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Schizophrenia (SZ), bipolar disorder (BD) and major depression disorder (MDD) have been regarded as highly diverged independent entities in current psychiatric diagnosis. However, ample new evidence suggests that they may have common biological traits. Neuroimaging studies showed that psychiatric disorders might associated with altered grey matter (GM) asymmetry compared to controls; however, the degree to which SZ, BD and MDD have common and/or distinct asymmetrical alterations in GM is still ambiguous. In this study, we analysed 169 voxel-based studies (including 3517 SZ patients, 1575 BD patients, 3280 MDD patients and 9733 controls) using activation likelihood estimation (ALE) meta-analysis to systematically review the existence of similar GM atrophy and asymmetrical alteration patterns among these psychiatric disorders, and the functional association between behaviour domains and topological alterations. We found that the right parahippocampal gyrus and left superior frontal gyrus showed commonly altered GM volume across all three illnesses, but did not identify common asymmetrical alteration. The asymmetrical alteration with leftward bias appeared in SZ and bipolar disorder at different locations, but more asymmetrical alteration with rightward bias appeared in MDD. Moreover, these changes have been confirmed to be associate with several symptoms and may have roles in functional networks. Our findings support the existence of common neurobiological damnification in these psychiatric disorders and provides valuable insights for the neural commonalties among different psychiatric disorders based on a large sample size., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Schizophrenia has often been viewed as a disorder of connectivity. The single nucleotide polymorphism rs1059004 in the oligodendrocyte lineage transcription factor 2 gene locus has been reported to be associated with schizophrenia. We measured the functional connectivity and functional brain network topology properties in 49 schizophrenic patients and 47 healthy controls. We compared the strength and diversity of the functional connectivity and topological properties of functional networks between different genotypes. The correlations among functional connectivity, topological properties and behavioral performances were also investigated in this study. We found that the connectivity strength of schizophrenic patients carrying the risk A allele was generally decreased whereas connectivity diversity was increased. Regarding topological properties, all groups showed small-world properties, the nodal efficiency showed significant differences in the right precuneus and left middle temporal pole between different genotypes in schizophrenic patients. Moreover, the nodal efficiency in the left middle temporal pole was positively correlated with the neuropsychological assessment battery results of the schizophrenic patients who were homozygous for the C allele. Our results elucidate the contribution of rs1059004 to the functional brain network, and may help enhance the present understanding of the role of risk gene in the functional dysconnectivity of schizophrenia., Competing Interests: Declaration of Competing Interests The authors declare that there are no actual or potential conflicts of interest including any financial, personal or other relationships with other people or organizations., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Disorganized communication among large-scale brain networks, especially in the salience network, default mode network and central executive network, have been consistently reported in schizophrenia (SZ) patients. However, abnormal patterns of the effective connectivity and abnormalities in the white matter of these networks remains unclear in patients with SZ. Fifty-six SZ patients and fifty-five healthy controls were enrolled in the present study and underwent resting state functional magnetic resonance and diffusion tensor imaging. Twelve main nodes within the triple networks were defined by independent components analysis. Effective connectivity between these main nodes was computed using Granger causality analysis. Voxel-based analysis of the diffusion tensor imaging data was conducted to explore white matter changes. The SZ patients showed abnormal effective connectivity between the anterior cingulate cortex and the dorsolateral prefrontal cortex. The abnormal white matter showed decreased fractional anisotropy localized in the bilateral anterior corona radiate and left superior long fasciculus in patients with SZ. These findings shed light on the importance of the triple network in the pathogenesis of SZ, which may facilitate the understanding of SZ., Competing Interests: Delarations of Competing Interest Nothing to report., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Negative symptoms in schizophrenia have been associated with functional changes in frontostriatal pathways. Dysregulation of the dopamine signal in frontostriatal pathways leads to the symptomology observed in schizophrenia. Although the catechol-O-methyltransferase (COMT) gene, one of the susceptibility genes for schizophrenia, has been associated with dopamine activities in prefrontal and striatal regions, it is still unclear whether the disease state and COMT val 158 met genotype have an interaction effect on the functional connectivity of frontostriatal pathways. In this study, we evaluated the possible interactions between COMT val 158 met variations and the disease state on the resting-state functional connectivity (RSFC) of frontostriatal pathways in fifty-one first episode schizophrenia (FES) patients (val/val: 29, met +: 22) with prominent negative symptoms and forty-eight healthy controls (val/val: 31, met +: 17). Regions of interest were