Regulation Of Social Behavior Research Articles

Imaging Analyses of Oxytocin: Visualization of Oxytocin and Its Implications

Oxytocin, long known for its peripheral action, is a strong regulator of social behaviors through its actions in the brain. Despite such recognition, its sites of actions and dynamics within the brain tissues remain poorly understood owing to the lack of appropriate tools for its visualization and characterization. Conventional fluorescence-tagging is not applicable for small-sized bioactive molecules like oxytocin. Herein, our attempt to overcome this limitation is introduced using our novel strategy, alkyne-tagging. Small-sized alkynes would facilitate specific tagging and subsequent visualization of oxytocin within the body, which would bring forth new insights into the modes of oxytocin's action in the brain.

Postnatal expression of CD38 in astrocytes regulates synapse formation and adult social memory.

Social behavior is essential for health, survival, and reproduction of animals; however, the role of astrocytes in social behavior remains largely unknown. The transmembrane protein CD38, which acts both as a receptor and ADP-ribosyl cyclase to produce cyclic ADP-ribose (cADPR) regulates social behaviors by promoting oxytocin release from hypothalamic neurons. CD38 is also abundantly expressed in astrocytes in the postnatal brain and is important for astroglial development. Here, we demonstrate that the astroglial-expressed CD38 plays an important role in social behavior during development. Selective deletion of CD38 in postnatal astrocytes, but not in adult astrocytes, impairs social memory without any other behavioral abnormalities. Morphological analysis shows that depletion of astroglial CD38 in the postnatal brain interferes with synapse formation in the medial prefrontal cortex (mPFC) and hippocampus. Moreover, astroglial CD38 expression promotes synaptogenesis of excitatory neurons by increasing the level of extracellular SPARCL1 (also known as Hevin), a synaptogenic protein. The release of SPARCL1 from astrocytes is regulated by CD38/cADPR/calcium signaling. These data demonstrate a novel developmental role of astrocytes in neural circuit formation and regulation of social behavior in adults.

Post-weaning social isolation in male mice leads to abnormal aggression and disrupted network organization in the prefrontal cortex: Contribution of parvalbumin interneurons with or without perineuronal nets

Adverse social experiences during childhood increase the risk of developing aggression-related psychopathologies. The prefrontal cortex (PFC) is a key regulator of social behavior, where experience-dependent network development is tied to the maturation of parvalbumin-positive (PV+) interneurons. Maltreatment in childhood could impact PFC development and lead to disturbances in social behavior during later life. However, our knowledge regarding the impact of early-life social stress on PFC operation and PV+ cell function is still scarce. Here, we used post-weaning social isolation (PWSI) to model early-life social neglect in mice and to study the associated neuronal changes in the PFC, additionally distinguishing between the two main subpopulations of PV+ interneurons, i.e. those without or those enwrapped by perineuronal nets (PNN). For the first time to such detailed extent in mice, we show that PWSI induced disturbances in social behavior, including abnormal aggression, excessive vigilance and fragmented behavioral organization. PWSI mice showed altered resting-state and fighting-induced co-activation patterns between orbitofrontal and medial PFC (mPFC) subregions, with a particularly highly elevated activity in the mPFC. Surprisingly, aggressive interaction was associated with a higher recruitment of mPFC PV+ neurons that were surrounded by PNN in PWSI mice that seemed to mediate the emergence of social deficits. PWSI did not affect the number of PV+ neurons and PNN density, but enhanced PV and PNN intensity as well as cortical and subcortical glutamatergic drive onto mPFC PV+ neurons. Our results suggest that the increased excitatory input of PV+ cells could emerge as a compensatory mechanism for the PV+ neuron-mediated impaired inhibition of mPFC layer 5 pyramidal neurons, since we found lower numbers of GABAergic PV+ puncta on the perisomatic region of these cells. In conclusion, PWSI leads to altered PV-PNN activity and impaired excitatory/inhibitory balance in the mPFC, which possibly contributes to social behavioral disruptions seen in PWSI mice. Our data advances our understanding on how early-life social stress can impact the maturing PFC and lead to the development of social abnormalities in adulthood.

