298
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects

      research-article
      1 , 1 , 2 , 3 , 1 , 1 , 1 , 4 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 5 , 1 , 6 , 1 , 1 , 1 , 1 , 1 , 1 , 2 , 7 , 7 , 8 , 8 , 8 , 9 , 9 , 9 , 10 , 11 , 11 , 1 , 1 , 12 , 1 , 13 , 13 , 14 , 15 , 16 , 16 , 16 , 17 , 18 , 18 , 19 , 20 , 19 , 20 , 21 , 22 , 1 , 23 , 2 , 3 , 24 , 1 , 1 , 25 ,
      Molecular Psychiatry
      Nature Publishing Group UK
      Neuroscience, Addiction

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Mental disorders are highly comorbid and occur together with physical diseases, which are often considered to arise from separate pathogenic pathways. We observed in alcohol-dependent patients increased serum activity of neutral sphingomyelinase. A genetic association analysis in 456,693 volunteers found associations of haplotypes of SMPD3 coding for NSM-2 (NSM) with alcohol consumption, but also with affective state, and bone mineralisation. Functional analysis in mice showed that NSM controls alcohol consumption, affective behaviour, and their interaction by regulating hippocampal volume, cortical connectivity, and monoaminergic responses. Furthermore, NSM controlled bone–brain communication by enhancing osteocalcin signalling, which can independently supress alcohol consumption and reduce depressive behaviour. Altogether, we identified a single gene source for multiple pathways originating in the brain and bone, which interlink disorders of a mental–physical co-morbidity trias of alcohol abuse—depression/anxiety—bone disorder. Targeting NSM and osteocalcin signalling may, thus, provide a new systems approach in the treatment of a mental–physical co-morbidity trias.

          Related collections

          Most cited references79

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age

          Cathie Sudlow and colleagues describe the UK Biobank, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            The UK Biobank resource with deep phenotyping and genomic data

            The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              A rapid method of total lipid extraction and purification.

