1. Clawson A, South M, Baldwin SA, Larson MJ. {{Electrophysiological Endophenotypes and the Error-Related Negativity (ERN) in Autism Spectrum Disorder: A Family Study}}. {J Autism Dev Disord}. 2017.
We examined the error-related negativity (ERN) as an endophenotype of ASD by comparing the ERN in families of ASD probands to control families. We hypothesized that ASD probands and families would display reduced-amplitude ERN relative to controls. Participants included 148 individuals within 39 families consisting of a mother, father, sibling, and proband. Robust ANOVAs revealed non-significant differences in ERN amplitude and behavioral performance among ASD probands relative to control youth. In subsequent multiple regression analyses group and kinship (proband, sibling, mother, father) did not significantly predict DeltaERN (error minus correct ERN) or behavioral performance. Results do not provide evidence for the ERN as an endophenotype of ASD. Future research is needed to examine state- or trait-related factors influencing ERN amplitudes in ASD.
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2. Ford TC, Woods W, Crewther DP. {{Mismatch field latency, but not power, may mark a shared autistic and schizotypal trait phenotype}}. {Int J Psychophysiol}. 2017.
The auditory mismatch negativity (MMN), a preattentive processing potential, and its magnetic counterpart (MMF) are consistently reported as reduced in schizophrenia and autism spectrum disorders. This study investigates whether MMF characteristics differ between subclinically high and low scorers on the recently discovered shared autism and schizophrenia phenotype, Social Disorganisation. A total of 18 low (10 female) and 19 high (9 female) Social Disorganisation scorers underwent magnetoencephalography (MEG) during a MMF paradigm of 50ms standard (1000Hz, 85%) and 100ms duration deviant tones. MMF was measured from the strongest active magnetometer over the right and left hemispheres (consistent across groups) after 100ms. No differences in MMF power were found, however there was a significant delay in the MMF peak (p= 0.007). The P3am (following the MMF) was significantly reduced across both hemispheres for the high Social Disorganisation group (p= 0.025), there were no specific hemispheric differences in P3am power or latency. Right MMF peak latency increased with higher scores on the schizotypal subscales Odd Speech, Odd Behaviour and Constricted Affect. Findings suggest that MMF peak latency delay marks a convergence of the autism and schizophrenia spectra at a subclinical. These findings have significant implications for future research methodology, as well as clinical practice.
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3. Govindaraj S, Shanmuganathan A, Rajan R. {{Maternal psychological stress-induced developmental disability, neonatal mortality and stillbirth in the offspring of Wistar albino rats}}. {PLoS One}. 2017; 12(2): e0171089.
BACKGROUND: Stress is an inevitable part of life, and maternal stress during the gestational period has dramatic effects in the early programming of the physiology and behavior of offspring. The developmental period is crucial for the well-being of the offspring. Prenatal stress influences the developmental outcomes of the fetus, in part because the developing brain is particularly vulnerable to stress. The etiology of birth defects of the offspring is reported to be 30-40% genetic and 7-10% multifactorial, with the remaining 50% still unknown and also there is no clear cause for neonatal mortality and still-birth. OBJECTIVE: The present study explores the association of maternal psychological stress on mother and the offspring’s incidence of birth defects, stillbirth, and neonatal mortality. STUDY DESIGN: Pregnant animals were restrained to induce psychological stress (3 times per day, 45 minutes per session). Except control group, other animals were exposed to restraint stress during the gestational period: early gestational stress (EGS, stress exposure during 1st day to 10th days of gestational period), late gestational stress (LGS, stress exposure during 11th day to till parturition), and full term gestational stress (FGS, stress exposure to the whole gestational period). The effects of maternal stress on the mother and their offspring were analyzed. RESULTS: Expectant female rats exposed to stress by physical restraint showed decreased body weight gain, food intake, and fecal pellet levels. Specifically, the offspring of female rats subjected to late gestational and full term gestational restraint stress showed more deleterious effects, such as physical impairment (LGS 24.44%, FGS 10%), neonatal mortality (EGS 2.56%, LGS 24.44%, FGS 17.5%), stillbirths (FGS 27.5%), low birth weight (EGS 5.42g, LGS 4.40g, FGS 4.12g), preterm births (EGS 539 Hrs, LGS 514 Hrs, FGS 520.6 Hrs), and delayed eyelid opening (EGS 15.16 Days, LGS 17 Days, FGS 17.67 Days). CONCLUSION: The results of this study reveal that maternal stress may be associated with the offspring’s abnormal structural phenotyping, preterm birth, stillbirth and neonatal mortality.
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4. Kofuji T, Hayashi Y, Fujiwara T, Sanada M, Tamaru M, Akagawa K. {{A part of patients with autism spectrum disorder has haploidy of HPC-1/syntaxin1A gene that possibly causes behavioral disturbance as in experimentally gene ablated mice}}. {Neurosci Lett}. 2017.
