Reduced social investigation and increased injurious behavior in transgenic 5xFAD mice.

Social withdrawal and agitation/aggression are common behavioral and psychological symptoms of dementia presented by Alzheimer's disease (AD) patients, with males exhibiting more aggressive behaviors than females. Some transgenic mouse models of AD also exhibit social withdrawal and aggression, but many of these models only recapitulate the early stages of the disease. By comparison, the 5xFAD mouse model of AD exhibits rapid, progressive neurodegeneration, and is suitable for modeling cognitive and behavioral deficits at early, mid-, and late-stage disease progression. Anecdotal reports suggest that transgenic 5xFAD males exhibit high levels of aggression compared to wild-type controls, but to date, indirect genetic effects in this strain have not been studied. We measured home-cage behaviors in 5xFAD males housed in three different group-housing conditions (transgenic-only, wild-type only, and mixed-genotype) and social approach behaviors when exposed to a novel free-roaming or restrained, wild-type or transgenic conspecific. Transgenic-only home cages required earlier separation due to injuries arising from aggression compared to wild-type-only or mixed-genotype cages, despite no obvious increase in the frequency of aggressive behaviors. Transgenic 5xFAD males and females also spent less time investigating free-roaming conspecifics compared to wild-type controls, but they showed normal investigation of restrained conspecifics; the genotype of the conspecific did not affect approach behavior, and there was no aggression observed in transgenic males. These findings provide evidence in an animal model that amyloid pathology ultimately leads to avoidance of novel social stimuli, and that frequent interactions between individuals exhibiting an AD phenotype further exacerbates aggressive behaviors.

Dual users' perceptions of the addictive properties of cigarettes versus E-cigarettes.

INTRODUCTION: Electronic cigarettes ("e-cigarettes") are commonly promoted as a less-harmful alternative to combustible cigarettes, yet many individuals concurrently use both products ("dual users"). Little is known about the extent to which dual users' perceptions of the addictive properties of these products differ, or to what extent there are differences in the factors that elicit craving for each product. METHODS: An online survey evaluated beliefs about the addictive properties of cigarettes vs e-cigarettes and the situational and affective precipitants of product craving, on a scale from 1 to 10, in a sample of Canadian adults that reported past-month use of combustible and e-cigarettes (N = 175; 79 female). RESULTS: Participants rated cigarettes as more addictive than e-cigarettes, and on average reported higher levels of dependence on combustible cigarettes. While the addictive properties of both combustible and e-cigarettes were largely attributed to nicotine, non-nicotine factors (e.g. flavouring, other non-nicotine ingredients) were believed to make a relatively stronger contribution to the addictive properties of e-cigarettes, particularly among women. Participants reported greater increases in craving for combustible cigarettes in response to negative affective states and situational factors, and these effects were strongest among participants that displayed greater dependence on combustible tobacco relative to e-cigarettes. CONCLUSIONS: Dual users perceived cigarettes to be more addictive than e-cigarettes and attributed the addictive properties of each product to different factors. Further, cravings for combustible cigarettes were more strongly linked to certain negative affective states and situational factors relative to e-cigarettes. Findings suggest that there may be limited substitutability between combustible and e-cigarettes.

Mental health and psychosocial support in humanitarian settings: research priorities for 2021-30.

We describe an effort to develop a consensus-based research agenda for mental health and psychosocial support (MHPSS) interventions in humanitarian settings for 2021-30. By engaging a broad group of stakeholders, we generated research questions through a qualitative study (in Indonesia, Lebanon, and Uganda; n=101), consultations led by humanitarian agencies (n=259), and an expert panel (n=227; 51% female participants and 49% male participants; 84% of participants based in low-income and middle-income countries). The expert panel selected and rated a final list of 20 research questions. After rating, the MHPSS research agenda favoured applied research questions (eg, regarding workforce strengthening and monitoring and evaluation practices). Compared with research priorities for the previous decade, there is a shift towards systems-oriented implementation research (eg, multisectoral integration and ensuring sustainability) rather than efficacy research. Answering these research questions selected and rated by the expert panel will require improved partnerships between researchers, practitioners, policy makers, and communities affected by humanitarian crises, and improved equity in funding for MHPSS research in low-income and middle-income countries.