Effects of a gut-selective integrin-targeted therapy in male mice exposed to early immune activation, a model for the study of autism spectrum disorder.

To clarify the role of gut mucosal immunity in ASD, we evaluated, in the early-life immune activation (EIA) mouse model, the effects of administration of a monoclonal antibody directed against the integrin alpha4 beta7 (α4ß7 mAb), blocking the leukocyte homing into the gut mucosa. EIA is a double-hit variant of the maternal immune-activation (MIA) model, including both prenatal (Poly I:C) and postnatal (LPS) immune challenges. In C57BL6/J EIA male adult offspring mice, IL-1ß and IL-17A mRNA colonic tissue content increased when compared with controls. Cytofluorimetric analyses of lymphocytes isolated from mesenteric lymph-nodes (MLN) and spleens of EIA mice show increased percentage of total and CD4+α4ß7+, unstimulated and stimulated IL-17A+ and stimulated IFN-γ+ lymphocytes in MLN and CD4+α4ß7+ unstimulated and stimulated IL-17A+ and stimulated IFN-γ+ lymphocytes in the spleen. Treatment with anti-α4ß7 mAb in EIA male mice was associated with colonic tissue IL-1ß, and IL-17A mRNA content and percentage of CD4+ IL-17A+ and IFN-γ+ lymphocytes in MLN and spleens comparable to control mice. The anti-α4ß7 mAb treatment rescue social novelty deficit showed in the three-chamber test by EIA male mice. Increased levels of IL-6 and IL-1ß and decreased CD68 and TGF-ß mRNAs were also observed in hippocampus and prefrontal cortex of EIA male mice together with a reduction of BDNF mRNA levels in all brain regions examined. Anti-α4ß7 mAb treatment restored the expression of BDNF, TGF-ß and CD68 in hippocampus and prefrontal cortex. Improvement of the gut inflammatory status, obtained by a pharmacological agent acting exclusively at gut level, ameliorates some ASD behavioral features and the neuroinflammatory status. Data provide the first preclinical indication for a therapeutic strategy against gut-immune activation in ASD subjects with peripheral increase of gut-derived (α4ß7+) lymphocytes expressing IL-17A.

Behavioral profile, lifestyle and social skills in Portuguese adolescents.

BACKGROUND: Seventy percent of premature deaths in adults are due to behaviors initiated during adolescence. Therefore, it is essential to promote individual and social behaviors that educate adolescents in the ability to make healthy choices. Accordingly, the main goals of this study were to characterize Lifestyles and Social Skills, as well as identify homogeneous subgroups, in a sample of Portuguese adolescents. METHODS: A cross-sectional study was conducted, including 1008 adolescents attending the 7th to the 9th grades of five middle schools from the Tâmega and Sousa regions of Portugal, and using the My Lifestyle Questionnaire and the Social Skills Inventory. To establish a profile of the participants, a Cluster Analysis (K-means) was performed, and the Jaccard coefficient was used to assess the stability of the solution found. RESULTS: From the total sample, 556 adolescents with a mean age of 13.43 years (SD = 1.1) were included in the analysis. The majority of the sample presented a healthy lifestyle (72.26%) and 50.7% of the adolescents had a highly elaborated repertoire of Social Skills. Moreover, three clusters were found. Cluster 1 (n = 92) showed a less elaborate repertoire of Social Skills and was designated as the "Adjusted". Cluster 2 (n = 115) comprised adolescents with a good repertoire of Social Skills and was named the "Sociable". Cluster 3 (n = 258) was composed of adolescents with a highly elaborate repertoire of Social Skills and the best Lifestyle indicators and was named the "Healthy". CONCLUSIONS: The group of adolescents in the cluster called the "Sociable" needs to be included in health education and Social Skills programs. Nutrition and Monitored Safety behaviors reveal low values and, therefore, present a greater need for awareness, sensitization, and intervention in the school context. For this reason, the promotion of a healthy lifestyle should be part of the academic curriculum and transversal to all academic disciplines.

Cognitive development in females with PCDH19 gene-related epilepsy.

