Adolescent social isolation disrupts developmental tuning of neuropeptide circuits in the hypothalamus to amygdala regulating social and defensive behavior.

Engaging in positive social (i.e., prosocial) interactions during adolescence acts to modulate neural circuits that determine adult adaptive behavior. While accumulating evidence indicates that a strong craving for prosocial behavior contributes to sustaining neural development, the consequences of social deprivation during adolescence on social neural circuits, including those involving oxytocin (OXT) and vasopressin (AVP), are poorly characterized. We evaluated adaptive behaviors in socially isolated mice, including anxiety-like, social, and defensive behaviors, along with OXT and AVP neural profiles in relevant brain regions. Social isolation from postnatal day (P-)22 to P-48 induced enhanced defensive and exploratory behaviors, in nonsocial and social contexts. Unlike OXT neurons, AVP+ cell density in the paraventricular nucleus of the hypothalamus increases with age in males. Social isolation also modulated gene expression in the medial amygdala (MeA), including the upregulation of OXT receptors in males and the downregulation of AVP1a receptors in both sexes. Socially isolated mice showed an enhanced defensive, anogenital approach toward a novel adult female during direct social interactions. Subsequent c-Fos mapping revealed diminished neural activity in restricted brain areas, including the MeA, lateral septum, and posterior intralaminar nucleus of the thalamus, in socially isolated mice. These data indicate that neural signals arising from daily social interactions invoke region-specific modification of neuropeptide expression that coordinates with altered defensiveness and neural responsivities, including OXT- and AVP-projecting regions. The present findings indicate an involvement of OXT and AVP circuits in adolescent neural and behavioral plasticity that is tuned by daily social interaction.

Independent inhibitory control mechanisms for aggressive motivation and action.

Social behaviors often consist of a motivational phase followed by action. Here we show that neurons in the ventromedial hypothalamus ventrolateral area (VMHvl) of mice encode the temporal sequence of aggressive motivation to action. The VMHvl receives local inhibitory input (VMHvl shell) and long-range input from the medial preoptic area (MPO) with functional coupling to neurons with specific temporal profiles. Encoding models reveal that during aggression, VMHvl shellvgat+ activity peaks at the start of an attack, whereas activity from the MPO-VMHvlvgat+ input peaks at specific interaction endpoints. Activation of the MPO-VMHvlvgat+ input promotes and prolongs a low motivation state, whereas activation of VMHvl shellvgat+ results in action-related deficits, acutely terminating attack. Moreover, stimulation of MPO-VMHvlvgat+ input is positively valenced and anxiolytic. Together, these data demonstrate how distinct inhibitory inputs to the hypothalamus can independently gate the motivational and action phases of aggression through a single locus of control.

Effectiveness of a blended school-based mindfulness program for the prevention of co-rumination and internalizing problems in Dutch secondary school girls: a cluster randomized controlled trial.

BACKGROUND: A growing body of literature indicates that adolescent girls who talk with close friends about interpersonal problems or worries in an excessive, speculative way, and with an intense focus on distress (i.e., co-rumination) are at heightened risk for developing internalizing symptoms and disorders as well as reduced friendship quality. However, to date, there are no prevention programs available that target high levels of co-rumination between adolescent girls. As such, we developed the blended school-based mindfulness prevention program Happy Friends, Positive Minds (HFPM) that targets co-rumination at the dyadic level, i.e., between two close female friends. The aim of this trial is to evaluate the effectiveness of HFPM to reduce co-rumination and internalizing problems and to enhance wellbeing and social-emotional behavior in Dutch adolescent girls. METHODS: A cluster Randomized Controlled Trial (cRCT) will be conducted to evaluate HFPM effectiveness. We will recruit 160 female friendship dyads (n = 320 girls) aged 13 to 15 years who will be characterized by high levels of self-reported co-rumination. The cRCT has two arms: (1) an intervention condition in which 160 girls (80 friendship dyads) will receive the 14-week HFPM program in two consecutive cohorts (cohort 1 in academic year 2023/2024 and cohort 2 in academic year 2024/2025, and (2) a control condition in which 160 girls (80 dyads) will receive care-as-usual (CAU) in two consecutive cohorts (cohort 1 in academic year 2023/2024 and cohort 2 in academic year 2024/2025). Data will be collected at baseline (T0), during the program (T1;T2; T3), immediately after the program (T4), and at 1-year follow-up (T5). Participant-level self-reported risk for (early onset) depression and anxiety, self-reported and observed co-rumination, self- and friend-reported friendship quality, self-reported positive and negative affect, self-reported interpersonal responses to positive affect, and self-reported anhedonia symptoms will be the outcome variables. DISCUSSION: This study will provide insights into the short-term and long-term effects of the HFPM program on girls' internalizing problems, wellbeing, and social-emotional behavior. TRIAL REGISTRATION: International Standard Randomized Controlled Trials, identifier: ISRCTN54246670. Registered on 27 February 2023.

