Chemogenetic manipulation of the bed nucleus of the stria terminalis counteracts social behavioral deficits induced by early life stress in C57BL/6J mice.

Trauma during critical periods of development can induce long-lasting adverse effects. To study neural aberrations resulting from early life stress (ELS), many studies utilize rodent maternal separation, whereby pups are intermittently deprived of maternal care necessary for proper development. This can produce adulthood behavioral deficits related to anxiety, reward, and social behavior. The bed nucleus of the stria terminalis (BNST) encodes aspects of anxiety-like and social behaviors, and also undergoes developmental maturation during the early postnatal period, rendering it vulnerable to effects of ELS. Mice underwent maternal separation (separation 4 hr/day during postnatal day (PD)2-5 and 8 hr/day on PD6-16) with early weaning on PD17, which induced behavioral deficits in adulthood performance on two-part social interaction task designed to test social motivation (choice between a same-sex novel conspecific or an empty cup) and social novelty preference (choice between the original-novel conspecific vs. a new-novel conspecific). We used chemogenetics to non-selectively silence or activate neurons in the BNST to examine its role in social motivation and social novelty preference, in mice with or without the history of ELS. Manipulation of BNST produced differing social behavior effects in non-stressed versus ELS mice; social motivation was decreased in non-stressed mice following BNST activation, but unchanged following BNST silencing, while ELS mice showed no change in social behavior after BNST activation, but exhibited enhancement of social motivation-for which they were deficient prior-following BNST silencing. Findings emphasize the BNST as a potential therapeutic target for social anxiety disorders instigated by childhood trauma.

Autism spectrum disorder and severe social impairment associated with elevated plasma interleukin-8.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unclear etiology and pathophysiology. Previous studies have indicated that the dysregulation of cytokines may be involved in the pathogenesis of ASD and that the levels of cytokines may serve as potential biomarkers of this disorder. METHODS: The current study employed a family triad-based case-control design to study the levels of plasma cytokines in families with ASD (n = 45 triads) and controls (n = 38 triads) with a Human Cytokine Twenty-Five-Plex Kit. The Social Responsiveness Scale (SRS) was used to measure social impairment of ASD children. RESULTS: After controlling for the levels of parental cytokines, we identified that interferon-α (IFN-α), interleukin-7 (IL-7), IL-8, IFN-γ-inducible protein-10, and macrophage inflammatory protein-1ß were associated with ASD, and IL-8 was the only cytokine also associated with the levels of both parental cytokines in the offspring-parents regression analysis and three subdomains of SRS (social awareness, cognition, and motivations) in the children with ASD. The receiver operating characteristic curve showed that the log-transformed IL-8 level discriminated children with autism from controls with an area under the curve of 0.858 (95% confidence interval: 0.777-0.939). CONCLUSIONS: Our study suggests that IL-8 is a potential biomarker for ASD and may be involved in the pathogenesis of ASD. IMPACT: The study suggests that IL-8 is a promising biomarker for ASD and may be involved in the pathogenesis of ASD. Only a very few studies have reported the parental cytokine levels. The significant strength of this article is that we applied the family triad-based approach to explore cytokine levels in families with autism and controls. There are no objective biomarkers, making the accurate diagnosis, prognostic prediction and effective treatment difficult, and our study provides promising results.

A standardized social preference protocol for measuring social deficits in mouse models of autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and other behavioral abnormalities. The three-chamber social preference test is often used to assess social deficits in mouse models of ASD. However, varying and often contradicting phenotypic descriptions of ASD mouse models can be found in the scientific literature, and the substantial variability in the methods used by researchers to assess social deficits in mice could be a contributing factor. Here we describe a standardized three-chamber social preference protocol, which is sensitive and reliable at detecting social preference deficits in several mouse models of ASD. This protocol comprises three phases that can all be completed within 1 d. The test mouse is first habituated to the apparatus containing two empty cups in the side chambers, followed by the pre-test phase in which the mouse can interact with two identical inanimate objects placed in the cups. During the test phase, the mouse is allowed to interact with a social stimulus (an unfamiliar wild-type (WT) mouse) contained in one cup and a novel non-social stimulus contained in the other cup. The protocol is thus designed to assess preference between social and non-social stimuli under conditions of equal salience. The broad implementation of the three-chamber social preference protocol presented here should improve the accuracy and consistency of assessments for social preference deficits associated with ASD and other psychiatric disorders.

