Autism and mood disorders.

Individuals with autism experience substantially higher rates of mood problems compared to the general population, which contribute to reduced quality of life and increased mortality through suicide. Here, we reviewed evidence for the clinical presentation, aetiology and therapeutic approaches for mood problems in autism. We identified a lack of validated tools for accurately identifying mood problems in individuals with autism, who may present with 'atypical' features (e.g. severe irritability). Risk factors for mood problems in autism appear to be largely overlapping with those identified in the general population, including shared genetic, environmental, cognitive, physiological/neurobiological mechanisms. However, these mechanisms are exacerbated directly/indirectly by lived experiences of autism, including increased vulnerability for chronic stress - often related to social-communication difficulties(/bullying) and sensory sensitivities. Lastly, current therapeutic approaches are based on recommendations for primary mood disorders, with little reference to the neurobiological/cognitive differences associated with autism. Thus, we recommend: 1) the development and validation of (objective) tools to identify mood problems in autism and measure therapeutic efficacy; 2) an interactive approach to investigating aetiologies in large-scale longitudinal studies, integrating different levels of analysis (e.g. cognitive, neurobiological) and lived experience; 3) testing potential treatments through high-quality (e.g. sufficiently powered, blinded) clinical trials, specifically for individuals with autism.

Clinical Outcomes and Modes of Death in Timothy Syndrome: A Multicenter International Study of a Rare Disorder.

OBJECTIVES: The objective of this study was to evaluate contemporary clinical outcomes and identify triggers for arrhythmias or sudden death in an international cohort of Timothy Syndrome (TS) patients including those with novel TS-associated CACNA1C mutations. BACKGROUND: TS is an extremely rare genetic disorder of the L-type cardiac channel Cav1.2 encoded by CACNA1C. The syndrome is characterized by multisystem abnormalities consisting of QT prolongation, congenital heart defects, syndactyly, facial dysmorphism, and neurological symptoms. METHODS: Patients diagnosed with TS between January 1, 1994, and April 1, 2016, from 12 international tertiary care pediatric centers were included in this retrospective study. Data were gathered via survey from the patients' electrophysiologists. RESULTS: Seventeen patients diagnosed with TS were identified. Length of follow-up was 4.9 years (range 3.0 to 19.0 years). Mean QTc was 640 ms (range 500 to 976 ms). All patients were treated with beta-blockers; 13 patients (76%) were also treated with an implantable defibrillator. Eleven patients experienced an episode of aborted cardiac arrest, 6 associated with general anesthesia and 2 with hypoglycemia. Four patients died suddenly due to ventricular fibrillation, 2 of whom had associated hypoglycemia. CONCLUSIONS: This study shows that mortality in TS patients is due to multifactorial mechanisms, which include ventricular arrhythmias, pulseless electrical activity, and hypoglycemia. A simple nomenclature for ongoing studies of TS and related syndromes is described. A worldwide prospective registry is needed for continued exploration of this syndrome.

Twenty-Five Year Survival of Children with Intellectual Disability in Western Australia.

OBJECTIVES: To investigate survival up to early adulthood for children with intellectual disability and compare their risk of mortality with that of children without intellectual disability. STUDY DESIGN: This was a retrospective cohort study of all live births in Western Australia between January 1, 1983 and December 31, 2010. Children with an intellectual disability (n = 10 593) were identified from the Western Australian Intellectual Disability Exploring Answers Database. Vital status was determined from linkage to the Western Australian Mortality database. Kaplan-Meier product limit estimates and 95% CIs were computed by level of intellectual disability. Hazard ratios (HRs) and 95% CIs were calculated from Cox proportional hazard regression models adjusting for potential confounders. RESULTS: After adjusting for potential confounders, compared with those without intellectual disability, children with intellectual disability had a 6-fold increased risk of mortality at 1-5 years of age (adjusted HR [aHR] = 6.0, 95%CI: 4.8, 7.6), a 12-fold increased risk at 6-10 years of age (aHR = 12.6, 95% CI: 9.0, 17.7) and a 5-fold increased risk at 11-25 years of age (aHR = 4.9, 95% CI: 3.9, 6.1). Children with severe intellectual disability were at even greater risk. No difference in survival was observed for Aboriginal children with intellectual disability compared with non-Aboriginal children with intellectual disability. CONCLUSIONS: Although children with intellectual disability experience higher mortality at all ages compared with those without intellectual disability, the greatest burden is for those with severe intellectual disability. However, even children with mild to moderate intellectual disability have increased risk of death compared with unaffected children.

Mortality in individuals with autism, with and without epilepsy.

Previous studies show higher mortality rates among individuals with autism than the general population. Comorbidity with epilepsy is an assumed, often ill-defined factor in the increased mortality rates of individuals with autism. Data from the Autism Tissue Program, a tissue donation program established to support biomedical research on autism, show that approximately one-third of its brain donors with autism also had epilepsy. Analysis of new data from the California State Department of Developmental Services is consistent with past reports showing that there is a higher than expected rate of mortality in individuals with autism and epilepsy than autism alone. Accurate, complete and accessible records on cause of death are necessary not just for brain research, but also for understanding risk factors that contribute to early death in individuals with autism spectrum disorders. Various national health care and state developmental disability agency initiatives to reduce risk of mortality are described.

Mortality in autism: a prospective longitudinal community-based study.

