1. Hullinger R, Li M, Wang J, Peng Y, Dowell JA, Bomba-Warczak E, Mitchell HA, Burger C, Chapman ER, Denu JM, Li L, Puglielli L. {{Increased expression of AT-1/SLC33A1 causes an autistic-like phenotype in mice by affecting dendritic branching and spine formation}}. {J Exp Med}. 2016; 213(7): 1267-84.
The import of acetyl-CoA into the lumen of the endoplasmic reticulum (ER) by AT-1/SLC33A1 regulates Nepsilon-lysine acetylation of ER-resident and -transiting proteins. Specifically, lysine acetylation within the ER appears to influence the efficiency of the secretory pathway by affecting ER-mediated quality control. Mutations or duplications in AT-1/SLC33A1 have been linked to diseases such as familial spastic paraplegia, developmental delay with premature death, and autism spectrum disorder with intellectual disability. In this study, we generated an AT-1 Tg mouse model that selectively overexpresses human AT-1 in neurons. These animals demonstrate cognitive deficits, autistic-like social behavior, aberrations in synaptic plasticity, an increased number of dendritic spines and branches, and widespread proteomic changes. We also found that AT-1 activity regulates acetyl-CoA flux, causing epigenetic modulation of the histone epitope H3K27 and mitochondrial adaptation. In conclusion, our results indicate that increased expression of AT-1 can cause an autistic-like phenotype by affecting key neuronal metabolic pathways.
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2. Ko C, Kim N, Kim E, Song DH, Cheon KA. {{The effect of epilepsy on autistic symptom severity assessed by the social responsiveness scale in children with autism spectrum disorder}}. {Behav Brain Funct}. 2016; 12(1): 20.
BACKGROUND: As the prevalence of autism spectrum disorders in people with epilepsy ranges from 15 to 47 % (Clarke et al. in Epilepsia 46:1970-1977, 2005), it is speculated that there is a special relationship between the two disorders, yet there has been a lack of systematic studies comparing the behavioral phenotype between autistic individuals and autistic individuals with epilepsy. This study aims to investigate how the co-occurrence of epilepsy and Autism Spectrum Disorder (ASD) affects autistic characteristics assessed by the Social Responsiveness Scale (SRS), which has been used as a measure of autism symptoms in previous studies. In this research we referred to all individuals with Autism or Autistic Disorder as individuals with ASD. METHODS: We reviewed the complete medical records of 182 participants who presented to a single tertiary care referral center from January 1, 2013 to July 28, 2015, and subsequently received complete child and adolescent psychiatric assessments. Of the 182 participants, 22 were diagnosed with Autism Spectrum Disorder and epilepsy. Types of epilepsy observed in these individuals included complex partial seizure, generalized tonic-clonic seizure, or infantile spasm. Using ‘Propensity Score Matching’ we selected 44 children, diagnosed with only Autism Spectrum Disorder, whose age, gender, and intelligence quotient (IQ) were closely matched with the 22 children diagnosed with Autism Spectrum Disorder and epilepsy. Social functioning of participants was assessed by the social responsiveness scale, which consists of five categories: social awareness, social cognition, social communication, social motivation, and autistic mannerisms. Bivariate analyses were conducted to compare the ASD participants with epilepsy group with the ASD-only group on demographic and clinical characteristics. Chi square and t test p values were calculated when appropriate. RESULTS: There was no significant difference in age (p = 0.172), gender (p > 0.999), IQ (FSIQ, p = 0.139; VIQ, p = 0.114; PIQ, p = 0.295) between the two groups. ASD participants with epilepsy were significantly more impaired than ASD participants on some measures of social functioning such as social awareness (p = 0.03) and social communication (p = 0.027). ASD participants with epilepsy also scored significantly higher on total SRS t-score than ASD participants (p = 0.023). CONCLUSIONS: Understanding the relationship between ASD and epilepsy is critical for appropriate management (e.g. social skills training, seizure control) of ASD participants with co-occurring epilepsy. Results of this study suggest that mechanisms involved in producing epilepsy may play a role in producing or augmenting autistic features such as poor social functioning. Prospective study with larger sample sizes is warranted to further explore this association.