Social deficits in high school students with attention-deficit/hyperactivity disorder and the role of emotion dysregulation.

Attention-deficit/hyperactivity disorder (ADHD) is strongly associated with social functioning deficits in adolescents. However, the factors underlying this relationship are not well understood. Prior research has established that emotion dysregulation (ED) mediates the relationship between ADHD symptoms and social skills in middle school students and that the mediational role of ED is moderated by youth's level of depression. The current study examined whether this model holds true in high school students with ADHD, despite developmental and environmental changes during maturation. Cross-sectional measures of ADHD symptoms, emotion regulation, depression, and social functioning were collected from 174 high school students with ADHD (M age = 14.51; 81.4% male). Analyses were conducted using the PROCESS macro for SPSS. Bootstrapping results of the omnibus effect of a multiple-mediational model indicated that ADHD and ED jointly account for 49% of the variance in parent-rated social skills (i.e., evidence of mediation by ED). However, counter to our hypothesis, depression did not moderate this relationship. This study provides evidence that ED accounts for the relationship between ADHD and social deficits in an older adolescent population. Results have significant implications for intervention strategies to improve emotional self-awareness and control in adolescents with ADHD. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Biocognitive Classification of Antisocial Individuals Without Explanatory Reductionism.

Effective and specifically targeted social and therapeutic responses for antisocial personality disorders and psychopathy are scarce. Some authors maintain that this scarcity should be overcome by revising current syndrome-based classifications of these conditions and devising better biocognitive classifications of antisocial individuals. The inspiration for the latter classifications has been embedded in the Research Domain Criteria (RDoC) approach. RDoC-type approaches to psychiatric research aim at transforming diagnosis, provide valid measures of disorders, aid clinical practice, and improve health outcomes by integrating the data on the genetic, neural, cognitive, and affective systems underlying psychiatric conditions. In the first part of the article, we discuss the benefits of such approaches compared with the dominant syndrome-based approaches and review recent attempts at building biocognitive classifications of antisocial individuals. Other researchers, however, have objected that biocognitive approaches in psychiatry are committed to an untenable form of explanatory reductionism. Explanatory reductionism is the view that psychological disorders can be exclusively categorized and explained in terms of their biological causes. In the second part of the article, we argue that RDoC-like approaches need not be associated with explanatory reductionism. Moreover, we argue how this is the case for a specific biocognitive approach to classifying antisocial individuals.

Emotion regulation as a transdiagnostic factor in Afghan refugees.

OBJECTIVE: In response to the high rates of comorbidity as well as the severe social impairment among refugees, the examination of transdiagnostic factors such as emotion regulation appears particularly promising in this group. This study investigates the contribution of difficulties in emotion regulation to the self-reported symptom levels of posttraumatic stress disorder (PTSD), depression, and anxiety/insomnia, which are highly prevalent symptoms among refugees. In addition, the link between emotion regulation and social impairment is examined. METHOD: Participants were 74 male Afghan refugees exposed to trauma. They completed measures of trauma exposure, difficulties in emotion regulation (Difficulties in Emotion Regulation Scale), PTSD (PTSD Checklist for DSM-5), depression, anxiety/insomnia, and social impairment (General Health Questionnaire-28). RESULTS: Higher symptom severities of PTSD, depression, and anxiety/insomnia were related to the Difficulties in Emotion Regulation Scale subscales nonacceptance, goals, impulse, strategies, and clarity, but none of our outcomes was related to lack of emotional awareness. Difficulties in emotion regulation accounted for significant variance in PTSD, depression, and anxiety/insomnia beyond demographics and trauma exposure. When predicting social impairment, difficulties in emotion regulation accounted for significant variance beyond PTSD and anxiety/insomnia but not beyond depression. CONCLUSION: The findings indicate that emotion regulation may be a transdiagnostic key factor contributing to symptoms of different mental disorders as well as social impairment in trauma-exposed refugees. It highlights the need and potential directions for transdiagnostic interventions that target these difficulties. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Lifelong consequences of brain injuries during development: From risk to resilience.

Traumatic brain injuries in children represent a major public health issue and even relatively mild injuries can have lifelong consequences. However, the outcomes from these injuries are highly heterogeneous, with most individuals recovering fully, but a substantial subset experiencing prolonged or permanent disabilities across a number of domains. Moreover, brain injuries predispose individuals to other kinds of neuropsychiatric and somatic illnesses. Critically, the severity of the injury only partially predicts subsequent outcomes, thus other factors must be involved. In this review, we discuss the psychological, social, neuroendocrine, and autonomic processes that are disrupted following traumatic brain injury during development, and consider the mechanisms the mediate risk or resilience after traumatic brain injury in this vulnerable population.

