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

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

Routledge International Handbook of Memory Studies

The field of Memory Studies continually refocuses and reinvents itself, searching for moments, events, and places in an effort to locate the multitude of ways that memory makes it way into lives, or in fact is life (see Del Giudice et al; Ventura; McCraty). At times overtly political and public, at other times, subtle and ephemeral, Memory Studies since the 1980s has gained an increasing amount of attention from scholars in widely varying disciplines and perspectives (Mendels 2007; Radstone and Schwartz 2010; Olick et al. 2011; Kattago 2015). As a consequence of this creative and intensive development, Memory Studies now represents a well-established field of research (Tulving and Craik 2005; Erll and Nunning 2010). However, this creative variety of perspectives has implied, to some extent, a theoretical isolationism, most often underpinned by disciplinary conventions. Even though Memory Studies has been investigated from different disciplinary homes (Rubin 1996; Climo and Cattell 2002; Dunlosky and Bjork 2008), there is often little exchange or collaboration between the different perspectives. Therefore, it is regularly the case that, for example, well-known phenomena in the field of neurophysiology are still ignored by social scientists working on the same topic and vice versa. Such theoretical isolationism within the field also derives from the variety of national contexts in which Memory Studies has emerged. Approaches to Memory Studies vary from country to country both in regards to their historical development, empirical focus and conceptual framework (Van Dyke and Alcock 2003; see Olick; Hutton; Inglis). In this respect the Handbook attempts to explore the dynamic tension between, for example, national memories, diasporas, and migrations while pointing toward research in transnational memory production (see Güran-Aydin with DeNora; Hagen). The implied idea is that the analytical framework that has emerged in different nations for the study of memories derives and is shaped by pasts in that particular nation. These memories are ultimately elaborated and inscribed in the national public discourse and drive the “methodological nationalism” present in much empirical work on memory (de Cesari and Ann Rigney 2014)

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

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