A comparative study of social cognition in epilepsy, brain injury, and Parkinson's disease.

The brain regions involved in social cognition and the regulation of social behavior form a widely distributed cortico-subcortical network. Therefore, many neurological disorders could affect social cognition and behavior. A persistent lack of valid tests and a rigid neuropsychological focus on language, attention, executive function, and memory have contributed to a long-standing neglect of social cognition in clinical diagnostics, although the DSM-5 recognizes it as one of the six core dimensions in neurocognitive disorders. To assess for the first time the diagnostic yield of a comprehensive social cognition battery (Networks of Emotion Processing [NEmo]), we administered several emotion recognition and theory of mind tests to three incidental clinical samples with different neurological conditions: temporal lobe epilepsy (n = 30), acquired brain injury (n = 24), Parkinson's disease (n = 19), and a healthy control group (n = 67). A multivariate analysis of covariance was performed to test the effect of group on subscales of the NEmo test battery, controlling for age and performance IQ. The results showed statistically significant differences between clinical groups and healthy controls. No differences were found for gender and lateralization of the predominant lesion side. In our incidental samples, 86% of individuals with temporal lobe epilepsy, 57% of individuals with acquired brain lesion, and 14% of individuals with Parkinson's disease underperformed on tests of social cognition compared with controls. These findings suggest a differential impact of neurological disorders on the risk of impaired social cognition and highlight the need to consider social cognition in diagnostics, counselling, therapy, and rehabilitation.

Regulation of social interaction in mice by a frontostriatal circuit modulated by established hierarchical relationships

Social hierarchies exert a powerful influence on behavior, but the neurobiological mechanisms that detect and regulate hierarchical interactions are not well understood, especially at the level of neural circuits. Here, we use fiber photometry and chemogenetic tools to record and manipulate the activity of nucleus accumbens-projecting cells in the ventromedial prefrontal cortex (vmPFC-NAcSh) during tube test social competitions. We show that vmPFC-NAcSh projections signal learned hierarchical relationships, and are selectively recruited by subordinate mice when they initiate effortful social dominance behavior during encounters with a dominant competitor from an established hierarchy. After repeated bouts of social defeat stress, this circuit is preferentially activated during social interactions initiated by stress resilient individuals, and plays a necessary role in supporting social approach behavior in subordinated mice. These results define a necessary role for vmPFC-NAcSh cells in the adaptive regulation of social interaction behavior based on prior hierarchical interactions.

Amygdala circuit transitions supporting developmentally-appropriate social behavior

Social behaviors dynamically change throughout the lifespan alongside the maturation of neural circuits. The basolateral region of the amygdala (BLA), in particular, undergoes substantial maturational changes from birth throughout adolescence that are characterized by changes in excitation, inhibition, and dopaminergic modulation. In this review, we detail the trajectory through which BLA circuits mature and are influenced by dopaminergic systems to guide transitions in social behavior in infancy and adolescence using data from rodents. In early life, social behavior is oriented towards approaching the attachment figure, with minimal BLA involvement. Around weaning age, dopaminergic innervation of the BLA introduces avoidance of novel peers into rat pups’ behavioral repertoire. In adolescence, social behavior transitions towards peer-peer interactions with a high incidence of social play-related behaviors. This transition coincides with an increasing role of the BLA in the regulation of social behavior. Adolescent BLA maturation can be characterized by an increasing integration and function of local inhibitory GABAergic circuits and their engagement by the medial prefrontal cortex (mPFC). Manipulation of these transitions using viral circuit dissection techniques and early adversity paradigms reveals the sensitivity of this system and its role in producing age-appropriate social behavior.

Validation of Self-Regulated Writing Strategies for Advanced EFL Learners in China: A Structural Equation Modeling Analysis.

