Age and severity-dependent gut microbiota alterations in Tunisian children with autism spectrum disorder.

Alterations in gut microbiota and short chain fatty acids (SCFA) have been reported in autism spectrum disorder (ASD). We analysed the gut microbiota and fecal SCFA in Tunisian autistic children from 4 to 10 years, and results were compared to those obtained from a group of siblings (SIB) and children from the general population (GP). ASD patients presented different gut microbiota profiles compared to SIB and GP, with differences in the levels of Bifidobacterium and Collinsella occurring in younger children (4-7 years) and that tend to be attenuated at older ages (8-10 years). The lower abundance of Bifidobacterium is the key feature of the microbiota composition associated with severe autism. ASD patients presented significantly higher levels of propionic and valeric acids than GP at 4-7 years, but these differences disappeared at 8-10 years. To the best of our knowledge, this is the first study on the gut microbiota profile of Tunisian autistic children using a metataxonomic approach. This exploratory study reveals more pronounced gut microbiota alterations at early than at advanced ages in ASD. Although we did not account for multiple testing, our findings suggest that early interventions might mitigate gut disorders and cognitive and neurodevelopment impairment associated to ASD.

An Overview on Fecal Profiles of Amino Acids and Related Amino-Derived Compounds in Children with Autism Spectrum Disorder in Tunisia.

Autism spectrum disorder (ASD) is a neurodevelopmental pathology characterized by the impairment of social interaction, difficulties in communication, and repetitive behaviors. Alterations in the metabolism of amino acids have been reported. We performed a chromatographic analysis of fecal amino acids, ammonium, biogenic amines, and gamma aminobutyric acid (GABA) in Tunisian autistic children from 4 to 10 years, and results were compared with their siblings (SIB) and children from the general population (GP). ASD presented significantly higher levels of fecal amino acids than SIB and GP; differences being more pronounced in younger (4-7 years) than in older (8-10 years) individuals whereas no changes were found for the remaining compounds. Lower levels of histidine were the only difference related with severe symptoms of autism (CARS scale). A linear discriminant analysis (LDA) based on fecal amino acid profiles clearly separated ASD, SIB, and GP at 4 to 7 years but not at more advanced age (8-10 years), evidencing more pronounced alterations in younger children. The relationship of fecal amino acids with autism needs deeper research integrating blood analytical parameters, brain metabolism, and intestinal microbiota. Fecal amino acids could be targeted for designing personalized diets to prevent or minimize cognitive impairments associated with ASD.

Challenges and unmet needs of mothers of preschool children with autism spectrum disorders in Tunisia: a qualitative study.

Introduction: Autism spectrum disorder (ASD) is a life-changing condition, not only for the child but also for the mother and the usual caregiver. In fact, a child recently diagnosed with ASD is a real challenge to mothers´ adaptation, involves their resources, and gives rise to a set of needs. This study explores the unmet needs and experiences of mothers of ASD children in the Tunisian context. Methods: a qualitative phenomenological design was chosen for this study and a semi-structured interview was used for eight mothers raising an autistic preschooler child. Results: the results indicate significant denial and rejection following the announcement of the diagnosis. To cope with this, reliance on religion has helped foster acceptance. Although informal support (from family and friends) has sometimes been mentioned, an increased need for training, social and financial support has been expressed and is a major concern given the high cost of TSA services. Conclusion: this study provides a deeper understanding of mothers' needs following the announcement of the diagnosis of ASD. These unmet needs should be taken into account when designing interventions strategies for children with ASD to help mothers cope and parent a child with ASD.

Yield of array-CGH analysis in Tunisian children with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic underpinnings. Microarray-based comparative genomic hybridization (aCGH) technology has been proposed as a first-level test in the genetic diagnosis of ASD and of neurodevelopmental disorders in general. METHODS: We performed aCGH on 98 Tunisian children (83 boys and 15 girls) diagnosed with ASD according to DSM-IV criteria. RESULTS: "Pathogenic" or "likely pathogenic" copy number variants (CNVs) were detected in 11 (11.2%) patients, CNVs of "uncertain clinical significance" in 26 (26.5%), "likely benign" or "benign" CNVs were found in 37 (37.8%) and 24 (24.5%) patients, respectively. Gene set enrichment analysis involving genes spanning rare "pathogenic," "likely pathogenic," or "uncertain clinical significance" CNVs, as well as SFARI database "autism genes" in common CNVs, detected eight neuronal Gene Ontology classes among the top 10 most significant, including synapse, neuron differentiation, synaptic signaling, neurogenesis, and others. Similar results were obtained performing g: Profiler analysis. Neither transcriptional regulation nor immune pathways reached significance. CONCLUSIONS: aCGH confirms its sizable diagnostic yield in a novel sample of autistic children from North Africa. Recruitment of additional families is under way, to verify whether genetic contributions to ASD in the Tunisian population, differently from other ethnic groups, may involve primarily neuronal genes, more than transcriptional regulation and immune-related pathways.

Risk factors in autism spectrum disorder: A Tunisian case-control study.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition that causes disability in social interaction, communication, and restrictive and repetitive behaviors. Common environmental factors like prenatal, perinatal, and/or postnatal factors play a key role in ASD etiologies. Moreover, specific metabolic disorders can be associated with ASD. Subjects and methods: We performed a retrospective case-control study in child psychiatry clinics, involving 51 children with ASD and 40 typical development controls (TDC). Results: We found a correlation between children being breastfed for less than 6 months, having fathers more than 40 years old at childbirth in ASD compared to TDC group. Our study also associated low blood cholesterol and low erythrocyte magnesium levels with increased risk for ASD. Conclusion: Findings support the implication of total cholesterol (TC) and erythrocyte magnesium level in defining autism outcome.

