The Imaging and Cognition Genetics Conference 2011, ICG 2011: A Meeting of Minds

In June 2011, 70 researchers from the disciplines of cognitive science, genetics, psychology, psychiatry, neurobiology, and computer science gathered in Os, Norway, for the first Imaging and Cognition Genetics meeting. The aim of the conference was to discuss progress, enhance collaboration, and maximize the sharing of resources within this new field. In this Perspective, we summarize the major themes that emerged from ICG 2011. The first is the importance of defining cognitive and imaging phenotypes and endophenotypes suitable for genetic analysis. These can come from differential psychology, cognitive science, structural MRI, tractography, and functional imaging. The second theme is the emergence of new methods for the analysis of complex traits. These include advanced computational and statistical techniques for analyzing complex datasets, and new ways of interpreting data from genome-wide association studies, such as jointly evaluating the contribution of SNPs in specific genes and pathways rather than considering single SNPs in isolation. The final theme is the importance of establishing functional correlates of newly identified genetic variants

Rockmate: an Efficient, Fast, Automatic and Generic Tool for Re-materialization in PyTorch

We propose Rockmate to control the memory requirements when training PyTorch DNN models. Rockmate is an automatic tool that starts from the model code and generates an equivalent model, using a predefined amount of memory for activations, at the cost of a few re-computations. Rockmate automatically detects the structure of computational and data dependencies and rewrites the initial model as a sequence of complex blocks. We show that such a structure is widespread and can be found in many models in the literature (Transformer based models, ResNet, RegNets,...). This structure allows us to solve the problem in a fast and efficient way, using an adaptation of Checkmate (too slow on the whole model but general) at the level of individual blocks and an adaptation of Rotor (fast but limited to sequential models) at the level of the sequence itself. We show through experiments on many models that Rockmate is as fast as Rotor and as efficient as Checkmate, and that it allows in many cases to obtain a significantly lower memory consumption for activations (by a factor of 2 to 5) for a rather negligible overhead (of the order of 10% to 20%). Rockmate is open source and available at https://github.com/topal-team/rockmate

Personality traits and hardiness as risk- and protective factors for mental distress during the COVID-19 pandemic: a Norwegian two-wave study

Background Several risk factors for anxious-depressive symptomatology during the COVID-19 pandemic have been established. However, few studies have examined the relationship between personality traits, hardiness, and such symptomatology during the pandemic. These constructs might serve as risk- and/or protective factors for such mental distress through the pandemic. Methods A sample of 5783 Norwegians responded to a survey at two time points within the first year of the pandemic. The first data collection was in April 2020 (T1) and the second in December 2020 (T2). Measures included the Ten-Item Personality-Inventory, the Revised Norwegian Dispositional Resilience Scale, and the Patient Health Questionnaire Anxiety and Depression Scale. Analyses were performed using Pearson’s correlations, multiple linear regression, and a moderation analysis. Results Anxious-depressive symptomatology in early phases (T1) of the pandemic was the strongest predictor for the presence of such symptomatology 9 months after the outbreak (T2). Personality and hardiness correlated significantly with mental distress at T1 and T2. Personality traits explained 5% variance in symptoms when controlling for age, gender, solitary living, negative economic impact, and mental distress at baseline. Higher neuroticism predicted higher mental distress, whereas higher conscientiousness and extraversion predicted less mental distress. Hardiness did not explain variance in outcome beyond personality traits. Hardiness did not significantly moderate the relationship between neuroticism and mental distress. Conclusion Individuals with high levels of neuroticism had greater difficulties adapting to the circumstances of the COVID-19 pandemic and were more prone to mental distress. Contrastingly, higher conscientiousness and extraversion may have served as protective factors for mental distress during the pandemic. The current findings might aid identification of vulnerable individuals and groups. Consequently, preventive interventions could be offered to those who need it the most.publishedVersio

Changes in mental health symptoms from April (COVID-19 outbreak) to December 2020 in Norway: A two-wave study

The main objective of the study was to investigate changes in mental health symptoms from the start of the pandemic in Norway (April) to December 2020. A total of 6017 participants completed an assessment of the survey at both time points. Main Outcome Measures: Symptoms of anxiety and depression were measured at both time points. Demographic variables and potential risk factors were assessed. There were significant changes (slight increase) in anxiety and depression, but effect sizes were small. Increases in symptoms in anxiety and depression occurred more in the general population than for people with pre-existing mental health problems. Baseline level of symptoms was the most important risk factor. Other significant risk factors included female sex, students, pre-existing mental health problems, increased tobacco use, lost job, and lacking government trust. The longitudinal results replicated findings from the first phase of the pandemic, suggesting that the number of risk factors experienced is associated with symptom severity. The results suggest that mental health symptoms have been quite stable from April to December but with a slight increase among people presenting with subclinical symptoms in April.publishedVersio

An epigenetic association analysis of childhood trauma in psychosis reveals possible overlap with methylation changes associated with PTSD

Patients with a severe mental disorder report significantly higher levels of childhood trauma (CT) than healthy individuals. Studies have suggested that CT may affect brain plasticity through epigenetic mechanisms and contribute to developing various psychiatric disorders. We performed a blood-based epigenome-wide association study using the Childhood Trauma Questionnaire-short form in 602 patients with a current severe mental illness, investigating DNA methylation association separately for five trauma subtypes and the total trauma score. The median trauma score was set as the predefined cutoff for determining whether the trauma was present or not. Additionally, we compared our genome-wide results with methylation probes annotated to candidate genes previously associated with CT. Of the patients, 83.2% reported CT above the cutoff in one or more trauma subtypes, and emotional neglect was the trauma subtype most frequently reported. We identified one significant differently methylated position associated with the gene TANGO6 for physical neglect. Seventeen differentially methylated regions (DMRs) were associated with different trauma categories. Several of these DMRs were annotated to genes previously associated with neuropsychiatric disorders such as post-traumatic stress disorder and cognitive impairments. Our results support a biomolecular association between CT and severe mental disorders. Genes that were previously identified as differentially methylated in CT-exposed subjects with and without psychosis did not show methylation differences in our analysis. We discuss this inconsistency, the relevance of our findings, and the limitations of our study.publishedVersio

