Diet Prevents Social Stress-Induced Maladaptive Neurobehavioural and Gut Microbiota Changes in a Histamine-Dependent Manner

Exposure to repeated social stress may cause maladaptive emotional reactions that can be reduced by healthy nutritional supplementation. Histaminergic neurotransmission has a central role in orchestrating specific behavioural responses depending on the homeostatic state of a subject, but it remains to be established if it participates in the protective effects against the insults of chronic stress afforded by a healthy diet. By using C57BL/6J male mice that do not synthesize histamine (Hdc−/−) and their wild type (Hdc+/+) congeners we evaluated if the histaminergic system participates in the protective action of a diet enriched with polyunsaturated fatty acids and vitamin A on the deleterious effect of chronic stress. Behavioural tests across domains relevant to cognition and anxiety were performed. Hippocampal synaptic plasticity, cytokine expression, hippocampal fatty acids, oxylipins and microbiota composition were also assessed. Chronic stress induced social avoidance, poor recognition memory, affected hippocampal long-term potentiation, changed the microbiota profile, brain cytokines, fatty acid and oxylipins composition of both Hdc−/−and Hdc+/+ mice. Dietary enrichment counteracted stress-induced deficits only in Hdc+/+ mice as histamine deficiency prevented almost all of the diet-related beneficial effects. Interpretation: Our results reveal a previously unexplored and novel role for brain histamine as a mediator of many favorable effects of the enriched diet. These data present long-reaching perspectives in the field of nutritional neuropsychopharmacology.

Reality in a sphere: A direct comparison of social attention in the laboratory and the real world

Humans often show reduced social attention in real situations, a finding rarely replicated in controlled laboratory studies. Virtual reality is supposed to allow for ecologically valid and at the same time highly controlled experiments. This study aimed to provide initial insights into the reliability and validity of using spherical videos viewed via a head-mounted display (HMD) to assess social attention. We chose five public places in the city of Würzburg and measured eye movements of 44 participants for 30 s at each location twice: Once in a real environment with mobile eye-tracking glasses and once in a virtual environment playing a spherical video of the location in an HMD with an integrated eye tracker. As hypothesized, participants demonstrated reduced social attention with less exploration of passengers in the real environment as compared to the virtual one. This is in line with earlier studies showing social avoidance in interactive situations. Furthermore, we only observed consistent gaze proportions on passengers across locations in virtual environments. These findings highlight that the potential for social interactions and an adherence to social norms are essential modulators of viewing behavior in social situations and cannot be easily simulated in laboratory contexts. However, spherical videos might be helpful for supplementing the range of methods in social cognition research and other fields. Data and analysis scripts are available at https://osf.io/hktdu/.

Characterizing the Behavioral and Neuroendocrine Features of Susceptibility and Resilience to Social Stress

Evaluating and coping with stressful social events as they unfold is a critical strategy in overcoming them without long-lasting detrimental effects. Individuals display a wide range of responses to stress, which can manifest in a variety of outcomes for the brain as well as subsequent behavior. Chronic Social Defeat Stress (CSDS) in mice has been widely used to model individual variation following a social stressor. Following a course of repeated intermittent psychological and physical stress, mice diverge into separate populations of social reactivity: resilient (socially interactive) and susceptible (socially avoidant) animals. A rich body of work reveals distinct neurobiological and behavioral consequences of this experience that map onto the resilient and susceptible groups. However, the range of factors that emerge over the course of defeat have not been fully described. Therefore, in the current study, we focused on characterizing behavioral, physiological, and neuroendocrine profiles of mice in three separate phases: before, during, and following CSDS. We found that following CSDS, traditional read-outs of anxiety-like and depression-like behaviors do not map on to the resilient and susceptible groups. By contrast, behavioral coping strategies used during the initial social stress encounter better predict which mice will eventually become resilient or susceptible. In particular, mice that will emerge as susceptible display greater escape behavior on Day 1 of social defeat than those that will emerge as resilient, indicating early differences in coping mechanisms used between the two groups. We further show that the social avoidance phenotype in susceptible mice is specific to the aggressor strain and does not generalize to conspecifics or other strains, indicating that there may be features of threat discrimination that are specific to the susceptible mice. Our findings suggest that there are costs and benefits to both the resilient and susceptible outcomes, reflected in their ability to cope and adapt to the social stressor.

The Impact of the COVID-19 Pandemic on Chinese Postgraduate Students’ Mental Health

To understand the mental health status of Chinese postgraduate students during the COVID-19 pandemic, we used three online questionnaires: self-rating anxiety (SAS) scale, self-rating depression (SDS) scale, and social avoidance and distress (SAD) scale. A total of 3137 postgraduate students from different regions of China participated in our study. We explored the relationship between participant characteristics and mental health using an analysis of variance (ANOVA). We found that the proportions of respondents with severe, mild, and moderate depression were 1.4%, 10.48%, and 21.99%, respectively, and the corresponding proportions of respondents with anxiety were 1.56%, 4.65%, and 14.69%, respectively. A one-way ANOVA revealed that the mental health statuses of the participants were different between the subgroups based on majors, classes, degree types, and the method of communication with advisors and students. A two-way ANOVA revealed significant effects on interaction and the method of communication with advisors and peers. These findings suggest that the mental health of postgraduate students should be monitored during the pandemic, especially when they are unable to communicate directly with their advisors or peers, and targeted psychological counselling must be focused on anxiety and depression.

Prefrontal-amygdalar oscillations related to social interaction behavior in mice

The medial prefrontal cortex and amygdala are involved in the regulation of social behavior and associated with psychiatric diseases but their detailed neurophysiological mechanisms at a network level remain unclear. We recorded local field potentials (LFPs) from the dorsal medial PFC (dmPFC) and basolateral amygdala (BLA) while mice engaged on social behavior. We found that in wild-type mice, both the dmPFC and BLA increased 4–7 Hz oscillation power and decreased 30–60 Hz power when they needed to attend to another target mouse. In mouse models with reduced social interactions, dmPFC 4–7 Hz power further increased especially when they exhibited social avoidance behavior. In contrast, dmPFC and BLA decreased 4–7 Hz power when wild-type mice socially approached a target mouse. Frequency-specific optogenetic manipulations of replicating social approach-related LFP patterns restored social interaction behavior in socially deficient mice. These results demonstrate a neurophysiological substrate of the prefrontal cortex and amygdala related to social behavior and provide a unified pathophysiological understanding of neuronal population dynamics underlying social behavioral deficits.