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Synchronous recruitment of fast-spiking (FS) parvalbumin (PV) interneurons generates gamma oscillations, rhythms that emerge during performance of cognitive tasks. Administration of N -methyl- D -aspartate (NMDA) receptor antagonists alters gamma rhythms, and can induce cognitive as well as psychosis-like symptoms in humans. The disruption of NMDA receptor (NMDAR) signaling specifically in FS PV interneurons is therefore hypothesized to give rise to neural network dysfunction that could underlie these symptoms. To address the connection between NMDAR activity, FS PV interneurons, gamma oscillations and behavior, we generated mice lacking NMDAR neurotransmission only in PV cells (PV-Cre/NR1f/f mice). Here, we show that mutant mice exhibit enhanced baseline cortical gamma rhythms, impaired gamma rhythm induction after optogenetic drive of PV interneurons and reduced sensitivity to the effects of NMDAR antagonists on gamma oscillations and stereotypies. Mutant mice show largely normal behaviors except for selective cognitive impairments, including deficits in habituation, working memory and associative learning. Our results provide evidence for the critical role of NMDAR in PV interneurons for expression of normal gamma rhythms and specific cognitive behaviors.

In a prior report, we showed that extended-release guanfacine (GEXR) is safe and effective for children with autism spectrum disorder (ASD) accompanied by ADHD symptoms. Here, we examine the impact of GEXR on oppositional behavior, anxiety, repetitive behavior, and sleep disturbance. Sixty-two subjects with ASD (53 boys, 9 girls; ages 5–14 years) were randomly assigned to GEXR (n = 30) or placebo (n = 32) for 8 weeks. Outcomes include the Home Situation Questionnaire-Modified for ASD (HSQ-ASD), Anxiety scale of the Child and Adolescent Symptom Inventory (CASI), Children’s Yale-Brown Obsessive-Compulsive Scale-Modified for ASD (CYBOCS-ASD), and Children’s Sleep Habits Questionnaire (CSHQ). A repeated measures linear mixed model was used to determine the effects of treatment group and time on HSQ scores. For other measures, change from baseline was evaluated with Analysis of Covariance (ANCOVA).After 8 weeks of treatment, parent ratings of oppositional behavior on the HSQ declined by 44% (per item mean from 3.4 to 1.9) in the GEXR group compared to 12% (from 3.3 to 2.9) for placebo (p = 0.004). Repetitive behavior on the CYBOCS-ASD showed a significantly greater decline in GEXR-treated participants compared to placebo (24% vs. <1%, p = 0.01). No group differences were observed on CASI Anxiety or CSHQ (p = 0.64 and 0.75, respectively). GEXR was effective in reducing oppositional behavior and, more modestly, repetitive behavior. GEXR was not superior to placebo for anxiety, though baseline anxiety ratings were low. GEXR did not significantly improve sleep habits. Future studies could focus on repetitive behavior or anxiety, symptoms with limited treatment options.

Many horses exhibit stereotypies, especially when living in human controlled environments that may prevent horses from satisfying natural needs in terms of feeding, drinking, moving, and socializing. In human medicine, obsessive compulsive disorder and other severe psychiatric disturbances are associated with stereotypic behaviors; salivary biomarkers evaluation is considered a reliable tool for diagnosis of common mental health disorders because saliva collection easy to obtain and noninvasive. In this study, we hypothesized that salivary cortisol concentrations, in addition to alpha-amylase (sAA) and butyrylcholinesterase (BChE) activities, are considered stress biomarkers that may be influenced in horses trained for racing competition with stereotypic behaviors. Saliva at rest condition was obtained from ten non-stereotypic Thoroughbreds horses involved in high-level competition; eleven Thoroughbreds high-level competition horses showing stereotypic behaviors, and five Thoroughbreds leisure non-competition horses. Cortisol was found to be higher in high-level competition non-stereotypic horses and sAA was significantly higher in non-stereotypic leisure horses when compared to horses involved in competition, while BChE did not change between groups. These results may represent the basis for further behavioural evaluation to elucidate how stereotypic horses and horses involved in competition overcome stressful situations.