How should we understand the absence of sex differences in the genetic and environmental origins of antisocial behavior?

Available twin-family data on sex differences in antisocial behavior (ASB) simultaneously suggest that ASB is far more prevalent in males than in females, and that its etiology (i.e. the effects of genes, environments, hormones, culture) does not differ across sex. This duality presents a conundrum: How do we make sense of mean sex differences in ASB if not via differences in genes, environments, hormones, and/or cultures? The current selective review and critique explores possible contributions to these seemingly incompatible sets of findings. We asked whether the presence of sex differences in behavior could be smaller than is typically assumed, or confined to a specific set of behaviors. We also asked whether there might be undetected differences in etiology across sex in twin-family studies. We found little evidence that bias or measurement invariance across sex account for phenotypic sex differences in ASB, but we did identify some key limitations to current twin-family approaches. These included the questionable ability of qualitative sex difference analyses to detect gender norms and prenatal exposure to testosterone, and concerns regarding specific analytic components of quantitative sex difference analyses. We conclude that the male preponderance in ASB is likely to reflect a true sex difference in observed behavior. It was less clear, however, that the genetic and environmental contributions to ASB are indeed identical across sex, as argued by prior twin-family studies. It is our hope that this review will inspire the development of new, genetically-informed methods for studying sex differences in etiology.

Atypical functional connectome hierarchy in autism.

One paradox of autism is the co-occurrence of deficits in sensory and higher-order socio-cognitive processing. Here, we examined whether these phenotypical patterns may relate to an overarching system-level imbalance-specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks. Combining connectome gradient and stepwise connectivity analysis based on task-free functional magnetic resonance imaging (fMRI), we demonstrated atypical connectivity transitions between sensory and higher-order default mode regions in a large cohort of individuals with autism relative to typically-developing controls. Further analyses indicated that reduced differentiation related to perturbed stepwise connectivity from sensory towards transmodal areas, as well as atypical long-range rich-club connectivity. Supervised pattern learning revealed that hierarchical features predicted deficits in social cognition and low-level behavioral symptoms, but not communication-related symptoms. Our findings provide new evidence for imbalances in network hierarchy in autism, which offers a parsimonious reference frame to consolidate its diverse features.

Disengaging from Evil: Longitudinal Associations Between the Dark Triad, Moral Disengagement, and Antisocial Behavior in Adolescence.

Previous work has identified important correlational linkages between the dark triad of personality (Machiavellianism, psychopathy, and narcissism) and antisocial behavior in adolescence. However, little is known about the longitudinal associations between these personality characteristics and antisocial behavior, and the processes underlying these linkages. We hypothesized positive bidirectional associations between the dark triad and antisocial behavior, and that increases in moral disengagement would underlie these longitudinal associations. In the current study, we examined these hypotheses in 502 Dutch adolescents (51.8% boys, Mage = 13.57, SD = 1.07) across three annual waves. Path models showed that antisocial behavior was positively associated with relative increases in moral disengagement, a general dark personality factor, and Machiavellianism specifically, but not the other way around. These paths were only observed in boys and more pronounced during the first year of the study. Finally, antisocial behavior was partly indirectly associated to psychopathy across time via antisocial behavior and moral disengagement at a later time point. Together, these findings suggest that dark personality characteristics and moral disengagement development are more likely to be the result of changes in antisocial behavior than the other way around.

Emotional Reactivity and Antisocial Behavior Relative to Posttraumatic Stress Symptom Expression: a Latent Profile Analysis.

This study examined whether emotional reactivity was associated with violent juvenile offending in a sample of detained boys (N = 198). It was predicted that Latent Profile Analysis (LPA) would reveal a "low reactivity" group, characterized by symptoms of emotional numbing and callous-unemotional (CU) traits, and a "high reactivity" group, characterized by symptoms of hyperarousal and emotional dysregulation. It was hypothesized that the low reactivity group would have higher rates of violent offending and proactive aggression than the high reactivity group. Contrary to expectations, results indicated that the presence of both emotional numbing and hyperarousal symptoms, but not hyperarousal symptoms alone, were associated with higher rates of violent offending, CU traits, and proactive aggression. Results indicate that the risk of serious aggressive behavior and violent offending may be highest among youth who are easily provoked to respond aggressively (i.e., hyperarousal symptoms) while simultaneously able to maintain emotional detachment (i.e., elevated emotional numbing symptoms and CU traits).