Mutations in the PCDH19 gene are now recognized to cause epilepsy in females and are claiming increasing interest in the scientific world. Clinical features and seizure semiology have been described as heterogeneous. Intellectual disability might be present, ranging from mild to severe; behavioral and psychiatric problems are a common feature of the disorder, including aggressiveness, depressed mood, and psychotic traits. The purpose of our study was to describe the cognitive development in 11 girls with a de novo mutation in PCDH19 and early-onset epilepsy. Six patients had average mental development or mild intellectual disability regardless of persistence of seizures in clusters. Five patients presented moderate or severe intellectual disability and autistic features. In younger patients, we found that despite an average developmental quotient, they all presented a delay of expressive language acquisition and lower scores at follow-up testing completed at older ages, underlining that subtle dysfunctions might be present. Larger cohort and long-term follow-up might be useful in defining cognitive features and in improving the care of patients with PCDH19.

Clinical differences in children with autism spectrum disorder with and without food selectivity.

Several studies have described the atypical eating behaviors frequently occurring in children with Autism Spectrum Disorder (ASD), and food selectivity is the most frequent of these problems. The everyday management of mealtime behaviors among children with ASD can have a negative impact on family routines and become a significant stressor for families. However, much remains unknown about why food selectivity is so prevalent among individuals with ASD. The objective of this study was to investigate clinical and behavioral features in individuals with ASD with the aim of identifying distinctive clinical profiles in children with and without food selectivity. A total of 158 children with ASD were enrolled in this study: 79 participants with food selectivity (FS) were age and sex matched with 79 participants without food selectivity (No FS). All participants and their parents completed a battery of psychological tests for a comprehensive evaluation of ASD symptoms, cognitive abilities, adaptive skills, behavioral problems and parental stress level. No statistically significant difference on gastrointestinal symptoms and growth adequacy was found between the FS group and the No FS group. Overall, the FS group showed significantly higher rates of ASD symptoms as compared to the No FS group in the questionnaires completed by parents. Furthermore, parents of the FS group reported significantly higher levels of parental stress and a larger degree of their children's behavioral problems as compared to the No FS group. Finally, there were no differences between the FS and the No FS group on any adaptive skill domain. Our findings suggest that the identification of distinctive clinical and behavioral patterns in children with ASD and food selectivity is a crucial issue for parents and therapists in the daily management.

Relationship between boldness and exploratory behavior in adult zebrafish.

Behavioral responses vary between individuals and may be repeated in different contexts over time. When a behavioral response set is linked and present regardless of the context, it characterizes a behavioral syndrome. By evaluating how bold and shy (profiles related to risk-taking) individuals perform about exploration and anxiety, we can predict relationships of behavioral syndromes and better understand how different axis of personality is formed. Here we classified the profiles by risk-taking and evaluated their exploration behavior in the open field test. In this context, the two groups showed significant differences in thigmotaxis behavior: bold individuals habituate faster and show decreased thigmotaxis (less anxiety), while shy ones are less prone to leave the security of the side areas of the open tank and present higher anxiety. We emphasized the importance of further investigating the behavior of these profiles in other contexts and the importance of each one for the evolution and fitness of the species, in addition to a better understanding of which behaviors are involved in the behavioral syndromes in zebrafish.

Potential roles of polyunsaturated fatty acid-enriched diets in modulating social stress-like features.

Fish oil or its major constituents, namely omega-3 poly-unsaturated fatty acid (n3-PUFA), are popular supplements to improve neurogenesis, neuroprotection, and overall brain functions. Our objective was to probe the implications of fat enriched diet with variable PUFAs supplements in ameliorating social stress (SS). We fed mice on either of the three diet types, namely the n-3 PUFA-enriched diet (ERD, n3:n6= 7:1), a balanced diet (BLD, n3:n6= 1:1) or a standard lab diet (STD, n3:n6= 1:6). With respect to the gross fat contents, the customized special diets, namely ERD and BLD were extreme diet, not reflecting the typical human dietary composition. Aggressor-exposed SS (Agg-E SS) model triggered behavioral deficiencies that lingered for 6 weeks (6w) post-stress in mice on STD. ERD and BLD elevated bodyweights but potentially helped in building the behavioral resilience to SS. STD adversely affected the gene networks of brain transcriptomics associated with the cell mortality, energy homeostasis and neurodevelopment disorder. Diverging from the ERD's influences on these networks, BLD showed potential long-term benefits in combatting Agg-E SS. The gene networks linked to cell mortality and energy homeostasis, and their subfamilies, such as cerebral disorder and obesity remained at the baseline level of Agg-E SS mice on BLD 6w post-stress. Moreover, neurodevelopment disorder network and its subfamilies like behavioral deficits remained inhibited in the cohort fed on BLD 6w post Agg-E SS.