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3. Li C, Liu C, Zhou B, Hu C, Xu X. {{Novel microduplication of CHL1 gene in a patient with autism spectrum disorder: a case report and a brief literature review}}. {Mol Cytogenet}. 2016; 9: 51.
BACKGROUND: The cell adhesion molecule L1-like (CHL1 or CALL) gene is located on chromosome 3p26.3, and it is highly expressed in the central and peripheral nervous systems. The protein encoded by this gene is a member of the L1 family of neural cell adhesion molecules, and it plays a role in nervous system development and synaptic plasticity. Moreover, studies of mice have revealed that CHL1 is a prime candidate gene for a dosage-sensitive autosomal form of mental retardation. To date, four patients with a microdeletion and two with a microduplication of 3p26.3 encompassing only the CHL1 gene have been reported in literature. CASE PRESENTATION: In the present study, we have described a 16-month-old boy with autism spectrum disorder (ASD), developmental delay and minor dysmorphic facial features. This is the first report of a duplication of 3p26.3 including only the CHL1 gene in an ASD patient, and this duplication is the smallest reported to date in this gene. We also reviewed CHL1 gene mutation cases and examined whether this gene has an important role in cognitive function. CONCLUSIONS: We conclude that both CHL1 deletions and duplications are likely responsible for the patient’s impaired cognitive function, and CHL1 may be an intriguing ASD candidate gene.
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4. Takahashi K, Miyatake N, Kurato R, Takahashi N. {{Prevalence of attention deficit hyperactivity disorder and/or autism spectrum disorder and its relation to lifestyle in female college students}}. {Environ Health Prev Med}. 2016.
OBJECTIVE: The aim of this study was to explore the prevalence of attention deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD) and its relation to lifestyle in female college students. SUBJECTS AND METHODS: A total of 375 female college students (19.2 +/- 1.3 years) among 439 students were enrolled in this cross-sectional study. Using a self-reported questionnaire, we measured the prevalence of ADHD using the ADHD Self-Report Scale-v1.1 (ASRS) and the prevalence of ASD using the Autism-Spectrum Quotient (AQ). In addition, lifestyle choices such as medications, physical activity, cigarette smoking, alcohol drinking and sleeping habits were also evaluated. RESULTS: The suspected prevalence of ADHD was 102 students (27.2 %) and the suspected prevalence of ASD was 4 students (1.1 %). Only one student (0.3 %) was thought to have both ADHD and ASD. Subjects with suspected ADHD had higher AQ scores compared with those without suspected ADHD. There were no unhealthy lifestyle choices in subjects with suspected ADHD and/or ASD. CONCLUSION: The prevalence of suspected ADHD and/or ASD may be relatively high even among female college students in Japan.
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5. van Schalkwyk GI, Beyer C, Martin A, Volkmar FR. {{College students with Autism Spectrum Disorders: A growing role for adult psychiatrists}}. {J Am Coll Health}. 2016: 0.
OBJECTIVE: Adolescents with autism spectrum disorders (ASD) are increasingly attending college. This case report highlights the nature of the psychiatric difficulties these individuals may face and the potential role for college mental health practitioners. PARTICIPANTS: A case of a female student with ASD presenting with significant inattentive symptoms. METHODS: We describe the unique features of this patient’s clinical presentation, relevant diagnostic considerations, and make recommendations about how to best approach treatment. RESULTS: This student presented with symptoms of ADHD which were first relevant during her time at college, owing to increased demands on planning and other executive functions. She was eventually responsive to treatment with a stimulant, but had more side-effects early on. CONCLUSIONS: As individuals with ASD attend college, their mental health needs will require treatment. However, such treatment draws on a comparatively limited evidence base, and providers need to be aware of potential challenges that may arise.
