Cerebrospinal fluid and plasma oxytocin concentrations are positively correlated and negatively predict anxiety in children.

The neuropeptide oxytocin (OXT) exerts anxiolytic and prosocial effects in the central nervous system of rodents. A number of recent studies have attempted to translate these findings by investigating the relationships between peripheral (e.g., blood, urinary and salivary) OXT concentrations and behavioral functioning in humans. Although peripheral samples are easy to obtain in humans, whether peripheral OXT measures are functionally related to central OXT activity remains unclear. To investigate a possible relationship, we quantified OXT concentrations in concomitantly collected cerebrospinal fluid (CSF) and blood samples from child and adult patients undergoing clinically indicated lumbar punctures or other CSF-related procedures. Anxiety scores were obtained in a subset of child participants whose parents completed psychometric assessments. Findings from this study indicate that plasma OXT concentrations significantly and positively predict CSF OXT concentrations (r=0.56, P=0.0064, N=27). Moreover, both plasma (r=-0.92, P=0.0262, N=10) and CSF (r=-0.91, P=0.0335, N=10) OXT concentrations significantly and negatively predicted trait anxiety scores, consistent with the preclinical literature. Importantly, plasma OXT concentrations significantly and positively (r=0.96, P=0.0115, N=10) predicted CSF OXT concentrations in the subset of child participants who provided behavioral data. This study provides the first empirical support for the use of blood measures of OXT as a surrogate for central OXT activity, validated in the context of behavioral functioning. These preliminary findings also suggest that impaired OXT signaling may be a biomarker of anxiety in humans, and a potential target for therapeutic development in individuals with anxiety disorders.

Brainstem volumetric alterations in children with autism.

BACKGROUND: Although several studies have examined brainstem volume in autism, results have been mixed and no investigation has specifically measured gray- and white-matter structures. The aim of this investigation was to assess gray- and white-matter volumes in children with autism. METHOD: Subjects included 22 right-handed, non-mentally retarded boys with autism and 22 gender- and age-matched controls. Magnetic resonance imaging (MRI) scans were obtained using a 1.5-T scanner and volumetric measurements were performed using the BRAINS2 software package. Gray- and white-matter volumes were measured using a semi-automated segmentation process. RESULTS: There were no significant differences in age and total brain volume (TBV) between the two groups but full-scale IQ was higher in controls. A decrease in brainstem gray-matter volume was observed in the autism group before and after controlling for TBV. No significant differences were observed in white-matter volume. A significant relationship was observed between brainstem gray-matter volume and oral sensory sensitivity as measured by the Sensory Profile Questionnaire (SPQ). CONCLUSIONS: Findings from this study are suggestive of brainstem abnormalities in autism involving gray-matter structures with evidence supporting the existence of a relationship between these alterations and sensory deficits. These results are consistent with previous investigations and support the existence of disturbances in brainstem circuitry thought to be implicated in the sensory dysfunction observed in autism.

Video modeling for the development of personal hygiene skills in youth with autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder mainly characterised by deficits in social communication as well as by narrow patterns of behaviour and interests (American Psychiatric Association, 2013), often accompanied by language, intellectual and sensory impairments. The severity of these impairments may lead to deficits in the development of daily living activities such as simple meal preparation and feeding, community skills (e.g. buying groceries), personal care (e.g. dressing) and personal hygiene skills (bathing, toileting, hand washing, teeth brushing) needed for independence. Among others, the lack of independence in personal hygiene skills increases the burden of the caregiver and makes children with ASD more dependent (Flynn & Healy, 2012). Therefore, it is important to develop tools for helping individuals with ASD in increasing their ability to perform these basic life activities which will lead to savings that can be invested in other critical areas of needs.

Adaptive behavior in autism: Minimal clinically important differences on the Vineland-II.

Autism Spectrum Disorder (ASD) is associated with persistent impairments in adaptive abilities across multiple domains. These social, personal, and communicative impairments become increasingly pronounced with development, and are present regardless of IQ. The Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) is the most commonly used instrument for quantifying these impairments, but minimal clinically important differences (MCIDs) on Vineland-II scores have not been rigorously established in ASD. We pooled data from several consortia/registries (EU-AIMS LEAP study, ABIDE-I, ABIDE-II, INFOR, Simons Simplex Collection and Autism Treatment Network [ATN]) and clinical investigations and trials (Stanford, Yale, Roche) resulting in a data set of over 9,000 individuals with ASD. Two approaches were used to estimate MCIDs: distribution-based methods and anchor-based methods. Distribution-based MCID [d-MCID] estimates included the standard error of the measurement, as well as one-fifth and one-half of the covariate-adjusted standard deviation (both cross-sectionally and longitudinally). Anchor-based MCID [a-MCID] estimates include the slope of linear regression of clinician ratings of severity on the Vineland-II score, the slope of linear regression of clinician ratings of longitudinal improvement category on Vineland-II change, the Vineland-II change score maximally differentiating clinical impressions of minimal versus no improvement, and equipercentile equating. Across strata, the Vineland-II Adaptive Behavior Composite standardized score MCID estimates range from 2.01 to 3.2 for distribution-based methods, and from 2.42 to 3.75 for sample-size-weighted anchor-based methods. Lower Vineland-II standardized score MCID estimates were observed for younger and more cognitively impaired populations. These MCID estimates enable users of Vineland-II to assess both the statistical and clinical significance of any observed change. Autism Res 2018, 11: 270-283. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The Vineland Adaptive Behavior Scales (2nd edition; Vineland-II) is the most widely used scale for assessing day-to-day "adaptive" skills. Yet, it is unknown how much Vineland-II scores must change for those changes to be regarded as clinically significant. We pooled data from over 9,000 individuals with ASD to show that changes of 2-3.75 points on the Vineland-II Composite score represent the "minimal clinically-important difference." These estimates will help evaluate the benefits of potential new treatments for ASD.

