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Item Aggression Results in the Phosphorylation of ERK1/2 in the Nucleus Accumbens and the Dephosphorylation of mTOR in the Medial Prefrontal Cortex in Female Syrian Hamsters(MDPI, 2023-01-10) Borland, Johnathan M.; Dempsey, Desarae A.; Peyla, Anna C.; Hall, Megan A. L.; Kohut-Jackson, Abigail L.; Mermelstein, Paul G.; Meisel, Robert L.; Neurology, School of MedicineLike many social behaviors, aggression can be rewarding, leading to behavioral plasticity. One outcome of reward-induced aggression is the long-term increase in the speed in which future aggression-based encounters is initiated. This form of aggression impacts dendritic structure and excitatory synaptic neurotransmission in the nucleus accumbens, a brain region well known to regulate motivated behaviors. Yet, little is known about the intracellular signaling mechanisms that drive these structural/functional changes and long-term changes in aggressive behavior. This study set out to further elucidate the intracellular signaling mechanisms regulating the plasticity in neurophysiology and behavior that underlie the rewarding consequences of aggressive interactions. Female Syrian hamsters experienced zero, two or five aggressive interactions and the phosphorylation of proteins in reward-associated regions was analyzed. We report that aggressive interactions result in a transient increase in the phosphorylation of extracellular-signal related kinase 1/2 (ERK1/2) in the nucleus accumbens. We also report that aggressive interactions result in a transient decrease in the phosphorylation of mammalian target of rapamycin (mTOR) in the medial prefrontal cortex, a major input structure to the nucleus accumbens. Thus, this study identifies ERK1/2 and mTOR as potential signaling pathways for regulating the long-term rewarding consequences of aggressive interactions. Furthermore, the recruitment profile of the ERK1/2 and the mTOR pathways are distinct in different brain regions.Item Androstadienone sensitivity is associated with attention to emotions, social interactions, and sexual behavior in older U.S. adults(Public Library of Science, 2023-01-13) Kern, David W.; Kaufmann, Gabriel T.; Hummer, Tom A.; Schumm, L. Philip; Wroblewski, Kristen E.; Pinto, Jayant M.; McClintock, Martha K.; Psychiatry, School of MedicineΔ 4,16-androstadien-3-one (androstadienone) is a putative human pheromone often linked to sexual attraction in young adults, although specific associations with sexual behavior are not yet established. Androstadienone also serves a broader social-emotional function beyond the sexual domain, specifically tuning the brain to efficiently process emotional information. Whether these effects persist throughout the lifespan into post-reproductive life is unknown. In a laboratory study of older adults, those with greater androstadienone odor sensitivity paid greater attention to subliminal emotional information, specifically, angry faces (p = 0.05), with a similar relationship to happy faces. In contrast, the physical odor n-butanol (a control) did not affect emotional attention (p = 0.49). We then extended this laboratory research and determined whether sensitivity to androstadienone affects the everyday lives of older adults by measuring their social and sexual behavior. In this second study, we surveyed in a nationally representative sample of US older adults living in their homes (National Social Life and Aging Project, 62-90 years; n = 2,086), along with their sensitivity to androstadienone, general olfactory function, health and demographics. Greater sensitivity to androstadienone was associated with richer social lives: having more friends, increased communication with close friends and family, and more participation in organized social events and volunteer activities (all p's ≤ 0.05, generalized linear models, adjusted for age and gender). It was also associated with more recent sexual activity, more frequent sexual thoughts, and viewing sex as an important part of life (all p's ≤ 0.05). General olfactory function did not explain these associations, supporting a specialized function for this pheromone during everyday life, and expanding its role to social life as well as sexual behavior, likely mediated by enhanced attention to emotional information.Item Development, validation, and characterization of a novel preclinical animal model of social familiarity-induced anxiolysis(2017-09-29) Lungwitz, Elizabeth Ann; Shekhar, Anantha; Truitt, William; Oxford, Gerry; Rodd, Zachary; Lapish, ChristopherSocial support is a powerful therapeutic against fear and anxiety