Anterior cingulate cortex orexin signaling mediates early-life stress-induced social impairment in females.

Early-life stress has long-term impacts on the structure and function of the anterior cingulate cortex (ACC), and raises the risk of adult neuropsychiatric disorders including social dysfunction. The underlying neural mechanisms, however, are still uncertain. Here, we show that, in female mice, maternal separation (MS) during the first three postnatal weeks results in social impairment accompanied with hypoactivity in pyramidal neurons (PNs) of the ACC. Activation of ACC PNs ameliorates MS-induced social impairment. Neuropeptide Hcrt, which encodes hypocretin (orexin), is the top down-regulated gene in the ACC of MS females. Activating ACC orexin terminals enhances the activity of ACC PNs and rescues the diminished sociability observed in MS females via an orexin receptor 2 (OxR2)-dependent mechanism. Our results suggest orexin signaling in the ACC is critical in mediating early-life stress-induced social impairment in females.

Canine hyper-sociability structural variants associated with altered three-dimensional chromatin state.

Strong selection on complex traits can lead to skewed trait means and reduced trait variability in populations. An example of this phenomenon can be evidenced in allele frequency changes and skewed trait distributions driven by persistent human-directed selective pressures in domesticated species. Dog domestication is linked to several genomic variants; however, the functional impacts of these variants may not always be straightforward when found in non-coding regions of the genome. Four polymorphic transposable elements (TE) found within non-coding sites along a 5 Mb region on canine CFA6 have evolved due to directional selection associated with heightened human-directed hyper-sociability in domesticated dogs. We found that the polymorphic TE in intron 17 of the canine GTF2I gene, which was previously reported to be negatively correlated with canid human-directed hyper-sociability, is associated with altered chromatin looping and hence distinct cis-regulatory landscapes. We reported supporting evidence of an E2F1-DNA binding peak concordant with the altered loop and higher expression of GTF2I exon 18, indicative of alternative splicing. Globally, we discovered differences in pathways regulating the extra-cellular matrix with respect to TE copy number. Overall, we reported evidence suggesting an intriguing molecular convergence between the emergence of hypersocial behaviors in dogs and the same genes that, when hemizygous, produce human Williams Beuren Syndrome characterized by cranio-facial defects and heightened social behaviors. Our results additionally emphasize the often-overlooked potential role of chromatin architecture in social evolution.

Maternal selenium dietary supplementation alters sociability and reinforcement learning deficits induced by in utero exposure to maternal immune activation in mice.

Maternal immune activation (MIA) during pregnancy increases the risk for the unborn foetus to develop neurodevelopmental conditions such as autism spectrum disorder and schizophrenia later in life. MIA mouse models recapitulate behavioural and biological phenotypes relevant to both conditions, and are valuable models to test novel treatment approaches. Selenium (Se) has potent anti-inflammatory properties suggesting it may be an effective prophylactic treatment against MIA. The aim of this study was to determine if Se supplementation during pregnancy can prevent adverse effects of MIA on offspring brain and behaviour in a mouse model. Selenium was administered via drinking water (1.5 ppm) to pregnant dams from gestational day (GD) 9 to birth, and MIA was induced at GD17 using polyinosinic:polycytidylic acid (poly-I:C, 20 mg/kg via intraperitoneal injection). Foetal placenta and brain cytokine levels were assessed using a Luminex assay and brain elemental nutrients assessed using inductively coupled plasma- mass spectrometry. Adult offspring were behaviourally assessed using a reinforcement learning paradigm, the three-chamber sociability test and the open field test. MIA elevated placental IL-1ß and IL-17, and Se supplementation successfully prevented this elevation. MIA caused an increase in foetal brain calcium, which was prevented by Se supplement. MIA caused in offspring a female-specific reduction in sociability, which was recovered by Se, and a male-specific reduction in social memory, which was not recovered by Se. Exposure to poly-I:C or selenium, but not both, reduced performance in the reinforcement learning task. Computational modelling indicated that this was predominantly due to increased exploratory behaviour, rather than reduced rate of learning the location of the food reward. This study demonstrates that while Se may be beneficial in ameliorating sociability deficits caused by MIA, it may have negative effects in other behavioural domains. Caution in the use of Se supplementation during pregnancy is therefore warranted.