This study aims to validate self-regulated writing strategies for advanced EFL learners through a structural equation modeling analysis. Two sets of advanced, university-level EFL learners in China were recruited on the basis of results from a nationwide standardized English test. Sample 1 consisted of 214 advanced learners and served mainly as a data source for exploratory factor analysis. Sample 2 consisted of 303 advanced learners; data from this group were used to conduct confirmatory factor analyses. The results confirmed the goodness of fit of the hierarchical, multidimensional structure of self-regulated writing strategies. This hierarchic model has the higher order of self-regulation and the second order of nine self-regulated writing strategies that belong to four dimensions. In terms of model comparisons, the indices of Model 1 (nine-factor correlated model of EFL writing strategies for SRL) and Model 2 (four-factor second-order model of EFL writing strategies for SRL) mark significant improvements in terms of fit over the indices of Model 3 (one-factor second-order model of EFL writing strategies for SRL). This means the four-factor model (cognition, metacognition, social behavior, and motivational regulation) offered a better explanation for advanced EFL learners than the model treating self-regulated writing strategies as a single convergent factor. These findings, in some ways, differ from the results of earlier research on EFL learners' self-regulated writing strategies, and the findings of this study have certain implications for L2 writing teaching and learning.

Involvement of oxytocin receptor deficiency in psychiatric disorders and behavioral abnormalities.

Oxytocin and its target receptor (oxytocin receptor, OXTR) exert important roles in the regulation of complex social behaviors and cognition. The oxytocin/OXTR system in the brain could activate and transduce several intracellular signaling pathways to affect neuronal functions or responses and then mediate physiological activities. The persistence and outcome of the oxytocin activity in the brain are closely linked to the regulation, state, and expression of OXTR. Increasing evidence has shown that genetic variations, epigenetic modification states, and the expression of OXTR have been implicated in psychiatric disorders characterized by social deficits, especially in autism. Among these variations and modifications, OXTR gene methylation and polymorphism have been found in many patients with psychiatric disorders and have been considered to be associated with those psychiatric disorders, behavioral abnormalities, and individual differences in response to social stimuli or others. Given the significance of these new findings, in this review, we focus on the progress of OXTR's functions, intrinsic mechanisms, and its correlations with psychiatric disorders or deficits in behaviors. We hope that this review can provide a deep insight into the study of OXTR-involved psychiatric disorders.

Oxytocin receptors in the Magel2 mouse model of autism: Specific region, age, sex and oxytocin treatment effects.

The neurohormone oxytocin (OXT) has been implicated in the regulation of social behavior and is intensively investigated as a potential therapeutic treatment in neurodevelopmental disorders characterized by social deficits. In the Magel2-knockout (KO) mouse, a model of Schaaf-Yang Syndrome, an early postnatal administration of OXT rescued autistic-like behavior and cognition at adulthood, making this model relevant for understanding the actions of OXT in (re)programming postnatal brain development. The oxytocin receptor (OXTR), the main brain target of OXT, was dysregulated in the hippocampus of Magel2-KO adult males, and normalized upon OXT treatment at birth. Here we have analyzed male and female Magel2-KO brains at postnatal day 8 (P8) and at postnatal day 90 (P90), investigating age, genotype and OXT treatment effects on OXTR levels in several regions of the brain. We found that, at P8, male and female Magel2-KOs displayed a widespread, substantial, down-regulation of OXTR levels compared to wild type (WT) animals. Most intriguingly, the postnatal OXT treatment did not affect Magel2-KO OXTR levels at P8 and, consistently, did not rescue the ultrasonic vocalization deficits observed at this age. On the contrary, the postnatal OXT treatment reduced OXTR levels at P90 in male Magel2-KO in a region-specific way, restoring normal OXTR levels in regions where the Magel2-KO OXTR was upregulated (central amygdala, hippocampus and piriform cortex). Interestingly, Magel2-KO females, previously shown to lack the social deficits observed in Magel2-KO males, were characterized by a different trend in receptor expression compared to males; as a result, the dimorphic expression of OXTR observed in WT animals, with higher OXTR expression observed in females, was abolished in Magel2-KO mice. In conclusion, our data indicate that in Magel2-KO mice, OXTRs undergo region-specific modifications related to age, sex and postnatal OXT treatment. These results are instrumental to design precisely-timed OXT-based therapeutic strategies that, by acting at specific brain regions, could modify the outcome of social deficits in Schaaf-Yang Syndrome patients.

