Beyond the metabolic effects induced by long- and short-acting glucagon-like peptide-1 receptor (GLP-1R) agonists, they modulate reward-related behaviors by acting on brain regions including lateral septum (LS) and neural pathways involving the nucleus tractus solitarii (NTS). While the short-acting GLP-1R agonist exendin-4 (Ex-4) reduces sexual behaviors in sexually naïve male mice, the effects of long- versus short-acting GLP-1R agonists on natural rewards, such as sexual and social behaviors, in females remain unexplored. In the current study, we investigate the effects of both long-acting (dulaglutide, liraglutide) and short-acting (Ex-4) GLP-1R agonists on sexual and social behaviors in sexually experienced female rats and mice. While the GLP-1R agonists decreased sexual behaviors in females, they appear to be drug- and species-specific. In female rats, Ex-4 reduced the time with the males, the number of mounts, intromissions, ejaculations, darts and hops, as well as the lordosis intensity. Female mice treated with liraglutide and dulaglutide display a reduction in time with male stimulatory mouse, and as a possible consequence, a lowered mounting and intromission duration, potentially involving increased noradrenaline levels in the NTS and altered glutamate, glutamine, and taurine levels in the LS. In the three-chamber test, dulaglutide decreased the social novelty, another behavior associated with reward/motivation. Moreover, the long-acting GLP-1R agonists increased sociability and the time to seek a novel object. These results highlight species-dependent and agonist-specific effects of GLP-1R activation on sexual and social function in females and expands our understanding of the broader role of GLP-1.

The physiological effects of glucagon-like peptide-1 (GLP-1) are vast, including food and glucose homeostasis. As the half-life is short, both short-acting, exendin-4 (Ex4) and long-acting, liraglutide and dulaglutide, GLP-1 receptor (GLP-1R) agonists have been developed and are approved for type 2 diabetes and/or obesity. They have also been found to reduce behaviors linked to addictive drugs through involvement of mesolimbic brain regions such as the medial amygdala. Additionally, Ex4 reduces sexual interactions in sexually naïve male mice and experienced females. However, the effects of GLP-1, short- and long-acting GLP-1R agonists on sexual behaviors in sexually experienced males remain unknown. Therefore, we examined how GLP-1 and Ex4 affect sexual behavior in experienced male mice, influenced associated neurochemical changes in the medial amygdala, and evaluated the potential modulatory factors through social behaviors. Additionally, we assess whether long-acting GLP-1R agonists impacted similar behaviors as well as the levels of corticosterone and insulin. Ex4 reducced the number of intromissions and ejaculations in sexually experienced male mice without GLP-1 having an effect. Moreover, social behaviors were unaffected by short-acting GLP-1R agonists. In the medial amygdala of these male mice treated with Ex4, the levels of glutamate and other amino acids were lower. Conversely, liraglutide and dulaglutide did not modify sexual behaviors but enhanced time in the social zone, with no effect on corticosterone or insulin levels. Together, these studies suggest that GLP-1R activation modulates both sexual and social behaviors, but the outcome depends on which agonists have been used.

Sociability is an evolutionarily conserved biological trait that promotes information exchange, protection, cooperation, and reproductive success. Its expression nevertheless differs substantially across species, from aggregation and social recognition to affiliation, cooperation, and higher-order social cognition. This review establishes a comparative, component-based framework for evaluating what different model organisms can and cannot reveal about human sociability and social dysfunction. We compare social-cue detection, recognition and memory, motivation and reward, contextual integration, and behavioral output across humans, non-human primates, rodents, sheep, zebrafish, frogs, Drosophila, bees, and Caenorhabditis elegans. Humans provide the reference framework, integrating conserved social processes with higher-order capacities such as empathy and Theory of Mind. Autism spectrum disorder is considered as an important translational example of how alterations across partially separable social components can produce heterogeneous phenotypes. Non-human primates permit investigation of social attention, gaze, affiliation, reciprocity, and social reward within neural systems broadly homologous to those of humans. Rodents enable genetic and circuit-level analysis of social approach, recognition, memory, bonding, and parental behavior, whereas sheep support ethologically grounded studies of individual recognition, maternal-offspring bonding, and group cohesion. Zebrafish and frogs provide complementary access to the development and sensory organization of vertebrate social behavior. Drosophila, bees, and C. elegans offer genetic precision for investigating aggregation, communication, social organization, and conserved molecular mechanisms. No single species reproduces the full complexity of human sociability or a complete clinical disorder. Instead, each provides experimental access to particular social components and mechanisms, with distinct strengths and interpretive limitations. Integrating findings across complementary models can therefore clarify the biological organization of sociability and strengthen translation to human social dysfunction.

