ABSTRACT
Recent researches suggested that the risk of drug-induced QTc prolongation is low in child and adolescent psychiatry setting. However, these cohorts enrolled mainly of Caucasian background. We aimed to assess the prevalence of QTc prolongation and its association with antipsychotic use in Japanese youth. The medical records of inpatients were reviewed. Two different definitions of QT prolongation, Bazett's corrected QT interval (QTcB) >450 msec and Fridericia's corrected QT interval (QTcF) >450 msec, were adopted. In 220 participants [age: 13.4 ± 2.3 years, antipsychotics according to the chlorpromazine equivalence: 50 (25th-75th percentiles; 0-150) mg/day], the prevalence of QTcB and QTcF prolongation was 13.6 and 2.3%, respectively. Patients with QTcB >450 msec had a significantly higher heart rate than those with QTcB ≤450 msec (91.2 ± 20.6 bpm vs. 76.1 ± 15.2 bpm; P < 0.001). The other variables, except potassium level (4.1 ± 0.4 mEq/L vs. 4.2 ± 0.3 mEq/L; P = 0.030), showed no significant difference. Clinically meaningful QTc prolongation was rare even in this Japanese cohort. This study also suggested that if QTcB is used, clinicians should be aware of possible overdiagnosis of QTc prolongation due to accelerated heart rate.
Subject(s)
Algorithms , Long QT Syndrome , Overdiagnosis , Adolescent , Antipsychotic Agents/adverse effects , Child , Humans , Inpatients/statistics & numerical data , Japan/epidemiology , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , Long QT Syndrome/epidemiology , Overdiagnosis/statistics & numerical data , Reproducibility of ResultsABSTRACT
Autism, characterized by profound impairment in social interactions and communicative skills, is the most common neurodevelopmental disorder, and its underlying molecular mechanisms remain unknown. Ca(2+)-dependent activator protein for secretion 2 (CADPS2; also known as CAPS2) mediates the exocytosis of dense-core vesicles, and the human CADPS2 is located within the autism susceptibility locus 1 on chromosome 7q. Here we show that Cadps2-knockout mice not only have impaired brain-derived neurotrophic factor release but also show autistic-like cellular and behavioral phenotypes. Moreover, we found an aberrant alternatively spliced CADPS2 mRNA that lacks exon 3 in some autistic patients. Exon 3 was shown to encode the dynactin 1-binding domain and affect axonal CADPS2 protein distribution. Our results suggest that a disturbance in CADPS2-mediated neurotrophin release contributes to autism susceptibility.