and is utilized in many psychotherapies. The concept that a familiar or friendly presence helps a person learn to overcome anxiety has been well-known for decades, yet, the basic neural mechanisms that regulate this psychosocial learning remain unknown. A first step towards elucidating these basic mechanisms is the development of a valid preclinical animal model. However, preclinical behavioral models exploring the use of a social presence in reducing anxiety have not been fully characterized. Therefore, it was our goal to identify a useful way in which to study the mechanisms of how a social presence can induce anxiolysis (the reduction of anxiety). We accomplished this goal by characterizing and validating a preclinical model, as well as demonstrating that the model was capable of measuring deficits in rats given a mild traumatic brain injury. To this end, we identified an existing, but uncharacterized model, the social interaction-habituation model, as an effective model of social familiarity-induced anxiolysis (SoFiA), which demonstrates socially enhanced safety learning, or psychosocial learning. We find that as social familiarity develops across time, anxiolysis develops. We identified that the use of a Bright Light Challenge is a useful anxiogenic stimulus to use during SI-habituation training. The anxiolysis acquired following SI-habituation testing is partner specific, and can be blocked by an inhibition of the medical prefrontal cortex, while it can be enhanced by D-cycloserine. We found that this model identified deficits in SoFiA acquisition in rodents exposed to a mild traumatic brain injury, which, in humans, has been linked to psychosocial deficits. This work is a step in creating ways in which we can study and better understand the regulatory processes of emotions mediated by social behavior.Item How students display dialogue, deliberation and civic-mindedness(2014-04-02) Weiss, H. Anne; Sheeler, Kristina Horn, 1965-; Goering, Elizabeth M.; Rossing, Jonathan P.Item Methamphetamine-induced deficits in social interaction are not observed following abstinence from single or repeated exposures(Wolters Kluwer, 2015-12) Janetsian, Sarine S.; McCane, Aqilah M.; Linsenbardt, David N.; Lapish, Christopher C.; Department of Psychology, School of ScienceThe purpose of the current study was to assess social interaction (SI) following acute and repeated methamphetamine (MA) administration. Rats were injected with 5.0 mg/kg of MA and SI was tested 30 minutes or 24 hours later. In another group of animals, MA sensitization was induced using 5.0 mg/kg of MA, and SI was assessed after one day or thirty days of abstinence. SI was reduced in rats injected with MA 30 minutes, but not 24 hours, prior to testing, compared with saline controls. Impaired SI was observed in combination with active avoidance of the conspecific animal. Repeated injections of MA progressively reduced locomotor activity and increased stereotypy, indicating that animals were sensitized. However, no differences in SI were observed 24 hours or 30 days following the induction of sensitization. The absence of detectable differences in SI following MA sensitization may be attributable to the relatively short regimen used to induce sensitization. However, the current series of experiments provides evidence that an acute injection of MA decreases SI and simultaneously increases avoidance behavior, which supports a link between psychostimulant use and impaired social functioning. These data suggest that the acute injection model may provide a useful model to explore the neural basis of impaired social functioning and antisocial behavior.Item Narrative enhancement and cognitive therapy (NECT) to improve social functioning in people with serious mental illness: study protocol for a stepped-wedge cluster randomized controlled trial(BMC, 2021-02-08) Dubreucq, J.; Faraldo, M.; Abbes, M.; Ycart, B.; Richard-Lepouriel, H.; Favre, S.; Jermann, F.; Attal, J.; Bakri, M.; Cohen, T.; Cervello, C.; Chereau, I.; Cognard, C.; De Clercq, M.; Douasbin, A.; Giordana, J.Y.; Giraud-Baro, E.; Guillard-Bouhet, N.; Legros-Lafarge, E.; Polosan, M.; Pouchon, A.; Rolland, M.; Rainteau, N.; Roussel, C.; Wangermez, C.; Yanos, P.T.; Lysaker, P.H.; Franck, N.; Psychiatry, School of MedicineBackground: Self-stigma is highly prevalent in serious mental illness (SMI) and is associated with poorer clinical and functional outcomes. Narrative enhancement and cognitive therapy (NECT) is a group-based intervention combining psychoeducation, cognitive restructuring and story-telling exercises to reduce self-stigma and its impact on