Microbes, oxytocin and stress: Converging players regulating eating behavior.

Oxytocin is a peptide-hormone extensively studied for its multifaceted biological functions and has recently gained attention for its role in eating behavior, through its action as an anorexigenic neuropeptide. Moreover, the gut microbiota is involved in oxytocinergic signaling through the brain-gut axis, specifically in the regulation of social behavior. The gut microbiota is also implicated in appetite regulation and is postulated to play a role in central regulation of hedonic eating. In this review, we provide an overview on oxytocin and its individual links with the microbiome, the homeostatic and non-homeostatic regulation of eating behavior as well as social behavior and stress.

Perturbation of maternal gut microbiota in mice during a critical perinatal window influences early neurobehavioral outcomes in offspring

The gut microbiota is increasingly recognized as a key environmental factor that shapes host development and physiology, including neural circuits formation and function. Concurrently, there has been growing concern that early-life antibiotic exposure may alter brain developmental trajectories, increasing the risk for neurodevelopmental disorders such as autism spectrum disorder (ASD). Here, we assessed whether perturbation of the maternal gut microbiota in mice during a narrow critical perinatal window (last week of pregnancy and first three postnatal days), induced by exposure to a commonly used broad-spectrum oral antibiotic (ampicillin), influences offspring neurobehavioral outcomes relevant to ASD. Our results demonstrate that neonatal offspring from antibiotic-treated dams display an altered pattern of ultrasonic communication, which was more pronounced in males. Moreover, juvenile male, but not female, offspring from antibiotic-treated dams showed reduced social motivation and social interaction, as well as context-dependent anxiety-like behavior. However, no changes were observed in locomotor or exploratory activity. This behavioral phenotype of exposed juvenile males was associated with reduced gene expression of the oxytocin receptor (OXTR) and several tight-junction proteins in the prefrontal cortex, a key region involved in the regulation of social and emotional behaviors, as well as a mild inflammatory response in the colon. Further, juvenile offspring from exposed dams also showed distinct alterations in several gut bacterial species, including, Lactobacillus murinus, and Parabacteroides goldsteinii. Overall, this study highlights the importance of the maternal microbiome in early-life, and how its perturbation by a widely used antibiotic could contribute to atypical social and emotional development of offspring in a sex-dependent manner.This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".

Olfactory sensitivity differentiates morphologically distinct worker castes in Camponotus floridanus

BackgroundCamponotus floridanus ant colonies are comprised of a single reproductive queen and thousands of sterile female offspring that consist of two morphologically distinct castes: smaller minors and larger majors. Minors perform most of the tasks within the colony, including brood care and food collection, whereas majors have fewer clear roles and have been hypothesized to act as a specialized solider caste associated with colony defense. The allocation of workers to these different tasks depends, in part, on the detection and processing of local information including pheromones and other chemical blends such as cuticular hydrocarbons. However, the role peripheral olfactory sensitivity plays in establishing and maintaining morphologically distinct worker castes and their associated behaviors remains largely unexplored.ResultsWe examined the electrophysiological responses to general odorants, cuticular extracts, and a trail pheromone in adult minor and major C. floridanus workers, revealing that the repertoire of social behaviors is positively correlated with olfactory sensitivity. Minors in particular display primarily excitatory responses to olfactory stimuli, whereas major workers primarily manifest suppressed, sub-solvent responses. The notable exception to this paradigm is that both minors and majors display robust, dose-dependent excitatory responses to conspecific, non-nestmate cuticular extracts. Moreover, while both minors and majors actively aggress non-nestmate foes, the larger and physiologically distinct majors display significantly enhanced capabilities to rapidly subdue and kill their adversaries.ConclusionsOur studies reveal the behavioral repertoire of minors and majors aligns with profound shifts in peripheral olfactory sensitivity and odor coding. The data reported here support the hypothesis that minors are multipotential workers with broad excitatory sensitivity, and majors are dedicated soldiers with a highly specialized olfactory system for distinguishing non-nestmate foes. Overall, we conclude that C. floridanus majors do indeed represent a physiologically and behaviorally specialized soldier caste in which caste-specific olfactory sensitivity plays an important role in task allocation and the regulation of social behavior in ant colonies.

