Effects of eight neuropsychiatric copy number variants on human brain structure

Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions

Neurocognitive and Neurobehavioral Phenotype of Youth with Schaaf-Yang Syndrome

Truncating variants of theMAGEL2gene, one of the protein-coding genes within the Prader-Willi syndrome (PWS) critical region on chromosome 15q11, cause Schaaf-Yang syndrome (SYS)-a neurodevelopmental disorder that shares several clinical features with PWS. The current study sought to characterize the neurobehavioral phenotype of SYS in a sample of 9 patients with molecularly-confirmed SYS. Participants received an assessment of developmental/intellectual functioning, adaptive functioning, autism symptomatology, and behavioral/emotional functioning. Compared to individuals with PWS, patients with SYS manifested more severe cognitive deficits, no obsessions or compulsions, and increased rates of autism spectrum disorder

Parent-led, Stepped-care Cognitive-behavioral Therapy for Youth with Autism and Co-occurring Anxiety: Study Rationale and Method

Anxiety disorders affect up to 50% of individuals with autism spectrum disorder (ASD) and are significantly impairing to the person affected, as well as to their loved ones. Cognitive-behavioral therapy (CBT) has been established as the gold-standard treatment for anxiety disorders among typically developing youth and adults, and demonstrates similar efficacy among youth with high-functioning autism (HFA). Many CBT interventions utilize a “full-package” treatment approach to treat co-occurring anxiety in youth with ASD. However, these service delivery systems are often therapist-intensive, costly, and impractical, thereby compromising full engagement and treatment adherence. This paper describes the design, rationale, and methodology of a study examining stepped-care CBT for youth with HFA and co-occurring anxiety – a clinical trial examining the efficacy of low-intensity, parent-led CBT as the first line of treatment and utilizing a more intensive, therapist-led intervention for nonresponders. The study will evaluate the potential benefits of stepped-care and parent-led therapist-assisted interventions, predictors of treatment response, and the economic value of using a stepped-care model. Implications for practice will be discussed

Parent-led, Stepped-care Cognitive-behavioral Therapy for Youth with Autism and Co-occurring Anxiety: Study Rationale and Method

Anxiety disorders affect up to 50% of individuals with autism spectrum disorder (ASD) and are significantly impairing to the person affected, as well as to their loved ones. Cognitive-behavioral therapy (CBT) has been established as the gold-standard treatment for anxiety disorders among typically developing youth and adults, and demonstrates similar efficacy among youth with high-functioning autism (HFA). Many CBT interventions utilize a “full-package” treatment approach to treat co-occurring anxiety in youth with ASD. However, these service delivery systems are often therapist-intensive, costly, and impractical, thereby compromising full engagement and treatment adherence. This paper describes the design, rationale, and methodology of a study examining stepped-care CBT for youth with HFA and co-occurring anxiety – a clinical trial examining the efficacy of low-intensity, parent-led CBT as the first line of treatment and utilizing a more intensive, therapist-led intervention for nonresponders. The study will evaluate the potential benefits of stepped-care and parent-led therapist-assisted interventions, predictors of treatment response, and the economic value of using a stepped-care model. Implications for practice will be discussed

MOVING THE NEEDLE ON TIME TO RESUSCITATION: AN EAST PROSPECTIVE MULTICENTER STUDY OF VASCULAR ACCESS IN HYPOTENSIVE INJURED PATIENTS USING TRAUMA VIDEO REVIEW.

INTRODUCTION: Vascular access in hypotensive trauma patients is challenging. Little evidence exists on the time required and success rates of vascular access types. We hypothesized that intraosseous (IO) access would be faster and more successful than peripheral IV (PIV) and central venous catheter (CVC) access in hypotensive patients. METHODS: An EAST prospective multicenter trial was performed; 19 centers provided data. Trauma video review (TVR) was used to evaluate the resuscitations of hypotensive (systolic blood pressure ≤ 90 mmHg) trauma patients. Highly granular data from video recordings were abstracted. Data collected included vascular access attempt type, location, success rate, and procedural time. Demographic and injury-specific variables were obtained from the medical record. Success rates, procedural durations, and time to resuscitation were compared among access strategies (IO vs PIV vs CVC). RESULTS: 1,410 access attempts occurred in 581 patients with a median age of 40[27-59] years and an ISS of 22[10-34]. 932 PIV, 204 IO and 249 CVC were attempted. 70% of access attempts were successful but were significantly less likely to be successful in females (64% vs. 71%, p = 0.01). Median time to any access was 5.0[3.2-8.0] minutes. IO had higher success rates than PIV or CVC (93% vs. 67% vs. 59%, p \u3c 0.001) and remained higher after subsequent failures (second attempt 85% vs. 59% vs. 69%, p = 0.08; third attempt 100% vs 33% vs. 67%, p = 0.002). Duration varied by access type (IO 36[23-60]sec; PIV 44[31-61]sec; CVC 171[105-298]sec) and was significantly different between IO vs. CVC (p \u3c 0.001) and PIV vs. CVC (p \u3c 0.001) but not PIV vs. IO. Time to resuscitation initiation was shorter in patients whose initial access attempt was IO, 5.8 minutes vs. 6.7 minutes (p = 0.015). This was more pronounced in patients arriving to the hospital with no established access (5.7 minutes vs. 7.5 minutes, p = 0.001). CONCLUSIONS: IO is as fast as PIV and more likely to be successful compared with other access strategies in hypotensive trauma patients. Patients whose initial access attempt was IO were resuscitated more expeditiously. IO access should be considered a first line therapy in hypotensive trauma patients. LEVEL OF EVIDENCE: Level II Therapeutic/Care Management