This study investigated the sex-specific effects of commonly prescribed appetite suppressants on body weight and the manifestation of motor side effects, specifically stereotypy. Employing video recordings and DeepLabCut (DLC) for precise behavioral quantification, we analyzed stereotypy, defined as purposeless, repetitive motor behaviors, in male and female rats. Under control (saline) conditions, male rats exhibited a greater propensity for weight gain compared to females. However, in contrast, female rats demonstrated greater and more homogenous weight loss than males following the administration of diethylpropion and tesofensine. Phentermine and mazindol induced comparable weight loss in both sexes, whereas cathine elicited weight reduction exclusively in males. 5-HTP and d-amphetamine administration only prevented weight gain relative to controls. Analysis of motor side effects revealed that drugs primarily targeting dopamine pathways – specifically, phentermine, mazindol, diethylpropion, cathine, and d-amphetamine – induced pronounced stereotypies, particularly head-weaving, in both sexes. Interestingly, tesofensine elicited head-weaving behavior exclusively in female subjects, albeit to a lesser extent than that observed with other dopaminergic agents; conversely, tesofensine was most frequently associated with orolingual dyskinesia. Male subjects treated with these same drugs exhibited an unexpected effect: spontaneous ejaculations, potentially attributable to the combined effects on dopamine and serotonin signaling in brain regions regulating sexual function. Network analysis and Markov transition matrices revealed distinct behavioral profiles associated with head-weaving, which emerged as the dominant attractor state, suggesting potential mechanistic differences among these drugs. Collectively, this study provides a valuable database characterizing the behavioral side effects of appetite suppressants.

Genetic analyses have linked microRNA-137 (MIR137) to neuropsychiatric disorders, including schizophrenia and autism spectrum disorder. miR-137 plays important roles in neurogenesis and neuronal maturation, but the impact of miR-137 loss-of-function in vivo remains unclear. Here we show the complete loss of miR-137 in the mouse germline knockout or nervous system knockout (cKO) leads to postnatal lethality, while heterozygous germline knockout and cKO mice remain viable. Partial loss of miR-137 in heterozygous cKO mice results in dysregulated synaptic plasticity, repetitive behavior, and impaired learning and social behavior. Transcriptomic and proteomic analyses revealed that the miR-137 mRNA target, phosphodiesterase 10a (Pde10a), is elevated in heterozygous knockout mice. Treatment with the Pde10a inhibitor papaverine or knockdown of Pde10a ameliorates the deficits observed in the heterozygous cKO mice. Collectively, our results suggest that MIR137 plays essential roles in postnatal neurodevelopment and that dysregulation of miR-137 potentially contributes to neuropsychiatric disorders in humans.

This quasi-experimental study investigated effects of Tai Chi Chuan training on stereotypic behavior of children with autism spectrum disorder. Twenty-three participants (mean age = 9.60 ± 1.40 years) were assigned to experimental (N = 12) and control (N = 11) groups. The experimental group received 12 weeks of Tai Chi training and all participants had pre, post, and one-month follow-up assessments. Stereotypic behavior measured using Gilliam Autism Rating Scale 2 Scores, was significantly altered by ~ 25% in the Tai Chi Chuan group. Behavioral change was maintained at follow up since there was no significant difference between that and the posttest. In conclusion, Tai Chi Chuan training is a useful and appropriate intervention to modulate behavior in individuals with autism spectrum disorder.

Research suggests that restricted and repetitive behaviors (RRBs) can be subdivided into Repetitive Sensory Motor (RSM) and Insistence on Sameness (IS) behaviors. However, because the majority of previous studies have used the Autism Diagnostic Interview-Revised (ADI-R), it is not clear whether these subcategories reflect the actual organization of RRBs in ASD. Using data from the Simons Simplex Collection (n = 1,825), we examined the association between scores on the ADI-R and the Repetitive Behavior Scale-Revised. Analyses supported the construct validity of RSM and IS subcategories. As in previous studies, IS behaviors showed no relationship with IQ. These findings support the continued use of RRB subcategories, particularly IS behaviors, as a means of creating more behaviorally homogeneous subgroups of children with ASD.