A dedicated hypothalamic oxytocin circuit controls aversive social learning.

To survive in a complex social group, one needs to know who to approach and, more importantly, who to avoid. In mice, a single defeat causes the losing mouse to stay away from the winner for weeks1. Here through a series of functional manipulation and recording experiments, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOROXT) and oxytocin-receptor-expressing cells in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part (aVMHvlOXTR) as a key circuit motif for defeat-induced social avoidance. Before defeat, aVMHvlOXTR cells minimally respond to aggressor cues. During defeat, aVMHvlOXTR cells are highly activated and, with the help of an exclusive oxytocin supply from the SOR, potentiate their responses to aggressor cues. After defeat, strong aggressor-induced aVMHvlOXTR cell activation drives the animal to avoid the aggressor and minimizes future defeat. Our study uncovers a neural process that supports rapid social learning caused by defeat and highlights the importance of the brain oxytocin system in social plasticity.

Characterization of social hierarchy formation and maintenance in same-sex, group-housed male and female C57BL/6 J mice.

Social hierarchies are a prevalent feature of all animal groups, and an individual's rank within the group can significantly affect their overall health, typically at the greatest expense of the lowest-ranked individuals, or omegas. These subjects have been shown to exhibit various stress-related phenotypes, such as increased hypothalamic-pituitary axis activity and increased amygdalar corticotropin-releasing factor levels compared to higher-ranked subjects. However, these findings have been primarily characterized in males and in models requiring exhibition of severe aggression. The goals of the current study, therefore, were to characterize the formation and maintenance of social hierarchies using the tube test and palatable liquid competition in same-sex groups of male and female C57BL/6 J mice. We also aimed to examine the effects of tube test-determined social rank on plasma and hypothalamic oxytocin and vasopressin levels, peptides with established roles in social behaviors and the stress response. Lastly, we assessed the effects of environmental enrichment and length of testing on the measures outlined above. Overall, we demonstrated that males and females develop social hierarchies and that these hierarchies can be determined using the tube test. While we were unable to establish a consistent connection between peptide levels and social rank, we observed transient changes in these peptides reflecting complex interactions between social rank, sex, environment, and length of testing. We also found that many male and female omegas began to exhibit passive coping behavior after repeated tube test losses, demonstrating the potential of this assay to serve as a model of chronic, mild psychosocial stress.

Lay Misperceptions of Culture as "Biological" and Suggestions for Reducing Them.

Culture is typically studied as socialized and learned. Yet lay intuitions may hold that culture is associated with biology via perceptions of race, presenting a problem for those who study culture: There may be a mismatch between how psychologists study culture and how their research is interpreted by lay audiences. This article is a call to researchers to recognize this mismatch as a problem and to critically evaluate the way we study culture. We first describe evidence that laypeople tend to associate culture with notions of folk biology. Next, we propose three suggestions for researchers: explicitly address whether biological processes are, or are not, relevant for studying culture in their work; consider using multiple methods because different methods for studying culture may come with assumptions about culture as more tied to socialization or biology; and represent all people as cultural by studying multiple forms of culture and by contextualizing all psychological research. Last, we provide an example for how researchers can implement these suggestions to encourage more accurate interpretations of findings.

Designing a Situational Judgment Test for Use in Medical School Admissions.