The gut-brain axis serves as a crucial communication pathway, with microbial metabolites such as short-chain fatty acids (SCFAs) playing a central role in regulating neuroinflammation and maintaining neuronal health. The gut microbiota’s impact on neurodevelopment is highlighted, particularly its relevance to autism, anxiety, and other psychiatric conditions. In this review, we explored the intricate relationship between the gut microbiota (GM) and the central nervous system (CNS), emphasizing the bidirectional communication that forms the gut-brain axis. Associations between specific gut microbiota and neurodegenerative diseases are explored, focusing on the role of certain bacteria in processes such as amyloid aggregation and neuroinflammation in Alzheimer’s disease (AD) and Parkinson’s disease (PD). The potential for therapeutic modulation of the gut microbiota is discussed, with a focus on dietary interventions and probiotics as strategies to improve outcomes in neurodegenerative diseases by restoring gut health. We concluded by emphasizing the significance of understanding the gut-brain connection and calls for further research to investigate therapeutic approaches targeting the gut microbiome for brain health.

Methyl CpG binding protein 2 (MECP2) is an essential global modulator of transcription and mutations in MECP2 are the most common cause of Rett syndrome, an X-linked neurodevelopmental disorder. Patients diagnosed with Rett syndrome have increased risk for epilepsy as well as problems with anxiety and social communication. Using the zebrafish mecp2Q63X line, this study aimed to increase our understanding of the role of Mecp2 function in regulation of pharmacologically-induced hyperlocomotion, developmental social preference, and adult socialization, anxiety-related behaviour, and baseline cortisol levels. To determine responses of mecp2−/− zebrafish to a stimulating convulsant, general locomotor activity was measured at 5 days post-fertilization (dpf) in sibling mecp2+/+, mecp2+/−, and mecp2−/− fish after treatment with a GABAA receptor antagonist pentylenetetrazol (PTZ) at varying concentrations. Responses to social stimulus were investigated in juvenile (21 dpf) and adult mecp2−/− and mecp2+/+ fish. Anxiety responses to a novel tank and whole-body cortisol levels were also measured in adult mecp2−/− and control mecp2+/+ zebrafish. The behavioural tests showed that mecp2−/− zebrafish displayed hypolocomotion at the larval stage, along with increased freezing time and thigmotaxis, and higher whole-body cortisol levels in adulthood. However, the hyper-locomotion response to PTZ at 5 dpf and social preference for visual social stimulus at 21 dpf and in adulthood were not affected by the lack of functional Mecp2. Functional Mecp2 modulated larval locomotion and behavioural anxiety at different ages and adult cortisol levels, but mecp2 null-mutation did not alter adult locomotion and socialization, and developmental sociability and PTZ-induced hyperlocomotion in zebrafish. Given the variability reported in patients and in rodent Mecp2 knockout models, studies using zebrafish can explore vital elements of MECP2’s role across development and improve our understanding of neural mechanisms underlying neurodevelopmental disorders.

