SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients.

Phelan-McDermid syndrome (PMDS) is a complex neurodevelopmental disorder characterized by global developmental delay, severely impaired speech, intellectual disability, and an increased risk of autism spectrum disorders (ASDs). PMDS is caused by heterozygous deletions of chromosome 22q13.3. Among the genes in the deleted region is SHANK3, which encodes a protein in the postsynaptic density (PSD). Rare mutations in SHANK3 have been associated with idiopathic ASDs, non-syndromic intellectual disability, and schizophrenia. Although SHANK3 is considered to be the most likely candidate gene for the neurological abnormalities in PMDS patients, the cellular and molecular phenotypes associated with this syndrome in human neurons are unknown. We generated induced pluripotent stem (iPS) cells from individuals with PMDS and autism and used them to produce functional neurons. We show that PMDS neurons have reduced SHANK3 expression and major defects in excitatory, but not inhibitory, synaptic transmission. Excitatory synaptic transmission in PMDS neurons can be corrected by restoring SHANK3 expression or by treating neurons with insulin-like growth factor 1 (IGF1). IGF1 treatment promotes formation of mature excitatory synapses that lack SHANK3 but contain PSD95 and N-methyl-D-aspartate (NMDA) receptors with fast deactivation kinetics. Our findings provide direct evidence for a disruption in the ratio of cellular excitation and inhibition in PMDS neurons, and point to a molecular pathway that can be recruited to restore it.

Handling clinical comorbidity in randomized clinical trials in psychiatry.

The purpose of this paper is to a) outline the importance of including patients with clinical comorbidities in Randomized Clinical Trials (RCTs) of psychiatric treatments; and b) to propose a specific approach for best handling, analyzing and interpreting the data on clinical comorbidities in terms of their impact on treatment outcomes. To do this we first define and describe clinical comorbidity and differentiate it from other forms of comorbidity. We then describe the methodological and analytical problems associated with excluding patients with clinically comorbid conditions from RCTs, including the impact on the outcomes of RCTs in psychiatry and the impact on evidence-based clinical decision-making. We then address the challenges inherent to including patients with clinical comorbidities in RCTs. Finally, we propose a methodological and analytic approach to deal with these issues in RCTs which aims to significantly improve the information yielded from RCTs in psychiatry, and thus improve clinical decision-making.

An evaluation of a positive youth development program for adolescents with chronic illness.

PURPOSE: Youth with chronic illness often struggle transitioning to adulthood and adult medical care. This article examines the outcomes of a group mentoring program called The Adolescent Leadership Council (TALC) that brings together high school participants and college mentors, all with chronic illness. TALC uses a positive youth development (PYD) approach, emphasizing strong relationships between youth and adults in an environment where youth can learn important life skills and take a leadership role. METHODS: A pre-/postprogram participant survey was conducted for high school participants using a loneliness scale and a transition readiness survey. An alumni survey was conducted with all high school and college mentor graduates to assess educational-, vocational-, and health care-related outcomes. RESULTS: Program records review and the alumni survey indicated that TALC was consistent with the PYD program model. Twenty high school students participated in the pre-/postprogram outcomes evaluation, which demonstrated a decrease in loneliness from 46 to 38.5 (p < .001) and an increase in health care self-advocacy from 3.8 to 4.2 (p < .001). Thirty-four alumni participated in the alumni survey. All high school and college mentor alumni had graduated from high school and college, respectively, and all were either currently in school or working. The majority of alumni were seeing adult providers for medical care. CONCLUSIONS: The TALC program applies the principles of PYD to support positive educational, vocational, and health care outcomes for youth with chronic illness. Program development using the PYD perspective is an important new approach for supporting adult development of youth with chronic illness.

Head circumferences in twins with and without Autism Spectrum Disorders.

To determine the genetic relationship between head circumference (HC) and Autism Spectrum Disorders (ASDs). Twin pairs with at least one twin with an ASD were assessed. HCs in affected and unaffected individuals were compared, as were HC correlations in monozygotic and dizygotic pairs. 404 subjects, ages 4-18, were included. 20 % of males and 27 % of females with an ASD had macrocephaly. Unaffected co-twins showed similar rates (16 % of males and 22 % of females). Statistical analysis revealed no significant difference in HCs between affected and unaffected twins. Twins with ASDs and unaffected co-twins have similar HCs and increased rates of macrocephaly. Correlations demonstrated partial inheritance of HCs. Thus, macrocephaly may represent an endophenotype in ASDs.

Case report: an example of international telemedicine success.

An 8-month old girl presented to the Angkor Hospital for Children in Siem Riep, Cambodia with fevers, bilateral eye discharge and an extensive body rash. The rash consisted of large, fluid-filled bullae and significant desquamation. The patient was admitted to the hospital and given intravenous cloxacillin for presumed bullous impetigo. Despite treatment with antibiotics, the skin lesions did not improve and the fevers continued. Telemedicine consultations were initiated by email between Angkor Hospital for Children and paediatric specialists in the USA. Several diagnoses were entertained throughout the subsequent collaborative dialogue. Ultimately, teleconsultation led to a diagnosis of chronic bullous dermatosis of childhood (CBDC), a rare sub-epidermal blistering disease. The child was started on appropriate medications. Within 24 hours, the lesions showed significant improvement and fevers resolved. By enabling advice from distant providers on diagnosis and treatment of paediatric patients, telemedicine may improve health care in developing countries.