The purposes of the present study were to establish the mortality rate in a representative group of individuals (n = 120) born in the years 1962-1984, diagnosed with autism/atypical autism in childhood and followed up at young adult age (>or=18 years of age), and examine the risk factors and causes of death. The study group, which constituted a total population sample of children with these diagnoses, were followed up in Swedish registers. Nine (7.5%) of the 120 individuals with autism had died at the time of follow-up, a rate 5.6 times higher than expected. The mortality rate was significantly higher among the females. Associated medical disorders (including epilepsy with cognitive impairment) and accidents accounted for most of the deaths, and it was not possible to determine whether autism "per se" actually carries an increased mortality risk.

Mortality and causes of death in autism spectrum disorders: an update.

This study compared mortality among Danish citizens with autism spectrum disorders (ASDs) with that of the general population. A clinical cohort of 341 Danish individuals with variants of ASD, previously followed over the period 1960-93, now on average 43 years of age, were updated with respect to mortality and causes of death. Standardized mortality ratios (SMRs) were calculated for various times after diagnosis. In all, 26 persons with ASD had died, whereas the expected number of deaths was 13.5. Thus the mortality risk among those with ASD was nearly twice that of the general population. The SMR was particularly high in females. The excess mortality risk has remained unchanged since our first study in 1993. Eight of the 26 deaths were associated with epilepsy and four died from epilepsy. Future staff education should focus on better managing of the complex relationships between ASD and physical illness to prevent avoidable deaths.

Estimating the burden of disease for autism spectrum disorders in Spain in 2003.

Autism Spectrum Disorders (ASD) are lifelong neurodevelopmental disabilities. Burden of Disease is an indicator that provides important information on health status and outcomes such as premature mortality and disability. In order to estimate the burden of disease of ASD in the Spanish population during 2003, we followed the procedures used in the WHO Global Burden of Disease Study. ASD generated 43,928 Disability Adjusted Life Years (DALY) in Spain in 2003, from which 33,797 were attributable to Autistic Disorder and 10,131 were caused by Asperger's Disorder and Pervasive Developmental Disorder-Not Otherwise Specified. DALY could be a useful tool for health policy makers for setting health service priorities, allocating available resources effectively and providing a comparable measure of output for early intervention.

[The course of infantile autism through adulthood. An overview of long-term follow-up data]. / Lebenswege frühkindlicher Autisten im Erwachsenenalter. Eine Ubersicht über langzeitkatamnestische Daten.

The symptoms of infantile autism were first described almost 60 years ago. In contrast to its course in puberty and adolescence, follow-up-data on the late course in adulthood are decidedly sparse. As the outcome of research in the literature, we found 21 methodologically heterogeneous follow-up-studies. The arithmetic mean age of all subjects investigated was 24.0 years. The results are supplemented by various case reports and sporadic biographical reports by affected persons. On the basis of the available data, the discontinuous and dynamic changes of course verified in puberty and adolescence are not applicable to the third and fourth decades to the same extent. Gains in competence and autonomy appear to develop in the vocational rather than in the domestic sphere. The significantly more favorable courses of the form described by Asperger are continued in adulthood. The disorder-associated lack of empathy and social interaction is by no means experienced in terms of self-satisfaction by those concerned but rather as a loss. Interpersonal sexual needs are expressed by a substantial proportion of autistic adults. The cumulative mortality rates of the follow-up-studies suggest that the mortality rate among autistic patients is higher than among their non-autistic peers.

Causes of death in autism.

The objective of this study was to determine which causes of death are more frequent in persons with autism, and by how much, compared with the general population. Subjects were 13,111 ambulatory Californians with autism, followed between 1983 and 1997. The units of study were person-years, each linked to the subject's age, sex, and cause of death (if any) for the specific year. Observed numbers of cause-specific deaths were compared with numbers expected according to general population mortality rates. Standardized mortality rates (SMRs) were computed for each mental retardation level. Elevated death rates were observed for several causes, including seizures and accidents such as suffocation and drowning; elevated mortality due to respiratory disease was observed among persons with severe mental retardation. Overall, excess mortality was especially marked for persons with severe mental retardation, but life expectancy is reduced even for persons who are fully ambulatory and who have only mild mental retardation.

Comparative mortality of persons with autism in California, 1980-1996.

The authors studied mortality rates of persons with autism, using the extensive California developmental disabilities registry. There was an overall mortality ratio (MR) of 213%. The MR for females (490%) was strikingly higher than for males (167%). The excess mortality rate (EDR) increased with age, while the mortality ratio (MR) decreased with age. Persons with autism are subject to increased mortality risk, as summarized in the provided tables.

Longitudinal examination of the behavioral, language, and social changes in a population of adolescents and young adults with autistic disorder.

This follow-up study evaluates the behavioral, language, and social outcomes in a population of autistic patients initially examined in childhood. We evaluated 102 (63%) of the 163 eligible subjects, including 54 adolescents (12-17 years of age) and 45 adults (> or = 18 years of age). Three patients had died in the interim. Behavior difficulties continued to be a problem in 69% of adolescents and adults. Thirty-five percent of adolescents and 49% of adults engaged in self-injurious behavior, and slightly more than 50% of adolescents and adults exhibited some stereotypic behaviors. Over 90% of both adolescents and adults had persisting social deficits. Language improved with age, although only 35% achieved normal or near-normal fluency. Comprehension also improved, although only 29% of subjects had achieved normal or near-normal comprehension of oral language. At the time of last follow-up, 28% of all patients and 53% of adults were living in residential placement. Only 11% of adults were employed on the open market, all in menial jobs; an additional 16% were employed in sheltered workshops. The social, behavioral, and language deficits identified in early life in autistic children tend to persist into adolescence and young adulthood.