Means, Intent, Lethality, Behaviors, and Psychiatric Diagnosis in Latina Adolescent Suicide Attempters.

This article describes the means, intent, lethality, behavioral profile, and psychiatric diagnosis of adolescent Latina suicide attempters. From a large mixed-methods project studying the sociocultural processes of Latina suicide attempts, we selected 76 subjects for this report. In addition to quantitative research data, medical records were available for all 76 subjects and qualitative data from in-depth interviews for 34 of them. Using the qualitative and quantitative research data, we explored the intent and behavioral profile of the suicidal adolescents. Medical records provided additional information about the means the adolescents used in their attempts and about their psychiatric diagnosis. The lethality of suicide attempts was coded using the LSARS and the LSARS-II. Findings showed that Latina adolescent suicide attempts are of low lethality. Consistent with the literature, most adolescents reported that they attempted by using means available in their homes (cutting and overdosing with medications were the predominant methods). Interesting discrepancies emerged when comparing adolescents' self-reported behavioral profiles with clinicians' psychiatric diagnoses. This report has implications for diagnosis and treatment approaches for both inpatient and outpatient service providers.

Covariation among behavioral traits and hatching time in zebrafish.

Individuals of the same population differ in several ways. For instance, in fish populations, individuals who hatch earlier show more active behavior and are more explorative than those that hatch later, which is a characteristic of the behavioral personality type. One of the aspects relevant to this theory is the consistency of behavioral differences between contexts and over time. Thus, the present study evaluated the relationship between hatching time and behavioral consistency in two ontogenetic stages: juvenile and adult, and different contexts in zebrafish (Danio rerio). For this, the animals were separated according to hatching time into early-hatching (EH) and late-hatching (LH) fish and tested in an anxiety-like context (black-white paradigm) at the 30th-day post fertilization (dpf) and the 120th dpf. The animals were also tested in a novel tank paradigm and novel object paradigm to access explorativeness and boldness, respectively. In the black-white test, EH animals presented shorter latency to enter the white area and stayed longer in the black area than LH animals. The EH individuals were more explorative and bold in the novel tank and novel object tests and showed less anxiety-like behavior than the LH. In general, the results obtained suggest that hatching time may indicate consistent differences for zebrafish behavioral profiles.

Status of socio-demographic and behavioral profile of younger and older HIV high risk groups in Chhattisgarh.

Background: The prevention of new infections in high-risk groups is a major thrust in National AIDS Control Program. There is enough evidence that many epidemiological and behavioral determinants which make High Risk Group vulnerable to HIV transmission. The most effective means of controlling the spread of HIV is through the implementation of Targeted Interventions (TIs) efforts by which services are catered to them. Furthermore, stigma and marginalization are often linked to this population, which may lead to difficulties while accessing social and health services (SHS) due to behavioral, cultural and language barriers or lack of knowledge of the system. So, finding the sociodemographic & behavioral profile can give a breakthrough in improving the quality of life of HIV high risk groups. Material and Methods: A cross sectional study was conducted during September to December 2019 in two districts (i.e., Raipur & Durg) among HRGs of Chhattisgarh. Training cum sensitization of survey team e.g., peer educators, outreach workers, counselors, project managers prior to the survey was done for data collection. Results: A Total of 3963 HRGs were registered with TI NGOs, 3418 (86.2%) were screened. The mean age of study participants was 27.69 ± 6.1. Compliance of participation was 86.2%. HRGs were observed to have malnutrition (BMI <18.5 &> 25.0). 7 cases of Pulmonary TB were found among IDUs. Prevalence of diabetes and Hypertension was 1.2% and 1.1% respectively. Substance abuse (i.e., for Alcohol and Tobacco) was significantly higher among IDUs and FSWs. Conclusion: This study reinforces the fact that for accessing High Risk Groups and retrieval of relevant information can best be obtained by their care givers i.e., TI NGOs personnel. Also understanding the sociodemographic and behavioral profiles are central to designing targeted HIV prevention interventions for them.