ABSTRACT: It has long been acknowledged that professional competencies are required for success in medical school, residency training, and medical practice. Over the last decade, medical schools have begun to introduce standardized assessments of professional competencies, but many still rely on interviews to assess these competencies, which occur after about half of the applicant pool has already been screened out. In this article, the authors discuss the development, evaluation, and launch of the Association of American Medical Colleges (AAMC) situational judgment test (SJT) for use in medical school admissions. The AAMC SJT is designed to assess an examinee's understanding of effective and ineffective behaviors related to the core competencies for entering medical students, including service orientation, social skills, cultural competence, teamwork, ethical responsibility to self and others, reliability and dependability, resilience and adaptability, and capacity for improvement. The authors evaluate the evidence for the need for SJTs in medical school admissions by exploring common derailers in medical school, gaps in the admissions process regarding information about professional competencies, and the challenge of conducting holistic review in a high-volume context. They summarize existing research from the employment, international medical education, and residency selection contexts suggesting that SJT scores are positively associated with subsequent performance and may add value to the admissions process. The authors discuss 5 goals that were the foundation for developing the AAMC SJT: (1) assess the professional competencies needed for success in medical school using a proven method, (2) enable holistic review in a high-volume admissions context, (3) create and share a program of research to support the appropriate use of SJT scores, (4) signal the need for preparation in professionalism to learners, and (5) balance the need for a new assessment with minimizing the burden and risk for applicants.

Social Interaction Elicits Activity in Glutamatergic Neurons in the Posterior Intralaminar Complex of the Thalamus.

BACKGROUND: The posterior intralaminar complex of the thalamus (PIL) is a multimodal nucleus that has been implicated in maternal behaviors and conspecific social behaviors in male and female rodents. Glutamatergic neurons are a major component of the PIL; however, their specific activity and role during social interactions has not yet been assessed. METHODS: We used immunohistochemistry for the immediate early gene c-fos as a proxy for neuronal activity in the PIL of mice exposed to a novel social stimulus, a novel object stimulus, or no stimulus. We then used fiber photometry to record neural activity of glutamatergic neurons in the PIL in real time during social and nonsocial interactions. Finally, we used inhibitory DREADDs (designer receptors exclusively activated by designer drugs) in glutamatergic PIL neurons and tested social preference and social habituation-dishabituation. RESULTS: We observed significantly more c-fos-positive cells in the PIL of mice exposed to a social stimulus versus an object stimulus or no stimulus. Neural activity of PIL glutamatergic neurons was increased when male and female mice were engaged in social interaction with a same-sex juvenile or opposite-sex adult, but not a toy mouse. Neural activity was positively correlated with social investigation bout length and negatively correlated with chronological order of bouts. Social preference was unaffected by inhibition; however, inhibiting activity of glutamatergic neurons in the PIL delayed the time that it took for female mice to form social habituation. CONCLUSIONS: Together, these findings suggest that glutamatergic PIL neurons respond to social stimuli in both male and female mice and may regulate perceptual encoding of social information to facilitate recognition of social stimuli.

Qualitative differences in perspective on children's quality of life between children with cerebral palsy and their parents.

BACKGROUND: Cerebral palsy (CP) is one of the most common childhood disabilities, impacting many areas of a child's life. Increasingly, quality of life (QOL) measures are used to capture holistic wellbeing of children with CP. However most validated QOL measures for children are based on adult perspective only, with limited focus on child perspective. Conceptual differences between children's and adults' definitions of QOL may reflect different underlying QOL models which contribute to measurement score divergence. This qualitative study investigated the conceptual meaning of QOL for children with CP, comparing child and parent perspectives. Eighteen families completed 8 child interviews and 18 parent interviews. Children (11 boys, 7 girls) represented the spectrum of motor functioning, with comorbidities including epilepsy, intellectual disability, and communication impairments. Child and parent interviews were analysed separately using constructivist grounded theory methods and then findings were integrated to examine similarities and differences. RESULTS: All participants sought child inclusion in social activities, education, and recreation, requiring negotiation, adaptations, and advocacy. Five conceptual categories emerged from child interviews: socialising, play, negotiating limitations, self-identity, and developing agency. This reflected an individual model of QOL supporting child development goals. Parent interview findings revealed concepts related to child-specific QOL (day-to-day functioning and enabling child goals), as well as parent and family functioning concepts aligned to models of "family QOL", embracing impacts of family relationships and the interdependence of QOL among family members. CONCLUSIONS: This study identified similarities and differences in child and parent perceptions of QOL for the child with CP. Children provided insights into the importance of play and peer support, and their developing self-identity and sense of agency. Self-directed free play, especially, was identified by children but not parents as a central everyday activity promoting wellbeing and social inclusion. Parents discussed family functioning and aspects outside of child sight, such as managing time and financial resources. Relying on parents' perspective alone to model child QOL misses valuable information that children contribute. Equally, child report alone misses parent experiences that directly influence child QOL. There is value in incorporating family QOL into parent reports while developing a conceptually separate child self-report QOL instrument.