Using Bayesian methods to update and expand the meta-analytic evidence of the five-factor model's relation to antisocial behavior.

The Five Factor Model (FFM) of personality is the dominant hierarchical model of personality. Previous work has demonstrated the importance of the FFM domains and facets in understanding a variety of antisocial behaviors ranging from non-violent antisocial behavior to a variety of aggression outcomes. The aim of the present meta-analysis was to quantitatively summarize the empirical work that has examined these relations, as well as update and expand previous work in this area using Bayesian meta-analytic methods. A comprehensive search of available literature on the FFM and antisocial behavior was conducted and posterior distributions of effect sizes were computed for the FFM domains (across 12 antisocial outcomes). The meta-analytic results supported the primary importance of (low) Agreeableness and (low) Conscientiousness in predicting antisocial behavior across antisocial outcomes, with the exception of the outcome related to child molestation. The importance of Neuroticism was more dependent on the specific antisocial outcome under examination. The results are discussed in the context of the descriptive research on the FFM and antisocial behavior, and how Bayesian methods provide additional utility in estimation and prediction compared to more common frequentist methods. Furthermore, we recommend that future work on the FFM and antisocial behavior move towards process-level analyses to further examine how traits are implicated in different forms of antisocial behavior.

Targeting the Oxytocin System: New Pharmacotherapeutic Approaches.

Deficits in social behavioral domains, such as interpersonal communication, emotion recognition, and empathy, are a characteristic symptom in several neuropsychiatric disorders, including schizophrenia and autism spectrum disorder (ASD). The neuropeptide oxytocin (OT) has emerged as a key regulator of diverse social behaviors in vertebrates and, thus, has been identified as a potential therapeutic target for improving social dysfunction. In recent years, the field of OT research has seen an explosion of scientific inquiry, producing a more comprehensive picture of oxytocinergic signaling and the pathways that regulate its release and degradation in the brain. In this review, we provide an analysis of how this information is being exploited to accelerate the discovery of novel oxytocinergic therapeutics.

[Perceived stress and subjective memory complaints in young adults: the mediating role of the executive functions]. / Estres percibido y quejas subjetivas de memoria en adultos jovenes: papel mediador de las funciones ejecutivas.

INTRODUCTION: Previous studies have shown that executive functions can be mediators between perceived stress and subjective memory complaints. However, it has not been evaluated which executive functions are those that most mediate this relationship. AIM: To determine if executive functions have a mediating role in the relationship between perceived stress and subjective memory complaints, and which ones have the greatest explanatory power. PATIENTS AND METHODS: The sample consisted of 743 university students (76.4% women), with an average age of 22.24 ± 3.64 years. The subjective memory complaints were evaluated with the Memory Failure of Everyday Questionnaire, the stress with the Perceived Stress Scale, and the executive functions with the Prefrontal Symptoms Inventory. RESULTS: The executive functions and the perceived stress explained altogether 57% of the subjective memory complaints, being the attentional problems and the executive control problems the two variables with a greater weight in the model. On the other hand, the executive control problems, attentional problems and social behaviour problems showed a mediating effect between perceived stress and subjective memory complaints. CONCLUSIONS: The executive control problems and the attentional problems could be factors of choice for clinical intervention, since they act on their own as generators of subjective memory complaints and, moreover, are involved in mediation processes of perceived stress.

TITLE: Estres percibido y quejas subjetivas de memoria en adultos jovenes: papel mediador de las funciones ejecutivas.Introduccion. En estudios previos se ha señalado que las funciones ejecutivas pueden actuar como mediadoras entre el estres percibido y las quejas subjetivas de memoria. Sin embargo, no se ha evaluado que funciones ejecutivas son las que median en mayor medida dicha relacion. Objetivo. Determinar si las funciones ejecutivas tienen un papel mediador en la relacion entre el estres percibido y las quejas subjetivas de memoria, y cuales son las que tienen un mayor poder explicativo. Pacientes y metodos. La muestra estuvo compuesta por 743 universitarios (76,4% mujeres), con una edad media de 22,24 ± 3,64 años. Las quejas subjetivas de memoria se evaluaron con el cuestionario de fallos de memoria de la vida cotidiana; el estres, con la escala de estres percibido; y las funciones ejecutivas, con el inventario de sintomas prefrontales. Resultados. Las funciones ejecutivas y el estres percibido explicaron en conjunto un 57% de las quejas subjetivas de memoria, y los problemas atencionales y los problemas del control ejecutivo fueron las dos variables con un mayor peso en el modelo. Por otro lado, los problemas del control ejecutivo, los problemas atencionales y los problemas de la conducta social mostraron un efecto mediador entre el estres percibido y las quejas subjetivas de memoria. Conclusiones. Los problemas del control ejecutivo y los problemas atencionales podrian ser factores de eleccion para la intervencion clinica, puesto que actuan por si solos como generadores de quejas subjetivas de memoria y ademas se encuentran implicados en procesos de mediacion del estres percibido.

