Plasma anandamide concentrations are lower in children with autism spectrum disorder

Background: Autism spectrum disorder (ASD) is a neurodevelopmentaldisorder characterized by restricted, stereotyped behaviors and impairments in social communication. Although the underlying biological mechanisms of ASD remain poorly understood, recent preclinical research has implicated the endogenous cannabinoid (or endocannabinoid), anandamide, as a significant neuromodulator in rodent models of ASD. Despite this promising preclinical evidence, no clinical studies to date have tested whether endocannabinoids are dysregulated in individuals with ASD. Here, we addressed this critical gap in knowledge by optimizing liquid chromatography-tandem mass spectrometry methodology to quantitatively analyze anandamide concentrations in banked blood samples collected from a cohort of children withand without ASD (N= 112). Findings: Anandamide concentrations significantly differentiated ASD cases (N= 59) from controls (N= 53), such that children with lower anandamide concentrations were more likely to have ASD (p= 0.041). In keeping with this notion, anandamide concentrations were also significantly lower in ASD compared to control children (p= 0.034). Conclusions: These findings are the first empirical human data to translate preclinical rodent findings to confirm a link between plasma anandamide concentrations in children with ASD. Although preliminary, these data suggest that impaired anandamide signaling may be involved in the pathophysiology of ASD

Supplementary Material, AUT775538_Supplementary_material – Effects of a parent-implemented Developmental Reciprocity Treatment Program for children with autism spectrum disorder

<p>Supplementary Material, AUT775538_Supplementary_material for Effects of a parent-implemented Developmental Reciprocity Treatment Program for children with autism spectrum disorder by Grace W Gengoux, Salena Schapp, Sarah Burton, Christina M Ardel, Robin A Libove, Gina Baldi, Kari L Berquist, Jennifer M Phillips and Antonio Y Hardan in Autism</p

Arginine Vasopressin Is a Blood-Based Biomarker of Social Functioning in Children with Autism.

Brain arginine vasopressin (AVP) critically regulates normative social behavior in mammals, and experimental disruption of the AVP signaling pathway produces social impairments in rodent models. We therefore hypothesized that AVP signaling deficits may contribute to social impairments in children with autism spectrum disorder (ASD). Since blood measures (which are far easier to obtain than brain measures) of AVP are most meaningful if they are related to brain AVP activity, Study 1 tested the relationship between AVP concentrations in concomitantly collected blood and CSF samples from children and adults (N = 28) undergoing clinical procedures. Study 2 tested whether blood AVP concentrations: 1) differed between children with ASD (N = 57), their ASD discordant siblings (N = 47), and neurotypical controls (N = 55); and 2) predicted social functioning (using the NEPSY-II Theory of Mind and Affect Recognition tasks and the Social Responsiveness Scale) in this large, well-characterized child cohort. Blood AVP concentrations significantly and positively predicted CSF AVP concentrations (F1,26 = 7.17, r = 0.46, p = 0.0127) in Study 1. In Study 2, blood AVP concentrations did not differ between groups or by sex, but significantly and positively predicted Theory of Mind performance, specifically in children with ASD, but not in non-ASD children (F1,144 = 5.83, p = 0.017). Blood AVP concentrations can be used: 1) as a surrogate for brain AVP activity in humans; and 2) as a robust biomarker of theory of mind ability in children with ASD. These findings also suggest that AVP biology may be a promising therapeutic target by which to improve social cognition in individuals with ASD

Understanding the heterogeneity of anxiety in autistic youth:A person-centered approach

The present study aimed to examine anxiety profiles among children and adolescents on the autism spectrum. It further aimed to characterize the association between the identified anxiety profiles and key clinical and developmental variables. The Spence Children's Anxiety Scale-Parent Version (SCAS-P) data from a large international pooled sample of 870 caregivers of autistic children and adolescents (Mage = 11.6 years, SDage = 2.77; 107 females) was used. Latent profile analysis identified a three-anxiety profile solution exhibiting high entropy (0.80) and high latent profile probabilities, with good classification accuracy. Identified profiles fell along the severity spectrum and were named as the mild (n = 498), moderate (n = 272) and severe (n = 100) anxiety profiles. There were no statistically significant differences between the three anxiety profiles in terms of sex distribution. Participants in the mild profile were significantly younger than those in the severe profile, had significantly fewer social communication difficulties than youth in the moderate anxiety profile group and had significantly fewer restricted and repetitive behaviors and lower cognitive functioning scores compared to participants in moderate and severe anxiety profiles. This is the first study to move beyond identifying associations and group-level differences to exploring and identifying characteristics of anxiety-based subgroups at an individual level that differ on key clinical and developmental variables. The subgroups identified in this study are a preliminary, yet important, first step towards informing future assessment and individualized interventions aiming to support young people on the autism spectrum to reduce and manage anxiety

Blood AVP concentration predicts NEPSY Theory of Mind score in ASD children (autistic and PDD-NOS) but not in non-ASD children (sibling and neurotypical control).

<p>Data have been corrected for the following blocking factors: age, sex, ethnicity, blood sample collection time, and full scale IQ. Data are plotted as a mean and standard error for each AVP quintile within the ASD and non-ASD groups. The means shown are of the log transformed plasma AVP values used in the analysis itself. ASD Quintile (Q) Q1 <i>n</i> = 11, Q2 <i>n</i> = 12, Q3 <i>n</i> = 11, Q4 <i>n</i> = 11, Q5 <i>n</i> = 12; Non-ASD Q1 <i>n</i> = 20, Q2 <i>n</i> = 21, Q3 <i>n</i> = 21, Q4 <i>n</i> = 19, Q5 <i>n</i> = 21.</p

Blood arginine vasopressin (AVP) concentration significantly and positively predicts cerebrospinal fluid (CSF) AVP concentration.

<p>Sample size is <i>n</i> = 28.</p

Patient demographics and medical characteristics.

<p>Abbreviations: AVP, arginine vasopressin; CSF, cerebrospinal fluid; ALL, acute lymphoblastic leukemia; AML, acute myeloblastic leukemia</p><p>¹indicates CSF collected from lumbar puncture</p><p>²indicates CSF collected from left ventricle</p><p>³indicates CSF collected from the cisterna magna.</p><p>Patient demographics and medical characteristics.</p

Participant characteristics.

<p><b>χ</b>² was used to test whether the distribution of individuals to different groups differed by sex and by ethnicity. Significant effects were found for each. However, post hoc tests failed to find any group that showed a significant difference from expected (by sex or by ethnicity). For age, full-scale IQ, and blood collection time, differences between groups were tested with a simple one-way general linear model. The values are expressed in mean ± SEM. Abbreviations</p><p>* = P < 0.05</p><p>^ns = not significant.</p><p>Values with different letter superscripts (i.e., ^a, ^b, or ^c) within the same column of the table differ significantly, whereas values with the same letter superscript (i.e., ^a, ^b, or ^c) within the same column of the table do not differ, according to Tukey’s post hoc test.</p><p>Participant characteristics.</p