD.

Neurocognitive effects of first- and second-generation antipsychotic drugs in early-stage schizophrenia: A naturalistic 12-month follow-up study

The study aimed to assess the cognitive effects of first- and second-generation antipsychotics on neurocognition under naturalistic treatment conditions. In a 12-month, open-label, multicenter study, 698 patients with early-stage schizophrenia (duration of illness ≤5 years) were prescribed chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine, or aripiprazole monotherapy. A neuropsychological battery including tests of attention, processing speed, learning/memory, and executive functioning was administered at baseline, 6- and 12-months. The primary outcome was change in a cognitive composite score after 12-months of treatment. At 12 months, treatment resulted in mild to moderate neurocognitive improvements of z=0.32 for chlorpromazine, 0.33 for sulpiride, 0.43 for clozapine, 0.51 for risperidone, 0.69 for olanzapine, 0.64 for quetiapine and 0.46 for aripiprazole. However, the olanzapine and quetiapine groups demonstrated greater improvement in the composite score and processing speed than did the chlorpromazine and sulpiride groups. Both first- and second-generation antipsychotics may improve cognitive function in patients with early-stage schizophrenia. Given that some neurocognitive improvement is attributable to a practice effect, any improvement is likely to be in the range of a small effect size.

A predictive model for diagnosing bipolar disorder based on the clinical characteristics of major depressive episodes in Chinese population.

BACKGROUND A correct timely diagnosis of bipolar depression remains a big challenge for clinicians. This study aimed to develop a clinical characteristic based model to predict the diagnosis of bipolar disorder among patients with current major depressive episodes. METHODS A prospective study was carried out on 344 patients with current major depressive episodes, with 268 completing 1-year follow-up. Data were collected through structured interviews. Univariate binary logistic regression was conducted to select potential predictive variables among 19 initial variables, and then multivariate binary logistic regression was performed to analyze the combination of risk factors and build a predictive model. Receiver operating characteristic (ROC) curve was plotted. RESULTS Of 19 initial variables, 13 variables were preliminarily selected, and then forward stepwise exercise produced a final model consisting of 6 variables: age at first onset, maximum duration of depressive episodes, somatalgia, hypersomnia, diurnal variation of mood, irritability. The correct prediction rate of this model was 78% (95%CI: 75%-86%) and the area under the ROC curve was 0.85 (95%CI: 0.80-0.90). The cut-off point for age at first onset was 28.5 years old, while the cut-off point for maximum duration of depressive episode was 7.5 months. LIMITATIONS The limitations of this study include small sample size, relatively short follow-up period and lack of treatment information. CONCLUSION Our predictive models based on six clinical characteristics of major depressive episodes prove to be robust and can help differentiate bipolar depression from unipolar depression.

The effect of DISC1 on regional gray matter density of schizophrenia in Han Chinese population

Schizophrenia is thought to arise in part from abnormal gray matter (GM), which are partly shared by the relatives of the probands. DISC1 is one of the most promising susceptibility genes of schizophrenia and a SNP rs821597 (A) in the gene was associated with schizophrenia in Han Chinese population. In this study, 61 healthy controls and 72 with schizophrenic patients were genotyped at rs821597, and underwent T1-weighted MRI for the density of GM. The results showed that the risk allele (A) carriers had higher GM density in regional left parahippocampal gyrus and right orbitofrontal cortex in schizophrenic patients, but had reduced GM density of these brain regions in healthy controls. The DISC1 variant rs821597 may confer risk for schizophrenia by its effects on the regional GM in left parahippocampal gyrus and right orbitofrontal cortex with other risk factors for schizophrenia.

Psychosis and Dandy-Walker complex: report of four cases.

Concurrence of psychosis and Dandy-Walker complex (DWC) has been reported in some medical literature. Here, we reported four patients with concurrent psychosis and DWC of all four subtypes. Some clinical features found were juvenile or young adult age onset, high frequency of family history of psychosis, atypical psychotic symptoms, and high prevalence of cognitive deficit and refractoriness to treatment, in line with the cases in previous reports. These findings might help further illuminate the role that the cerebellum plays in the etiology of schizophrenia or bipolar disorder.

ZNF804A rs1344706 is associated with cortical thickness, surface area, and cortical volume of the unmedicated first episode schizophrenia and healthy controls.

The effects of ZNF804A rs1344706, a prominent susceptibility gene for schizophrenia, on gray matter (GM) structure in unmedicated schizophrenia (SZ) patients are still unknown, although several previous studies investigated the effects in medicated SZ patients and healthy controls (HC). Analyzing cortical thickness, surface area, and GM volume simultaneously may provide a more precise and complete picture of the effects. We genotyped 59 unmedicated first episode SZ patients and 60 healthy controls for the ZNF804A single nucleotide polymorphism (SNP) rs1344706, and examined between‐group differences in cortical thickness, surface area, and cortical volume using a full‐factorial 2 × 2 analysis of variance (ANOVA). We found the risk allele (T) in ZNF804A rs1344706, compared to the non‐risk allele (G), was associated with thinner cortex in the bilateral precuneus, left precentral gyrus, and several other regions, associated with a smaller cortical surface area in the left superior parietal, precuneus cortex and left superior frontal, and associated with a lower cortical volume in the left superior frontal, left precentral, and right precuneus in SZ patients. In contrast, in the controls, the T allele was associated with the increased cortical measurements compared to the G allele in the same regions as those mentioned above. ZNF804A rs1344706 has significant, but different, effects on cortical thickness, surface area, and cortical volume in multiple regions of the brain cortex. Our findings suggest that ZNF804A rs1344706 may aggravate the risk for schizophrenia by exerting its effects on cortical thickness, surface area, and cortical volume in these brain regions.