Autism spectrum disorder (ASD) is highly heritable and encompasses a various set of neuropsychiatric disorders with a wide-ranging presentation. HPC-1/syntaxin1A (STX1A) encodes a neuronal plasma membrane protein that regulates the secretion of neurotransmitters and neuromodulators. STX1A gene ablated mice (null and heterozygote mutant) exhibit abnormal behavioral profiles similar to human autistic symptoms, accompanied by reduction of monoamine secretion. To determine whether copy number variation of STX1A gene and the change of its expression correlate with ASD as in STX1A gene ablated mice, we performed copy number assay and real-time quantitative RT-PCR using blood or saliva samples from ASD patients. We found that some ASD patients were haploid for the STX1A gene similar to STX1A heterozygote mutant mice. However, copy number of STX1A gene was normal in the parents and siblings of ASD patients with STX1A gene haploidy. In ASD patients with gene haploidy, STX1A mRNA expression was reduced to about half of their parents. Thus, a part of ASD patients had haploidy of STX1A gene and lower STX1A gene expression.
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5. O’Connor RM, Stone EF, Wayne CR, Marcinkevicius EV, Ulgherait M, Delventhal R, Pantalia MM, Hill VM, Zhou CG, McAllister S, Chen A, Ziegenfuss JS, Grueber WB, Canman JC, Shirasu-Hiza MM. {{A Drosophila model of Fragile X syndrome exhibits defects in phagocytosis by innate immune cells}}. {J Cell Biol}. 2017.
Fragile X syndrome, the most common known monogenic cause of autism, results from the loss of FMR1, a conserved, ubiquitously expressed RNA-binding protein. Recent evidence suggests that Fragile X syndrome and other types of autism are associated with immune system defects. We found that Drosophila melanogaster Fmr1 mutants exhibit increased sensitivity to bacterial infection and decreased phagocytosis of bacteria by systemic immune cells. Using tissue-specific RNAi-mediated knockdown, we showed that Fmr1 plays a cell-autonomous role in the phagocytosis of bacteria. Fmr1 mutants also exhibit delays in two processes that require phagocytosis by glial cells, the immune cells in the brain: neuronal clearance after injury in adults and the development of the mushroom body, a brain structure required for learning and memory. Delayed neuronal clearance is associated with reduced recruitment of activated glia to the site of injury. These results suggest a previously unrecognized role for Fmr1 in regulating the activation of phagocytic immune cells both in the body and the brain.
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6. Sacrey LR, Zwaigenbaum L, Szatmari P, Bryson S, Georgiades S, Brian J, Smith IM, Vaillancourt T, Garon N, Roncadin C, Elsabbagh M. {{Brief Report: Characteristics of preschool children with ASD vary by ascertainment}}. {J Autism Dev Disord}. 2017.
Prospective studies of infant siblings of children diagnosed with autism spectrum disorder (ASD) provide a unique opportunity to characterize ASD as it unfolds. A critical question that remains unanswered is whether and how these children with ASD resemble other children identified from the community, including those with no family history. The purpose of this study was to compare clinical characteristics of children with ASD identified by each method (n = 86 per group), drawn from two Canadian longitudinal research cohorts. Children ascertained from a prospective cohort were less severely affected and included a larger proportion of girls, compared to the clinically referred sample. These results may have important implications for conclusions drawn from studies of high-risk and clinically referred cohorts.
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7. Ziegler A, Rudolph-Rothfeld W, Vonthein R. {{Genetic Testing for Autism Spectrum Disorder is Lacking Evidence of Cost-Effectiveness. A Systematic Review}}. {Methods Inf Med}. 2017.
BACKGROUND: Autism Spectrum Disorder (ASD) is a highly heritable neural development disorder characterized by social impairment. The earlier the diagnosis is made, the higher are the chances of obtaining relief of symptoms. A very early diagnosis uses molecular genetic tests, which are also offered commercially. OBJECTIVE: Systematic review of the economic impact of genetic tests in ASD. METHODS: We performed a systematic search of databases Pubmed, Medline, Cochrane, Econlit and the NHS Center for Reviews and Dissemination for articles in English and German from January 1, 2000 to December 31, 2015. Original articles published in peer-reviewed journals were screened in a two-step process. First, we focused our search on economic evaluations of genetic tests for ASD. Second, we searched for any economic evaluation (EE) of genetic tests. RESULTS: We identified 185 EE of genetic tests for various diseases. However, not a single EE of genetic tests has been found for ASD. The outcomes used in the EE of the genetic tests were heterogeneous, and results were generally not comparable. CONCLUSION: There is no evidence for cost-effectiveness of any genetic diagnostic test for ASD, although such genetic tests are available commercially. Cost-effectiveness analyses for genetic diagnostic tests for ASD are urgently required. There is a clear lack in research for EE of genetic tests.