Early social isolation disrupts adult personality expression in group-living mites.

Animal personalities are characterized by intra-individual consistency and consistent inter-individual variability in behaviour across time and contexts. Personalities abound in animals, ranging from sea anemones to insects, arachnids, birds, fish and primates, yet the pathways mediating personality formation and expression remain elusive. Social conditions during the early postnatal period are known determinants of mean behavioural trait expressions later in life, but their relevance in shaping personality trajectories is unknown. Here, we investigated the consequences of early social isolation on adult personality expression in plant-inhabiting predatory mites Phytoseiulus persimilis. These mites are adapted to live in groups. We hypothesized that transient experience of social isolation early in life, that is, deprivation of any social contact during a sensitive window in the post-hatching phase, has enduring adverse effects on adult personality expression. Newly hatched mites were transiently reared in isolation or in groups and tested as adults for repeatability of various within-group behaviours, such as movement patterns and mutual interactions including sociability, defined as the propensity to associate and interact benignly with conspecifics, and activity patterns when alone. Groups composed of individuals with the same or different early-life experiences were repeatedly videotaped and individual behaviours were automatically analysed using AnimalTA. Social experiences early in life had persistent effects on mean behavioural traits as well as adult personality expression, as measured by intraclass correlation coefficients (indicating repeatability). On average, isolation-reared females moved at higher speeds, meandered less, kept greater distances from others and had fewer immediate neighbours than group-reared females. Group-reared females were highly repeatable in inter-individual distance, moving speed, meandering and area explored, whereas isolation-reared females were repeatable only in the number of immediate neighbours. Activity, quantified as the proportion of time spent moving within groups, was only repeatable in group-reared females, whereas activity, quantified as the proportion of time spent moving when alone, was only repeatable in females reared in isolation. Strikingly, also the early-life experiences of male mates influenced personality expression of mated females, with isolation-reared males boosting the repeatability of behavioural traits of group-reared females. Overall, our study provides evidence that a transient phase of social isolation during a critical period early in life has lasting effects that extend into adulthood, impairing adult personality expression. These effects should cascade upward, changing the phenotypic composition and diversity within populations.

Sociability Alcohol Expectancies Shape Predictions of Drinking Behavior and Anxiety in a Novel Affective Forecasting Task.

Background: Existing work proposes that people with higher social anxiety symptoms and sociability alcohol expectancies believe alcohol can lower their anxiety. However, studies have primarily analyzed retrospective reports, not anticipatory motives. Since predictions of future emotion (i.e., affective forecasts) strongly influence behavior, it is critical to understand how people predict alcohol will influence their anxiety. Additionally, intolerance of uncertainty (IU) is related to the use of alcohol as a coping tool, but there is a dearth of work testing whether IU influences alcohol-related forecasts. Objectives: Utilizing a novel affective forecasting task, we tested the prediction that social anxiety symptoms, sociability alcohol expectancies, and IU would relate to predictions about alcohol use. In an initial study and preregistered replication, participants imagined themselves in stressful social scenarios and forecasted how anxious they would feel when drinking and when sober. In the replication, participants also forecasted whether they would drink in the imagined scenarios. Results: Contrary to hypotheses, social anxiety symptoms and IU did not significantly predict higher forecasted anxiety across studies, nor did they predict forecasted drinking. Exploratory analyses showed that participants with higher sociability alcohol expectancies forecasted being more likely to drink, and forecasted feeling less anxious when drinking (versus being sober). Even after statistically controlling for social anxiety, the effect of sociability expectancies remained significant in predicting forecasted anxiety and forecasted drinking. Conclusions: Clinicians could consider specifically targeting sociability expectancies for alcohol use difficulties, and future research should continue utilizing affective forecasting paradigms to test links between social anxiety, alcohol expectancies, and alcohol-use problems.

Longitudinal Changes in Psychosocial Adjustment Before and During the COVID-19 Pandemic for Adolescents with Differential Patterns of Solitude and Sociability.