Micro-Vesicles of Moringa oleifera Seeds in Heterozygous Rats for DAT Gene: Effects of Oral Intake on Behavioral Profile and Hematological Parameters.

Previous studies have shown multiple biological properties of Moringa oleifera, a plant native to Africa and Asia. In the present study, potential physiological properties of microvesicles extracted from Moringa oleifera seeds were assessed. For this purpose, we investigated behavioral profile and hematological parameters in a recent rat model characterized by dysregulation in dopamine transporter, a key regulator of dopaminergic system. Experimental design consisted of male Wistar-DAT rats aged between two and four months: wild-type (WT) (n = 5) and heterozygous (DATHET) (n = 4) control groups, which drank tap water; WT (n = 5) and DATHET (n = 6) groups which drank a solution of Moringa microvesicles and water (2: 68 mL per day), which was orally administered for two months. Rats were monitored for spontaneous locomotor activity on a 24/7 basis. In the early lit hours, treated DATHET subjects showed higher locomotor activity, proposing a sleep-delay effect of Moringa. In forced swimming test, WT subjects who took Moringa exhibited more depressive behavior. In DATHET rats, Moringa seemed to potentiate the struggle to find a way out, counteracting an initial panic. Hemoglobin and hematocrit underwent opposite changes in either genotype, supporting the opposite effects on behavioral phenotype observed. Future work is clearly needed to further explore these preliminary profiles.

An individual based, multidimensional approach to identify emotional reactivity profiles in inbred mice.

BACKGROUND: Despite extensive environmental standardization and the use of genetically and microbiologically defined mice of similar age and sex, individuals of the same mouse inbred strain commonly differ in quantitative traits. This is a major issue as it affects the quality of experimental results. Standard analysis practices summarize numerical data by means and associated measures of dispersion, while individual values are ignored. Perhaps taking individual values into account in statistical analysis may improve the quality of results. NEW METHOD: The present study re-inspected existing data on emotional reactivity profiles in 125 BALB/cJ and 129 mice, which displayed contrasting patterns of habituation and sensitization when repeatedly exposed to a novel environment (modified Hole Board). Behaviors were re-analyzed on an individual level, using a multivariate approach, in order to explore whether this yielded new information regarding subtypes of response, and their expression between and within strains. RESULTS: Clustering individual mice across multiple behavioral dimensions identified two response profiles: a habituation and a sensitization cluster. COMPARISON WITH EXISTING METHOD(S): These retrospect analyses identified habituation and sensitization profiles that were similar to those observed in the original data but also yielded new information such as a more pronounced sensitization response. Also, it allowed for the identification of individuals that deviated from the predominant response profile within a strain. CONCLUSIONS: The present approach allows for the behavioral characterization of experimental animals on an individual level and as such provides a valuable contribution to existing approaches that take individual variation into account in statistical analysis.

Linked factors to access to sexual health checkups of female sex workers in the metropolitan region of Chile.

OBJECTIVES: To describe and compare the profile of female sex workers (FSWs) that access or do not access sexual health checkups (SHC). The research question was what are the factors linked to access to SHC for FSWs in the metropolitan region (RM) of Chile? METHODS: A cross-sectional study was conducted in the RM with FSWs over the age of 18. A sample of 370 FSWs was selected by using the time-location sampling method in closed venues and at street-level locations. A survey was applied, validated, and included clinical-epidemiological, behavioral and socio-demographic variables. RESULTS: 38.6% (n = 140) of FSWs that answered the question never used SHC and 37.6% (n = 84) received checkups in a specialized health center for FSWs. FSWs with no SHC were younger, prone to have more group sex, preferably with occasional or no stable partner, and did not know where to get an HIV test. CONCLUSIONS: FSWs have had uncertain access to sexual health controls. FSWs with no SHC and young FSWs presented higher-risk behaviors.

