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Females of the Northern House mosquito, Culex pipiens, are important disease vectors as they transmit pathogens including West Nile virus. These females survive the winter by entering diapause, a state of dormancy, characterized by the accumulation of lipids, cessation of blood-feeding, and reproductive arrest. Diapause is cued by photoperiod, so as days become short in late summer and early fall, female Cx. pipiens prepare to overwinter and disease transmission decreases. We previously demonstrated that Artificial light at night (ALAN) causes female Cx. pipiens to avert diapause and continue to blood-feed when reared under short-day conditions. Additionally, light pollution alters seasonal differences in mosquito activity and nutrient reserves. However, it is unclear how exposure to ALAN affects blood-feeding and fecundity in long-day reared females, as well as the survival of Cx. pipiens exposed under both short and long-day conditions. In this study, we hypothesized that females exposed to ALAN in long-day conditions would have a lower proclivity to blood-feed, reduced fecundity, and reduced survival. Results from our lab-based experiments demonstrate that females exposed to ALAN in long-day conditions were less likely to blood-feed but were more fecund than long-day reared females that were not exposed to ALAN, and that ALAN exposure did not affect lifespan of long-day reared females. Additionally, we hypothesized ALAN exposure under short-day conditions would reduce survival, and our data supports this hypothesis. Overall, our results demonstrate that ALAN is an important urban stressor that has the potential to affect reproduction and lifespan in mosquitoes, and therefore has the potential to create evolutionary tradeoffs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Behavioral phenotypes that predict future weight gain are needed to identify children susceptible to obesity., Objectives: This prospective study developed an eating behavior risk score to predict change in adiposity over 1 y in children., Methods: Data from 6 baseline visits (Time 1, T1) and a 1-y follow-up visit (Time 2, T2) were collected from 76, 7- to 8-y-old healthy children recruited from Central Pennsylvania. At T1, children had body mass index (BMI) percentiles <90 and were classified with either high (n = 33; maternal BMI ≥30 kg/m 2 ) or low (n = 43; maternal BMI ≤25 kg/m 2 ) familial risk for obesity. Appetitive traits and eating behaviors were assessed at T1. Adiposity was measured at T1 and T2 using dual-energy x-ray absorptiometry, with a main outcome of fat mass index (FMI; total body fat mass divided by height in meters squared). Hierarchical linear regressions determined which eating measures improved prediction of T2 FMI after adjustment for covariates in the baseline model (T1 FMI, sex, income, familial risk, and Tanner stage)., Results: Four eating measures-Portion susceptibility, Appetitive traits, loss of control eating, and eating rate-were combined into a standardized summary score called PACE. PACE improved the baseline model to predict 80% variance in T2 FMI. PACE was positively associated with the increase in FMI in children from T1 to T2, independent of familial risk (r = 0.58, P < 0.001). Although PACE was higher in girls than boys (P < 0.05), it did not differ by familial risk, income, or education., Conclusions: PACE represents a cumulative eating behavior risk score that predicts adiposity gain over 1 y in middle childhood. If PACE similarly predicts adiposity gain in a cohort with greater racial and socioeconomic diversity, it will inform the development of interventions to prevent obesity. This trial was registered at clinicaltrials.gov as NCT03341247., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Expanding knowledge about the cellular composition of subcortical brain regions demonstrates large heterogeneity and differences from the cortical architecture. Previously we described three subtypes of somatostatin-expressing (Sst) neurons in the mouse ventral tegmental area (VTA) and showed their local inhibitory action on the neighboring dopaminergic neurons (Nagaeva et al., 2020). Here, we report that Sst+ neurons especially from the anterolateral part of the mouse VTA also project far outside the VTA and innervate forebrain regions that are mainly involved in the regulation of emotional behavior, including the ventral pallidum, lateral hypothalamus, the medial part of the central amygdala, anterolateral division of the bed nucleus of stria terminalis, and paraventricular thalamic nucleus. Deletion of these VTA Sst neurons in mice affected several behaviors, such as home cage activity, sensitization of locomotor activity to morphine, fear conditioning responses, and reactions to the inescapable stress of forced swimming, often in a sex-dependent manner. Together, these data demonstrate that VTA Sst neurons have selective projection targets distinct from the main targets of VTA dopamine neurons. VTA Sst neurons are involved in the regulation of behaviors primarily associated with the stress response, making them a relevant addition to the efferent VTA pathways and stress-related neuronal network., Competing Interests: Authors declare no competing conflicts of interest., (Copyright © 2023 Nagaeva et al.)