recovery-related outcomes. Despite evidence of its effectiveness on self-stigma in schizophrenia-related disorders, it is unclear whether NECT can impact social functioning. Methods: This is a 12-centre stepped-wedge cluster randomized controlled trial of NECT effectiveness on social functioning in SMI, compared to treatment as usual. One hundred and twenty participants diagnosed with schizophrenia, bipolar disorder or borderline personality disorder will be recruited across the 12 sites. The 12 centres participating to the study will be randomized into two groups: one group (group 1) receiving the intervention at the beginning of the study (T0) and one group (group 2) being a control group for the first 6 months and receiving the intervention after (T1). Outcomes will be compared in both groups at T0 and T1, and 6-month and 12-month outcomes for groups 1 and 2 will be measured without a control group at T2 (to evaluate the stability of the effects over time). Evaluations will be conducted by assessors blind to treatment allocation. The primary outcome is personal and social performance compared across randomization groups. Secondary outcomes include self-stigma, self-esteem, wellbeing, quality of life, illness severity, depressive symptoms and personal recovery. Discussion: NECT is a promising intervention for reducing self-stigma and improving recovery-related outcomes in SMI. If shown to be effective in this trial, it is likely that NECT will be implemented in psychiatric rehabilitation services with subsequent implications for routine clinical practice.Item Poly(I:C)-exposed zebrafish shows autism-like behaviors which are ameliorated by fabp2 gene knockout(Frontiers Media, 2023-01-05) Wu, Jing; Lin, Xueting; Wu, Dian; Yan, Binhong; Bao, Mengyi; Zheng, Peilei; Wang, Jiangping; Yang, Cuiwei; Li, Zhongxia; Jin, Xiaoming; Jiang, Kewen; Anatomy, Cell Biology and Physiology, School of MedicineIntroduction: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders mainly representing impaired social communication. The etiology of ASD includes genetic and environmental risk factors. Rodent models containing ASD risk gene mutations or environmental risk factors, such as exposure to maternal inflammation, show abnormal behavior. Although zebrafish conserves many important brain structures of humans and has sophisticated and fine behaviors in social interaction, it is unknown whether the social behaviors of their offspring would be impaired due to exposure to maternal inflammation. Methods: We exposed zebrafish to maternal immune activation (MIA) by injection with polyinosinic:polycytidylic acid [poly(I:C)], and screened their behaviors through social behavioral tests such as social preference and shoaling behavior tests. We compared phenotypes resulted from different ways of poly(I:C) exposure. RNA sequencing was performed to explore the differential expression genes (DEGs). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analysis was performed with the detected DEGs to find the concentrated pathways. Finally, we knocked out the fatty acid-binding protein 2 (fabp2), a key node of the concentrated PPI network, to find its rescues on the altered social behavior. Results: We reported here that MIA offspring born to mothers injected with poly(I:C) exhibited impaired social approach and social cohesion that mimicked human ASD phenotypes. Both maternal exposure and direct embryo exposure to poly(I:C) resulted in activations of the innate immune system through toll-like receptors 3 and 4. RNA-sequencing results from MIA brain tissues illustrated that the numbers of overexpressed genes were significantly more than that of underexpressed genes. GO and KEGG analyses found that MIA-induced DEGs were mainly concentrated in complement and coagulation cascade pathways. PPI network analyses suggested that villin-1 (vil1) pathway might play a key role in MIA-induced ASD. Knockout of fabp2 in F0 zebrafish rescued the social behavior deficits in MIA offspring. Conclusions: Overall, our work established an ASD model with assessable behavior phenotype in zebrafish and provided key insights into environmental risk factor in ASD etiology and the influence of fabp2 gene on ASD-like behavior.Item Role of Basolateral Amygdalar Somatostatin 2 Receptors in a Rat Model of Chronic Anxiety(Elsevier, 2021) Gaskins, Denise L.; Burke, Andrew R.; Sajdyk, Tammy J.; Truitt, William A.; Dietrich, Amy D.; Shekhar, Anantha; Anatomy, Cell Biology and Physiology, School of MedicineRepeated exposure to stress has been implicated in inducing chronic anxiety states. Stress related increases in anxiety responses are likely