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Highlights • The RSFC of DLPFC-related pathways are increased in FES patients. • COMT val158met genotypes have significant effect on RSFC of DLPFC. • The RSFC of DLPFC have correlations with negative symptoms in FES with val/val. Abstract 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 val158met 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 val158met 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. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (APOE) ε4 allele is the genetic risk factor with the most established evidence for sporadic Alzheimer’s disease. Previous neuroimaging studies have demonstrated insufficiently consistent functional and structural changes among healthy APOE ε4 carriers when compared to non-carriers. Here, in a cognitively intact elderly group (a total of 110: 45 APOE ε4 carriers, 65 non-carriers), we aimed to investigate the potential role of APOE ε4 in the modulation of grey matter activity, white matter integrity, and brain morphology before the development of clinically significant symptoms and signs, by methods of: amplitude of low frequency fluctuations and regional homogeneity analysis based on resting state fMRI, and fiber tractography approach based on diffusion tensor imaging. Our results revealed that compared to non-carriers, APOE ε4 carriers showed: (1) an inconsistent pattern of activity change in the default mode network, including increased gray matter activity in anterior cingulate cortex and medial prefrontal cortex and decreased activity in precuneus; (2) lower mean diffusivity (MD) in fibers of corona radiata and corpus callosum, and lower axial diffusivity in genu of corpus callosum; and (3) significant positive correlation between the MD value of the right superior corona radiate and gross white matter volume; significant negative correlation between the MD value of the right superior corona radiate and Mini-Mental State Examination (MMSE) score. Our results suggested that APOE ε4 gene can modulate gray matter activity and white matter integrity in cognitive and memory related regions, even before any clinical or neuropsychic symtoms or signs of imminent disease. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease. Mild cognitive impairment (MCI) represents a state of cognitive function between normal cognition and dementia. Longitudinal studies showed that some MCI patients remained in a state of MCI, and some developed AD. The reason for these different conversions from MCI remains to be investigated. 180 MCI participants were followed for eight years. 143 MCI patients maintained the MCI state (MCI_S), and the remaining thirty-seven MCI patients were re-evaluated as having AD (MCI_AD). We obtained 1,036 structural brain characteristics and 15,481 gene expression values from the 180 MCI participants and applied weighted gene co-expression network analysis (WGCNA) to explore the relationship between structural brain features and gene expression. Regulating mediator effect analysis was employed to explore the relationships among gene expression, brain region measurements and clinical phenotypes. We found that 60 genes from the MCI_S group and 18 genes from the MCI_AD group respectively had the most significant correlations with left paracentral lobule and sulcus (L.PTS) and right subparietal sulcus (R.SubPS) thickness; CTCF, UQCR11 and WDR5B were the mutual genes between the two groups. The expression of CTCF gene and clinical score are completely mediated by L.PTS thickness, and the UQCR11 and WDR5B gene expression levels significantly regulate the mediating effect pathway. In conclusion, the factors affecting the different conversions from MCI are closely related to L.PTS thickness and the CTCF, UQCR11 and WDR5B gene expression levels. Our results add a theoretical foundation of imaging genetics for conversion from MCI to AD. [ABSTRACT FROM AUTHOR]

• Risk A allele carriers have reduced FC in both SZ patients and HCs. • There is a positive correlation between FC and verbal fluency in SZ patients. • There is a negative correlation between FC and verbal fluency in HCs. • The rs1059004 polymorphism and SZ have synergistic effects on brain connections. 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. [ABSTRACT FROM AUTHOR]