Previous research has lacked a comprehensive, longitudinal analysis of characteristics of solitude and sociability, and how they are associated with changes in psychosocial adjustment before and during the pandemic. The current study surveyed 1071 adolescents (Mage = 10.6, SD = 1.69, 49.86% female, age range = 8-14 years at Year 1) over six years (three years before pandemic, three years during pandemic). Piecewise linear mixed-effects analysis showed that adolescents with higher solitude and lower sociability reported improvements in adjustment during the pandemic, whereas adolescents with lower solitude and higher sociability reported declines in adjustment. The findings highlight the importance of considering multiple characteristics of solitude and sociability, as well as contextual factors (e.g., pandemic), to better understand the implications of solitude on adolescent adjustment.

Sociability across Eastern-Western cultures: Is it the same underlying construct?

In this study, we examined cross-cultural differences in sociability, a core personality facet of the higher order extraversion trait, which has been reported at lower levels in Eastern versus Western cultures several decades ago. Up until now, however, East-West cultural comparisons on the Western-defined construct of sociability have been limited, despite the extensive research published on extraversion indicating that this personality dimension is globally relevant across cultures. Following current practices, we first assessed for measurement invariance (MI) on the Cheek and Buss sociability scale between Chinese (n = 816, 47.2% male, M = 18.51 years, SD = 1.26 years) and Canadian (n = 995, 30.8% male, M = 19.62 years, SD = 1.25 years) young adult samples to ensure any comparisons would be valid and meaningful. Results from a multigroup confirmatory factor analysis (exact invariance) showed that there was measurement non-invariance at the scalar level in the sociability construct across country and country by sex, and the newer alignment method (approximate invariance) confirmed these results, suggesting that mean level comparisons of sociability were biased and noninformative. Our findings indicated that although a few of the higher-level personality dimensions such as extraversion are considered universal, the facets underlying their meaning, like sociability, are not as clearly delineated between cultures. Alongside the present-day pursuit of understanding personality across cultures through an indigenous measurement lens in tandem with the notion of universality, researchers should also consider narrowing their focus onto lower-level facets, each of which is likely to be uniquely embedded into a cultural context.

Technical profiles of child sexual exploitation material offenders.

The idiographic technical profiles of child sexual exploitation material (CSEM) offenders provide insight into their behaviours and context for their interactions with technology, but minimal quantitative work has been done to evaluate their sociability, technical ability and technophilia compared to non-offenders. This work used an online survey to compare an offender group consisting of English-speaking adults previously convicted of CSEM offenses (N = 78) with a reference population of non-offenders (N = 254). The survey assessed sociability, technical ability and technophilia through self-rating and information on occupation, level of education and device ownership. The study found that CSEM offenders had slightly lower sociability than non-offenders, though not at a level of clinical interest. Additionally, CSEM offenders had no statistically significant difference in technical ability and lower overall technophilia when compared to non-offenders. This study fails to support popular perceptions of CSEM offenders being technically savvy loners who are early adopters of new technologies.

Polygenic risk for schizophrenia predicting social trajectories in a general population sample.

BACKGROUND: We investigated (a) whether polygenic risk for schizophrenia predicts different trajectories of social development among those who have not developed psychoses and (b) whether possible associations are PRSSCZ-specific or evident also for any polygenic risk for mental disorders, e.g. for major depression. METHODS: Participants came from the population-based Young Finns Study (n = 2377). We calculated a polygenic risk score for schizophrenia (PRSSCZ) and for major depression (PRSDEP). Diagnoses of psychotic disorders were derived from the hospital care register. Social development from adolescence to middle age was measured by (a) perceived social support from friends, family, and a close other, (b) perceived sociability, and (c) family structure (partnership status, number of children, age of first-time parenthood). RESULTS: Among those without manifest psychoses, high PRSSCZ predicted lower experienced support from friends (B = -0.04, p = 0.009-0.035) and family (B = -0.04, p = 0.009-0.035) especially after early adulthood, and also lower perceived sociability (B = -0.05, p = 0.010-0.026). PRSSCZ was not related to family structure. PRSDEP did not predict any domain of social development. CONCLUSIONS: Individuals at high PRSSCZ (not converted to psychosis) seem to experience a lower preference to be with others over being alone. Individuals with high (v. low) PRSSCZ seem to have a similar family structure in terms of partnership status or number of children but, nevertheless, they experience less support from their family. Among those not converted to psychosis in a typical age period, high PRSSCZ may predict a 'later risk phase' and reduced functional resilience when approaching middle age.