External sources of information influence human actions. However, psychological traits (PTs), considered internal variables, also play a crucial role in decision making. PTs are stable across time and contexts and define the set of behavioral repertoires that individuals express. Here, we explored how multiple metrics of adaptive behavior under uncertainty related to several PTs. Participants solved a reversal-learning task with volatile contingencies, from which we characterized a detailed behavioral profile based on their response sequences. We then tested the relationship between this multimetric behavioral profile and scores obtained from self-report psychological questionnaires. The PT measurements were based on the Hierarchical Taxonomy Of Psychopathology (HiTOP) model. By using multiple linear regression models (MLRMs), we found that the learning curves predicted important differences in the PTs and task response times. We confirmed the significance of these relationships by using random permutations of the predictors of the MLRM. Therefore, the behavioral profile configurations predicted the PTs and served as a "fingerprint" to identify participants with a high certainty level. We discuss briefly how this characterization and approach could contribute to better nosological classifications., (© 2023 Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Objectives: Overeating interventions and research often focus on single determinants and use subjective or nonpersonalized measures. We aim to (1) identify automatically detectable features that predict overeating and (2) build clusters of eating episodes that identify theoretically meaningful and clinically known problematic overeating behaviors (e.g., stress eating), as well as new phenotypes based on social and psychological features., Method: Up to 60 adults with obesity in the Chicagoland area will be recruited for a 14-day free-living observational study. Participants will complete ecological momentary assessments and wear 3 sensors designed to capture features of overeating episodes (e.g., chews) that can be visually confirmed. Participants will also complete daily dietitian-administered 24-hour recalls of all food and beverages consumed., Analysis: Overeating is defined as caloric consumption exceeding 1 standard deviation of an individual's mean consumption per eating episode. To identify features that predict overeating, we will apply 2 complementary machine learning methods: correlation-based feature selection and wrapper-based feature selection. We will then generate clusters of overeating types and assess how they align with clinically meaningful overeating phenotypes., Conclusions: This study will be the first to assess characteristics of eating episodes in situ over a multiweek period with visual confirmation of eating behaviors. An additional strength of this study is the assessment of predictors of problematic eating during periods when individuals are not on a structured diet and/or engaged in a weight loss intervention. Our assessment of overeating episodes in real-world settings is likely to yield new insights regarding determinants of overeating that may translate into novel interventions., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Despite inconsistent results across studies, emerging evidence suggests that the microbial micro-environment may be associated with autism spectrum disorder (ASD). Geographical and cultural factors highly impact microbial profiles, and there is a shortage of data from East Asian populations. This study aimed to comprehensively characterize microbial profiles in an East Asian sample and explore whether gut microbiota contributes to clinical symptoms, emotional/behavioral problems, and GI symptoms in ASD., Methods: We assessed 82 boys and young men with ASD and 31 typically developing controls (TDC), aged 6-25 years. We analyzed the stool sample of all participants with 16S V3-V4 rRNA sequencing and correlated its profile with GI symptoms, autistic symptoms, and emotional/behavioral problems., Results: Autistic individuals, compared to TDC, had worse GI symptoms. There were no group differences in alpha diversity of species richness estimates (Shannon-wiener and Simpson diversity indices). Participants with ASD had an increased relative abundance of Fusobacterium, Ruminococcus torques group (at the genus level), and Bacteroides plebeius DSM 17135 (at the species level), while a decreased relative abundance of Ruminococcaceae UCG 013, Ervsipelotrichaceae UCG 003, Parasutterella, Clostridium sensu stricto 1, Turicibacter (at the genus level), and Clostridium spiroforme DSM 1552 and Intestinimonas butyriciproducens (at the species level). Altered taxonomic diversity in ASD significantly correlated with autistic symptoms, thought problems, delinquent behaviors, self dysregulation, and somatic complaints. We did not find an association between gut symptoms and gut microbial dysbiosis., Conclusions: Our findings suggest that altered microbiota are associated with behavioral phenotypes but not GI symptoms in ASD. The function of the identified microbial profiles mainly involves the immune pathway, supporting the hypothesis of a complex relationship between altered microbiome, immune dysregulation, and ASD that may advance the discovery of molecular biomarkers for ASD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Objective: ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 ( ST8SIA2 ) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. Some population and animal studies have indicated an association between the ST8SIA2 gene and autism spectrum disorder (ASD). However, there is limited information on the correlation between ST8SIA2 and autistic behavioral symptoms., Methods: In this study, 69 ASD and 76 normal control children who were age- and sex-matched were recruited. ST8SIA2 expression and methylation levels were measured by reverse transcription quantitative real-time PCR and pyrosequencing, respectively, and the behavioral phenotypes of ASD children were assessed., Results: The ASD group had lower ST8SIA2 gene expression levels than the control group [ t (0.05/2,143) = 2.582, p = 0.011]. Moreover, ST8SIA2 expression levels were positively correlated with daily life skills ( r s = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group ( r s = -0.510, p = 0.004). The methylation levels of the Chr. 15: 92984625 and Chr. 15: 92998561 sites of the ST8SIA2 gene in ASD children were higher than those of controls. The Chr. 15: 92984625 site was positively correlated with the stereotyped behaviors of ASD children ( r s = 0.41, p = 0.039)., Conclusion: This study provides a scientific basis to elucidate the relationship between the ST8SIA2 gene and behavioral phenotypes of ASD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Li, Chai and Liu.)