Endocannabinoid signaling in social functioning: an RDoC perspective.

Core deficits in social functioning are associated with various neuropsychiatric and neurodevelopmental disorders, yet biomarker identification and the development of effective pharmacological interventions has been limited. Recent data suggest the intriguing possibility that endogenous cannabinoids, a class of lipid neuromodulators generally implicated in the regulation of neurotransmitter release, may contribute to species-typical social functioning. Systematic study of the endogenous cannabinoid signaling could, therefore, yield novel approaches to understand the neurobiological underpinnings of atypical social functioning. This article provides a critical review of the major components of the endogenous cannabinoid system (for example, primary receptors and effectors-Δ9-tetrahydrocannabinol, cannabidiol, anandamide and 2-arachidonoylglycerol) and the contributions of cannabinoid signaling to social functioning. Data are evaluated in the context of Research Domain Criteria constructs (for example, anxiety, chronic stress, reward learning, motivation, declarative and working memory, affiliation and attachment, and social communication) to enable interrogation of endogenous cannabinoid signaling in social functioning across diagnostic categories. The empirical evidence reviewed strongly supports the role for dysregulated cannabinoid signaling in the pathophysiology of social functioning deficits observed in brain disorders, such as autism spectrum disorder, schizophrenia, major depressive disorder, posttraumatic stress disorder and bipolar disorder. Moreover, these findings indicate that the endogenous cannabinoid system holds exceptional promise as a biological marker of, and potential treatment target for, neuropsychiatric and neurodevelopmental disorders characterized by impairments in social functioning.

Corpus callosum size in autism.

The size of the seven subregions of the corpus callosum was measured on MRI scans from 22 non-mentally retarded autistic subjects and 22 individually matched controls. Areas of the anterior subregions were smaller in the autistic group. In a subsample, measurements were adjusted for intracranial, total brain, and white matter volumes and the differences between groups remained significant. No differences were found in the other subregions. This observation is consistent with the frontal lobe dysfunction reported in autism.

Posterior fossa magnetic resonance imaging in autism.

OBJECTIVE: To determine whether the sizes and volumes of the posterior fossa structures are abnormal in non-mentally retarded autistic adolescents and adults. METHOD: Volume measurements of the cerebellum, vermis, and brainstem were obtained from coronal magnetic resonance imaging scans in 16 autistic subjects and 19 group-matched healthy controls. For the purpose of comparison with previous studies, area measurements of the midbrain, pons, medulla, total cerebellar vermis, and its three subregions were also obtained from a larger sample of 22 autistic males (mean age: 22.4 years; range: 12.2-51.8 years) and 22 individually matched controls (mean age 22.4 years; range: 12.9-52.2 years). RESULTS: The total volume of the cerebellum and the cerebellar hemispheres were significantly larger in the autistic subjects with and without correcting for total brain volume. Volumes of the vermis and the brainstem and all area measurements did not differ significantly between groups. CONCLUSIONS: There is an increase in the volume of the cerebellum in people with autism consistent with the increase in regional and total brain size reported in this developmental disorder. This finding is also concordant with evidence of cerebellar abnormalities from neuropathological and neuropsychological studies that point to the role of this structure, as part of a complex neural system, in the pathophysiology of autism.

Brain volume in autism.

Increased brain size has been observed in individuals with autism with a wide range of cognitive functioning. The purpose of this investigation was to obtain measurements of the brain volume in a sample of nonmentally retarded autistic individuals. Magnetic resonance imaging scans from 16 nonmentally retarded individuals with autism and 19 male volunteer comparison subjects were obtained and the following structures were measured: third, fourth, and lateral ventricles and intracranial and cerebral volumes. Mean cerebral and third ventricle volumes in the autistic subjects were significantly greater than in the controls when adjusted for intracranial volume. No other significant results were found. Our finding of increased brain volume in autism is consistent with previous reports in the literature. Additional longitudinal neuroimaging and, more importantly, neuropathologic studies are warranted to provide a better understanding of the complexities underlying increased brain size in autism.

Basal ganglia and restricted and repetitive behaviours in Autism Spectrum Disorders: current status and future perspectives.

This editorial offers a concise overview of the recent structural magnetic resonance imaging studies that evaluate the basal ganglia (BG) volumes in autism spectrum disorders (ASD). The putative relationship between the repetitive or stereotyped behaviours of ASD and BG volumes is also explored, with a focus on possible translational approaches.