Агрессия в иммерсивной виртуальной среде: поведенческие стратегии подростков и эффект свидетеля

The spread of virtual reality technologies raises the question of the formation of new practices of digital sociality, including encountering destructive communication. The article is devoted to an experimental study of the behavioral reactions of adolescents acting as bystanders of cyberaggression situation in an immersive virtual environment, including depending on the differences in the expression of social responsibility and moral attitudes. Adolescents (N=50) were asked to complete a task to search for an object in the VRChat virtual environment, in which they faced a real-time cyberaggression situation. The participants of the experiment were divided into control and experimental groups, the members of the latter were additionally instructed to observe and maintain the rules of communication in the virtual environment. Two types of behavior were identified: “passive bystanders” (58%), who chose an avoidance strategy or engaged in communication only to solve the task and “active defenders” (42%), who were divided into aggressive and non-aggressive. It is shown that the choice of behavioral strategies aimed at helping the “victim” in a cyberaggression situation in virtual space is determined to a greater extent by such personal characteristics as the severity of social responsibility and the level of moral development, which make more important contribution to the regulation of social behavior, than by the instruction received “at the entrance to the situation” on the need to comply with the rules of positive culture communication. The social responsibility as a personal characteristic, as opposed to the phenomenon of diffusion of responsibility, revealed within the framework of the bystander effect, turns out to be more characteristic of the defenders of the “victim” and their prosocial role compared to passive observers.

Degradation of Perineuronal Nets in the Cerebellar Interpositus Nucleus Ameliorated Social Deficits in Shank3-deficient Mice

Perineuronal nets (PNNs) are structures that contain extracellular matrix chondroitin sulfate proteoglycan and surround the soma and dendrites of various neuronal cell types. They are involved in synaptic plasticity and undertake important physiological functions. Altered expression of PNNs has been demonstrated in the brains of autism-related animal models. However, the underlying mechanism is still unknown. In this study, we demonstrated that the PNNs in the cerebellum are involved in modulating social and repetitive/inflexible behaviors in Shank3B–/– mice, an established animal model of autism spectrum disorder. First, we performed wisteria floribunda agglutinin staining of the whole brain of Shank3B–/– mice, and found wisteria floribunda agglutinin-positive PNNs are significantly increased in the cerebellar interpositus nucleus (IntP) in Shank3B–/– mice compared to control littermates. After degradation of PNNs in the IntP by chondroitinase ABC, the repetitive behaviors of Shank3B–/– mice were decreased, while their social behaviors were ameliorated. These results suggested that PNNs homeostasis is involved in the regulation of social behavior, revealing a potential therapeutic strategy targeting PNNs in the IntP for the treatment of autism spectrum disorder.