Background and Aim: There is mounting evidence highlighting that Cornelia de Lange Syndrome (CdLS) and Rubinstein-Taybi Syndrome's (RSTS) behavioral phenotypes are not stable over individual developmental trajectories and that several psychiatric disorders might arise with age. Our study aims to examine the specific hallmarks of psychopathology and behavioral phenotypes in four different age ranges: infancy and toddlerhood, early childhood, middle childhood, and adolescence, in both genetic syndromes., Method: The sample included 44 patients with CdLS (48% boys, age = 6.67 ± 4.36) and 31 with RSTS (48% boys, age = 6.89 ± 4.58) recruited through follow-ups. Cognitive, behavioral, and autism assessments were carried out with Griffith's scales or the Leiter-R, the Child Behavior Checklist, and the Child Autism Rating Scales 2. Multiple ANOVA 2 × 4 were run to outline behavioral phenotypic age-related syndromic markers and ANCOVA to value the weight of IQ and ASD-related traits on the psychopathological outcome., Results: Findings showed that anxiety is a crucial phenotypic hallmark, independent of IQ but associated with autistic traits, that increases from infancy to adolescence in both CdLS and RSTS., Conclusion and Implications: Being aware of the developmental challenges that growing children are called to face is essential for drawing up proper standards of assessment turning into target age-related interventions, ensuring these patients personalized healthcare and improvement in life quality., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Humans are ubiquitously exposed to neurotoxicants in air pollution, causing increased risk for psychiatric outcomes. Effects of prenatal exposure to air pollution on early emerging behavioral phenotypes that increase risk of psychopathology remain understudied. We review animal models that represent analogues of human behavioral phenotypes that are risk markers for internalizing and externalizing problems (behavioral inhibition, behavioral exuberance, irritability), and identify commonalities among the neural mechanisms underlying these behavioral phenotypes and the neural targets of three types of air pollutants (polycyclic aromatic hydrocarbons, traffic-related air pollutants, fine particulate matter < 2.5 µm). We conclude that prenatal exposure to air pollutants increases risk for behavioral inhibition and irritability through distinct mechanisms, including altered dopaminergic signaling and hippocampal morphology, neuroinflammation, and decreased brain-derived neurotrophic factor expression. Future studies should investigate these effects in human longitudinal studies incorporating complex exposure measurement methods, neuroimaging, and behavioral characterization of temperament phenotypes and neurocognitive processing to facilitate efforts aimed at improving long-lasting developmental benefits for children, particularly those living in areas with high levels of exposure., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Threatening stimuli challenging animal homeostasis are the primary events triggering defensive responses, including TI. The stress-response system (allostasis) is signaled by increased corticosteroid basal levels. In bird animal lines genetically selected for stress-induced corticosterone, there is a covariation between stress physiology and coping styles. Rabbit studies, in which the effects of TI are dissociated from those of induction per se, support the view that TI takes part in the homeostatic stress-response system. An increase of corticosterone is recorded just after the end of the induction procedure but not in the corresponding groups in which induction is followed by TI, suggesting a recovery process during TI. Similarly to corticosterone but in opposite direction, testosterone plasma levels decrease following induction and recover during TI. Recovery mechanisms are also suggested in two bird genotypes selected for long and short TI duration. The positive relation between