1. Awadalla P, Gauthier J, Myers RA, Casals F, Hamdan FF, Griffing AR, Cote M, Henrion E, Spiegelman D, Tarabeux J, Piton A, Yang Y, Boyko A, Bustamante C, Xiong L, Rapoport JL, Addington AM, Delisi JL, Krebs MO, Joober R, Millet B, Fombonne E, Mottron L, Zilversmit M, Keebler J, Daoud H, Marineau C, Roy-Gagnon MH, Dube MP, Eyre-Walker A, Drapeau P, Stone EA, Lafreniere RG, Rouleau GA. {{Direct Measure of the De Novo Mutation Rate in Autism and Schizophrenia Cohorts}}. {Am J Hum Genet} (Aug 25)
The role of de novo mutations (DNMs) in common diseases remains largely unknown. Nonetheless, the rate of de novo deleterious mutations and the strength of selection against de novo mutations are critical to understanding the genetic architecture of a disease. Discovery of high-impact DNMs requires substantial high-resolution interrogation of partial or complete genomes of families via resequencing. We hypothesized that deleterious DNMs may play a role in cases of autism spectrum disorders (ASD) and schizophrenia (SCZ), two etiologically heterogeneous disorders with significantly reduced reproductive fitness. We present a direct measure of the de novo mutation rate (mu) and selective constraints from DNMs estimated from a deep resequencing data set generated from a large cohort of ASD and SCZ cases (n = 285) and population control individuals (n = 285) with available parental DNA. A survey of approximately 430 Mb of DNA from 401 synapse-expressed genes across all cases and 25 Mb of DNA in controls found 28 candidate DNMs, 13 of which were cell line artifacts. Our calculated direct neutral mutation rate (1.36 x 10(-8)) is similar to previous indirect estimates, but we observed a significant excess of potentially deleterious DNMs in ASD and SCZ individuals. Our results emphasize the importance of DNMs as genetic mechanisms in ASD and SCZ and the limitations of using DNA from archived cell lines to identify functional variants.
2. Henriksen MG, Skodlar B, Sass LA, Parnas J. {{Autism and Perplexity: A Qualitative and Theoretical Study of Basic Subjective Experiences in Schizophrenia}}. {Psychopathology} (Aug 25);43(6):357-368.
Background: Autistic traits and perplexity are considered core features of schizophrenia in phenomenological psychiatry. They express a fundamental disturbance of the self-world relation (including disturbances of self and intersubjectivity). The aim of our study was to examine this disturbance by exploring in detail how autism and perplexity are experienced subjectively. Methods: It is a qualitative single-case study. In order to fully examine our patient’s experiences within the context of his experiential world and not only as isolated or decontextualized symptoms, we applied a heideggerian framework, i.e. Heidegger’s exhaustive account of the self-world relation (care). Results: Through the framework of care, we discovered a profound disturbance of the self-world relation in our patient, characterized by subtle experiences of estrangement, anxiety and exposure. We found these experiences to be enduring, pervasive and generative for the development of other symptoms. Conclusions: We argue that these experiences can be seen as experiential correlates of schizotypy and of vulnerability to schizophrenia, and furthermore that an understanding of these experiences can play a role in diagnostic and differential diagnostic procedures, e.g. in early detection or in the search for high-risk individuals, as well as in the psychotherapy of schizophrenia.
3. Keil A, Daniels JL, Forssen U, Hultman C, Cnattingius S, Soderberg KC, Feychting M, Sparen P. {{Parental Autoimmune Diseases Associated With Autism Spectrum Disorders in Offspring}}. {Epidemiology} (Aug 25)
BACKGROUND:: Autism spectrum disorders are often idiopathic. Studies have suggested associations between immune response and these disorders. We explored associations between parental autoimmune disorders and children’s diagnosis of autism by linking Swedish registries. METHODS:: Data for each participant were linked across 3 Swedish registries. The study includes 1227 cases and 25 matched controls for each case (30,693 controls with parental linkage). Parental diagnoses comprised 19 autoimmune disorders. We estimated odds ratios (ORs) using multivariable conditional logistic regression. RESULTS:: Parental autoimmune disorder was weakly associated with autism spectrum disorders in offspring (maternal OR = 1.6 [95% confidence interval = 1.1-2.2]; paternal OR = 1.4 [1.0-2.0]). Several maternal autoimmune diseases were correlated with autism. For both parents, rheumatic fever was associated with autism spectrum disorders. CONCLUSIONS:: These data support previously reported associations between parental autoimmune disorders and autism spectrum disorders. Parental autoimmune disorders may represent a critical pathway that warrants more detailed investigation.
4. Smith LO, Elder JH. {{Siblings and family environments of persons with autism spectrum disorder: a review of the literature}}. {J Child Adolesc Psychiatr Nurs} (Aug);23(3):189-195.
OBJECTIVES: The purpose of this literature review is to summarize studies on siblings of individuals with autism spectrum disorders (ASD) in four major areas, to identify gaps in the literature, and to propose future directions for research of siblings of persons with ASD. DESIGN AND METHODS: A systematic review of research published within the past 10 years in peer review journals includes investigations on siblings’ and parental characteristics, as well as sibling behaviors, relationships, and adaptation. Twelve studies are synthesized to include purpose, findings, and discussion relating it to previous work. RESULTS: Siblings are influenced by the context of their families that are impacted by biological, psychological, sociological, and ecological factors. Research studies are primarily exploratory and no intervention studies are identified. CONCLUSION: The literature review of parental and sibling characteristics, relationships, and adaptation support intervention measures for siblings and family members of persons with autism. Assessment of siblings is necessary to identify those who may be at risk for future adjustment problems and maladaptive behaviors.