Faded neural projection from the posterior bed nucleus of the stria terminalis to the lateral habenula contributes to social signaling deficit in male BTBR mice as a mouse model of autism

BTBR T+ Itpr3tf/J (BTBR) mice display several behavioral characteristics, including social deficits resembling the core symptoms of human autism. Atypical social behaviors include sequential processes of assembled cognitive-behavior components, such as recognition, investigatory assessment, and signaling response. This study aimed to elucidate the neural circuits responsible for the regulation of the social signaling response, as shown by scent marking behavior in male mice. We first assessed the recognition and investigatory patterns of male BTBR mice compared to those of C57BL/6 J (B6) mice. Next, we examined their scent-marking behavior as innate social signaling responses adjusted to a confronted feature of social stimuli and situations, along with the expression of c-Fos as a marker of neuronal activity in selected brain areas involved in the regulation of social behavior. The function of the targeted brain area was confirmed by chemogenetic manipulation. We also examined the social peptides, oxytocin and vasopressin neurons of the major brain regions that are associated with the regulation of social behavior. Our data indicate that male BTBR mice are less responsive to the presentation of social stimuli and the expression of social signaling responses, which is paralleled by blunted c-Fos responsivity and vasopressin neurons morphological changes in selected brain areas, including the posterior bed nucleus of the stria terminalis (pBnST) and lateral habenula (LHb) in BTBR mice. Further investigation of LHb function revealed that chemogenetic inhibition and activation of LHb activity can induce a change in scent marking responses in both B6 and BTBR mice. Our elucidation of the downstream LHb circuits controlling scent marking behavior indicates intact function in BTBR mice. The altered morphological characteristics of oxytocin neurons in the paraventricular nucleus of the hypothalamus and vasopressin-positive neurons and axonal projections in the pBnST and LHb appear to underlie the dysfunction of scent marking responses in BTBR mice.(300/300 words)

Multiscale entropy as a metric of brain maturation in a large cohort of typically developing children born preterm using longitudinal high-density EEG in the first two years of life

Objective. We aimed to analyze whether complexity of brain electrical activity (EEG) measured by multiscale entropy (MSE) increases with brain maturation during the first two years of life. We also aimed to investigate whether this complexity shows regional differences across the brain, and whether changes in complexity are influenced by extrauterine life experience duration. Approach. We measured MSE of EEG signals recorded longitudinally using a high-density setup (64 or 128 electrodes) in 84 typically developing infants born preterm (<32 weeks’ gestation) from term age to two years. We analyzed the complexity index and maximum value of MSE over increasing age, across brain regions, and in function of extrauterine life duration, and used correlation matrices as a metric of functional connectivity of the cerebral cortex. Main results. We found an increase of strong inter-channel correlation of MSE (R > 0.8) with increasing age. Regional analysis showed significantly increased MSE between 3 and 24 months of corrected age in the posterior and middle regions with respect to the anterior region. We found a weak relationship (adjusted R2 = 0.135) between MSE and extrauterine life duration. Significance. These findings suggest that brain functional connectivity increases with maturation during the first two years of life. EEG complexity shows regional differences with earlier maturation of the visual cortex and brain regions involved in joint attention than of regions involved in cognitive analysis, abstract thought, and social behavior regulation. Finally, our MSE analysis suggested only a weak influence of early extrauterine life experiences (prior to term age) on EEG complexity.

Christian Theological Grounds of Jurisprudence: Historical and Contemporary Aspects

Relevance of Christian theological grounds of jurisprudence stems from the fact that a religion in general and Christianity in particular, remains one of the main regulators of social behavior, whereby the question of the connection between the law and religion as well as the question of the relationship between the Christian theology and jurisprudence arises. The purpose of this study is to reveal historical and contemporary aspects of the similarity, difference and interaction of Christian and legal spheres of the social reality. In particular, the interdisciplinary approach provided the combination of exegesis and hermeneutics, dialectics, dogmatic and historical methodological tools, and was used to retrace the evolution of the law and to disclose various connections between legal and religious prescriptions and the content. The main intersection points of the law and religion, particularly Christianity, such as sacredness, values, morality and axiomatic assertions are disclosed as well as the religious basis of the historical and contemporary law is proved in the article. The outcomes of the study are of practical value for implementating and affirming the rule of law, for strengthening of authorityof the legal system and legal order in Ukraine with the means of the Christian religion and religious institutions.

