Effects of Intraperitoneal N-methyl-D-aspartate (NMDA) Administration on Nociceptive/Repetitive Behaviors in Juvenile Mice

Dysregulation of excitatory neurotransmission has been implicated in the pathogenesis of neuropsychiatric disorders. Pharmacological inhibition of N-methyl-D-aspartate (NMDA) receptors is widely used to model neurobehavioral pathologies and underlying mechanisms. There is ample evidence that overstimulation of NMDA-dependent neurotransmission may induce neurobehavioral abnormalities, such as repetitive behaviors and hypersensitization to nociception and cognitive disruption, pharmacological modeling using NMDA has been limited due to the induction of neurotoxicity and blood brain barrier breakdown, especially in young animals. In this study, we examined the effects of intraperitoneal NMDA-administration on nociceptive and repetitive behaviors in ICR mice. Intraperitoneal injection of NMDA induced repetitive grooming and tail biting/licking behaviors in a dose- and age-dependent manner. Nociceptive and repetitive behaviors were more prominent in juvenile mice than adult mice. We did not observe extensive blood brain barrier breakdown or neuronal cell death after peritoneal injection of NMDA, indicating limited neurotoxic effects despite a significant increase in NMDA concentration in the cerebrospinal fluid. These findings suggest that the observed behavioral changes were not mediated by general NMDA toxicity. In the hot plate test, we found that the latency of paw licking and jumping decreased in the NMDA-exposed mice especially in the 75 mg/kg group, suggesting increased nociceptive sensitivity in NMDA-treated animals. Repetitive behaviors and increased pain sensitivity are often comorbid in psychiatric disorders (e.g., autism spectrum disorder). Therefore, the behavioral characteristics of intraperitoneal NMDA-administered mice described herein may be valuable for studying the mechanisms underlying relevant disorders and screening candidate therapeutic molecules.

Nail tic disorders: Manifestations, pathogenesis and management.

Nail tic disorders are classic examples of overlap between the domains of dermatology and psychiatry. They are examples of body-focused repetitive behaviors in which there is an irresistible urge or impulse to perform a certain behavior. The behavior is reinforced as it results in some degree of relief and pleasure. Nail tic disorders are common, yet poorly studied and understood. The literature on nail tic disorders is relatively scarce. Common nail tics include nail biting or onychophagia, onychotillomania and the habit tic deformity. Some uncommon and rare nail tic disorders are onychoteiromania, onychotemnomania, onychodaknomania and bidet nails. Onychophagia is chronic nail biting behavior which usually starts during childhood. It is often regarded as a tension reducing measure. Onychotillomania is recurrent picking and manicuring of the fi ngernails and/or toenails. In severe cases, it may lead to onychoatrophy due to irreversible scarring of the nail matrix. Very often, they occur in psychologically normal children but may sometimes be associated with anxiety. In severe cases, onychotillomania may be an expression of obsessive-compulsive disorders. Management of nail tic disorders is challenging. Frequent applications of distasteful topical preparations on the nail and periungual skin can discourage patients from biting and chewing their fi ngernails. Habit-tic deformity can be helped by bandaging the digit daily with permeable adhesive tape. Fluoxetine in high doses can be helpful in interrupting these compulsive disorders in adults. For a complete diagnosis and accurate management, it is imperative to assess the patient’s mental health and simultaneously treat the underlying psychiatric comorbidity, if any.

New Therapeutic Options for Autism Spectrum Disorder: Experimental Evidences

Autism spectrum disorder (ASD) is characterized by impairment in two behavioral domains: social interaction/communication together with the presence of stereotyped behaviors and restricted interests. The heterogeneity in the phenotype among patients and the complex etiology of the disorder have long impeded the advancement of the development of successful pharmacotherapies. However, in the recent years, the integration of findings of multiple levels of research, from human genetics to mouse models, have made considerable progress towards the understanding of ASD pathophysiology, allowing the development of more effective targeted drug therapies. The present review discusses the current state of pharmacological research in ASD based on the emerging common pathophysiology signature.

Stereotyped movement disorder in ICD-11

According to current proposals for ICD-11, stereotyped movement disorder will be classified in the grouping of neurodevelopmental disorders, with a qualifier to indicate whether self-injury is present, similar to the classification of stereotypic movement disorder in DSM-5. At the same time, the WHO ICD-11 Working Group on the Classification of Obsessive-Compulsive and Related Disorders has proposed a grouping of body-focused repetitive behavior disorders within the obsessive-compulsive and related disorders (OCRD) cluster to include trichotillomania and skin-picking disorder. DSM-5 has taken a slightly different approach: trichotillomania and excoriation (skin picking) disorder are included in the OCRD grouping, while body-focused repetitive behavior disorder is listed under other specified forms of OCRD. DSM-5 also includes a separate category of nonsuicidal self-injury in the section on “conditions for further study.” There are a number of unresolved nosological questions regarding the relationships among stereotyped movement disorder, body-focused repetitive behavior disorders, and nonsuicidal self-injury. In this article, we attempt to provide preliminary answers to some of these questions as they relate to the ICD-11 classification of mental and behavioral disorders.

Level of Plasma Polyunsaturated Fatty Acid in Autism / 中国康复理论与实践

@#Objective To explore the level of polyunsaturated fatty acids (PUFAs) in blood plasma and its relation with the behavior ofchildren with autism. Methods High performance liquid chromatography was used to measure the level of free PUFAs of blood plasma in30 autistic children and 20 healthy children. Conner's Parent Rating Scale (parents) and the Repetitive Behavior Scale-Revised (RBS-R) RatingScale were used to evaluate the behavior of the children, and the relationship between the PUFAs level and abnormal behavior in the childrenwas also analyzed. Results The level of α-linolenic acid (ALA), docosahexenoic acid (DHA) and total n-3 PUFAs were lower in autisticchildren than in healthy children (P<0.05), especially lower in DHA (P<0.01). There was no significant difference in n-3 PUFAs betweentwo groups (P>0.05); There were negatively correlations between the level of DHA and total n-3 PUFAs in blood plasma and impulsion-hyperactivity,hyperactivity index, learning, anxiety, stereotypic behavior, self-injurious behavior, compulsions, ritualistic behavior and samenessbehavior. Conclusion The level of n-3 PUFAs in blood plasma of autistic children was lower than the healthy children and the level ofPUFAs were correlated with the behavior of autistic children.