mediated by activation of corticotropin-releasing factor receptors (CRFR) in the amygdala, particularly the basolateral amygdala (BLA). Within the BLA, acute injections of the CRFR agonist urocortin 1 (Ucn1) leads to acute anxiety, whereas repeated daily injections of subthreshold-doses of Ucn1 produces a long-lasting, persistent anxiety-like phenotype, a phenomenon referred to as Ucn1-priming. Relative gene expressions from the BLA of vehicle and Ucn1-primed rats were analyzed with quantitative RT-PCR using a predesigned panel of 82 neuroscience-related genes. Compared to vehicle-primed rats, only expression of the somatostatin receptor 2 gene (Sstr2) was significantly reduced in the BLA of Ucn1-primed rats. The contribution of Sstr2 on an anxiety phenotype was tested by injecting a Sstr2 antagonist into the BLA in un-primed rats. The Sstr2 antagonist increased anxiety-like behavior. Notably, pretreatment with Sstr2 agonist injected into the BLA blocked anxiety-inducing effects of acute Ucn1 BLA-injections and delayed anxiety expression during Ucn1-priming. However, concomitant Sstr2 agonist pretreatment during Ucn-1 priming did not prevent either the development of a chronic anxiety state or a reduction of BLA Sstr2 expression induced by priming. The data demonstrate that the persistent anxiety-like phenotype observed with Ucn1-priming in the BLA is associated with a selective reduction of Sstr2 gene expression. Although Sstr2 activation in the BLA blocks acute anxiogenic effects of stress and down-regulation of BLA Sstr2, it does not suppress the long-term consequences of prolonged exposure to stress-related challenges.Item The Story of Medicine: From Paternalism to Partnership(2013-01-09) Marks, Jennifer Lynn; Parrish-Sprowl, John; Sheeler, Kristina K. Horn; Karnick, Kristine Brunovska, 1958-Physicians were interviewed and asked about their perspectives on communicating with patients, media, and the ways in which the biomedical and biopsychosocial models function in the practice of medicine. Fisher’s Narrative Paradigm was the primary critical method applied to themes that emerged from the interviews. Those emergent themes included the importance of a team approach to patient care; perspectives on physicians as bad communicators; and successful communication strategies when talking to patients. Physicians rely on nurses and other support staff, but the most important partnership is that between the physician and patient. Narrative fidelity and probability are satisfied by strategies physicians use in communicating with patients: using understandable language when talking to patients; engaging in nonverbal tactics of sitting down with patients, making eye contact with patients, and making appropriate physical contact with them in the form of a handshake or a light touch on the arm. Physicians are frustrated by media’s reporting of preliminary study results that omit details as well as media’s fostering of expectations for quick diagnostic processes and magical cures within the public. Furthermore, physicians see the biomedical and biopsychosocial models becoming increasingly interdependent in the practice of medicine, which carries the story of contemporary medicine further into the realm of partnership, revealing its humanity as well as its fading paternalism.Item Stuck Inside: How Social Functioning in Schizophrenia Changed During the COVID-19 Pandemic(Wolters Kluwer, 2022) Minor, Kyle S.; Myers, Evan J.; Abel, Danielle B.; Mickens, Jessica L.; Ayala, Alexandra; Warren, Kiara K.; Vohs, Jenifer L.; Psychology, School of ScienceSocial distancing policies enacted during the COVID-19 pandemic altered our social interactions. People with schizophrenia, who already exhibit social deficits, may have been disproportionally impacted. In this pilot study, we a) compared prepandemic social functioning to functioning during the pandemic in people with schizophrenia ( n = 21) who had data at both time points; and b) examined if patterns of decline in schizophrenia differed from healthy controls ( n = 21) across a series of repeated-measures analyses of variance. We observed larger declines in social functioning in schizophrenia (η 2 = 0.07, medium effect size) during the pandemic compared with the control group. Between-group declines did not extend to other domains, suggesting that declines are specific to social functioning. Our findings signal that treatments focusing on reconnecting people with schizophrenia to their social networks should be prioritized. Future studies should continue tracking social functioning after the pandemic to illustrate patterns of recovery.