corticosterone levels and TI duration has been confirmed after exogenous corticosterone administration., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Previous studies have demonstrated overlapping behavioral features between substance-use disorders and food addiction, the latter of which is particularly prevalent among individuals with overweight or obesity. However, the unique attributes of food addiction as a possible phenotype within overweight and obesity are not fully understood., Methods: This cross-sectional study recruited participants (n = 46) with overweight or obesity, nearly half (n = 20) of whom met the criteria for food addiction based on the Yale Food Addiction Scale 2.0 (YFAS 2.0) and examined responses to self-report questionnaires that indexed behavioral characteristics relevant to addictive disorders., Results: Individuals with food addiction exhibited significantly higher scores on the Palatable Eating Motives Scale overall score (p < .001) and subscales for coping (p < .001) and enhancement (p < .001) of emotions, Dutch Eating Behavior Questionnaire Emotional Eating subscale (p < .001), UPPS-P Impulsivity Scale negative urgency (p < .001) and lack of perseverance (p = .01) subscales, and the Food Craving Inventory overall score (p = .02) and subscales of cravings for sweets (p < .01) and fast food fats (p = .02)., Conclusion: Food addiction appears to represent a distinct phenotype within overweight and obesity, marked by greater emotion dysregulation, impulsivity, and cravings, which have been observed in prior studies examining features of individuals with addictive disorders., Level of Evidence: Level III: Evidence obtained from well-designed cohort or case-control analytic studies., (© 2020. Springer Nature Switzerland AG.)

Repetitive transcranial magnetic stimulation (rTMS) is considered a promising therapeutic tool for treating neuropsychiatric diseases. Previously, we found intermittent theta-burst stimulation (iTBS) rTMS to be most effective in modulating cortical excitation-inhibition balance in rats, accompanied by improved cortical sensory processing and sensory learning performance. Using an animal schizophrenia model based on maternal immune activation (MIA) we tested if iTBS applied to either adult or juvenile rats can affect the behavioral phenotype in a therapeutic or preventive manner, respectively. In a sham-controlled fashion, iTBS effects in MIA rats were compared with rats receiving vehicle NaCl injection instead of the synthetic viral strand. Prior to iTBS, adult MIA rats showed deficits in sensory gating, as tested with prepulse inhibition (PPI) of the acoustic startle reflex, and deficits in novel object recognition (NOR). No differences between MIA and control rats were evident with regard to signs of anxiety, anhedonia and depression but MIA rats were somewhat superior to controls during the training phase of Morris Water Maze (MWM) test. MIA but not control rats significantly improved in PPI following iTBS at adulthood but without significant differences between verum and sham application. If applied during adolescence, verum but not sham-iTBS improved NOR at adulthood but no difference in PPI was evident in rats treated either with sham or verum-iTBS. MIA and control rat responses to sham-iTBS applied at adulthood differed remarkably, indicating a different physiological reaction to the experimental experiences. Although verum-iTBS was not superior to sham-iTBS, MIA rats seemed to benefit from the treatment procedure in general, since differences-in relation to control rats declined or disappeared. Even if classical placebo effects can be excluded, motor or cognitive challenges or the entire handling procedure during the experiments appear to alleviate the behavioral impairments of MIA rats., Competing Interests: GB was employed by the company AIO-Studien-gGmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest, (Copyright © 2021 Rittweger, Ishorst, Barmashenko, Aliane, Winter and Funke.)