Намёк как регулятор социального поведения представителей немецкой лингвокультуры (на примере административных объявлений)

The aim of the study is to identify the features of the hint in the German everyday urban discourse. The paper is the first to determine two main types of implicit illocutionary acts in the indirect speech act “hint” presented in German administrative announcements. Scientific originality of the study also lies in considering the hint as a regulator of social behaviour of the representatives of German linguoculture. The paper provides a comprehensive comparative analysis of the implicit and explicit illocutionary act and presents the typology of the implicit illocutionary act in the German everyday urban discourse. As a result of the study, the following types of implicit illocutionary acts have been identified: “a demand (suggestion, request) for the addressee not to perform any action at this time / in the near future” and “a demand (suggestion, request) for the addressee to perform an action at this time / in the near future”. The addresser strives to achieve a situation of reality that is beneficial for themselves, the addressee and all the participants in the situation. The addresser formulates the statement as a fact due to the detachment of the verbalised situation from the addressee or from the addressee and the current moment. The addressee perceives the literal meaning and decodes the implicit information.

Rescue of social deficits by early-life melatonin supplementation through modulation of gut microbiota in a murine model of autism

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a rapidly increasing global prevalence. Early unstable and immature microbiota are often observed in ASD patients, resulting in neurobehavioral dysfunction. Since the establishment of stable gut microbiota in early life falls into the same critical time window as neurodevelopment, manipulations of the gut microbiota during early life could become a promising strategy for ASD. Melatonin is an endogenous hormone and can restore gut microbial dysbiosis under various disease conditions. Here, we explored the effects of melatonin supplementation during early life on the gut microbiota of the offspring and the subsequent impact on ASD-associated behaviors. Using the valproic acid (VPA) - induced mouse model of autism, we found that melatonin supplementation during late gestation and early postnatal development rescued the social deficits of the offspring. In addition, melatonin restored gut microbial dysbiosis in the VPA-exposed offspring, which was characterized by the significant upregulation of Akkermansia spp. Furthermore, supplementation of Akkermansia spp. alleviated the social deficits induced by VPA exposure via activating the dopaminergic neurons in the ventral tegmental area. These findings discover a novel mechanism underlying the gut microbiota regulation of social behaviors and provide the biological basis for developing gut microbiota-based therapeutics for ASD

The Relationship Between Chronic Fatigue Syndrome and Depression: Mediating Roles of Executive Functions in Patients With Relapsing-Remitting Multiple Sclerosis

Objective: This study aimed to investigate the relationship between chronic fatigue syndrome (CFS) and depression with the mediating role of executive functions (EFs) in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: The statistical population of this descriptive correlational study included all patients with RRMS who were referred to Tehran neurologists in the summer of 2021 and among them, 208 samples who were eligible to enter the study, were selected via available sampling methods. To collect data, Krupp et al.'s (1988) fatigue severity scale (FSS), Nejati's cognitive abilities (NCA), and Beck depression inventory (II-BDI) were used. Pearson correlation method and structural equation modeling (SEM) were used to analyze the data. Results: Of seven subscales of EFs, the subscales of working memory, inhibitory control, selective attention, planning, and cognitive flexibility, which are called "cold" processes of EFs, were approved as mediators at the level (P&lt;0.001), but the subscales of cognitive functioning, decision-making, and controlled attention, which are hot functions and require emotional awareness and regulation of personal social behaviors and decision-making with emotional and personal interpretation and empathy, were not approved as mediating roles. The results also showed that in patients with RRMS, there was a significant relationship between CFS and depression, between CFS and EFs, and between EFs and depression (P&lt;0.001). Conclusion: The results of the present study can be used in cognitive rehabilitation to improve EFs and consequently improve depression in patients with MS.