Vinkers, C. | Search bioRxiv

bioRxiv2020

Lipid suppressed and tissue-fraction corrected metabolic distributions in human central brain structures using 2D 1H Magnetic Resonance Spectroscopic Imaging at 7 tesla

Magnetic resonance spectroscopic imaging (MRSI) has the potential to add a layer of understanding of the neurobiological mechanisms underlying brain diseases, disease progression, and treatment efficacy. Limitations related to metabolite fitting of low SNR data, signal variations due to partial volume effects, acquisition and extra-cranial lipid artefacts, along with clinically relevant aspects such as scan-time constraints, are among the factors that hinder the widespread implementation of in vivo MRSI. The aim of this work was to address these factors and to develop an acquisition, reconstruction and post-processing pipeline to derive lipid suppressed metabolite values based on Free Induction Decay (FID-MRSI) measurements made using a 7 tesla MR scanner. Anatomical images were used to perform high-resolution (1mm3) partial-volume correction to account for grey matter, white matter and cerebral-spinal fluid signal contributions. Implementation of automatic quality control thresholds and normalization of metabolic maps from 23 subjects to the MNI standard atlas facilitated the creation of high-resolution average metabolite maps of several clinically relevant metabolites in central brain regions, while accounting for macromolecular distributions. Reported metabolite values include glutamate, choline, (phospo)creatine, myo-inositol, glutathione, N-acetyl aspartyl glutamate(and glutamine) and N-acetyl aspartate. MNI-registered average metabolite maps facilitate group-based analysis; thus offering the possibility to mitigate uncertainty in variable MRSI.

neuroscience↗

bioRxiv2019

Meta-analysis of longitudinal epigenome-wide association studies of military cohorts reveals multiple CpG sites associated with post-traumatic stress disorder

BackgroundEpigenetic mechanisms have been suggested to play a role in the development of post-traumatic stress disorder (PTSD). Here, blood-derived DNA methylation data (HumanMethylation450 BeadChip) collected prior to and following combat exposure in three cohorts composed of male military members were combined to assess whether DNA methylation profiles are associated with the development of PTSD.\n\nMethodsA total of 123 cases and 143 trauma-exposed controls were included. The Psychiatric Genomics Consortium (PGC) PTSD EWAS QC pipeline was used on all cohorts, and results were combined using a sample size weighted meta-analysis. We first combined two cohorts in a discovery stage (N=126 and 78), sought targeted replication in the third cohort (N=62) and then performed a meta-analysis of all three datasets.\n\nResultsThe discovery stage identified four CpG sites in which, conditional on pre-deployment DNA methylation, post-deployment DNA methylation was associated with PTSD status after adjustment for multiple comparisons. The most significant CpG (p = 1.0 x 10-08) was located on 5q31 and replicated in the third cohort. When combining all cohorts, this intergenic site remained most significant along with two CpGs located in MAD1L1 and HEXDC. Interestingly, the CpG site of MAD1L1 had an underlying single nucleotide polymorphism (SNP) which was located within the same LD block as a recently identified PTSD-associated SNP. Twelve differential methylated regions (DMRs) were also identified, one of which was located in MAD1L1 and four were situated in the human leukocyte antigen (HLA) region.\n\nConclusionThis study suggests that the development of PTSD is associated with distinct methylation patterns in several genomic positions and regions. Our most prominent finding points to the involvement of MAD1L1 which was previously associated with PTSD.

genetics↗