Analysis of first-episode and chronic schizophrenia using multi-modal magnetic resonance imaging.

OBJECTIVE: The brain structure and function differences among first-episode schizophrenia (FESZ) patients, chronic schizophrenia (CSZ) patients, and normal control (NC) subjects were investigated using structural and functional magnetic resonance imaging (MRI). Also, a support vector machine (SVM) combined with recursive feature elimination (RFE) was used for classification. PATIENTS AND METHODS: First, 44 FESZ patients, 44 CSZ patients, and 56 NC subjects were recruited, and structural MRI images were acquired. The regional gray matter volumes (GMVs) of 90 regions of interest (ROIs) were calculated, two-sample t-tests were conducted to analyze the GMV differences among the groups, and the partial correlations between the Positive and Negative Syndrome Scale (PANSS) scores and altered regional GMVs were calculated. Individual functional MRI images of the three groups were measured. The individual regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and degree of centrality (DC) values of the 90 ROIs were calculated and used to evaluate the differences among the groups. Then, the partial correlations between the PANSS scores and altered regional ReHo, ALFF, and DC were determined. An SVM combined with RFE was employed for classification using both structural and functional MRI input features. The sensitivity and specificity were measured to quantify the SVM performance. RESULTS: The GMVs in the bilateral calcarine of FESZ and CSZ patients were significantly lower than that of NC subjects. Compared to the NC group, the GMV was significantly reduced in numerous additional brain regions of the CSZ group. In comparison to the NC group, the patient groups exhibited significant ReHo increases in several regions and ReHo reductions in the occipital lobe. ReHo in the insula and left postcentral gyrus of CSZ patients were significantly lower than that of the NC subjects. Compared with the NC group, both patient groups exhibited ALFF aberrances in numerous regions. A significant reduction of ReHo, ALFF, and DC in certain regions were also found in patient groups compared with that of NC group. Significant positive correlations were found between the PANSS scores and ReHo and ALFF of the temporal and frontal lobes, while these correlations were negative in the occipital lobe. The SVM with RFE achieved excellent classification performance. The best performance was obtained using the following inputs: the ReHo and ALFF for FESZ/NC classification; the DC, ReHo, and ALFF for FESZ/CSZ classification; and the ReHo and ALFF for CSZ/NC classification. CONCLUSIONS: Our data indicate that compared with the FESZ patients, brain GMV aberrances was increased in the CSZ patients. The functional features including DC, ReHo, and ALFF, could facilitate FESZ diagnosis, which is more sensitive than structural features in classification. The SVM with RFE presents excellent classification performance and assists SZ diagnosis.

N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive N-acetylcysteine (NAC), an antioxidant drug, in treating major depressive disorder (MDD), bipolar disorder, and schizophrenia. METHODS: The PubMed, Cochrane Library, PsycINFO, CNKI, CBM, and WanFang databases were independently searched and screened by two researchers. Standardized mean differences (SMDs), risk ratios, and their 95% confidence intervals (CIs) were computed. RESULTS: Six RCTs (n = 701) of NAC for schizophrenia (three RCTs, n = 307), bipolar disorder (two RCTs, n = 125), and MDD (one RCT, n = 269) were identified and analyzed as separate groups. Adjunctive NAC significantly improved total psychopathology (SMD = -0.74, 95% CI: -1.43, -0.06; I2 = 84%, P = 0.03) in schizophrenia, but it had no significant effect on depressive and manic symptoms as assessed by the Young Mania Rating Scale in bipolar disorder and only a small effect on major depressive symptoms. Adverse drug reactions to NAC and discontinuation rates between the NAC and control groups were similar across the three disorders. CONCLUSIONS: Adjunctive NAC appears to be a safe treatment that has efficacy for schizophrenia, but not for bipolar disorder or MDD. Further higher quality RCTs are warranted to determine the role of adjunctive NAC in the treatment of major psychiatric disorders.

Adjunctive memantine for schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials.

BACKGROUND: Dysfunction of N-methyl-D-aspartate receptor (NMDAR) is involved in the pathophysiology of schizophrenia. A meta-analysis of randomized controlled trials (RCTs) was conducted to examine the efficacy and safety of memantine, a non-competitive NMDAR antagonist, in the treatment of schizophrenia. METHODS: Standardized/weighted mean differences (SMDs/WMDs), risk ratio (RR), and their 95% confidence intervals (CIs) were calculated and analyzed. RESULTS: Included in the meta-analysis were eight RCTs (n = 452) of 11.5 ± 2.6 weeks duration, with 229 patients on memantine (20 mg/day) and 223 patients on placebo. Adjunctive memantine outperformed placebo in the measures of Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale negative symptoms [SMD: -0.63 (95% CI -1.10 to -0.16), p = 0.009, I 2 = 77%], but not in the total, positive and general symptoms [SMD: -0.46 to -0.08 (95% CI -0.93 to 0.22), p = 0.06-0.60, I 2 = 0-74%] or the Clinical Global Impression Severity Scale [WMD: 0.04 (95% CI -0.24 to 0.32), p = 0.78]. The negative symptoms remained significant after excluding one outlying RCT [SMD: -0.41 (95% CI -0.72 to -0.11), p = 0.008, I 2 = 47%]. Compared with the placebo group, adjunctive memantine was associated with significant improvement in neurocognitive function using the Mini-Mental State Examination (MMSE) [WMD: 3.09, (95% CI 1.77-4.42), p < 0.00001, I 2 = 22%]. There was no significant difference in the discontinuation rate [RR: 1.34 (95% CI 0.76-2.37), p = 0.31, I 2 = 0%] and adverse drug reactions between the two groups. CONCLUSIONS: This meta-analysis showed that adjunctive memantine appears to be an efficacious and safe treatment for improving negative symptoms and neurocognitive performance in schizophrenia. Higher quality RCTs with larger samples are warranted to confirm these findings.

Burnout and cognitive impairment: Associated with serum BDNF in a Chinese Han population.

BACKGROUND: Some studies have demonstrated that subjects with chronic burnout showed cognitive impairments; however, cognitive performance in burnout has been under-investigated. Increasing evidence show that brain-derived neurotrophic factor (BDNF) plays a critical role in cognitive function. We hypothesized that decreased BDNF may be associated with cognitive impairments in burnout, which has not been investigated yet. The aim of the present study was to examine the association of BDNF with cognitive impairment in burnout. METHOD: Using a cross-sectional design, 712 healthy subjects were recruited from a general hospital and they were all measured with the Maslach Burnout Inventory (MBI). We assessed part of subjects on the repeatable battery for the assessment of neuropsychological status (RBANS) (n=192) and serum BDNF levels (n=127). RESULTS: 30.5% of the subjects had burnout. Compared to those non-burnout subjects, the burnout subjects were younger, had significant lower BDNF levels (p=0.003) and scored lower on immediate memory, RBANS total score and attention (all p<0.05). Interestingly, after the Bonferroni correction, there were negative correlations between BDNF and MBI total score or reduced professional accomplishment (PA). Moreover, BDNF was positively associated with immediate memory, attention and RBANS total score. Further multiple regression analysis showed that BDNF was an independent contributor to the RBANS total score and attention, and BDNF and MBI depersonalization (DP) were independent contributors to immediate memory. In addition, there was mediating effect of BDNF in the relation between burnout and cognitive impairments. CONCLUSIONS: Our results suggest that burnout is associated with significant cognitive impairments and decreased BDNF. Moreover, decreased BDNF is associated with cognitive impairments in burnout.