Biology subjects

Thompson, P.

Publications and source records attributed to Thompson, P..

4 recordsLinked to original sources

bioRxiv2018

Smaller Hippocampal CA-1 Subfield Volume in Posttraumatic Stress Disorder

BackgroundSmaller hippocampal volume in patients with PTSD represents the most consistently reported structural alteration in the brain. Subfields of the hippocampus play distinct roles in encoding and processing of memories, which are disrupted in PTSD. We examined PTSD-associated alterations in 12 hippocampal subfields in relation to global hippocampal shape, and clinical features.\n\nMethodsCase-control cross-sectional study of US military veterans (n=282) from the Iraq and Afghanistan era were grouped into PTSD (n=142) and trauma-exposed controls (n=140). Participants underwent clinical evaluation for PTSD and associated clinical parameters followed by MRI at 3-Tesla. Segmentation with Free Surfer v6.0 produced hippocampal subfield volumes for the left and right CA1, CA3, CA4, DG, fimbria, fissure, hippocampus-amygdala transition area, molecular layer, parasubiculum, presubiculum, subiculum, and tail, as well as hippocampal meshes. Covariates included age, gender, trauma exposure, alcohol use, depressive symptoms, antidepressant medication use, total hippocampal volume, and MRI scanner model.\n\nResultsSignificantly lower subfield volumes were associated with PTSD in left CA1 (p=.01; d=.21; uncorrected), CA3 (p=.04; d=.08; uncorrected), and right CA3 (p=.02; d=.07; uncorrected) only if ipsilateral whole hippocampal volume was included as a covariate. A trend level association of L-CA1 with PTSD [F4, 221=3.32, p = 0.07] is present and the other subfield findings are non-significant if ipsilateral whole hippocampal volume is not included as a covariate. PTSD associated differences in global hippocampal shape were non-significant.\n\nConclusionsThe present finding of smaller hippocampal CA1 in PTSD is consistent with model systems in rodents that exhibit increased anxiety-like behavior from repeated exposure to acute stress. Behavioral correlations with hippocampal subfield volume differences in PTSD will elucidate their relevance to PTSD, particularly behaviors of associative fear learning, extinction training, and formation of false memories.

neuroscience↗

bioRxiv2018

Large-scale neuroimaging and genetic study reveals genetic architecture of brain white matter microstructure

Microstructural changes of white matter (WM) tracts are known to be associated with various neuropsychiatric disorders/diseases. Heritability of structural changes of WM tracts has been examined using diffusion tensor imaging (DTI) in family-based studies for different age groups. The availability of genetic and DTI data from recent large population-based studies offers opportunity to further improve our understanding of genetic contributions. Here, we analyzed the genetic architecture of WM tracts using DTI and single-nucleotide polymorphism (SNP) data of unrelated individuals in the UK Biobank (n [~] 8000). The DTI parameters were generated using the ENIGMA-DTI pipeline. We found that DTI parameters are substantially heritable on most WM tracts. We observed a highly polygenic or omnigenic architecture of genetic influence across the genome as well as the enrichment of SNPs in active chromatin regions. Our bivariate analyses showed strong genetic correlations for several pairs of WM tracts as well as pairs of DTI parameters. We performed voxel-based analysis to illustrate the pattern of genetic effects on selected parts of the tract-based spatial statistics skeleton. Comparing the estimates from the UK Biobank to those from small population-based studies, we illustrated that sufficiently large sample size is essential for genetic architecture discovery in imaging genetics. We confirmed this finding with a simulation study.

genetics↗

bioRxiv2017

Polygenic selection underlies evolution of human brain structure and behavioral traits

Seemingly paradoxical characteristics of psychiatric disorders, including moderate to high prevalence, reduced fecundity, and high heritability have motivated explanations for the persistence of common risk alleles for severe psychiatric phenotypes throughout human evolution. Proposed mechanisms include balancing selection, drift, and weak polygenic adaptation acting either directly, or indirectly through selection on correlated traits. While many mechanisms have been proposed, few have been empirically tested. Leveraging publicly available data of unprecedented sample size, we studied twenty-five traits (i.e., ten neuropsychiatric disorders, three personality traits, total intracranial volume, seven subcortical brain structure volume traits, and four complex traits without neuropsychiatric associations) for evidence of several different signatures of selection over a range of evolutionary time scales. Consistent with the largely polygenic architecture of neuropsychiatric traits, we found no enrichment of trait-associated single-nucleotide polymorphisms (SNPs) in regions of the genome that underwent classical selective sweeps (i.e., events which would have driven selected alleles to near fixation). However, we discovered that SNPs associated with some, but not all, behaviors and brain structure volumes are enriched in genomic regions under selection since divergence from Neanderthals ~600,000 years ago, and show further evidence for signatures of ancient and recent polygenic adaptation. Individual subcortical brain structure volumes demonstrate genome-wide evidence in support of a mosaic theory of brain evolution while total intracranial volume and height appear to share evolutionary constraints consistent with concerted evolution. We further characterized the biological processes potentially targeted by selection, through expression Quantitative Trait Locus (eQTL) and Gene Ontology (GO) enrichment analyses and found evidence for the role of regulatory functions among selected SNPs in immune and brain tissues. Taken together, our results suggest that alleles associated with neuropsychiatric, behavioral, and brain volume phenotypes have experienced both ancient and recent polygenic adaptation in human evolution, acting through neurodevelopmental and immune-mediated pathways.

evolutionary biology↗

bioRxiv2017

Evaluating 35 Methods to Generate Structural Connectomes Using Pairwise Classification

There is no consensus on how to construct structural brain networks from diffusion MRI. How variations in pre-processing steps affect network reliability and its ability to distinguish subjects remains opaque. In this work, we address this issue by comparing 35 structural connectome-building pipelines. We vary diffusion reconstruction models, tractography algorithms and parcellations. Next, we classify structural connectome pairs as either belonging to the same individual or not. Connectome weights and eight topological derivative measures form our feature set. For experiments, we use three test-retest datasets from the Consortium for Reliability and Reproducibility (CoRR) comprised of a total of 105 individuals. We also compare pairwise classification results to a commonly used parametric test-retest measure, Intraclass Correlation Coefficient (ICC){ddagger}.

neuroscience↗