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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects
Molecular Psychiatry, Volume 26, No. 12, Year 2021
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Description
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. © 2021, The Author(s).
Authors & Co-Authors
Jia, Tianye
China, Shanghai
Fudan University
United Kingdom, London
King's College London
Rhein, Cosima
Germany, Erlangen
Friedrich-alexander-universität Erlangen-nürnberg
Abdel-Hafiz, Laila
Germany, Dusseldorf
Heinrich-heine-universität Düsseldorf
Lourdusamy, Anbarasu
United Kingdom, Nottingham
University of Nottingham
Ekici, Arif Bülent
Germany, Erlangen
Friedrich-alexander-universität Erlangen-nürnberg
M Saied, Essa M.
Germany, Berlin
Humboldt-universität zu Berlin
Arenz, Christoph
Germany, Berlin
Humboldt-universität zu Berlin
Bozec, Aline
Germany, Erlangen
Friedrich-alexander-universität Erlangen-nürnberg
Heß, Andreas
Germany, Erlangen
Friedrich-alexander-universität Erlangen-nürnberg
Bäuerle, Tobias J.
Germany, Erlangen
Universitätsklinikum Erlangen
Gulbins, Erich
Germany, Duisburg
Universität Duisburg-essen
United States, Cincinnati
University of Cincinnati
Schumann, Gunter
China, Shanghai
Fudan University
United Kingdom, London
King's College London
Germany, Berlin
Charité – Universitätsmedizin Berlin
Kornhuber, Johannes
Germany, Erlangen
Friedrich-alexander-universität Erlangen-nürnberg
Müller, Christian P.
Germany, Erlangen
Friedrich-alexander-universität Erlangen-nürnberg
Malaysia, Minden
Universiti Sains Malaysia
Statistics
Citations: 22
Authors: 14
Affiliations: 18
Identifiers
Doi:
10.1038/s41380-021-01304-w
ISSN:
13594184
Research Areas
Genetics And Genomics
Mental Health
Substance Abuse