Physical exercise has been demonstrated to effectively mitigate repetitive behaviors in children with autism spectrum disorder (ASD), but the underlying dynamic brain network mechanisms are poorly understood. The triple network model consists of three brain networks that jointly regulate cognitive and emotional processes and is considered to be the core network underlying the aberrant manifestations of ASD. This study investigated whether a mini-basketball training program (MBTP) could alter repetitive behaviors and the dynamic connectivity of the triple network. 28 male children with ASD were scanned twice with resting-state functional MRI and assessed for repetitive behaviors using the repetitive behavior scale (RBS-R). 15 children in the exercise group participated in a 12-week MBTP, while 13 in the control group maintained their regular routines. The feature of Dynamic independent component analysis (dyn-ICA) is its ability to capture the rate of change in connectivity between brain regions. In this study, it was specifically employed to examine the triple network dynamic connectivity in both groups. Compared to the control group, the exercise group exhibited distinct dynamic connectivity patterns in two networks: Network 1 involved cross-network dynamic connectivity changes within the triple network, and Network 2 pertained to dynamic connectivity alterations within the default mode network. Furthermore, a reduction in the RBS-R Total score was observed in the exercise group, reflecting improvements in self-injurious behavior and restricted behavior. Correlation analysis revealed that the amelioration of repetitive behaviors was associated with enhanced dynamic connectivity in parts of the triple network. These findings suggest that MBTP can improve repetitive behaviors in ASD children and is linked to changes in triple network dynamic connectivity.

Sex differences have been found amongst toddlers and young children with autism spectrum disorder (ASD). We investigated the presence and stability of these ASD sex differences throughout childhood and adolescence. Participants ( N  = 325, 52 females; aged 3–18 years) consecutively received an ASD diagnosis at a clinic for assessing high-functioning ASD (mean verbal IQ = 92.6). There were no IQ sex differences. By parent report and direct observation, females had less repetitive stereotyped behaviour (RSB), with male-equivalent levels of social and communication impairment. Teachers reported males with ASD as having greater externalising and social problems than females. The female phenotype we describe was stable across our sample’s age range. Their milder RSBs and less severe difficulties at school may lead to under-recognition of ASD in females.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex clinical manifestations that arise between 18 and 36 months of age. Social interaction deficiencies, a restricted range of interests, and repetitive stereotyped behaviors are characteristics which are sometimes difficult to detect early. Several studies show that microRNAs (miRs/miRNAs) are strongly implicated in the development of the disorder and affect the expression of genes related to different neurological pathways involved in ASD. The present systematic review and meta-analysis addresses the current status of miRNA studies in different body fluids and the most frequently dysregulated miRNAs in patients with ASD. We used a combined approach to summarize miRNA fold changes in different studies using the mean values. In addition, we summarized p values for differential miRNA expression using the Fisher method. Our literature search yielded a total of 133 relevant articles, 27 of which were selected for qualitative analysis based on the inclusion and exclusion criteria, and 16 studies evaluating miRNAs whose data were completely reported were ultimately included in the meta-analysis. The most frequently dysregulated miRNAs across the analyzed studies were miR-451a, miR-144-3p, miR-23b, miR-106b, miR150-5p, miR320a, miR92a-2-5p, and miR486-3p. Among the most dysregulated miRNAs in individuals with ASD, miR-451a is the most relevant to clinical practice and is associated with impaired social interaction. Other miRNAs, including miR19a-3p, miR-494, miR-142-3p, miR-3687, and miR-27a-3p, are differentially expressed in various tissues and body fluids of patients with ASD. Therefore, all these miRNAs can be considered candidates for ASD biomarkers. Saliva may be the optimal biological fluid for miRNA measurements, because it is easy to collect from children compared to other biological fluids.