Vergence eye movements in patients with schizophrenia

AbstractPrevious studies have shown that smooth pursuit eye movements are impaired in patients with schizophrenia. However, under normal viewing conditions, targets move not only in the frontoparallel plane but also in depth, and tracking them requires both smooth pursuit and vergence eye movements. Although previous studies in humans and non-human primates suggest that these two eye movement subsystems are relatively independent of one another, to our knowledge, there have been no prior studies of vergence tracking behavior in patients with schizophrenia. Therefore, we have investigated these eye movements in patients with schizophrenia and in healthy controls. We found that patients with schizophrenia exhibited substantially lower gains compared to healthy controls during vergence tracking at all tested speeds (e.g. 0.25Hz vergence tracking mean gain of 0.59 vs. 0.86). Further, consistent with previous reports, patients with schizophrenia exhibited significantly lower gains than healthy controls during smooth pursuit at higher target speeds (e.g. 0.5Hz smooth pursuit mean gain of 0.64 vs. 0.73). In addition, there was a modest (r≈0.5), but significant, correlation between smooth pursuit and vergence tracking performance in patients with schizophrenia. Our observations clearly demonstrate substantial vergence tracking deficits in patients with schizophrenia. In these patients, deficits for smooth pursuit and vergence tracking are partially correlated suggesting overlap in the central control of smooth pursuit and vergence eye movements

Gyrification Connectomes in Unmedicated Patients With Schizophrenia and Following a Short Course of Antipsychotic Drug Treatment

Schizophrenia (SZ) is a d isease characterized by brain dysconnectivity and abnormal brain development. The study of cortical gyrification in schizophrenia may capture underlying alterations reflective of neurodevelopmental abnormalities more accurately than other imaging modalities. Graph-based connectomic approaches have been previously used in schizophrenia to study structural and functional brain covariance using a diversity of techniques. The goal of the present study was to evaluate morphological covariance using a measure of local gyrification index in patients with schizophrenia. The aims of this study were two-fold: (1) Evaluate the structural covariance of local gyrification index using graph theory measures of integration and segregation in unmedicated patients with schizophrenia compared to healthy controls and (2) investigate changes in these measures following a short antipsychotic drug (APD) treatment. Using a longitudinal prospective design, structural scans were obtained prior to treatment in 34 unmedicated patients with SZ and after 6 weeks of treatment with risperidone. To control for the effect of time, 23 matched healthy controls (HC) were also scanned twice, 6 weeks apart. The cortical surface of each structural image was reconstructed and local gyrification index values were computed using FreeSurfer. Local gyrification index values where then parcellated into atlas based regions and entered into a 68 × 68 correlation matrix to construct local gyrification index connectomes for each group at each time point. Longitudinal comparisons showed significant group by time interactions for measures of segregation (clustering, local efficiency) and modularity, but not for measures of integration (path length, global efficiency). Post-hoc tests showed increased clustering, local efficiency, and modularity connectomes in unmedicated patients with SZ at baseline compared to HC. Post-hoc tests did not show significant within group differences for HCs or patients with SZ. After 6 weeks of treatment, there were no significant differences between the groups on these measures. Abnormal cortical topography is detected in schizophrenia and is modified by short term APD treatment reflective of decreases in hyper-specialization in network connectivity. We speculate that changes in the structural organization of the brain is achieved through the neuroplastic effects that APDs have on brain tissue, thus promoting more efficient brain connections and, possibly, a therapeutic effect

A Longitudinal Multimodal Neuroimaging Study to Examine Relationships Between Resting State Glutamate and Task Related BOLD Response in Schizophrenia

Previous studies have observed impairments in both brain function and neurometabolite levels in schizophrenia. In this study, we investigated the relationship between brain activity and neurochemistry in off-medication patients with schizophrenia and if this relationship is altered following antipsychotic medication by combining proton magnetic resonance spectroscopy (1H-MRS) with functional magnetic resonance imaging (fMRI). We used single voxel MRS acquired in the bilateral dorsal anterior cingulate cortex (ACC) and fMRI during performance of a Stroop color-naming task in 22 patients with schizophrenia (SZ), initially off-medication and after a 6-week course of risperidone, and 20 matched healthy controls (HC) twice, 6 weeks apart. We observed a significant decrease in ACC glutamate + glutamine (Glx)/Creatine (Cr) levels in medicated SZ patients compared to HC but not compared to their off-medication baseline. In off-medication SZ, the relationship between ACC Glx/Cr levels and the blood oxygen level-dependent (BOLD) response in regions of the salience network (SN) and posterior default mode network (DMN) was opposite than of HC. After 6 weeks, the relationship between Glx and the BOLD response was still opposite between the groups; however for both groups the direction of the relationship changed from baseline to week 6. These results suggest a mechanism whereby alterations in the relationship between cortical glutamate and BOLD response is disrupting the modulation of major neural networks subserving cognitive processes, potentially affecting cognition. While these relationships appear to normalize with treatment in patients, the interpretations of the results are confounded by significant group differences in Glx levels, as well as the variability of the relationship between Glx and BOLD response in HC over time, which may be driven by factors including habituation to task or scanner environment

Genome-wide association meta-analysis of fish and EPA plus DHA consumption in 17 US and European cohorts

Background Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. Objective To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. Design We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts. Results Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (Freq(A) = 0.015) was associated with 0.029 servings/day (similar to 1 serving/month) lower fish consumption (P = 1.96x10(-8)). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10(-7)). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA. Conclusions These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.Peer reviewe

Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts

Background: Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. Objective: To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. Design: We conducted genome-wide association (GWA) meta-analysis of fish (n = 86, 467) and EPA +DHA (n = 62, 265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts. Results: Heritability estimates for fish and EPA+DHA consumption ranged from 0.13

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.Peer reviewe

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk

Формирование эмоциональной культуры как компонента инновационной культуры студентов

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been