Medication-free mental health treatment: a focus group study of milieu therapeutic settings.

BACKGROUND: Medication-free treatment within mental health care aims to offer therapeutic support as an alternative to psychotropic medication. Introducing milieu therapy for severely mentally ill persons in a medication-free unit requires significant changes to the traditional medication-based psychiatric setting. The present study examines how milieu therapists experience working with medication-free treatment for people with severe mental health challenges. The research question was "What may be required to succeed with medication-free treatment in milieu therapeutic settings?" METHODS: A qualitative study with four focus groups were conducted with 23 milieu therapists from three inpatient units in two mental health institutions. Thematic analysis was performed. RESULTS: One main theme was identified: medication-free treatment involves therapists and patients working together on holistic and personal health promotion. This common thread links the four themes: helping patients to make changes in their life; having time to focus on the individual patient; being a professional companion; and working together as a team with the patient. CONCLUSIONS: A holistic approach is necessary for medication-free treatment to succeed. This requires working together in multidisciplinary teams with a focus on the individual patient. Milieu therapists must engage and take more responsibility in the patient's process of health promotion. A change from a medical to a humanistic paradigm within mental health care is needed.

Hypothalamic control of innate social behaviors.

Sexual, parental, and aggressive behaviors are central to the reproductive success of individuals and species survival and thus are supported by hardwired neural circuits. The reproductive behavior control column (RBCC), which comprises the medial preoptic nucleus (MPN), the ventrolateral part of the ventromedial hypothalamus (VMHvl), and the ventral premammillary nucleus (PMv), is essential for all social behaviors. The RBCC integrates diverse hormonal and metabolic cues and adjusts an animal's physical activity, hence the chance of social encounters. The RBCC further engages the mesolimbic dopamine system to maintain social interest and reinforces cues and actions that are time-locked with social behaviors. We propose that the RBCC and brainstem form a dual-control system for generating moment-to-moment social actions. This Review summarizes recent progress regarding the identities of RBCC cells and their pathways that drive different aspects of social behaviors.

Contrasting patterns of foraging behavior in neotropical stingless bees using pollen and honey metabarcoding.

Stingless bees are major flower visitors in the tropics, but their foraging preferences and behavior are still poorly understood. Studying stingless bee interactions with angiosperms is methodologically challenging due to the high tropical plant diversity and inaccessibility of upper canopy flowers in forested habitats. Pollen DNA metabarcoding offers an opportunity of assessing floral visitation efficiently and was applied here to understand stingless bee floral resources spectra and foraging behavior. We analyzed pollen and honey from nests of three distantly related stingless bee species, with different body size and social behavior: Melipona rufiventris, Scaptotrigona postica and Tetragonisca angustula. Simultaneously, we evaluate the local floristic components through seventeen rapid botanical surveys conducted at different distances from the nests. We discovered a broad set of explored floral sources, with 46.3 plant species per bee species in honey samples and 53.67 in pollen samples. Plant families Myrtaceae, Asteraceae, Euphorbiaceae, Melastomataceae and Malpighiaceae dominated the records, indicating stingless bee preferences for abundant resources that flowers of these families provide in the region. Results also reinforce the preference of stingless bees for forest trees, even if only available at long distances. Our high-resolution results encourage future bee-plant studies using pollen and honey metabarcoding in hyper-diverse tropical environments.