Background: The rate of habituation to food and reinforcing value of food are processes that are related to food intake and body weight. Reinforcing value of food provides an index of the motivation to eat, while habituation provides an index on how repeated presentations of food relate to reduced behavioral and physiological responses to that food., Objective: To investigate the relationship between habituation phenotypes to salty, sweet and savory foods and reinforcing value of those foods., Design: A sample of 229 8-12-year-old children at risk for obesity completed reinforcing value and habituation tasks for foods that varied in savory, sweet or salty tastes. Multivariate Group Based Trajectory Modeling was used to create four unique patterns of habitation to foods based on detailed 10 s epochs of responding for food over a 24 min task. Differences in reinforcing value of food were assessed for these habituation phenotypes., Results: Results showed a graded relationship between the overall habituation phenotypes and reinforcing value of food, as those with the relatively flat habituation phenotype found food more reinforcing than those with phenotypes that showed rapidly decelerating responding across all taste categories., Conclusions: Those who habituated slower found food more reinforcing than those with a rapid habituation phenotype. Implications of these phenotypes for understanding how habituation relates to food intake are discussed., Competing Interests: Declaration of competing interest Dr. Epstein was a consultant and had equity in Daltri when the study was implemented. The other authors do not declare any conflict of interest with respect to the authorship or publication of this article., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Public goods, ranging from judiciary to sanitation to parkland, permeate daily life. They have been a subject of intense interdisciplinary study, with a traditional focus being on participation levels in isolated public goods games (PGGs) as opposed to a more recent focus on participation in PGGs embedded into complex social networks. We merged the two perspectives by arranging voluntary participants into one of three network configurations, upon which volunteers played a number of iterated PGGs within their network neighborhood. The purpose was to test whether the topology of social networks or a freedom to express preferences for some local public goods over others affect participation. The results show that changes in social networks are of little consequence, yet volunteers significantly increase participation when they freely express preferences. Surprisingly, the increase in participation happens from the very beginning of the game experiment, before any information about how others play can be gathered. Such information does get used later in the game as volunteers seek to correlate contributions with higher returns, thus adding significant value to public goods overall. These results are ascribable to a small number of behavioral phenotypes, and suggest that societies may be better off with bottom-up schemes for public goods provision., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Limited information is available concerning the specificity of the forms and functions of aggressive behavior exhibited by boys with fragile X syndrome (FXS). To investigate these relationships, we conducted indirect functional assessments of aggressive behavior exhibited by 41 adolescent boys with FXS and 59 age and symptom-matched controls with intellectual and developmental disability (IDD) and compared the data between groups. Results showed that boys with FXS were more likely to exhibit specific forms of aggressive behavior (i.e., scratching others and biting others) compared to controls, but the sources of reinforcement identified for aggression were similar across groups. Boys with FXS who were prescribed psychotropic medications were more likely to be older and to exhibit more forms of aggression. The implications for the treatment of aggressive behavior during this critical developmental period in FXS are discussed., (©AAIDD.)

Schizophrenia is frequently accompanied by depressive symptoms, but the pathological mechanisms remain to be elucidated. In this study, we used chronic unpredicted mild stress plus MK801 injection to generate a mouse model of schizophrenia with depression, in which in vivo 2-photon calcium imaging and electrophysiological recordings were performed in conjunction with behavioral phenotyping. Compared to mice models with classical depression or to schizophrenia models, the animal models with schizophrenia and depression comorbidity presented worse psychotic and depressive symptoms. These behavioral deficits are associated with impaired neuronal calcium activities in the frontal cortex and thalamic nuclei. Moreover, in sharp contrast to classical models that have a satisfactory response to antipsychotic or antidepressant drugs, this novel schizophrenia with depression model is resilient to combined drug treatment in terms of behavioral and functional recovery. Taken together, these data indicate that schizophrenia with depression likely involves a unique pathophysiology that is different from schizophrenia or depression alone., (Copyright © 2020 Zhou, Kong, Zhu, Wu, Xue, Li, Xu, Liu, Tian and Zhuo.)

Angelman syndrome (AS) is a genetic disorder which entails autism, intellectual disability, lack of speech, motor deficits, and seizure susceptibility. It is caused by the lack of UBE3A protein expression, which is an E3-ubiquitin ligase. Despite AS equal prevalence in males and females, not much data on how sex affects the syndrome was reported. In the herein study, we thoroughly characterized many behavioral phenotypes of AS mice. The behavioral data acquired was analyzed with respect to sex. In addition, we generated a new mRNA sequencing dataset. We analyzed the coding transcriptome expression profiles with respect to the effects of genotype and sex observed in the behavioral phenotypes. We identified several neurobehavioral aspects, especially sensory perception, where AS mice either lack the male-to-female differences observed in wild-type littermates or even show opposed differences. However, motor phenotypes did not show male-to-female variation between wild-type (WT) and AS mice. In addition, by utilizing the mRNA sequencing, we identified genes and isoforms with expression profiles that mirror the sensory perception results. These genes are differentially regulated in the two sexes with inverse expression profiles in AS mice compared to WT littermates. Some of these are known pain-related and estrogen-dependent genes. The observed differences in sex-dependent neurobehavioral phenotypes and the differential transcriptome expression profiles in AS mice strengthen the evidence for molecular cross talk between Ube3a protein and sex hormone receptors or their elicited pathways. These interactions are essential for understanding Ube3a deletion effects, beyond its E3-ligase activity.