Genetic variations in single nucleotide polymorphisms (SNPs) within oxytocin pathway genes have been linked to social behavior and neurodevelopmental conditions. However, the neurobiological mechanisms underlying these associations remain elusive. In this study, we investigated the relationship between variations of 10 SNPs in oxytocin pathway genes and resting-state functional connectivity among 55 independent components using a large sample from the UK Biobank (N ≈ 30,000). Our findings revealed that individuals with the GG genotype at rs4813627 within the oxytocin structural gene (OXT) exhibited weaker resting-state functional connectivity in the corticostriatal circuit compared to those with the GA/AA genotypes. Empirical evidence has linked the GG genotype at OXT rs4813627 with a behavioral tendency of insensitivity to others. These results inform the neural mechanisms by which oxytocin-related genetic factors can influence social behavior.

The role of oxytocin-related genes in social-cognitive function has been previously established, but structural brain mechanisms underlying this link remain poorly understood. Utilizing a substantial dataset from the UK Biobank (N ≈ 30,000), this research determined associations between variations in ten single nucleotide polymorphisms (SNPs) within three oxytocin pathway genes (i.e., the oxytocin/neurophysin I prepropetide gene, the cluster of differentiation 38 glycoprotein gene, the oxytocin receptor gene) and whole-brain gray matter volume. Carriers of the AA or AG genotypes of the oxytocin receptor gene rs237851 SNP exhibited significantly larger hippocampal volume than carriers of the GG genotype. These results support the link between variations in the oxytocin receptor gene and hippocampal structure, with possible impact on social-cognitive function such as social recognition memory.

Several copy number variations (CNVs) are associated with increased risk for neurodevelopmental and psychiatric disorders. The CNV 15q11.2 (BP1‐BP2) deletion has been associated with learning difficulties, attention deficit hyperactivity disorder (ADHD), epilepsy, and brain morphology; however, many carriers present mild or no symptoms. Carrying the reciprocal duplication does not seem to confer risk for these disorders or traits. Our aim was to examine the impact of carrying either 15q11.2 deletion and reciprocal duplication on neurodevelopmental problems in a population‐based sample of children.

Autism Spectrum Disorders (ASD) are heterogeneous neurodevelopmental disorders with considerably increased risk in male infants born preterm and with neonatal infection. Here we investigated the role of postnatal immune activation on hippocampal synaptopathology by targeting Reelin+ cells in mice with ASD-like behavior. C57/Bl6 mouse pups of both sexes received lipopolysaccharide (LPS, 1mg/kg) on postnatal day (P) 5. At P45, animal behavior was examined by marble burying and sociability test, followed by ex-vivo brain MRI diffusion kurtosis imaging (DKI). Hippocampal synaptogenesis, number and morphology of Reelin+ cells, and mRNA expression of trans-synaptic genes, including neurexin-3, neuroligin-1, and cell-adhesion molecule nectin-1 were analyzed at P12 and P45. Social withdrawal and increased stereotypic activities in males were related to increased mean diffusivity on MRI-DKI and overgrowth in hippocampus together with retention of long-thin immature synapses on apical dendrites, decreased volume and number of Reelin+ cells as well as reduced expression of trans-synaptic and cell-adhesion molecules. The study provides new insights into sex-dependent mechanisms that may underlie ASD-like behavior in males following PIA. We identify GABAergic interneurons as core components of dysmaturation of excitatory synapses in the hippocampus following postnatal infection and provide cellular and molecular substrates for the MRI findings with translational value.