Direct and indirect phenotypic effects on sociability indicate potential to evolve.

The decision to leave or join a group is important as group size influences many aspects of organisms' lives and their fitness. This tendency to socialise with others, sociability, should be influenced by genes carried by focal individuals (direct genetic effects) and by genes in partner individuals (indirect genetic effects), indicating the trait's evolution could be slower or faster than expected. However, estimating these genetic parameters is difficult. Here, in a laboratory population of the cockroach Blaptica dubia, I estimate phenotypic parameters for sociability: repeatability (R) and repeatable influence (RI), that indicate whether direct and indirect genetic effects respectively are likely. I also estimate the interaction coefficient (Ψ), which quantifies how strongly a partner's trait influences the phenotype of the focal individual and is key in models for the evolution of interacting phenotypes. Focal individuals were somewhat repeatable for sociability across a 3-week period (R = 0.080), and partners also had marginally consistent effects on focal sociability (RI = 0.053). The interaction coefficient was non-zero, although in opposite sign for the sexes; males preferred to associate with larger individuals (Ψmale  = -0.129), while females preferred to associate with smaller individuals (Ψfemale  = 0.071). Individual sociability was consistent between dyadic trials and in social networks of groups. These results provide phenotypic evidence that direct and indirect genetic effects have limited influence on sociability, with perhaps most evolutionary potential stemming from heritable effects of the body mass of partners. Sex-specific interaction coefficients may produce sexual conflict and the evolution of sexual dimorphism in social behaviour.

Cross species review of the physiological role of D-serine in translationally relevant behaviors.

Bridging the gap between preclinical models of neurological and psychiatric disorders with their human manifestations is necessary to understand their underlying mechanisms, identify biomarkers, and develop novel therapeutics. Cognitive and social impairments underlie multiple neuropsychiatric and neurological disorders and are often comorbid with sleep disturbances, which can exacerbate poor outcomes. Importantly, many symptoms are conserved between vertebrates and invertebrates, although they may have subtle differences. Therefore, it is essential to determine the molecular mechanisms underlying these behaviors across different species and their translatability to humans. Genome-wide association studies have indicated an association between glutamatergic gene variants and both the risk and frequency of psychiatric disorders such as schizophrenia, bipolar disorder, and autism spectrum disorder. For example, changes in glutamatergic neurotransmission, such as glutamate receptor subtype N-methyl-D-aspartate receptor (NMDAR) hypofunction, have been shown to contribute to the pathophysiology of schizophrenia. Furthermore, in neurological disorders, such as traumatic brain injury and Alzheimer's disease, hyperactivation of NMDARs leads to synaptic damage. In addition to glutamate binding, NMDARs require the binding of a co-agonist D-serine or glycine to the GluN1 subunit to open. D-serine, which is racemized from L-serine by the neuronal enzyme serine racemase (SRR), and both SRR and D-serine are enriched in cortico-limbic brain regions. D-serine is critical for complex behaviors, such as cognition and social behavior, where dysregulation of its synthesis and release has been implicated in many pathological conditions. In this review, we explore the role of D-serine in behaviors that are translationally relevant to multiple psychiatric and neurological disorders in different models across species.

Socially active neighborhoods: construct operationalization for aging in place, health promotion and psychometric testing.