Background and Objective: Autism spectrum disorder (ASD) is a heterogeneous disorder. Research has explored potential ASD subgroups with preliminary evidence supporting the existence of behaviorally and genetically distinct subgroups; however, research has yet to leverage machine learning to identify phenotypes on a scale large enough to robustly examine treatment response across such subgroups. The purpose of the present study was to apply Gaussian Mixture Models and Hierarchical Clustering to identify behavioral phenotypes of ASD and examine treatment response across the learned phenotypes., Materials and Methods: The present study included a sample of children with ASD (N = 2400), the largest of its kind to date. Unsupervised machine learning was applied to model ASD subgroups as well as their taxonomic relationships. Retrospective treatment data were available for a portion of the sample (n  = 1034). Treatment response was examined within each subgroup via regression., Results: The application of a Gaussian Mixture Model revealed 16 subgroups. Further examination of the subgroups through Hierarchical Agglomerative Clustering suggested 2 overlying behavioral phenotypes with unique deficit profiles each composed of subgroups that differed in severity of those deficits. Furthermore, differentiated response to treatment was found across subtypes, with a substantially higher amount of variance accounted for due to the homogenization effect of the clustering., Discussion: The high amount of variance explained by the regression models indicates that clustering provides a basis for homogenization, and thus an opportunity to tailor treatment based on cluster memberships. These findings have significant implications on prognosis and targeted treatment of ASD, and pave the way for personalized intervention based on unsupervised machine learning., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The study presents the results of behavioral phenotyping of rats with experimental chronic obstructive pulmonary disease (eCOPD) of different severity modeled by using a combination of inductors (purified papain and bacterial LPS) in increasing concentrations. Locomotor and exploratory activity, spatial memory, and anxiety were evaluated. In mild eCOPD, locomotor and exploratory activity increased, while other parameters did not differ from the control values. Rats with moderate eCOPD demonstrated moderately restricted locomotor function and increased anxiety. Severe eCOPD was associated with pronounced changes in all analyzed parameters. Correlation analysis revealed relationships between some behavioral parameters and blood oxygen saturation, inspiratory lung volume, and respiration rate. This indicates the role of respiratory failure in the pathogenesis of cognitive disorders.

Children with Down syndrome (DS) are at higher risk for both delayed expressive language and poor speech intelligibility. The current study utilized the quantitative automated language environment analysis (LENA) to depict mother and child vocalizations and conversational patterns in the home of 43 children with DS, chronologically aged 24-64 months. Children with DS displayed fewer utterances than typically developing children; however, there was wide variability. Furthermore, children with DS did not show increased vocalization counts across their chronological ages. In contrast to previous findings, this study found that the mothers of children with DS had a reduced number of vocalizations. However, the vocalizations increased with age in comparison to mothers of typically developing children. Implications for targeted interventions that facilitate learning opportunities in bidirectional contexts for children with DS and their parents are discussed, with particular attention to quantify behavioral phenotypes utilizing a novel expressive language assessment tool.

The manner in which laboratory rodents are housed is driven by economics (minimal use of space and resources), ergonomics (ease of handling and visibility of animals), hygiene, and standardization (reduction of variation). This has resulted in housing conditions that lack sensory and motor stimulation and restrict the expression of species-typical behavior. In mice, such housing conditions have been associated with indicators of impaired welfare, including abnormal repetitive behavior (stereotypies, compulsive behavior), enhanced anxiety and stress reactivity, and thermal stress. However, due to concerns that more complex environmental conditions might increase variation in experimental results, there has been considerable resistance to the implementation of environmental enrichment beyond the provision of nesting material. Here, using 96 C57BL/6 and SWISS female mice, respectively, we systematically varied environmental enrichment across four levels spanning the range of common enrichment strategies: (1) bedding alone; (2) bedding + nesting material; (3) deeper bedding + nesting material + shelter + increased vertical space; and (4) semi-naturalistic conditions, including weekly changes of enrichment items. We studied how these different forms of environmental enrichment affected measures of animal welfare, including home-cage behavior (time-budget and stereotypic behavior), anxiety (open field behavior, elevated plus-maze behavior), growth (food and water intake, body mass), stress physiology (glucocorticoid metabolites in fecal boluses and adrenal mass), brain function (recurrent perseveration in a two-choice guessing task) and emotional valence (judgment bias). Our results highlight the difficulty in making general recommendations across common strains of mice and for selecting enrichment strategies within specific strains. Overall, the greatest benefit was observed in animals housed with the greatest degree of enrichment. Thus, in the super-enriched housing condition, stereotypic behavior, behavioral measures of anxiety, growth and stress physiology varied in a manner consistent with improved animal welfare compared to the other housing conditions with less enrichment. Similar to other studies, we found no evidence, in the measures assessed here, that environmental enrichment increased variation in experimental results.