The SNPMaP package for R: a framework for genome-wide association using DNA pooling on microarrays

Summary: Large-scale genome-wide association (GWA) studies using thousands of high-density SNP microarrays are becoming an essential tool in the search for loci related to heritable variation in many phenotypes. However, the cost of GWA remains beyond the reach of many researchers. Fortunately, the majority of statistical power can still be obtained by estimating allele frequencies from DNA pools, reducing the cost to that of tens, rather than thousands of arrays. We present a set of software tools for processing SNPMaP (SNP microarrays and pooling) data from CEL files to Relative Allele Scores in the rich R statistical computing environment

Differences in white blood cell proportions between schizophrenia cases and controls are influenced by medication and variations in time of day

Cases with schizophrenia (SCZ) and healthy controls show differences in white blood cell (WBC) counts and blood inflammation markers. Here, we investigate whether time of blood draw and treatment with psychiatric medications are related to differences in estimated WBC proportions between SCZ cases and controls. DNA methylation data from whole blood was used to estimate proportions of six subtypes of WBCs in SCZ patients (n = 333) and healthy controls (n = 396). We tested the association of case-control status with estimated cell-type proportions and the neutrophil-to-lymphocyte ratio (NLR) in 4 models: with/without adjusting for time of blood draw, and then compared results from blood samples drawn during a 12-h (07:00–19:00) or 7-h (07:00-14:00) period. We also investigated WBC proportions in a subgroup of medication-free patients (n = 51). Neutrophil proportions were significantly higher in SCZ cases (mean=54.1%) vs. controls (mean=51.1%; p = <0.001), and CD8+T lymphocyte proportions were lower in SCZ cases (mean=12.1%) vs. controls (mean=13.2%; p = 0.001). The effect sizes in the 12-h sample (07:00–19:00) showed a significant difference between SCZ vs. controls for neutrophils, CD4+T, CD8+T, and B-cells, which remained significant after adjusting for time of blood draw. In the samples matched for time of blood draw during 07.00–14.00, we also observed an association with neutrophils, CD4+T, CD8+T, and B-cells that was unaffected by further adjustment for time of blood draw. In the medication-free patients, we observed differences that remained significant in neutrophils (p = 0.01) and CD4+T (p = 0.01) after adjusting for time of day. The association of SCZ with NLR was significant in all models (range: p < 0.001 to p = 0.03) in both medicated and unmedicated patients. In conclusion, controlling for pharmacological treatment and circadian cycling of WBC is necessary for unbiased estimates in case-control studies. Nevertheless, the association of WBC with SCZ remains, even after adjusting for the time of day.publishedVersio

Nationwide Genomic Study in Denmark Reveals Remarkable Population Homogeneity

Denmark has played a substantial role in the history of Northern Europe. Through a nationwide scientific outreach initiative, we collected genetic and anthropometrical data from ∼800 high school students and used them to elucidate the genetic makeup of the Danish population, as well as to assess polygenic predictions of phenotypic traits in adolescents. We observed remarkable homogeneity across different geographic regions, although we could still detect weak signals of genetic structure reflecting the history of the country. Denmark presented genomic affinity with primarily neighboring countries with overall resemblance of decreasing weight from Britain, Sweden, Norway, Germany, and France. A Polish admixture signal was detected in Zealand and Funen, and our date estimates coincided with historical evidence of Wend settlements in the south of Denmark. We also observed considerably diverse demographic histories among Scandinavian countries, with Denmark having the smallest current effective population size compared to Norway and Sweden. Finally, we found that polygenic prediction of self-reported adolescent height in the population was remarkably accurate (R2 = 0.639 ± 0.015). The high homogeneity of the Danish population could render population structure a lesser concern for the upcoming large-scale gene-mapping studies in the country

Variants in Doublecortin- and Calmodulin Kinase Like 1, a Gene Up-Regulated by BDNF, Are Associated with Memory and General Cognitive Abilities

Human memory and general cognitive abilities are complex functions of high heritability and wide variability in the population. The brain-derived neurotrophic factor (BDNF) plays an important role in mammalian memory formation.Based on the identification of genes markedly up-regulated during BDNF-induced synaptic consolidation in the hippocampus, we selected genetic variants that were tested in three independent samples, from Norway and Scotland, of adult individuals examined for cognitive abilities. In all samples, we show that markers in the doublecortin- and calmodulin kinase like 1 (DCLK1) gene, are significantly associated with general cognition (IQ scores) and verbal memory function, resisting multiple testing. DCLK1 is a complex gene with multiple transcripts which vary in expression and function. We show that the short variants are all up-regulated after BDNF treatment in the rat hippocampus, and that they are expressed in the adult human brain (mostly in cortices and hippocampus). We demonstrate that several of the associated variants are located in potential alternative promoter- and cis-regulatory elements of the gene and that they affect BDNF-mediated expression of short DCLK1 transcripts in a reporter system.These data present DCLK1 as a functionally pertinent gene involved in human memory and cognitive functions