1. Chaddad A, Desrosiers C, Hassan L, Tanougast C. {{Hippocampus and amygdala radiomic biomarkers for the study of autism spectrum disorder}}. {BMC Neurosci};2017 (Jul 11);18(1):52.
BACKGROUND: Emerging evidence suggests the presence of neuroanatomical abnormalities in subjects with autism spectrum disorder (ASD). Identifying anatomical correlates could thus prove useful for the automated diagnosis of ASD. Radiomic analyses based on MRI texture features have shown a great potential for characterizing differences occurring from tissue heterogeneity, and for identifying abnormalities related to these differences. However, only a limited number of studies have investigated the link between image texture and ASD. This paper proposes the study of texture features based on grey level co-occurrence matrix (GLCM) as a means for characterizing differences between ASD and development control (DC) subjects. Our study uses 64 T1-weighted MRI scans acquired from two groups of subjects: 28 typical age range subjects 4-15 years old (14 ASD and 14 DC, age-matched), and 36 non-typical age range subjects 10-24 years old (20 ASD and 16 DC). GLCM matrices are computed from manually labeled hippocampus and amygdala regions, and then encoded as texture features by applying 11 standard Haralick quantifier functions. Significance tests are performed to identify texture differences between ASD and DC subjects. An analysis using SVM and random forest classifiers is then carried out to find the most discriminative features, and use these features for classifying ASD from DC subjects. RESULTS: Preliminary results show that all 11 features derived from the hippocampus (typical and non-typical age) and 4 features extracted from the amygdala (non-typical age) have significantly different distributions in ASD subjects compared to DC subjects, with a significance of p < 0.05 following Holm-Bonferroni correction. Features derived from hippocampal regions also demonstrate high discriminative power for differentiating between ASD and DC subjects, with classifier accuracy of 67.85%, sensitivity of 62.50%, specificity of 71.42%, and the area under the ROC curve (AUC) of 76.80% for age-matched subjects with typical age range. CONCLUSIONS: Results demonstrate the potential of hippocampal texture features as a biomarker for the diagnosis and characterization of ASD. Lien vers le texte intégral (Open Access ou abonnement)
2. Noroozi R, Ghafouri-Fard S, Omrani MD, Habibi M, Sayad A, Taheri M. {{Association study of the vesicular monoamine transporter 1 (VMAT1) gene with autism in an Iranian population}}. {Gene};2017 (Aug 20);625:10-14.
Autism Spectrum Disorders (ASD) (MIM 209850) are a group of neurodevelopmental disorders distinguished by destructed social interaction and communication abilities along with peculiar repetitive behavior. Several genetic loci have been linked to this disorder. Vesicular monoamine transporter 1 (VMAT1/SLC18A1) is an attractive candidate gene for psychiatric disorders because of its participation in regulation monoamines. In the present case-control study, we evaluated the link between three non-synonymous single nucleotide polymorphisms (SNPs) (rs2270641 [Pro4Thr], rs2270637 [Thr98Ser] and rs1390938 [Thr136Ile]) and one intronic SNP (rs2279709) across the VMAT1 gene and ASD in a group of Iranian patients. Allele frequency analyses showed significant over-presentation of rs1390938-G allele in cases compared with controls (P<0.001). The analysis under different genetic models showed that the AA genotype of the rs1390938 was protective against ASD under dominant and recessive models. The rs2270641 SNP was associated with ASD risk only in over-dominant model. Other SNPs showed no significant difference in allele or genotype frequencies between two groups. Haplotype analysis revealed that C A T T and C A T G haplotypes (rs2270637, rs1390938, rs2279709 and rs2270641 respectively) have a protective effect against ASD. Consequently, the functional rs1390938 SNP in VMAT1 is associated with ASD in Iranian population. Considering the role of VMAT1 in regulation of monoamines, the dysregulated expression of this protein during early stages of brain development might be implicated in ASD. Lien vers le texte intégral (Open Access ou abonnement)
3. Sheppard JJ, Malandraki GA, Pifer P, Cuff J, Troche M, Hemsley B, Balandin S, Mishra A, Hochman R. {{Validation of the Choking Risk Assessment and Pneumonia Risk Assessment for adults with Intellectual and Developmental Disability (IDD)}}. {Res Dev Disabil};2017 (Aug 16);69:61-76.
BACKGROUND: Risk assessments are needed to identify adults with intellectual and developmental disability (IDD) at high risk of choking and pneumonia. AIM: To describe the development and validation of the Choking Risk Assessment (CRA) and the Pneumonia Risk Assessment (PRA) for adults with IDD. METHODS: Test items were identified through literature review and focus groups. Five-year retrospective chart reviews identified a positive choking group (PCG), a negative choking group (NCG), a positive pneumonia group (PPG), and a negative pneumonia group (NPG). Participants were tested with the CRA and PRA by clinicians blind to these testing conditions. RESULTS: The CRA and PRA differentiated the PCG (n=93) from the NCG (n=526) and the PPG (n=63) from the NPG (n=209) with high specificity (0.91 and 0.92 respectively) and moderate to average sensitivity (0.53 and 0.62 respectively). Further analyses revealed associations between clinical diagnoses of dysphagia and choking (p=0.043), and pneumonia (p<0.001). CONCLUSIONS: The CRA and PRA are reliable, valid risk indicators for choking and pneumonia in adults with IDD. Precautions for mitigating choking and pneumonia risks can be applied selectively thus avoiding undue impacts on quality of life and unnecessary interventions for low risk individuals. Lien vers le texte intégral (Open Access ou abonnement)
4. Sjaarda CP, Hecht P, McNaughton AJM, Zhou A, Hudson ML, Will MJ, Smith G, Ayub M, Liang P, Chen N, Beversdorf D, Liu X. {{Interplay between maternal Slc6a4 mutation and prenatal stress: a possible mechanism for autistic behavior development}}. {Sci Rep};2017 (Aug 18);7(1):8735.
The low activity allele of the maternal polymorphism, 5HTTLPR, in the serotonin transporter, SLC6A4, coupled with prenatal stress is reported to increase the risk for children to develop autism spectrum disorder (ASD). Similarly, maternal Slc6a4 knock-out and prenatal stress in rodents results in offspring demonstrating ASD-like characteristics. The present study uses an integrative genomics approach to explore mechanistic changes in early brain development in mouse embryos exposed to this maternal gene-environment phenomenon. Restraint stress was applied to pregnant Slc6a4 +/+ and Slc6a4 +/- mice and post-stress embryonic brains were assessed for whole genome level profiling of methylome, transcriptome and miRNA using Next Generation Sequencing. Embryos of stressed Slc6a4 +/+ dams exhibited significantly altered methylation profiles and differential expression of 157 miRNAs and 1009 genes affecting neuron development and cellular adhesion pathways, which may function as a coping mechanism to prenatal stress. In striking contrast, the response of embryos of stressed Slc6a4 +/- dams was found to be attenuated, shown by significantly reduced numbers of differentially expressed genes (458) and miRNA (0) and genome hypermethylation. This attenuated response may pose increased risks on typical brain development resulting in development of ASD-like characteristics in offspring of mothers with deficits in serotonin related pathways during stressful pregnancies.
