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Recent large-scale, genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with general intelligence. The cumulative influence of these loci on brain structure is unknown. We examined if cortical morphology mediates the relationship between GWAS-derived polygenic scores for intelligence (PSi) and g-factor. Using the effect sizes from one of the largest GWAS meta-analysis on general intelligence to date, PSi were calculated among 10 P value thresholds. PSi were assessed for the association with g-factor performance, cortical thickness (CT), and surface area (SA) in two large imaging-genetics samples (IMAGEN N = 1651; IntegraMooDS N = 742). PSi explained up to 5.1% of the variance of g-factor in IMAGEN (F1,1640 = 12.2-94.3; P < 0.005), and up to 3.0% in IntegraMooDS (F1,725 = 10.0-21.0; P < 0.005). The association between polygenic scores and g-factor was partially mediated by SA and CT in prefrontal, anterior cingulate, insula, and medial temporal cortices in both samples (PFWER-corrected < 0.005). The variance explained by mediation was up to 0.75% in IMAGEN and 0.77% in IntegraMooDS. Our results provide evidence that cumulative genetic load influences g-factor via cortical structure. The consistency of our results across samples suggests that cortex morphology could be a novel potential biomarker for neurocognitive dysfunction that is among the most intractable psychiatric symptoms., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The mismatch negativity (MMN) deficit in schizophrenia is a consistently replicated finding and is considered a potential biomarker. From the cognitive neuroscience perspective, MMN represents a cortical correlate of the prediction error, a fundamental computational operator that may be at the core of various cognitive and clinical deficits observed in schizophrenia. The impact of emotion on cognitive processes in schizophrenia is insufficiently understood, and its impact on basic operators of cortical computation is largely unknown. In the visual domain, the facial expression mismatch negativity (EMMN) offers an opportunity to investigate basic computational operators in purely cognitive and in emotional contexts. In this study, we asked whether emotional context enhances cortical prediction error responses in patients with schizophrenia, as is the case in normal subjects. Therefore, seventeen patients with schizophrenia and eighteen controls completed a visual sequence oddball task, which allows for directly comparing MMN components evoked by deviants with high, intermediate and low emotional engagement. Interestingly, patients with schizophrenia showed pronounced deficits in response to neutral stimuli, but almost normal responses to emotional stimuli. The dissociation between impaired MMN and normal EMMN suggests that emotional context not only enhances, but restores cortical prediction error responses in patients with schizophrenia to near-normal levels. Our results show that emotional processing in schizophrenia is not necessarily defect; more likely, emotional processing heterogeneously impacts on cognition in schizophrenia. In fact, this study suggests that emotional context may even compensate for cognitive deficits in schizophrenia that are, in a different sensory domain, discussed as biomarkers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The rs1625579 variant near the microRNA-137 (MIR137) gene is one of the best-supported schizophrenia variants in genome-wide association studies (GWAS), and microRNA-137 functionally regulates other GWAS identified schizophrenia risk variants. Schizophrenia patients with the MIR137 rs1625579 risk genotype (homozygous for the schizophrenia risk variant) also have aberrant brain structure. It is unclear if the effect of MIR137 among schizophrenia patients is due to potential epistasis with genetic risk for schizophrenia or other factors of the disorder. Here, we investigated the effect of MIR137 genotype on white matter fractional anisotropy (FA), cortical thickness (CT), and surface area (SA) in a sample comprising healthy control subjects, and individuals with familial risk for psychosis (first-degree relatives of patients with schizophrenia or bipolar disorder; N=426). In voxel-wise analyses of FA, we observed a significant genotype-by-group interaction (P FWE <0.05). The familial risk group with risk genotype had lower FA (P FWE <0.05), but there was no genetic association in controls. In vertex-wise analyses of SA, we also observed a significant genotype-by-group interaction (P FWE <0.05). Relatives with MIR137 risk genotype had lower SA, however the risk genotype was associated with higher SA in the controls (all P FWE <0.05). These results show that MIR137 risk genotype is associated with lower FA in psychosis relatives that is similar to previous imaging-genetics findings in patients with schizophrenia. Furthermore, MIR137 genotype may also be a risk factor in a subclinical population with wide reductions in white matter FA and cortical SA., (Copyright © 2017 Elsevier B.V. All rights reserved.)