                Bookmark

                Author and article information

                Contributors
                Christian.Mueller@uk-erlangen.de
                Journal
                Mol Psychiatry
                Mol Psychiatry
                Molecular Psychiatry
                Nature Publishing Group UK (London )
                1359-4184
                1476-5578
                28 September 2021
                28 September 2021
                2021
                : 26
                : 12
                : 7403-7416
                Affiliations
                [1 ]GRID grid.5330.5, ISNI 0000 0001 2107 3311, Department of Psychiatry and Psychotherapy, University Clinic, , Friedrich-Alexander-University Erlangen-Nürnberg, ; Erlangen, Germany
                [2 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, The Centre for Population Neuroscience and Stratified Medicine (PONS), ISTBI, , Fudan University, ; Shanghai, China
                [3 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, PONS Centre and SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, , King’s College London, ; London, UK
                [4 ]GRID grid.9647.c, ISNI 0000 0004 7669 9786, Department for Anesthesiology and Intensive Care, Faculty of Medicine, , University of Leipzig, ; Leipzig, Germany
                [5 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Faculty of Medicine, , Ludwig-Maximilians-Universität München, ; Munich, Germany
                [6 ]GRID grid.5330.5, ISNI 0000 0001 2107 3311, Department of Psychosomatic Medicine and Psychotherapy, , Friedrich-Alexander-University of Erlangen-Nürnberg, ; Erlangen, Germany
                [7 ]GRID grid.7886.1, ISNI 0000 0001 0768 2743, School of Biomolecular and Biomedical Science, UCD Conway Institute, , University College Dublin, ; Dublin, Ireland
                [8 ]GRID grid.411327.2, ISNI 0000 0001 2176 9917, Center for Behavioral Neuroscience, Institute of Experimental Psychology, , University of Düsseldorf, ; Düsseldorf, Germany
                [9 ]GRID grid.413454.3, ISNI 0000 0001 1958 0162, Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, , Polish Academy of Sciences, ; Kraków, Poland
                [10 ]GRID grid.4563.4, ISNI 0000 0004 1936 8868, Division of Child Health, Obstetrics and Gynaecology, School of Medicine, , University of Nottingham, ; Nottingham, UK
                [11 ]GRID grid.5330.5, ISNI 0000 0001 2107 3311, Institute of Human Genetics, , Friedrich-Alexander-University of Erlangen-Nuremberg (FAU), ; Erlangen, Germany
                [12 ]GRID grid.5330.5, ISNI 0000 0001 2107 3311, Department of Biology, Animal Physiology, , Friedrich-Alexander-University of Erlangen-Nürnberg, ; Erlangen, Germany
                [13 ]GRID grid.7468.d, ISNI 0000 0001 2248 7639, Institute for Chemistry, , Humboldt University, ; Berlin, Germany
                [14 ]GRID grid.5330.5, ISNI 0000 0001 2107 3311, Department of Internal Medicine 3—Rheumatology and Immunology, , Friedrich-Alexander-University of Erlangen- Nürnberg, ; Erlangen, Germany
                [15 ]GRID grid.5330.5, ISNI 0000 0001 2107 3311, Deutsches Zentrum für Immuntherapie (DZI), , Friedrich-Alexander-University of Erlangen-Nuremberg (FAU), ; Erlangen, Germany
                [16 ]GRID grid.5330.5, ISNI 0000 0001 2107 3311, Department of Experimental and Clinical Pharmacology and Toxicology, Emil Fischer Center, , Friedrich-Alexander-University of Erlangen-Nuremberg (FAU), ; Erlangen, Germany
                [17 ]GRID grid.411668.c, ISNI 0000 0000 9935 6525, Preclinical Imaging Platform Erlangen, Institute of Radiology, , University Hospital Erlangen, ; Erlangen, Germany
                [18 ]GRID grid.465524.4, Centro Biologia Molecular Severo Ochoa (CSIC-UAM), ; Madrid, Spain
                [19 ]GRID grid.10328.38, ISNI 0000 0001 2159 175X, Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus Gualtar, , University of Minho, ; Braga, Portugal
                [20 ]GRID grid.10328.38, ISNI 0000 0001 2159 175X, ICVS/3B’s—PT Government Associate Laboratory, ; Braga/Guimarães, Portugal
                [21 ]GRID grid.5718.b, ISNI 0000 0001 2187 5445, Department of Molecular Biology, , University of Duisburg-Essen, ; Essen, Germany
                [22 ]GRID grid.24827.3b, ISNI 0000 0001 2179 9593, Department of Surgery, College of Medicine, , University of Cincinnati, ; Cincinnati, OH USA
                [23 ]GRID grid.7700.0, ISNI 0000 0001 2190 4373, Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (CIMH), Medical Faculty Mannheim, , Heidelberg University, ; Mannheim, Germany
                [24 ]GRID grid.6363.0, ISNI 0000 0001 2218 4662, PONS Centre, Charite Mental Health, Dept. of Psychiatry and Psychotherapie, CCM, , Charite Universitaetsmedizin Berlin, ; Berlin, Germany
                [25 ]GRID grid.11875.3a, ISNI 0000 0001 2294 3534, Centre for Drug Research, , Universiti Sains Malaysia, ; Minden, Penang Malaysia
                Author information
                http://orcid.org/0000-0001-7517-9154
                http://orcid.org/0000-0001-6657-5796
                http://orcid.org/0000-0002-5073-9693
                http://orcid.org/0000-0002-1307-408X
                http://orcid.org/0000-0002-5949-8355
                http://orcid.org/0000-0002-6646-6140
                http://orcid.org/0000-0002-1978-6301
                http://orcid.org/0000-0001-6099-7066
                http://orcid.org/0000-0002-1815-4409
                http://orcid.org/0000-0001-7613-9437
                http://orcid.org/0000-0001-8174-2118
                http://orcid.org/0000-0002-5679-6891
                http://orcid.org/0000-0001-6086-0924
                http://orcid.org/0000-0002-8096-3987
                http://orcid.org/0000-0002-5325-9900
                Article
                1304
                10.1038/s41380-021-01304-w
                8872992
                34584229
                4a74dc49-fa3c-40fa-9fca-a2a20ec228ab
                © The Author(s) 2021

                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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 7 July 2021
                : 6 September 2021
                : 9 September 2021
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft (German Research Foundation);
                Award ID: GRK2162/2
                Award ID: HU 306/27-3
                Award ID: GU 335/29-2
                Award ID: GU 335/29-3
                Award ID: KO 947/13-3
                Award ID: KO 947/15-2
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s), under exclusive licence to Springer Nature Limited 2021

                Molecular medicine
                neuroscience,addiction
                Molecular medicine
                neuroscience, addiction

                Comments

                Comment on this article