defined by the result of a meta-analysis of frontostriatal pathways using the Neurosynth database. We found a significant genotype × disease interaction effect on the RSFC between the bilateral anterior cingulate (ACC) and right caudate, which overlapped with the main effect of the disease state. Behavioural regression analysis suggested that RSFC between the right ACC and right caudate correlated with the severity of SANS avolition-apathy scores in patients who were met carriers but not in patients who were val homozygous. Our findings suggest that the RSFC of frontostriatal pathways may differentially affected by an individual's COMT val 158 met genotype., (© 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The rs1059004 in the oligodendrocyte lineage transcription factor 2 (OLIG2) gene has been reported to be a candidate single nucleotide polymorphism (SNP) for schizophrenia (SZ). A variety of functional magnetic resonance imaging (fMRI) studies have revealed disconnection in SZ. We aimed to investigate the association of rs1059004 polymorphism with whole-brain functional connectivity (FC) and to further explore the correlation between altered FC and cognitive behavioral scales. Fifty-five SZ patients and fifty-three matched healthy controls were included in this study. The general linear model was used to test the role of rs1059004 polymorphism in whole-brain FC based on resting-state fMRI. Spearman's rank correlation test was used to calculate the correlation coefficient between FC strength and behavior score. In the whole-brain FC analysis, we found that the FC pattern in SZ patients differs from healthy controls. Furthermore, compared to homozygous C carriers, risk A allele carriers have reduced FC strength in both SZ patients and healthy controls. For the correlation analysis in risk A allele carriers, we found a positive correlation between FC strength and verbal fluency score in SZ patients, while healthy controls appeared to have the opposite result. Our results revealed that participants carrying the risk A allele show FC patterns differing from those of homozygous C carriers. This result suggests that rs1059004 polymorphism and SZ have synergistic effects on brain connections. The correlation analysis result suggests that special attention should be paid to SZ patients who carry the risk A allele because the patients perform worse in verbal fluency., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The 5-hydroxytryptamine 2A receptor (5-HT2A) and dopamine D3 receptor (DRD3) have been extensively studied as promising candidate genes for schizophrenia. Magnetic resonance imaging studies have demonstrated that schizophrenia is associated with widespread structural and functional abnormalities in the brain. Serotonin and dopamine receptors play crucial roles in the development of the human cerebral cortex and brain activity. However, how the 5-HT2A and DRD3 genes impact brain structure and function in schizophrenia remains unknown. In the present study, we investigated the main effect of disease state and the interaction effect between disease state and genotype of these two genes on cortical volume, thickness, surface area and functional connectivity density (FCD) in fifty-five drug-naïve first episode schizophrenia patients and fifty-three healthy controls. We found that the differences in local FCD (lFCD) and global FCD (gFCD) between patients and healthy controls were predominantly located in brain hub regions. The significant interaction effects of disease state and 5-HT2A and DRD3 genes on brain structure and function were mainly located in the temporal cortex. Our findings may help to improve the understanding of the relationship between 5-HT2A and DRD3 genotypes and schizophrenia pathogenesis., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2019. Published by Elsevier B.V.)

The rs6994992 polymorphism has been reported as a candidate variant associated with schizophrenia (SZ). Neuroimaging studies have revealed that SZ is associated with widespread structural and functional alterations in brain. However, whether the allele dosage of rs6994992 is associated with brain structural or functional features is unclear. We aimed to investigate the association between the risk allele dosage of rs6994992 and whole-brain structural and functional characteristics and to further explore the relationship between these characteristics and cognition. Magnetic resonance images and the rs6994992 genotype were obtained from 53 healthy participants. A general linear model was used to determine the effects of risk allele dosage of rs6994992 on brain characteristics. Spearman correlation analysis was employed to calculate the correlation between altered brain characteristics and cognitive scores. Our results demonstrated that regions with significant differences in structural characteristics between groups with different dosages of rs6994992 were mainly located in the frontal and temporal lobes, hippocampus and angular gyrus. Moreover, significant regions of functional connectivity (FC) partly overlapped with the structural results. Measurements in those significant regions and FCs were correlated with the cognition scales. This association can inform our understanding of the mechanisms through which rs6994992 variants increase the risk for SZ., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Catechol-O-methyltransferase (COMT) gene variants have been reported to be implicated in the pathogenesis of psychotic symptoms in schizophrenia, especially in negative symptoms. These symptoms including apathy, blunted affect, social withdrawal and motor retardation. Neuroimaging studies suggested that negative symptoms appear to be associated with impaired activities of the prefrontal cortex in particular the dorsolateral prefrontal cortex (DLPFC). Given that the COMT gene is highly