Background: Epidemiological studies suggest that hyponutrition during the fetal period increases the risk of mental disorders such as attention deficit hyperactivity disorder and autism-spectrum disorder, which has been experimentally supported using animal models. However, previous experimental hyponutrition or protein-restricted (PR) diets affected stages other than the fetal stage, such as formation of the egg before insemination, milk composition during lactation, and maternal nursing behavior., Results: We conducted in vitro fertilization and embryo transfer in mice and allowed PR diet and folic acid-supplemented PR diet to affect only fetal environments. Comprehensive phenotyping of PR and control-diet progenies showed moderate differences in fear/anxiety-like, novelty-seeking, and prosocial behaviors, irrespective of folic-acid supplementation. Changes were also detected in gene expression and genomic methylation in the brain., Conclusions: These results suggest that epigenetic factors in the embryo/fetus influence behavioral and epigenetic phenotypes of progenies. Significant epigenetic alterations in the brains of the progenies induced by the maternal-protein restriction were observed in the present study. To our knowledge, this is first study to evaluate the effect of maternal hyponutrition on behavioral phenotypes using reproductive technology.

Few comparative studies have evaluated the heterogeneity of sociability across a range of neurodevelopmental disorders. The Sociability Questionnaire for People with Intellectual Disability (SQID) was completed by caregivers of individuals with Cornelia de Lange (n = 98), Angelman (n = 66), Fragile X (n = 142), Down (n = 117) and Rubinstein Taybi (n = 88) syndromes and autism spectrum disorder (ASD; n = 107). Between groups and age-band (<12yrs; 12-18yrs; >18yrs) comparisons of SQID scores were conducted. Rates of behaviors indicative of selective mutism were also examined. Fragile X syndrome achieved the lowest SQID scores. Cornelia de Lange, ASD, and Fragile X groups scored significantly lower than Angelman, Down and Rubinstein Taybi groups. Selective mutism characteristics were highest in Cornelia de Lange (40%) followed by Fragile X (17.8%) and ASD (18.2%). Age-band differences were identified in Cornelia de Lange and Down syndrome.

This study was undertaken to describe seizure phenotypes, natural progression, sleep-wake patterns, as well as periodicity of seizures in Kcna-1 null mutant mice. These mice were implanted with epidural electroencephalography (EEG) and electromyography (EMG) electrodes, and simultaneous video-EEG recordings were obtained while animals were individually housed under either diurnal (LD) condition or constant darkness (DD) over ten days of recording. The video-EEG data were analyzed to identify electrographic and behavioral phenotypes and natural progression and to examine the periodicity of seizures. Sleep-wake patterns were analyzed to understand the distribution and onset of seizures across the sleep-wake cycle. Four electrographically and behaviorally distinct seizure types were observed. Regardless of lighting condition that animals were housed in, Kcna-1 null mice initially expressed only a few of the most severe seizure types that progressively increased in frequency and decreased in seizure severity. In addition, a circadian periodicity was noted, with seizures peaking in the first 12h of the Zeitgeber time (ZT) cycle, regardless of lighting conditions. Interestingly, seizure onset differed between lighting conditions where more seizures arose out of sleep in LD conditions, whereas under DD conditions, the majority occurred out of the wakeful state. We suggest that this model be used to understand the circadian pattern of seizures as well as the pathophysiological implications of sleep and circadian disturbances in limbic epilepsies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A large volume of behavioral research has explored the variable number of tandem repeat (VNTR) polymorphism on the dopamine receptor D4 gene (DRD4). However, findings are inconsistent and there is no agreement about what constitutes "functional" and "less functional" variants at this locus. First, we systematically review studies exploring biological differences between DRD4 VNTRs (k=21). Second, we systematically review studies relating DRD4 variation to behavioral traits in population-based, non-clinical samples of children and adolescents (k=46; N=13,195), highlighting the various genotypic classifications previously used. Third, we use meta-analyses to examine associations of DRD4 VNTRs with five broadly-defined behavioral outcomes (externalizing and attention problems, executive function, social/emotional development, and "reactive" temperament). We identify a significant association of "longer" DRD4 variants with lower levels of executive function and social/emotional development, but not independent of the choice of genotypic classification. We suggest that until the functionality of DRD4 VNTRs is established, researchers should report