From the year 2003 when the first walkability scale was published to date, person-environment fit models and empirical research, some of which was published in Health Promotion International, have encapsulated healthy communities in 'neighborhood walkability'. While there is no doubt that neighborhood walkability positively influences health-seeking behaviors and health, recent models suggest that their measurement and conceptualization have not emphasized the role played by psychosocial and personal factors in aging in place. Thus, the development of scales measuring human ecosystem factors has not recognized all critical factors suited for older adults. In this paper, we aim to draw on relevant literature to frame a more holistic construct, hereby referred to as Socially Active Neighborhoods (SAN), that would better support aging in place in older populations. Through a narrative review based on a systematic search of the literature, we define the scope of SAN and delineate some contextual implications for gerontology, health promotion and psychometric testing. SAN, unlike neighborhood walkability in its current measurement and conceptualization, incorporates critical theory-informed psychosocial factors (i.e. safety and disability friendliness of neighborhood infrastructure) that can encourage older adults with physiological and cognitive limitations to maintain physical and social activities as well as health in later life. The SAN is the result of our adaptation of key person-environment models, including the Context Dynamics in Aging (CODA) framework, that recognizes the role of context in healthy aging.

Does sexuality matter? A cross-sectional study of drug use, social injecting, and access to injection-specific care among men who inject drugs in Melbourne, Australia.

BACKGROUND: Gay, bisexual and other men who have sex with men (GBMSM) are overrepresented in cohorts of people who inject drugs. GBMSM's substance use is usually explored in the context of its contribution to sexual risk. We examined drug use practices, connectedness to other people who inject drugs, peer-to-peer injecting, and access to care among men who inject drugs in Melbourne, Australia. We aim to describe similarities and differences in these parameters for GBMSM and other men. METHODS: Data were drawn from a prospective cohort study of people who inject drugs conducted in Melbourne, Australia, since 2009. This cross-sectional study used data collected between 2016 and 2021. Descriptive statistics were used to assess differences between GBMSM and other men. RESULTS: Of 525 men who injected drugs over the study period, 48 (9%) identified as gay or bisexual, or reported sex with other men in the past 12 months. GBMSM and other men reported similar socio-demographics, drug practices (age of injecting initiation, most injected drug, peer-to-peer injecting, receptive syringe sharing) and access to injecting-specific care (drug treatment, source of needle-syringes). A significantly greater percentage of GBMSM reported past 12-month hepatitis C testing (69% vs. 52%, p = 0.028) and preferring methamphetamine (31% vs. 16%, p = 0.022). A higher percentage of GBMSM reported knowing > 50 other people who inject drugs (46% vs. 37%), but this difference was not statistically significant. Both groups primarily obtained injecting equipment from needle-syringe programs; a minority had accessed injecting-specific primary care. CONCLUSION: Men who injected drugs in this cohort and those who identified as GBMSM reported similar drug and health-seeking practices. The higher prevalence of methamphetamine injecting among GBMSM may warrant different harm reduction support for this group. Health promotion should utilise opportunities to connect men who inject drugs in Melbourne to injecting-specific primary health care.

Sericin improves memory and sociability impairments evoked by transient global cerebral ischemia through suppression of hippocampal oxidative stress, inflammation, and apoptosis.

Sericin (Ser) is a natural neuroactive macromolecule with diverse pharmacological properties, and our previous findings have shown its neuroprotective potentials. This study aimed to investigate the therapeutic potential of Ser on cognitive dysfunction induced by transient global cerebral ischemia/reperfusion (tGI/R) and its mechanism of action. The tGI/R was induced in BALB/c mice by bilateral occlusion of the common carotid arteries for two 5 min followed by a 10-min reperfusion period. After 24 h, mice were treated with normal saline or different doses of Ser (100, 200, and 300 mg/kg) for 10 days. Cognitive performances were assessed using the Barnes maze and social interaction tasks. Oxidative stress markers including superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant capacity (TAC), and malondialdehyde (MDA) as well as pro-inflammatory cytokines (interleukin (IL)-6 and tumor necrosis factor-alpha) and anti-inflammatory cytokine (IL-10) were assessed in the hippocampus. Markers of apoptosis (pro- and cleaved caspase-9 and 3, Bax, and Bcl-2) were assessed by Western blotting. Besides, transferase-mediated dUTP nick end-labeling assay was used to detect apoptotic cell death. We show here that Ser administration improved tGI/R-induced cognitive deficits, enhanced the activity of SOD and GPx, increased TAC levels, while reduced MDA levels. Notably, Ser decreased neuronal apoptotic cell death in the hippocampal dentate gyrus (DG) region, accompanied by suppression of neuroinflammation, downregulation of pro-apoptotic proteins (caspase-9, caspases-3, and Bax), and upregulation of anti-apoptotic protein, Bcl-2. Taken together, Ser administration protected hippocampal neurons from apoptotic cell death by impeding oxidative stress and inflammatory responses and, in turn, improved cognitive function in the tGI/R mice.