expressed in the DLPFC, it is poorly understood whether the disease state and COMT val 158 met polymorphisms have main and interactive effect on the resting state functional connectivity (RSFC) of DLPFC-related pathways. To this end, fifty-five first episode schizophrenia (FES) and fifty-three healthy controls were genotyped using blood samples and underwent magnetic resonance imaging scanning. Seed-based voxel wise functional connectivity analysis was performed by placing bilateral pairs of seeds with DLPFC in area 46 defined by Brodmann's atlas. A two-ways ANCOVA model was performed with val 158 met genotypes and disease state as the between subjects factors. Significant disease × COMT interactive effect was found mainly in the left DLPFC with the left anterior cingulate cortex, right precuneus, right superior parietal gyrus, which were overlapped with disease main effect. And these RSFC had positive correlations with affective blunting scores in FES patients with val homozygotes, but not with met carriers. Our results showed that the disease and the genotypes in COMT gene have significant interactive effect on RSFC of DLPFC and provided evidence for a disease-dependent pattern of gene action., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The aberrant orchestration between the triple networks has been suggested as a backbone for some cognitive and clinical features of schizophrenia. The salience network (SN) plays a general role in switching between the central executive network (CEN) and the default mode network (DMN) mediated by dopamine activity. Whether the disease state and dopamine associated gene, catechol-O-methyltransferase (COMT), has an interactive effect on the function and structure of the triple network has not been understood. To this end, independent component analysis was used to identify the triple network. Then, cortical thickness and inter-regional resting state functional connectivity (RSFC) of the triple network was investigated in 55 first episode schizophrenia (FES) patients and 53 age-, gender-, and education- matched healthy controls. Finally, we investigated if there exist interactive effect between disease and COMT gene variation on the abnormal brain structure and function. Our results show that patients with FES exhibited significantly increased RSFC between anterior cingulate cortex and left dorsolateral prefrontal cortex (DLPFC) compared with healthy controls. The cortical thickness of the left DLPFC was thinner in FES patients. Significant interaction effect between COMT and disease was found in cortical thickness of the left DLPFC. Specifically, cortical thinning in this region was evident with the val homozygotes group of the COMT gene in FES. This findings suggest abnormal RSFC between CEN and SN and thinker cortical thickness in FES. And the val homozygotes of COMT may contribute to further cortical thinning in FES patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: The frontal-striatum-thalamus pathway is important in the glutamic neural circuit. The hypofunction of GRIN1 and GRIA2 subunits from glutamic receptors has been hypothesized as the primary process in the etiology of schizophrenia. Identified gene polymorphism involved in the pathogenesis of schizophrenia may uncover relevant mechanism pathways. Methods: We selected two loci of rs11146020 and rs3813296 distributed in GRIN1 and GRIA2 genes and tested their main and interaction effects on causality connections and structural characteristics in the frontal-striatum-thalamus pathway in 55 Han Chinese first-episode negative schizophrenia patients. Results: We found that: (1) rs11146020 has a significant main effect on the causality connections between the bilateral dorsolateral prefrontal cortex, and rs3813296 mainly influences those of the descending pathway from the prefrontal cortex to the striatum; (2) interaction effect of rs11146020 and rs3813296 on causality connections are located in the ascending pathway from the pallidum to the dorsolateral prefrontal cortex; and (3) the two loci have effects on the volumes of several regions of this pathway. Conclusion: Our results suggested there is modulation on glutamic frontal-striatum-thalamus pathway by rs11146020 and rs3813296 gene polymorphism. Patients with different genotypes have different neuroimaging characteristics, which indirectly reminded clinicians those patients should receive different clinical interventions. [ABSTRACT FROM AUTHOR]

Schizophrenia (SZ) is categorized as positive SZ and negative SZ in terms of the predominant symptom. In this study, we proposed the hypothesis that positive SZ had more information interaction and negative SZ had less information interaction between brain regions compared with normal controls. To verify the hypothesis, firstly, we recorded and preprocessed the electroencephalogram data with 32 electrodes from 28 schizophrenic patients (14 with positive symptoms and 14 with negative symptoms) and 14 normal controls. Then, mutual information (MI) was used to construct the functional brain networks, and these networks were analyzed by the method of graph theory. We calculated and analyzed several network metrics which reflected the ability of the information processing in the network. The results showed smaller clustering coefficient, larger average characteristic path length, lower global efficiency, lower local efficiency and smaller degrees in SZ functional brain networks compared with normal controls. We conclude that there are fewer information interactions in SZ patients than that in normal controls, while positive SZ has more information interactions than negative SZ does, and patients tend to have slower and less efficient information transfer between brain regions. These findings have a great significance to deeply understand the pathogenesis of SZ. [ABSTRACT FROM AUTHOR]