Aggression is a complex social behavior, which is provoked in the defense of limited resources including food and mates. Recent advances show that the gut-brain hormone ghrelin modulates aggressive behaviors. As the gut-brain hormone glucagon-like peptide-1 (GLP-1) reduces food intake and sexual behaviors its potential role in aggressive behaviors is likely. Therefore, we investigated a tentative link between GLP-1 and aggressive behaviors by combining preclinical and human genetic-association studies. The influence of acute or repeated injections of a GLP-1 receptor (GLP-1R) agonist, exendin-4 (Ex4), on aggressive behaviors was assessed in male mice exposed to the resident-intruder paradigm. Besides, possible mechanisms participating in the ability of Ex4 to reduce aggressive behaviors were evaluated. Associations of polymorphisms in GLP-1R genes and overt aggression in males of the CATSS cohort were assessed. In male mice, repeated, but not acute, Ex4 treatment dose-dependently reduced aggressive behaviors. Neurochemical and western blot studies further revealed that putative serotonergic and noradrenergic signaling in nucleus accumbens, specifically the shell compartment, may participate in the interaction between Ex4 and aggression. As high-fat diet (HFD) impairs the responsiveness to GLP-1 on various behaviors the possibility that HFD blunts the ability of Ex4 to reduce aggressive behaviors was explored. Indeed, the levels of aggression was similar in vehicle and Ex4 treated mice consuming HFD. In humans, there were no associations between polymorphisms of the GLP-1R genes and overt aggression. Overall, GLP-1 signaling suppresses acquisition of aggressive behaviors via central neurotransmission and additional studies exploring this link are warranted.

Oxytocin is central to pair-bonding in non-human animals. We assessed effects of intranasal oxytocin on bond formation between two opposite-sex strangers. In a double-blind placebo-controlled design, 50 pairs of one man and one woman received oxytocin or placebo spray intranasally. After treatment, they played a social interaction game, followed by tasks designed to measure first impressions of the opposite-sex co-participant, and a virtual ball-tossing game (cyberball), designed to measure reactions to rejection by the co-participant. We found no evidence that intranasal oxytocin can improve first impressions of an opposite-sex stranger, and some Bayesian support against this hypothesis. For rejection sensitivity, we observed a sex-and-context-dependent drug effect on post-ostracism mood ratings, consistent with recent studies indicating that interindividual variation and social context can interact with intranasal oxytocin effects. Further research is needed to determine the generalisability of these findings, i.e. if oxytocin can improve first impressions in humans under different conditions.

Twin studies can help us understand the relative contributions of genes and environment to phenotypic trait variation, including attentional and brain activation measures. In terms of applying methodologies such as electroencephalography (EEG) and eye tracking, which are key methods in developmental neuroscience, infant twin studies are almost nonexistent. Here, we describe the Babytwins Study Sweden (BATSS), a multi-method longitudinal twin study of 177 MZ and 134 DZ twin pairs (i.e., 622 individual infants) covering the 5-36 month time period. The study includes EEG, eye tracking and genetics, together with more traditional measures based on in-person testing, direct observation and questionnaires. The results show that interest in participation in research among twin parents is high, despite the comprehensive protocol. DNA analysis from saliva samples was possible in virtually all participants, allowing for both zygosity confirmation and polygenic score analyses. Combining a longitudinal twin design with advanced technologies in developmental cognitive neuroscience and genomics, BATSS represents a new approach in infancy research, which we hope to have impact across multiple disciplines in the coming years.

With a strong tendency to socialise, the zebrafish is a useful model to study social behaviour, with implications for better treatments of social impairments, for instance in autism spectrum disorders. Although oxytocin is crucial for social behaviour in mammals, the importance of the fish orthologue – isotocin or zebrafish oxytocin (zOT) – for social behaviour in zebrafish is unclear. The aims of this study were firstly, to elucidate the receptor specificity of zOT and the related vasotocin or zebrafish vasopressin (zVP; the orthologue of mammalian vasopressin) and the nonpeptidergic oxytocin receptor antagonist L-368,899, and secondly to investigate if L-368,899 inhibits social preference in zebrafish. The potencies of ligands were evaluated for zOT/zVP family receptors in HEK293 cells. Adult and larval zebrafish were treated with L-368,899 or vehicle and subsequently assessed for social behaviour and anxiety (adults only). The antagonist L-368,899 specifically inhibited the two zOT receptors, but not the two zVP-1 receptors. The antagonist decreased social preference in adult and larval zebrafish. It did not affect anxiety in adults. These results indicate that endogenous zOT, and possibly zVP, is involved in social behaviour in zebrafish via either or both of the two zOT receptors, and show promise for future explorations of the anatomy and evolution of networks underlying social behaviour.