Cognitive behavioural therapy for aggression among individuals with moderate to severe acquired brain injury: a systematic review and meta-analysis.

BACKGROUND: Aggression is common after an acquired brain injury (ABI). Cognitive behavioural therapy (CBT) is a form of psychotherapy, in which therapists help patients to identify their maladaptive behaviours. OBJECTIVE: The objective of this systematic review and meta-analysis was to evaluate the effectiveness of CBT interventions in treating aggression in an ABI population. METHODS: A systematic literature search was conducted using: PubMed/MEDLINE, CINAHL, EMBASE and PsycINFO from database inception to August 2016. English articles were included if: at least 50% of the study sample had a moderate to severe ABI, there were at least three adult human participants, and use of a CBT intervention for the treatment of aggression. RESULTS: Seven articles met inclusion criteria: one RCT, an RCT crossover and five pre-post trials. Of these, four articles were included in a pre-post meta-analysis for treatment efficacy on subscales of the State Trait Anger Expression Inventory (STAXI) and STAXI-2 outcome measures. The meta-analysis found CBT was effective in moderating the external behaviours of aggression, but not internal anger. CONCLUSION: The differences in outcomes may be related to the differential management of anger expression and anger suppression. CBT shows promise, but further studies with comparator groups are needed before conclusions about its efficacy can be made.

Neural Circuit Mechanisms of Social Behavior.

We live in a world that is largely socially constructed, and we are constantly involved in and fundamentally influenced by a broad array of complex social interactions. Social behaviors among conspecifics, either conflictive or cooperative, are exhibited by all sexually reproducing animal species and are essential for the health, survival, and reproduction of animals. Conversely, impairment in social function is a prominent feature of several neuropsychiatric disorders, such as autism spectrum disorders and schizophrenia. Despite the importance of social behaviors, many fundamental questions remain unanswered. How is social sensory information processed and integrated in the nervous system? How are different social behavioral decisions selected and modulated in brain circuits? Here we discuss conceptual issues and recent advances in our understanding of brain regions and neural circuit mechanisms underlying the regulation of social behaviors.

Prospective test of the developmental propensity model of antisocial behavior: from childhood and adolescence into early adulthood.

BACKGROUND: The developmental propensity model of antisocial behavior posits that several dispositional characteristics of children transact with the environment to influence the likelihood of learning antisocial behavior across development. Specifically, greater dispositional negative emotionality, greater daring, and lower prosociality-operationally, the inverse of callousness- and lower cognitive abilities are each predicted to increase risk for developing antisocial behavior. METHODS: Prospective tests of key predictions derived from the model were conducted in a high-risk sample of 499 twins who were assessed on dispositions at 10-17 years of age and assessed for antisocial personality disorder (APD) symptoms at 22-31 years of age. Predictions were tested separately for parent and youth informants on the dispositions using multiple regressions that adjusted for oversampling, nonresponse, and clustering within twin pairs, controlling demographic factors and time since the first assessment. RESULTS: Consistent with predictions, greater numbers of APD symptoms in adulthood were independently predicted over a 10-15 year span by higher youth ratings on negative emotionality and daring and lower youth ratings on prosociality, and by parent ratings of greater negative emotionality and lower prosociality. A measure of working memory did not predict APD symptoms. CONCLUSIONS: These findings support future research on the role of these dispositions in the development of antisocial behavior.

Neuropsychiatric Symptoms in Mild Cognitive Impairment.