all genotypic classifications to ensure full transparency and allow for further meta-analytic work., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Transactive response DNA-binding protein 43 (TDP-43) mislocalization and aggregation are hallmark features of amyotrophic lateral sclerosis and frontotemporal dementia (FTD). We have previously shown in mice that inducible overexpression of a cytoplasmically localized form of TDP-43 (TDP-43-ΔNLS) in forebrain neurons evokes neuropathological changes that recapitulate several features of TDP-43 proteinopathies. Detailed behavioral phenotyping could provide further validation for its usage as a model for FTD. In the present study, we performed a battery of behavioral tests to evaluate motor, cognitive, and social phenotypes in this model. We found that transgene (Tg) induction by doxycycline removal at weaning led to motor abnormalities including hyperlocomotion in the open field test, impaired coordination and balance in the rotarod test, and increased spasticity as shown by a clasping phenotype. Cognitive assessment demonstrated impaired recognition and spatial memory, measured by novel object recognition and Y-maze tests. Remarkably, TDP-43-ΔNLS mice displayed deficits in social behavior, mimicking a key aspect of FTD. To determine whether these symptoms were reversible, we suppressed Tg expression for 14 d in 1.5-month-old mice showing an established behavioral phenotype but modest neurodegeneration and found that motor and cognitive deficits were ameliorated; however, social performance remained altered. When Tg expression was suppressed in 6.5-month-old mice showing overt neurodegeneration, motor deficits were irreversible. These results indicate that TDP-43-ΔNLS mice display several core behavioral features of FTD with motor neuron disease, possibly due to functional changes in surviving neurons, and might serve as a valuable tool to unveil the underlying mechanisms of this and other TDP-43 proteinopathies., (Copyright © 2014 the authors 0270-6474/14/3415244-16$15.00/0.)

Fragile X syndrome (FXS) is a monogenic disease caused by mutations in the FMR1 gene. The Fmr1 knockout (KO) mice show many aspects of FXS-related phenotypes, and have been used as a major pre-clinical model for FXS. Although FXS occurs in both male and female patients, most studies on the mouse model use male animals. Few studies test whether gender affects the face validity of the mouse model. Here, we examined multiple behavioral phenotypes with male hemizygous and female homozygous Fmr1 KO mice on C57BL/6 background. For each behavioral paradigm, we examined multiple cohorts from different litters. We found that both male and female Fmr1 KO mice displayed significant audiogenic seizures, hyperactivity in the open field test, deficits in passive avoidance and contextual fear memory, and significant enhancement of PPI at low stimulus intensity. Male and female Fmr1 KO mice also showed more transitional movement between the lit and dark chambers in the light-dark tests. The lack of gender effects suggests that the Fmr1 KO mouse is a reasonable tool to test the efficacy of potential FXS therapies., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Studies of individuals with Cornelia de Lange syndrome (CdLS) have described changes in mood and behavior with age, although no empirical or longitudinal studies have been conducted. Caregivers of individuals with CdLS (N  =  67), cri du chat syndrome (CdCS; N  =  42), and Fragile X syndrome (FXS; N  =  142) completed the Mood, Interest and Pleasure Questionnaire (MIPQ) at Time 1 and 2 years later (Time 2). Scores on the MIPQ were significantly lower in the CdLS group compared with the CdCS and FXS groups at Time 1 and Time 2. Lower MIPQ scores were characteristic of older adolescents (> 15 years) and adults with CdLS. However, there were no significant differences in MIPQ scores between Time 1 and Time 2. Age and insistence on sameness predicted MIPQ scores in CdLS.

Angelman syndrome has been suggested as a disease model of neurogenetic developmental condition with a specific behavioral phenotype. It is due to lack of expression of the UBE3A gene, an imprinted gene located on chromosome 15q. Here we review the main features of this phenotype, characterized by happy demeanor with prominent smiling, poorly specific laughing and general exuberance, associated with hypermotor behavior, stereotypies, and reduced behavioral adaptive skills despite proactive social contact. All these phenotypic characteristics are currently difficult to quantify and have been subject to some differences in interpretation. For example, prevalence of autistic disorder is still debated. Many of these features may occur in other syndromic or nonsyndromic forms of severe intellectual disability, but their combination, with particularly prominent laughter and smiling may be specific of Angelman syndrome. Management of problematic behaviors is primarily based on behavioral approaches, though psychoactive medication (eg, neuroleptics or antidepressants) may be required.