Psychotropic Medication Use in Children and Youth with Autism Enrolled in Medicaid.

Children with autism frequently present with complex mental health diagnoses and psychotropic medications are often a component of comprehensive biopsychosocial treatment plans for these conditions. The purpose of this study is to provide rates and patterns of psychotropic medication use, and predictors thereof, in children and youth with autism enrolled in Medicaid across the US. This study examined national Medicaid claims from 2008 to 2016 of all children and youth with autism ages 0-21 years enrolled in Medicaid. Psychotropic medication use was examined across several child and youth characteristics, including age, co-occurring mental health conditions, sex, and race and ethnicity. About half of children and youth with autism enrolled in Medicaid had at least one psychotropic prescription in a year, a number that decreased slightly across the study period due to decreases in the prescription of antipsychotics. As new medications for autism or co-occurring conditions are developed and deployed, and as the understanding of the characteristics of the population of children with autism evolves, studying rates of medication usage helps to understand utilization patterns and differences in access to quality care.

Mouse model of OPRM1 (A118G) polymorphism increases sociability and dominance and confers resilience to social defeat.

A single nucleotide polymorphism (SNP) in the human µ-opioid receptor gene (OPRM1 A118G) has been widely studied for its association in drug addiction, pain sensitivity, and, more recently, social behavior. The endogenous opioid system has been shown to regulate social distress and reward in a variety of animal models. However, mechanisms underlying the associations between the OPRM1 A118G SNP and these behaviors have not been clarified. We used a mouse model possessing the human equivalent nucleotide/amino acid substitution to study social affiliation and social defeat behaviors. In mice with the Oprm1 A112G SNP, we demonstrate that the G allele is associated with an increase in home-cage dominance and increased motivation for nonaggressive social interactions, similar to what is reported in human populations. When challenged by a resident aggressor, G-allele carriers expressed less submissive behavior and exhibited resilience to social defeat, demonstrated by a lack of subsequent social avoidance and reductions in anhedonia as measured by intracranial self-stimulation. Protection from social defeat in G-allele carriers was associated with a greater induction of c-fos in a resilience circuit comprising the nucleus accumbens and periaqueductal gray. These findings led us to test the role of endogenous opioids in the A112G mice. We demonstrate that the increase in social affiliation in G carriers is blocked by pretreatment with naloxone. Together, these data suggest a mechanism involving altered hedonic state and neural activation as well as altered endogenous opioid tone in the differential response to aversive and rewarding social stimuli in G-allele carriers.

Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice.

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in neurodevelopmental disorders including atypical Rett syndrome (RTT), autism spectrum disorders (ASDs), and early infantile epileptic encephalopathy. The biological function of CDKL5 and its role in the etiology of these disorders, however, remain unclear. Here we report the development of a unique knockout mouse model of CDKL5-related disorders and demonstrate that mice lacking CDKL5 show autistic-like deficits in social interaction, as well as impairments in motor control and fear memory. Neurophysiological recordings reveal alterations in event-related potentials (ERPs) similar to those observed in RTT and ASDs. Moreover, kinome profiling uncovers disruption of multiple signal transduction pathways, including the AKT-mammalian target of rapamycin (mTOR) cascade, upon Cdkl5 loss-of-function. These data demonstrate that CDKL5 regulates signal transduction pathways and mediates autistic-like phenotypes and together establish a causal role for Cdkl5 loss-of-function in neurodevelopmental disorders.

Prevalence and correlates of autism in a state psychiatric hospital.

This study estimated the ASD prevalence in a psychiatric hospital and evaluated the Social Responsiveness Scale (SRS) combined with other information for differential diagnosis. Chart review, SRS and clinical interviews were collected for 141 patients at one hospital. Diagnosis was determined at case conference. Receiver operating characteristic (ROC) curves were used to evaluate the SRS as a screening instrument. Chi-squared Automatic Interaction Detector (CHAID) analysis estimated the role of other variables, in combination with the SRS, in separating cases and non-cases. Ten percent of the sample had ASD. More than other patients, their onset was prior to 12 years of age, they had gait problems and intellectual disability, and were less likely to have a history of criminal involvement or substance abuse. Sensitivity (0.86) and specificity (0.60) of the SRS were maximized at a score of 84. Adding age of onset < 12 years and cigarette use among those with SRS <80 increased sensitivity to 1.00 without lowering specificity. Adding a history substance abuse among those with SRS >80 increased specificity to 0.90 but dropped sensitivity to 0.79. Undiagnosed ASD may be common in psychiatric hospitals. The SRS, combined with other information, may discriminate well between ASD and other disorders.