When is Solitude Maladaptive for Adolescents? A Comprehensive Study of Sociability and Characteristics of Solitude.

Research examining the link between solitude and psychosocial adjustment among adolescents has lacked a comprehensive, person-centered examination of differential patterns of both solitude and sociability. The current study surveyed 1071 adolescents (Mage = 12.48, SD = 1.71, 49.86% female, age range = 10-16 years). Using latent-profile analysis, four groups were identified with differential patterns of characteristics of solitude (i.e., enjoyment, motivations, preference, frequency) and sociability. Results indicated that worse psychosocial adjustment across time points was associated with membership in the PFS-NonSociable group (characterized by high enjoyment, preference, and frequency of solitude; low sociability) compared to all other groups. Findings suggest that solitude for adolescents appears to be linked to worse psychosocial adjustment only if accompanied by a lack of sociability.

Cosmopolis: public spaces, cosmopolitanism, and democracy.

What is the role of public spaces in contemporary cities? Despite the growing interest in the theme of public spaces in the last decades, a significant number of authors appeal, directly or indirectly, to ideas of the "regression", "decay", and "crisis" of public life, public sphere, and public spaces. Without disregarding this hegemonic point of view, in the present article we would like to consider other perspectives, which recognize the importance of public spaces, public sociability, and cosmopolitanism for the democratic societies in the context of the contemporary city, the cosmopolis. We therefore propose a bibliographic review that deals with the political nature of public spaces, the dimension of contestation within public sociability, the advent of virtual public spaces, and the geography of cosmopolitan encounters. The article concludes that urban public spaces remain essential for the existence and functioning of democratic societies and institutions.

Neonatal exposure to sevoflurane impairs preference for social novelty in C57BL/6 female mice at early-adulthood.

Social interaction deficit is core symptom of children with autism, owing to interaction of genetic predisposition and environmental toxins. Sevoflurane could induce neurotoxicity in developing brain in rodent models. This study aims to investigate whether sevoflurane anesthesia in neonatal period could impair social behaviors in male and female mice. Twenty-eight male and thirty-one female mice were randomly assigned to receive 3.0% sevoflurane or 60% oxygen on postnatal day 6. They were tested for social interaction behaviors at one- and two-month-old. In addition, the cortex and hippocampus of neonatal mice undergoing sevoflurane anesthesia were harvested for immunoblotting analysis. As a result, both male and female mice undergoing sevoflurane anesthesia showed strong sociability and weak preference for social novelty at juvenile age. In addition, the male mice developed normal preference for social novelty at early-adulthood; However, the female mice remained weak preference for social novelty. Furthurmore, sevoflurane anesthesia could decrease the levels of PSD95 but not Neuroligin-1 in the hippocampus but not cortex of neonatal mice. In conclusion, sevoflurane anesthesia in neonatal period could disturb development of social memory and impair preference for social novelty in female mice at early-adulthood, with the potential mechanism of decreasing PSD95 expression in the hippocampus of C57BL/6 mice.

The CRF1 receptor mediates social behavior deficits induced by opiate withdrawal.