OBJECTIVE: Neuropsychiatric symptoms (NPS) may be the first manifestation of an underlying neurocognitive disorder. We undertook a review to provide an update on the epidemiology and etiological mechanisms of NPS that occur in mild cognitive impairment (MCI) and just before the onset of MCI. We discuss common clinical presentations and the implications for diagnosis and care. METHOD: The authors conducted a selective review of the literature regarding the emergence of NPS in late life, before and after the onset of MCI. We discuss recent publications that explore the epidemiology and etiological mechanisms of NPS in the earliest clinical stages of these disorders. RESULTS: NPS have been reported in 35% to 85% of adults with MCI and also occur in advance of cognitive decline. The occurrence of NPS for the first time in later life should increase suspicion for an underlying neurocognitive disorder. The presenting symptom may provide a clue regarding the etiology of the underlying disorder, and the co-occurrence of NPS may herald a more accelerated cognitive decline. CONCLUSIONS: NPS are prevalent in the early clinical stages of neurocognitive disorders and can serve as both useful diagnostic and prognostic indicators. Recognition of NPS as early manifestations of neurocognitive disorders will become increasingly important as we move towards preventative strategies and disease-modifying treatments that may be most effective when deployed in the earliest stages of disease.

Mismatch field latency, but not power, may mark a shared autistic and schizotypal trait phenotype.

The auditory mismatch negativity (MMN), a preattentive processing potential, and its magnetic counterpart (MMF) are consistently reported as reduced in schizophrenia and autism spectrum disorders. This study investigates whether MMF characteristics differ between subclinically high and low scorers on the recently discovered shared autism and schizophrenia phenotype, Social Disorganisation. A total of 18 low (10 females) and 19 high (9 females) Social Disorganisation scorers underwent magnetoencephalography (MEG) during a MMF paradigm of 50ms standard (1000Hz, 85%) and 100ms duration deviant tones. MMF was measured from the strongest active magnetometer over the right and left hemispheres (consistent across groups) after 100ms. No differences in MMF power were found, however there was a significant delay in the MMF peak (p=0.007). The P3am (following the MMF) was significantly reduced across both hemispheres for the high Social Disorganisation group (p=0.025), there were no specific hemispheric differences in P3am power or latency. Right MMF peak latency increased with higher scores on the schizotypal subscales Odd Speech, Odd Behaviour and Constricted Affect. Findings suggest that MMF peak latency delay marks a convergence of the autism and schizophrenia spectra at a subclinical. These findings have significant implications for future research methodology, as well as clinical practice.

Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons.

The mechanisms underlying social dysfunction in neuropsychiatric conditions such as obsessive-compulsive disorder and Tourette syndrome remain uncertain. However, it is known that dysfunctions in basal ganglia, including a reduced number of striatal cholinergic interneurons (SCIN), are involved in their pathophysiology. To explore the role of SCIN in relation to perseverative behaviors, we characterized a new transgenic mouse model in which inducible ablation of SCIN is achieved with high efficiency in a cell-type- and region-specific manner. Mice were subjected to extensive behavioral testing, including assessment of social behaviors, and corticostriatal functional connectivity was evaluated in vivo Selective SCIN ablation leads to altered social interactions together with exacerbated spontaneously emitted repetitive behaviors. Lesioned mice showed normal motor coordination, balance, and general locomotion. Interestingly, only environmentally driven, but not self-directed, repetitive behaviors were exacerbated in lesioned mice. Remarkably, in mice with SCIN ablation, the normal pattern of social exploration was replayed continuously. The emerging pattern of social interactions is highly predictable and invariant across time. In vivo electrophysiological recordings indicate that SCIN ablation results in an increase of the functional connectivity between different cortical areas and the motor, but not associative, region of the striatum. Our results identify a role of SCIN in suppressing perseverative behaviors, including socially related ones. In sum, SCIN ablation in mice leads to exacerbated ritualistic-like behaviors that affect social performance, providing a link between SCIN dysfunction and the social impairments present in psychiatric disorders.SIGNIFICANCE STATEMENT We sought to uncover the impact of striatal cholinergic interneuron (SCIN) degeneration on perseverative behaviors related to obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). We found that extensive SCIN ablation results in exacerbated social interactions, in which normal social contacts were replayed continuously in a highly stereotyped, ritualistic pattern. SCIN ablation also leads to an increase in other spontaneously emitted repetitive behaviors without alteration of motor coordination, balance, or locomotion. Moreover, we identify an increase of functional connectivity between frontal cortical areas and the motor region of the striatum as a putative substrate for the observed behavioral alterations. Therefore, perseveration induced by SCIN ablation extends to social performance as occurs in neuropsychiatric conditions such as OCD and TS.