Microstructural Correlates of Resilience against Major Depressive Disorder: Epigenetic Mechanisms?

Mental disorders are a major cause of long-term disability and are a direct cause of mortality, with approximately 800.000 individuals dying from suicide every year worldwide - a high proportion of them related to major depressive disorder (MDD)^1^. Healthy relatives of patients with major depressive disorder (MDD) are at risk to develop the disease. This higher vulnerability is associated with structural^2-4^ and functional brain changes^5^. However, we found using high angular resolution diffusion imaging (HARDI) with 61 diffusion directions that neuron tracts between frontal cortices and limbic as well as temporal and parietal brain regions are characterized by better diffusion coefficients in unaffected relatives (UHR), who managed to stay healthy, compared to healthy volunteers without any family history for a psychiatric disease (HC). Moreover, those UHR with stronger fibre connections better managed incidences of adversity in early life without later developing depression, while in HC axonal connections were found to be decreased when they had early-life adversity. Altogether these findings indicate the presence of stronger neural fibre connections in UHR, which seem to be associated with resilience against environmental stressors, which we suggest occur through epigenetic mechanisms

Living in Limbo: Single Asset Reorganizations within the Financially Distressed Fifth Circuit.

Abstract Forthcoming

Recent Decisions

Comments on recent decisions by Arthur C. Callaghan, Thomas Meaney, Jr., Richard John Audino, Richard R. Murphy, Robert L. Berry, Joseph F. MacKrell, William J. Hurley, Wallace F. Neyerlin, Lawrence S. May, Jr., Richard F. Welter, Martin J. Rodgers, Anthony V. Amodio, and Robert F. McCoy

Side chain oxidized oxysterols in cerebrospinal fluid and the integrity of blood-brain and blood-cerebrospinal fluid barriers.

The side chain oxidized oxysterol 24S-hydroxycholesterol (24-OH-chol) is formed almost exclusively in the brain, and there is a continuous passage of this oxysterol through the circulation to the liver. 27-Hydroxycholesterol (27-OH-chol) is produced in most organs and is also taken up by the liver. The 27-OH-chol-24-OH-chol ratio is about 0.1 in the brain and about 2 in the circulation. This ratio was found to be about 0.4 in cerebrospinal fluid (CSF) of asymptomatic patients, consistent with a major contribution from the circulation in the case of 27-OH-chol. In accordance with this, we demonstrated a significant flux of deuterium labeled 27-OH-chol from plasma to the CSF in a healthy volunteer. Patients with a defective blood-brain barrier were found to have markedly increased absolute levels (up to 10-fold) of both 27-OH-chol and 24-OH-chol in CSF, with a ratio between the two sterols reaching up to 2. There was a significant positive correlation between the levels of both oxysterols in CSF and the albuminCSF-albuminplasma ratio. The 27-OH-cholCSF-24-OH-cholCSF ratio was found to be about normal in patients with active multiple sclerosis and significantly increased in patients with meningitis, polyneuropathy, or hemorrhages. Results are discussed in relation to the possible use of 24-OH-cholCSF as a surrogate marker of central nervous system demyelination and/or neuronal death

Implementation of a Data Management Quality Management Framework at the Marine Institute, Ireland

Peer reviewed Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.The International Oceanographic Data and Information Exchange of UNESCO’s Intergovernmental Oceanographic Commission (IOC-IODE) released a quality management framework for its National Oceanographic Data Centre (NODC) network in 2013. This document is intended, amongst other goals, to provide a means of assistance for NODCs to establish organisational data management quality management systems. The IOC-IODE’s framework also promotes the accreditation of NODCs which have implemented a Data Management Quality Management Framework adhering to the guidelines laid out in the IOC-IODE’s framework. In its submission for IOCE-IODE accreditation, Ireland’s National Marine Data Centre (hosted by the Marine Institute) included a Data Management Quality Management model; a manual detailing this model and how it is implemented across the scientific and environmental data producing areas of the Marine Institute; and, at a more practical level, an implementation pack consisting of a number of templates to assist in the compilation of the documentation required by the model and the manual.This work is part supported by the Irish Government and the European Maritime & Fisheries Fund as part of the EMFF Operational Programme for 2014-2020