Poor sociability and aggressive behavior are key clinical features of opioid use disorders. The corticotropin-releasing factor (CRF) system may mediate behavioral effects of substances of abuse but its implication in substance-induced social behavior deficits and outward-directed hostility remains largely unknown. CRF signaling is mediated by two receptor types, termed CRF1 and CRF2 . The present study aimed at understanding the role for the CRF1 receptor in social and aggressive behavior induced by withdrawal from repeated opiate administration. Thus, wild-type (CRF1 +/+), CRF1 receptor heterozygous (CRF1 +/-), and null mutant (CRF1 -/-) female and male mice were treated with saline or escalating doses of morphine (20-100 mg/kg, i.p.) during six consecutive days and tested in the three-chamber task for sociability (i.e., preference for an unfamiliar same-sex conspecific vs. an object) 7 days after the last administration. Moreover, aggressive biting behavior toward the unfamiliar conspecific was assessed during the three-chamber test. Opiate withdrawal disrupted sociability in CRF1 +/+ and CRF1 +/-, but not in CRF1 -/-, female mice, without affecting aggressive biting behavior in any genotype. In contrast, opiate withdrawal did not affect sociability but increased aggressive biting behavior in male mice, independently of CRF1 receptor-deficiency. Nevertheless, in opiate-withdrawn CRF1 +/+, but not CRF1 +/- and CRF1 -/-, male mice, sociability directly correlated with aggressive biting behavior, suggesting a role for the CRF1 receptor in hostility-linked social approach. These findings demonstrate the implication of the CRF1 receptor in social behavior deficits associated with repeated opiate administration and withdrawal, revealing a new potential target for the treatment of opioid use disorders.

Integrin ß3 in forebrain Emx1-expressing cells regulates repetitive self-grooming and sociability in mice.

BACKGROUND: Autism spectrum disorder (ASD) is characterized by repetitive behaviors, deficits in communication, and overall impaired social interaction. Of all the integrin subunit mutations, mutations in integrin ß3 (Itgb3) may be the most closely associated with ASD. Integrin ß3 is required for normal structural plasticity of dendrites and synapses specifically in excitatory cortical and hippocampal circuitry. However, the behavioral consequences of Itgb3 function in the forebrain have not been assessed. We tested the hypothesis that behaviors that are typically abnormal in ASD-such as self-grooming and sociability behaviors-are disrupted with conditional Itgb3 loss of function in forebrain circuitry in male and female mice. METHODS: We generated male and female conditional knockouts (cKO) and conditional heterozygotes (cHET) of Itgb3 in excitatory neurons and glia that were derived from Emx1-expressing forebrain cells during development. We used several different assays to determine whether male and female cKO and cHET mice have repetitive self-grooming behaviors, anxiety-like behaviors, abnormal locomotion, compulsive-like behaviors, or abnormal social behaviors, when compared to male and female wildtype (WT) mice. RESULTS: Our findings indicate that only self-grooming and sociability are altered in cKO, but not cHET or WT mice, suggesting that Itgb3 is specifically required in forebrain Emx1-expressing cells for normal repetitive self-grooming and social behaviors. Furthermore, in cKO (but not cHET or WT), we observed an interaction effect for sex and self-grooming environment and an interaction effect for sex and sociability test chamber. LIMITATIONS: While this study demonstrated a role for forebrain Itgb3 in specific repetitive and social behaviors, it was unable to determine whether forebrain Itgb3 is required for a preference for social novelty, whether cHET are haploinsufficient with respect to repetitive self-grooming and social behaviors, or the nature of the interaction effect for sex and environment/chamber in affected behaviors of cKO. CONCLUSIONS: Together, these findings strengthen the idea that Itgb3 has a specific role in shaping forebrain circuitry that is relevant to endophenotypes of autism spectrum disorder.

Sickness and the Social Brain: How the Immune System Regulates Behavior across Species.

Many instances of sickness critically involve the immune system. The immune system talks to the brain in a bidirectional loop. This discourse affords the immune system immense control, such that it can influence behavior and optimize recovery from illness. These behavioral responses to infection are called sickness behaviors and can manifest in many ways, including changes in mood, motivation, or energy. Fascinatingly, most of these changes are conserved across species, and most organisms demonstrate some form of sickness behaviors. One of the most interesting sickness behaviors, and not immediately obvious, is altered sociability. Here, we discuss how the immune system impacts social behavior, by examining the brain regions and immune mediators involved in this process. We first outline how social behavior changes in response to infection in various species. Next, we explore which brain regions control social behavior and their evolutionary origins. Finally, we describe which immune mediators establish the link between illness and social behavior, in the context of both normal development and infection. Overall, we hope to make clear the striking similarities between the mechanisms that facilitate changes in sociability in derived and ancestral vertebrate, as well as invertebrate, species.