The mechanisms underlying the role of oxytocin (OT) as a regulator of social behavior in mammals are only partly understood. Recently, it has been proposed that OT increases the salience of social stimuli. We carried out a randomized, double-blind, cross-over study of the effects of OT on binocular rivalry, a visual phenomenon underpinned by the interplay of excitation and inhibition in the cortex. A final sample of 45 participants viewed images of social stimuli (faces with different emotional expressions) and non-social stimuli (houses and Gabor patches). We demonstrate a robust effect that intranasal OT increases the salience of human faces in binocular rivalry, such that dominance durations of faces are longer-this effect is not modulated by the facial expression. We tentatively show that OT treatment increases dominance durations for non-social stimuli. Our results lend support to the social salience hypothesis of OT, and in addition offer provisional support for the role of OT in influencing excitation-inhibition balance in the brain.

Emerging evidence suggest that appetite-regulating peptides modulate social behaviors. We here investigate whether the anorexigenic peptide neuromedin U (NMU) modulates sexual behavior in male mice. However, instead of modulating sexual behaviors, NMU administered into the third ventricle increased self-grooming behavior. In addition, NMU-treatment increased self-grooming behavior when exposed to other mice or olfactory social-cues, but not when exposed to non-social environments. As the neuropeptide oxytocin is released during social investigation and exogenous oxytocin induces self-grooming, its role in NMU-induced self-grooming behavior was investigated. In line with our hypothesis, the oxytocin receptor antagonist inhibited NMU-induced self-grooming behavior in mice exposed to olfactory social-cues. Moreover, dopamine in the mesocorticolimbic system is known to be a key regulator of self-grooming behavior. In line with this, we proved that infusion of NMU into nucleus accumbens increased self-grooming behavior in mice confronted with an olfactory social-cue and that this behavior was inhibited by antagonism of dopamine D2, but not D1/D5, receptors. Moreover repeated NMU treatment enhanced ex vivo dopamine levels and decreased the expression of dopamine D2 receptors in nucleus accumbens in socially housed mice. On the other hand, the olfactory stimuli-dependent NMU-induced self-grooming was not affected by a corticotrophin-releasing hormone antagonist, and NMU-treatment did not influence repetitive behaviors in the marble burying test. In conclusion, our results suggest that NMU treatment and, social cues - potentially triggering oxytocin release - together induce excessive grooming behavior in male mice. The mesolimbic dopamine system, including accumbal dopamine D2 receptors, was identified as a crucial downstream mechanism.

The hypothalamic neuropeptides of the vasopressin-oxytocin family (and their homologs for non-mammalian species) are key modulators of the Social Brain Network, acting via specific receptors reported in all the nuclei of this network. Different conclusive examples have proven the context-dependency actions of hypothalamic nonapeptides on social behavior in several vertebrate taxa. Teleost fishes provide endless possibilities of experimental model systems to explore the underlying mechanisms of nonapeptide actions on social behavior given that they are the most diverse group of vertebrates. Although it has been difficult to identify commonalities of nonapeptide actions across species, indisputable evidence in many teleost species have demonstrated a clear role of vasotocin in the modulation of aggressive and sexual behaviors. Though Neotropical South American fish contribute an important percentage of teleost diversity, most native species remain unexplored as model systems for the study of the neuroendocrine bases of social behavior. In this review, we will revise recent data on the two model systems of Neotropical fish, South American cichlids and weakly electric fish that have contributed to this issue.