Loss of TRPC2 function in mice alters sex differences in brain regions regulating social behaviors.

The transient receptor potential cation channel 2 (TRPC2) conveys pheromonal information from the vomeronasal organ (VNO) to the brain. Both male and female mice lacking this gene show altered sex-typical behavior as adults. We asked whether TRPC2, highly expressed in the VNO, normally participates in the development of VNO-recipient brain regions controlling mounting and aggression, two behaviors affected by TRPC2 loss. We now report significant effects of TRPC2 loss in both the posterodorsal aspect of the medial amygdala (MePD) and ventromedial nucleus of the hypothalamus (VMH) of male and female mice. In the MePD, a sex difference in neuron number was eliminated by the TRPC2 knockout (KO), but the effect was complex, with fewer neurons in the right MePD of females, and fewer neurons in the left MePD of males. In contrast, MePD astrocytes were unaffected by the KO. In the ventrolateral (vl) aspect of the VMH, KO females were like wildtype (WT) females, but TRPC2 loss had a dramatic effect in males, with fewer neurons than WT males and a smaller VMHvl overall. We also discovered a glial sex difference in VMHvl of WTs, with females having more astrocytes than males. Interestingly, TRPC2 loss increased astrocyte number in males in this region. We conclude that TRPC2 normally participates in the sexual differentiation of the mouse MePD and VMHvl. These changes in two key VNO-recipient regions may underlie the effects of the TRPC2 KO on behavior.

Intra- and inter-brain synchrony oscillations underlying social adjustment.

Humans naturally synchronize their behavior with other people. However, although it happens almost automatically, adjusting behavior and conformity to others is a complex phenomenon whose neural mechanisms are still yet to be understood entirely. The present experiment aimed to study the oscillatory synchronization mechanisms underlying automatic dyadic convergence in an EEG hyperscanning experiment. Thirty-six people performed a cooperative decision-making task where dyads had to guess the correct position of a point on a line. A reinforcement learning algorithm was used to model different aspects of the participants' behavior and their expectations of their peers. Intra- and inter-connectivity among electrode sites were assessed using inter-site phase clustering in three main frequency bands (theta, alpha, beta) using a two-level Bayesian mixed-effects modeling approach. The results showed two oscillatory synchronization dynamics related to attention and executive functions in alpha and reinforcement learning in theta. In addition, inter-brain synchrony was mainly driven by beta oscillations. This study contributes preliminary evidence on the phase-coherence mechanism underlying inter-personal behavioral adjustment.

Homocysteine Modulates Social Isolation-Induced Depressive-Like Behaviors Through BDNF in Aged Mice.

Social isolation is an unpleasant experience associated with an increased risk of mental disorders. Exploring whether these experiences affect behaviors in aged people is particularly important, as the elderly is very likely to suffer from periods of social isolation during their late-life. In this study, we analyzed the depressive-like behaviors, plasma concentrations of homocysteine (Hcy), and brain-derived neurotropic factor (BDNF) levels in aged mice undergoing social isolation. Results showed that depressive-like behavioral performance and decreased BDNF level were correlated with increased Hcy levels that were detected in 2-month isolated mice. Elevated Hcy induced by high methionine diet mimicked the depressive-like behaviors and BDNF downregulation in the same manner as social isolation, while administration of vitamin B complex supplements to reduce Hcy alleviated the depressive-like behaviors and BDNF reduction in socially isolated mice. Altogether, our results indicated that Hcy played a critical role in social isolation-induced depressive-like behaviors and BDNF reduction, suggesting the possibility of Hcy as a potential therapeutic target and vitamin B intake as a potential value in the prevention of stress-induced depression.

The social environment alters neural responses to a lipopolysaccharide challenge.

