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Grey matter (GM) reduction is a consistent observation in established late stages of schizophrenia, but patients in the untreated early stages of illness display an increase as well as a decrease in GM distribution relative to healthy controls (HC). The relative excess of GM may indicate putative compensatory responses, though to date its relevance is unclear.
343 first-episode treatment-naïve patients with schizophrenia (FES) and 342 HC were recruited. Multivariate source-based morphometry was performed to identify covarying ‘networks' of grey matter concentration (GMC). Neurocognitive scores using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and symptom burden using the Positive and Negative Symptoms Scale (PANSS) were obtained. Bivariate linear relationships between GMC and cognition/symptoms were studied.
Compared to healthy subjects, FES had prominently lower GMC in two components; the first consists of the anterior insula, inferior frontal gyrus, anterior cingulate and the second component with the superior temporal gyrus, precuneus, inferior/superior parietal lobule, cuneus, and lingual gyrus. Higher GMC was seen in adjacent areas of the middle and superior temporal gyrus, middle frontal gyrus, inferior parietal cortex and putamen. Greater GMC of this component was associated with lower duration of untreated psychosis, less severe positive symptoms and better performance on cognitive tests.
In untreated stages of schizophrenia, both a distributed lower and higher GMC is observable. While the higher GMC is relatively modest, it occurs across frontoparietal, temporal and subcortical regions in association with reduced illness burden suggesting a compensatory role for higher GMC in the early stages of schizophrenia.
Deficits in event-related potential (ERP) including duration mismatch negativity (MMN) and P3a have been demonstrated widely in chronic schizophrenia (SZ) but inconsistent findings were reported in first-episode patients. Psychotropic medications and diagnosis might contribute to different findings on MMN/P3a ERP in first-episode patients. The present study examined MMN and P3a in first episode drug naïve SZ and bipolar disorder (BPD) patients and explored the relationships among ERPs, neurocognition and global functioning.
Twenty SZ, 24 BPD and 49 age and sex-matched healthy controls were enrolled in this study. Data of clinical symptoms [Positive and Negative Symptoms Scale (PANSS), Young Manic Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD)], neurocognition [Wechsler Adult Intelligence Scale (WAIS), Cattell's Culture Fair Intelligence Test (CCFT), Delay Matching to Sample (DMS), Rapid Visual Information Processing (RVP)], and functioning [Functioning Assessment Short Test (FAST)] were collected. P3a and MMN were elicited using a passive auditory oddball paradigm.
Significant MMN and P3a deficits and impaired neurocognition were found in both SZ and BPD patients. In SZ, MMN was significantly correlated with FAST (r = 0.48) and CCFT (r = −0.31). In BPD, MMN was significantly correlated with DMS (r = −0.54). For P3a, RVP and FAST scores were significant predictors in SZ, whereas RVP, WAIS and FAST were significant predictors in BPD.
The present study found deficits in MMN, P3a, neurocognition in drug naïve SZ and BPD patients. These deficits appeared to link with levels of higher-order cognition and functioning.
Previous studies have inferred a strong genetic component in schizophrenia. However, the genetic variants involved in the susceptibility to schizophrenia remain unclear.
To detect potential gene pathways and networks associated with schizophrenia, and to explore the relationship between common and rare variants in these pathways and abnormal white matter integrity in schizophrenia.
The analysis included 100 first-episode treatment-naïve patients with schizophrenia and 140 healthy controls. A network-based analysis was carried out on the data collected from the Psychiatric Genomics Consortium Phase I (PGC-I). Based on our genome-wide association study and whole-exome sequencing data-sets, we performed a gene-set analysis to detect associations between the combining effects of common and rare genetic variants and abnormal white matter integrity in schizophrenia.
Patients had significantly reduced functional anisotropy in the left and right anterior cingulate cortex, left and right precuneus and extra-nuclear (t = 4.61–5.10, PFDR < 0.01), compared with controls. Generated from co-expression network analysis of the PGC-1 summary statistics of schizophrenia, a subnetwork of 207 genes associated with schizophrenia was identified (P < 0.01), and 176 genes were co-expressed in four gene modules. Functional enrichment analysis for genes in each module revealed that the yellow module was enriched with highly co-expressed, innate immune response genes. Furthermore, rare variants of enriched genes in the yellow module were associated with reduced functional anisotropy in the left anterior cingulate cortex (P = 0.006; Padjusted = 0.024) in patients only.
The pathogenesis of schizophrenia may be substantially influenced by genes involved in the immune system, via both pathway and network.
A new route for atom-economical synthesis of functional polymers was developed. Oxidative polycoupling of 3,5-dimethyl-1-phenylpyrazole with 4,4’-(α,ω-alkylenedioxy) bis(diphenylacetylene)s and 1,2-diphenyl-1,2-bis[4-(phenylethynyl)phenyl]ethene, respectively, were catalyzed by [Cp*RhCl2]2, 1,2,3,4-tetraphenylcyclopenta-1,3-diene and copper(II) acetate in dimethylformamide under stoichiometric imbalance conditions, affording soluble poly(pyrazolylnaphthalene)s in satisfactory yields (isolation yield up to 82%) with high molecular weights (Mw up to 35700). All the polymers were thermally stable, losing little of their weight at high temperatures of 323–422 oC. They possessed good film-forming property and their thin solid films showed high refractive indices (RI = 1.747–1.593) in a wide wavelength region of 400−1000 nm. The polymer carrying tetraphenylethene unit displayed a phenomenon of aggregation-induced emission and showed enhanced light emission in the aggregated state.
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