Social experiences during adolescence affect anxiety-like behavior but not aggressiveness in male mice.

Adolescence has lately been recognized as a key developmental phase during which an individual's behavior can be shaped. In a recent study with male mice varying in the expression of the serotonin transporter, escapable adverse social experiences during adolescence led to decreased anxiety-like behavior and increased exploratory and aggressive behavior compared to throughout beneficial experiences. Since in this study some behavioral tests took place with a delay of one week after the last social experiences have been made, it was not clear whether the observed effects really reflected the consequences of the experienced different social environments. To test this, the present study focused on the direct effects of beneficial and adverse social experiences on aggressiveness and anxiety-like behavior in C57BL/6J mice. In contrast to the previous study, behavioral testing took place immediately after the last social experiences had been made. Interestingly, whereas individuals from an escapable adverse environment showed significantly lower levels of anxiety-like and higher levels of exploratory behavior than animals from a beneficial environment, aggressive behavior was not affected. From this, we conclude that different social experiences during adolescence exert immediate effects on anxiety-like but not aggressive behavior in male mice.

Complex Genetics of Behavior: BXDs in the Automated Home-Cage.

This chapter describes a use case for the genetic dissection and automated analysis of complex behavioral traits using the genetically diverse panel of BXD mouse recombinant inbred strains. Strains of the BXD resource differ widely in terms of gene and protein expression in the brain, as well as in their behavioral repertoire. A large mouse resource opens the possibility for gene finding studies underlying distinct behavioral phenotypes, however, such a resource poses a challenge in behavioral phenotyping. To address the specifics of large-scale screening we describe how to investigate: (1) how to assess mouse behavior systematically in addressing a large genetic cohort, (2) how to dissect automation-derived longitudinal mouse behavior into quantitative parameters, and (3) how to map these quantitative traits to the genome, deriving loci underlying aspects of behavior.

Consequences of serotonin transporter genotype and early adversity on behavioral profile - pathology or adaptation?

This review focuses on how behavioral profile is shaped by early adversity in individuals with varying serotonin transporter (5-HTT) genotype. In a recent study on 5-HTT knockout mice Heiming et al. (2009) simulated a 'dangerous environment' by confronting pregnant and lactating females with odor cues of unfamiliar males, indicating the risk of infant killing. Growing up in a dangerous environment induced increased anxiety-related behavior and decreased exploratory locomotion in the offspring, the effects being most pronounced in mice lacking 5-HTT expression. We argue that these alterations in behavioral profile represent adaptive maternal effects that help the individuals to cope with adversity. In principle, such effects of adversity on behavioral profile should not automatically be regarded as pathological. Rather and in accordance with modern evolutionary theory they may represent adaptations, although individuals with 5-HTT genotype induced susceptibility to adversity may be at risk of developing pathologies.

Living in a dangerous world: the shaping of behavioral profile by early environment and 5-HTT genotype.

Anxiety and anxiety disorders are influenced by both, environmental and genetic factors. One genetic factor under scrutiny for anxiety disorders is the genetically encoded variation of the serotonin transporter (5-HTT). The aim of this study was to elucidate the effects of a threatening environment during early phases of life on anxiety-like (ANX) and exploratory behavior (EXP) in adult mice, varying in serotonin transporter (5-HTT) genotype. For this purpose, pregnant and lactating 5-HTT +/- dams were repeatedly exposed to olfactory cues of unfamiliar adult males by introducing small amounts of soiled bedding to their home cage. These stimuli signal the danger of infanticide and simulate a threatening environment. Control females were treated with neutral bedding. The offspring (5-HTT +/+, +/-, -/-) were examined for their ANX and EXP. The main results were: (1) a main effect of genotype existed, with 5-HTT -/- showing higher levels of ANX and lower levels of EXP than 5-HTT +/- and wildtypes. (2) When mothers had lived in a threatening environment, their offspring showed increased ANX and reduced EXP compared to controls. (3) These effects were most pronounced in 5-HTT -/- mice. By applying a new ecologically relevant paradigm we conclude: If 5-HTT +/- mothers live in a threatening environment during pregnancy and lactation, their offspring behavioral profile will, in principle, be shaped in an adaptive way preparing the young for an adverse environment. This process is, however, modulated by 5-HTT genotype, bearing the risk that individuals with impaired serotonergic neurotransmission (5-HTT -/-) will develop an exaggerated, potentially pathological level of anxiety from gene x environment interactions.