Sick animals display drastic changes in their behavioral patterns, including decreased activity, decreased food and water intake, and decreased interest in social interactions. These behaviors, collectively called "sickness behaviors", can be socially modulated. For example, when provided with mating opportunities, males of several species show reduced sickness behaviors. While the behavior is known to change, how the social environment affects neural molecular responses to sickness is not known. Here, we used a species, the zebra finch, Taeniopygia guttata, where males have been shown to decrease sickness behaviors when presented with novel females. Using this paradigm, we obtained samples from three brain regions (the hypothalamus, the bed nucleus of the stria terminalis, and the nucleus taeniae) from lipopolysaccharide (LPS) or control treated males housed under four different social environments. Manipulation of the social environment rapidly changed the strength and co-expression patterns of the neural molecular responses to the immune challenge in all brain regions tested, therefore suggesting that the social environment plays a significant role in determining the neural responses to an infection. In particular, brains of males paired with a novel female showed muted immune responses to LPS, as well as altered synaptic signaling. Neural metabolic activity in response to the LPS challenge was also affected by the social environment. Our results provide new insights into the effects of the social environment on brain responses to an infection, thereby improving our understanding of how the social environment can affect health.

Hypothalamic neurons that mirror aggression.

Social interactions require awareness and understanding of the behavior of others. Mirror neurons, cells representing an action by self and others, have been proposed to be integral to the cognitive substrates that enable such awareness and understanding. Mirror neurons of the primate neocortex represent skilled motor tasks, but it is unclear if they are critical for the actions they embody, enable social behaviors, or exist in non-cortical regions. We demonstrate that the activity of individual VMHvlPR neurons in the mouse hypothalamus represents aggression performed by self and others. We used a genetically encoded mirror-TRAP strategy to functionally interrogate these aggression-mirroring neurons. We find that their activity is essential for fighting and that forced activation of these cells triggers aggressive displays by mice, even toward their mirror image. Together, we have discovered a mirroring center in an evolutionarily ancient region that provides a subcortical cognitive substrate essential for a social behavior.

A Human-Centered Design Approach to Develop Oral Health Nursing Interventions in Patients with a Psychotic Disorder.

In mental health, oral health is often given little attention. Mental health nurses (MHNs) are professionally the appropriate target group to support maintaining and increasing oral health. We aimed to develop and validate personas that reflect the attitudes and needs of MHNs regarding oral health in patients with a psychotic disorder. We used a human-centered design with contextual interviews (n = 10) to address the key issues of the problems and needs of MHNs working with patients with a psychotic disorder. We analyzed the data thematically and reflected on insights into unique personas, which were then validated by conducting semi-structured interviews (n = 19) and member checking. Four personas were found based on attitudes and perspectives, barriers, needs, suggestions for interventions, and site conditions regarding practicing oral care in this patient group. Our findings were as follows: the attitudes and perspectives differed from not feeling any responsibility to a holistic obligation, including oral health; suggestions for interventions for MHNs ranged from interventions focusing on improving skills and knowledge to using practical tools; most MHNs recognized themselves within a persona that had a holistic obligation that included oral health; in addition, the MHNs indicated that they considered the issue of oral health in this patient group important, but, in practice, took little responsibility for that role. These findings suggest that a toolkit with interventions for MHNs that are tailored to the personas that emerged from our research should be developed by MHNs in co-creation with designers. The differences between the perceived role and MHNs' practice in oral health highlighted the need for role clarification and professional leadership of MHNs regarding oral health, which should be considered when developing interventions.

An approximate line attractor in the hypothalamus encodes an aggressive state.

The hypothalamus regulates innate social behaviors, including mating and aggression. These behaviors can be evoked by optogenetic stimulation of specific neuronal subpopulations within MPOA and VMHvl, respectively. Here, we perform dynamical systems modeling of population neuronal activity in these nuclei during social behaviors. In VMHvl, unsupervised analysis identified a dominant dimension of neural activity with a large time constant (>50 s), generating an approximate line attractor in neural state space. Progression of the neural trajectory along this attractor was correlated with an escalation of agonistic behavior, suggesting that it may encode a scalable state of aggressiveness. Consistent with this, individual differences in the magnitude of the integration dimension time constant were strongly correlated with differences in aggressiveness. In contrast, approximate line attractors were not observed in MPOA during mating; instead, neurons with fast dynamics were tuned to specific actions. Thus, different hypothalamic nuclei employ distinct neural population codes to represent similar social behaviors.