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.

Alcohol use, abuse, and addiction, and resulting health hazards are highly sex-dependent with unknown mechanisms. Previously, strong links between the SMPD3 gene and its coded protein neutral sphingomyelinase 2 (NSM) and alcohol abuse, emotional behavior, and bone defects were discovered and multiple mechanisms were identified for females. Here we report strong sex-dimorphisms for central, but not for peripheral mechanisms of NSM action in mouse models. Reduced NSM activity resulted in enhanced alcohol consumption in males, but delayed conditioned rewarding effects. It enhanced the acute dopamine response to alcohol, but decreased monoaminergic systems adaptations to chronic alcohol. Reduced NSM activity increased depression- and anxiety-like behavior, but was not involved in alcohol use for the self-management of the emotional state. Constitutively reduced NSM activity impaired structural development in the brain and enhanced lipidomic sensitivity to chronic alcohol. While the central effects were mostly opposite to NSM function in females, similar roles in bone-mediated osteocalcin release and its effects on alcohol drinking and emotional behavior were observed. These findings support the view that the NSM and multiple downstream mechanism may be a source of the sex-differences in alcohol use and emotional behavior.

The synthesis and characterization of an ovel DNA-encodedl ibraryo fm acrocyclic peptided erivatives are described;t he macrocyclesa re based on three sets of proteinogenic and non-proteinogenic amino acid building blocks and featuring the use of copper(I)-catalyzeda lkyneazide cycloaddition (CuAAC) reactionf or ring closure. The library (termedY O-DEL) whichc ontains1254 838 compounds, was encoded with DNA in single-stranded format andw as screened against target proteins of interest using affinity capturep rocedures and photocrosslinking. YO-DEL selections yieldeds pecific binders against serum albumins, carbonic anhydrases and NKp46, am arker of activated Natural Killer cells.

Zusammenfassung. Emotionsregulation ist eines der zentralen Themen der Entwicklungspsychopathologie. Der überwiegende Anteil an Forschungsarbeiten widmet sich der Frage zur Entwicklung von Emotionsregulation, welche als zentrale Entwicklungsaufgabe im Kindesalter erachtet wird. Die Herausbildung einer altersangemessenen Emotionsregulation besitzt eine entscheidende Bedeutung für die psychische Gesundheit und dem späteren Schulerfolg eines Kindes. Obwohl die elterliche Emotionsregulation als ein zentraler Aspekt des Erziehungsverhaltens verstanden wird, ist noch immer nicht hinreichend geklärt, wie Eltern ihre eigenen Gefühle im Erziehungskontext regulieren. Dieser Beitrag bietet einen Überblick zum aktuellen Forschungsstand zu den Auswirkungen einer elterlichen Emotions(dys)regulation auf familiäre Prozesse der kindlichen Emotionsregulation und den Entwicklungsergebnissen des Kindes. Empfehlungen für die klinische Praxis werden diskutiert.

!In recent decades, the understanding of the short and longer term effects of health-damaging behaviors and mental health problems in pregnant women and the underlying mechanisms of these behaviors and illnesses has significantly increased. In contrast, little is known about the factors affecting individual pregnant women which contribute to health-damaging behaviors and mental illness. The aim of this paper was therefore to summarize the current state of research into the consequences of nicotine and alcohol consumption, malnutrition, excessive weight gain or obesity, and impaired mental health (depression and anxiety) during pregnancy. In addition, the characteristics of pregnant women which increase their risk of developing such behaviors or mental disorders are described. A better knowledge of these risks should make it easier for clinicians to identify cases at risk early on and put measures of support in place. A review of the literature has shown that certain characteristics of pregnant women (e.g. her relationship with her partner, a previous history of mental illness prior to pregnancy) are associated with various healthdamaging behaviors as well as with impaired mental health. Affected women often show an accumulated psychosocial stress which was already present prior to the pregnancy and which may persist even after the birth of the child. Zusammenfassung Consequences and Possible Predictors of Health-damaging Behaviors and Mental Health Problems in Pregnancy -A ReviewAuswirkungen und mögliche Prädiktoren gesundheitsschädigender Verhaltensweisen und psychischer Beeinträchtigungen in der Schwangerschaft -ein Überblick