To further improve the search ability of the decomposition based many/multi-objective evolutionary algorithm (MOEA/D) in the tackling many-objective optimization problems (MaOPs) possessing complex characteristics (e.g., disconnected, degenerate, inverted, extremely convex or differently-scaled), we suggest an adaptive MOEA/D with better versatility, where the weight vector adaption and selection mechanism are improved. Firstly, a new niche-guided scheme by considering both the vector angle and Euclidean distance is proposed to leverage the search direction adaption upon different evolution phases, which is expected to be more robust for handling different types of irregular Pareto fronts (PFs). Secondly, in mating selection, a coordinated selection scheme aided by a multi-criterion decision procedure is utilized to enhance the effectiveness of recombination. Finally, in environmental selection, a steady state replacement strategy considering both the ensemble ranking of favorite subproblems with respect to solutions and improvement region restriction of subproblems is employed to alleviate misleading selection. Comparison experiments on benchmark MaOPs with diverse characteristics have been performed and the empirical results demonstrate the superiority of our proposal. The effects of direction vector adaption mechanism and other pertinent enhancements are also investigated.

Aggressive behaviour is of crucial importance in the defence for limited resources including food and mates and involves central serotonin as well as dopamine signalling. As ghrelin modulates food intake and sexual behaviour we initially investigated the hypothesis that central ghrelin signalling regulates aggressive behaviour in the resident intruder paradigm in male mice. Moreover, interaction between ghrelin signalling and serotonergic, noradrenergic as well as dopaminergic neurotransmission in aggression was investigated. The relevance of ghrelin for human aggression per se as well as for aggression induced by alcohol was evaluated in a human genetic association study comprising young men (n = 784) from the normal population assessed for anti-social behaviours. The present study demonstrates that central ghrelin infusion, but not ghrelin administered systemically, increases aggression. Moreover aggressive behaviour is decreased by pharmacological suppression of the growth hormone secretagogue receptor-1 A (GHSR-1A) by JMV2959. As indicated by the ex vivo biochemical data serotonin, rather than dopamine or noradrenaline, in amygdala may have central roles for the ability of JMV2959 to reduce aggression. This link between central serotonin, GHSR-1A and aggression is further substantiated by the behavioural data showing that JMV2959 cannot decrease aggression following depletion of central serotonin signalling. The genetic association study demonstrates that males carrying the Leu72Leu genotype of the pre-pro-ghrelin gene and displaying hazardous alcohol use are more aggressive when compared to the group carrying the Met-allele. Collectively, this contributes to the identification of central ghrelin pathway as an important modulator in the onset of aggressive behaviours in male mice.

Psychopathy is characterized by callous affect, interpersonal manipulation, a deviant lifestyle, and antisocial behavior. Previous research has linked psychopathic traits to childhood trauma, but also to the upstream variable number tandem repeat (uVNTR) polymorphism of the monoamine oxidase A (MAOA) gene. An interaction between childhood trauma and MAOA genotype has been associated with antisocial behavior, but so far little is known about interaction effects of childhood trauma and the MAOA uVNTR on psychopathy. In order to bridge this gap, we used data of 1531 male and 1265 female twins and their siblings from a Finnish community sample to estimate structural equation models. The psychopathy and childhood trauma constructs were conceptualized as bifactor models with one general and two orthogonal group factors. Data comprised self-reports on childhood trauma and psychopathic traits as well as MAOA uVNTR genotype. In both genders, childhood trauma was associated with the general factor that represents the overarching psychopathy construct, and with the group factor that captures social deviance, but not with the group factor capturing psychopathic core personality traits. Women with a low activity variant of the MAOA uVNTR reported slightly higher levels of psychopathy than those with a high activity allele, but only with respect to the general psychopathy factor. There was no evidence for an interaction effect between MAOA uVNTR genotype and childhood trauma on psychopathy in either gender. Our results suggest that psychopathy in general and social deviance in particular are associated with childhood trauma in men and women, and that psychopathic traits are subject to variation in the MAOA uVNTR genotype in women.