Perfil comportamental de crianças e adolescentes com síndrome de Prader-Willi e obesidade exógena / Behavioral profile of children and adolescents with Prader-Willi syndrome and exogenous obesity / Perfil conductual de niños y adolescentes con síndrome de Prader-Willi y obesidad exógena

O presente estudo teve como objetivo comparar o perfil comportamental de dois grupos distintos de crianças e adolescentes portadores de obesidade. Dez participantes apresentavam diagnóstico de obesidade exógena (OE) e dez tinham síndrome de Prader- Willi (SPW). A SPW é uma doença genética cujo sintoma comportamental de maior gravidade é a hiperfagia. Os dois grupos foram pareados por sexo e idade, com idade média de 12 anos. Na avaliação do perfil comportamental, foi usado o inventário dos comportamentos de crianças e adolescentes de 6 a 18 anos (CBCL/6-18). Os principais resultados apontaram que, de modo geral, os participantes com obesidade de causas exógenas obtiveram melhores resultados do que os diagnosticados com SPW. Em comparações, em que utilizaram análises de variância (ANOVA) univariadas, observaram-se diferenças estatisticamente significantes entre os grupos de SPW e OE nas escalas: escola (p = 0,001), problemas sociais (p = 0,012), problemas de pensamento (p = 0,001), problemas de atenção (p = 0,048), comportamento de quebrar regras (p = 0,019), comportamento agressivo (p = 0,003) e transtorno de conduta (p = 0,001). As diferenças encontradas sugerem a necessidade de estratégias de atendimento psicológico para o grupo com SPW.

The objective of present study was compared the behavioral profile of two different groups of children and adolescents with obesity. Ten subjects presented diagnoses of exogenous obesity and ten Prader-Willi syndrome. The Prader-Willi syndrome is a genetic disease which the main behavioral symptom is hyperphagia. The samples were paired by sex and age, with mean age of 12 years. In the evaluation of behavioral profile was utilized Child Behavior Checklist (CBCL/6-18). In the most cases children with exogenous obesity have obtained better results than the referred with Prader-Willi Syndrome. Into the comparison by mean of ANOVA univariate identified significant differences between the groups in the scales: school (p = 0.001), social problems (p = 0.012), thought problems (p = 0.001), attention problems (p = 0.048), rule-breaking behavior (p = 0.019); aggressive behavior (p = 0.003) and conduct problems (p = 0.001). The differences suggested the need of counseling psychological strategies in the Prader-Willi syndrome group.

El presente estudio tuvo como objetivos comparar el perfil comportamental de dos grupos distintos de niños y adolescentes portadores de obesidad. Diez participantes apresentaban diagnóstico de obesidad exógena y diez con síndrome de Prader-Willi. El síndrome de Prader-Willi es una enfermedad genética que tiene como un de los síntomas comportamentales de mayor gravedad el desarrollo de la hiperfagia. Los dos grupos fueron pareados por sexo y por edad, con edad media de 12 años. Para la evaluación del perfil comportamental fué usado el inventário de los comportamientos de niños y adolescentes de 6 a 18 años (CBCL/6-18). Los principales resultados apuntaron que de modo general, los participantes con obesidad de causas exógenas obtuvieron mejores resultados que los diagnosticados con síndrome de Prader-Willi. En comparaciones utilizando ANOVAS univariadas, fueron observadas diferencias estadisticamente significativas entre los grupos en las escalas: escuela (p = 0,001), problemas sociales (p = 0,012), problemas de pensamiento (p = 0,001), problemas de atención (p = 0,048), comportamiento de romper reglas (p = 0,019), comportamiento agresivo (p = 0,003) y trastornos de conducta (p = 0,001). Los datos sugieren la necesidad de estrategias de atención psicológica para el grupo con síndrome de Prader-Willi.