Impaired reward processing in the human prefrontal cortex distinguishes between persistent and remittent attention deficit hyperactivity disorder

Symptoms of attention deficit hyperactivity disorder (ADHD) in children often persist into adulthood and can lead to severe antisocial behavior. However, to-date it remains unclear whether neuro-functional abnormalities cause ADHD, which in turn can then provide a marker of persistent ADHD. Using event-related functional magnetic resonance imaging (fMRI), we measured blood oxygenation level dependent (BOLD) signal changes in subjects during a reversal learning task in which choice of the correct stimulus led to a probabilistically determined ‘monetary’ reward or punishment. Participants were diagnosed with ADHD during their childhood (N = 32) and were paired with age, gender, and education matched healthy controls (N = 32). Reassessment of the ADHD group as adults resulted in a split between either persistent (persisters, N = 17) or remitted ADHDs (remitters, N = 15). All three groups showed significantly decreased activation in the medial prefrontal cortex (PFC) and the left striatum during punished correct responses, however only remitters and controls presented significant psycho-physiological interaction between these fronto-striatal reward and outcome valence networks. Comparing persisters to remitters and controls showed significantly inverted responses to punishment (P < 0.05, family-wise error corrected) in left PFC region. Interestingly, the decreased activation shown after punishment was located in different areas of the PFC for remitters compared with controls, suggesting that remitters might have learned compensation strategies to overcome their ADHD symptoms. Thus, fMRI helps understanding the neuro-functional basis of ADHD related behavior differences and differentiates between persistent and remittent ADHD

Cytoplasmic BK\u3csub\u3eCa\u3c/sub\u3e channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neurons

High single-channel conductance K+ channels, which respond jointly to membrane depolarization and micromolar concentrations of intracellular Ca2+ ions, arise from extensive cell-specific alternative splicing of pore-forming α-subunit mRNAs. Here, we report the discovery of an endogenous BKCa channel α-subunit intron-containing mRNA in the cytoplasm of hippocampal neurons. This partially processed mRNA, which comprises ≈10% of the total BKCa channel α-subunit mRNAs, is distributed in a gradient throughout the somatodendritic space. We selectively reduced endogenous cytoplasmic levels of this intron-containing transcript by RNA interference without altering levels of the mature splice forms of the BKCa channel mRNAs. In doing so, we could demonstrate that changes in a unique BKCa channel α-subunit introncontaining splice variant mRNA can greatly impact the distribution of the BKCa channel protein to dendritic spines and intrinsic firing properties of hippocampal neurons. These data suggest a new regulatory mechanism for modulating the membrane properties and ion channel gradients of hippocampal neurons

Childhood-Diagnosed ADHD, Symptom Progression, and Reversal Learning in Adulthood

Objective: ADHD persists in up to 60% into adulthood, and the reasons for persistence are not fully understood. The objective of this study was to characterize the neurofunctional basis of decision making in those with a childhood diagnosis of ADHD with either persistent or remitted symptoms in adulthood versus healthy control participants. Method: Thirty-two adults diagnosed with ADHD as children were split into persistent (n = 18) or remitted (n = 14) ADHD groups. Their neural activity and neurofunctional connectivity during a probabilistic reversal learning task were compared with 32 healthy controls. Results: Remitters showed significantly higher neural connectivity in final reversal error and probabilistic error conditions, and persisters depict higher neural connectivity in reversal errors than controls at a family-wise error (FWE) corrected whole-brain corrected threshold. Conclusion: Remitters may have utilized higher neural connectivity than controls to make successful decisions. Also, remitters may have utilized compensatory strategies to override any potential underlying ADHD deficits