The status of chemical elements in the blood plasma of children with autism spectrum disorder in Tunisia: a case-control study.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders defined by a deficit in social interactions and the presence of restricted and stereotypical behaviors or interests. The etiologies of autism remain mostly unknown. Many genetic and environmental factors have been suspected. Among these environmental factors, exposure to several chemical elements has been previously studied. The purpose of this study was to compare the levels of trace elements in the blood plasma of children with ASD with typically developed children (TDC). The participants in this study consisted of 89 children with ASD (14 girls and 74 boys) and 70 TD children (29 girls and 41 boys). The levels of 33 chemical elements have been analyzed by inductively coupled plasma spectrometry (ICP-MS). We detected significant differences in the levels of eight elements between the two groups, among which there were three rare earth elements (REEs): Eu, Pr, and Sc (p = 0.000, p = 0.023, and p < 0.001 respectively); four heavy metals: Bi, Tl, Ti, and V (p = 0.004, p < 0.001, p = 0.001, and p = 0.001 respectively); and one essential element: Cu (p = 0.043). Children with ASD had higher levels of Er, Pr, Sc, Bi, Tl, Ti, and V, and lower levels of Cu in comparison with the TD group. The children exposed to passive smoking had lower levels of lead (Pb) compared with children without exposure (p = 0.018). Four elements (Cr, Er, Dy, and Pr) were negatively correlated to the severity of ASD. The level of Cu was significantly associated with autistic children's behavior (p = 0.014). These results suggest that children with ASD might have abnormal plasma levels of certain chemical elements (including Er, Pr, Sc, Bi, Tl, Ti, and V, and Cu), and some of these elements might be associated with certain clinical features.

Novel MED12 variant in a multiplex Fragile X syndrome family: dual molecular etiology of two X-linked intellectual disabilities with autism in the same family.

Studies of X-linked pedigrees were the first to identify genes implicated in intellectual disability (ID) and autism spectrum disorder (ASD). However, some pedigrees present a huge clinical variability between the affected members. This intrafamilial heterogeneity may be due to cooccurrence of two disorders. In the present study, we describe a multiplex X-linked pedigree in which three siblings have ID, ASD and dysmorphic features but with variable severity. Through Fragile X syndrome test, we identified the full FMR1 mutation in only two males. Whole exome sequencing allowed us to identify a novel hemizygous variant (p.Gln2080_Gln2083del) in MED12 gene in two males. So, the first patient has FXS, the second has both FMR1 and MED12 mutations while the third has only the MED12 variant. MED12 mutations are implicated in several forms of X-linked ID. Family segregation and genotype-phenotype-correlation were in favor of a cooccurrence of two forms of X-linked ID. Our work provides further evidence of the involvement of MED12 in XLID. Moreover, through these results, it is noteworthy to raise awareness that intrafamilial heterogeneity in FXS multiplex families could result from the cooccurrence of multiple clinical entities involving at least two separate genetic loci. This should be taken into consideration for genetic testing and counselling in patients/families with atypical disease symptoms.

Suicidal ideation and suicide attempts among Tunisian adolescents: prevalence and associated factors.

INTRODUCTION: Studies directed on suicidal behavior in North African adolescents are rare. This study was conducted to estimate the prevalence of suicidal thoughts and attempts among high school students in Tunisia and to determine factors associated with this suicidal behavior. METHODS: This is an analytical cross-sectional study composed of a population containing 821 high school students obtained through cluster sampling. The participants completed a pre-established form related to socio-demographic characteristics and anxiety symptoms, the Suicide Behavior Questionnaire-Revised, the Beck depression scale, and the Rosenberg self-esteem scale. RESULTS: The mean age of the adolescents was 17.7±0.97 years. Prevalence of suicidal behavior was 26.9% for brief passing suicidal thoughts, 9.6% for serious suicidal thoughts, and 7.3% for suicide attempts. Six determining factors of suicidal behavior were found: female gender (OR=2.56 (1.32-4.95); p= 0.005), personal history of depression (OR=2.29 (1.38-3.80); p=0.001), tobacco smoking (OR=3.59 (1.61-8.01); p=0.002), current depression symptoms (OR=5.50 (2.14-14.11); p<0.001), history of non-suicidal self-injurious behavior (OR= 3.16 (2.05-4.86); p<0.001), and low self-esteem (OR=2.74 (1.71-4.38); p<0.001). CONCLUSION: Suicidal ideation and attempts are frequent among Tunisian adolescents and represent a serious public health problem. An urgent national prevention program is required.

ADHD in Tunisian Adolescents: Prevalence and Associated Factors.

OBJECTIVE: The aims of the study were to determine the prevalence of ADHD in a population of high school students and to explore the factors associated with this disorder. METHOD: This was a cross-sectional study that had included 447 high school students. The diagnosis of ADHD was made by the Adult ADHD Self-Report Scale translated in Arabic language. The sociodemographic and clinical characteristics were evaluated by a preestablished questionnaire. The self-esteem was assessed by the Rosenberg Self-Esteem Scale. RESULTS: The prevalence of ADHD was 18.1%. The logistic regression analysis showed an association between the diagnosis of ADHD and the bad relationships with parents (odds ratio [OR] = 16.43; p < 10-3), the presence of personal psychiatric antecedents (OR = 12.16; p < 10-3), internet misuse (OR = 2.39; p = .014), and maltreatment antecedents (OR = 3.16; p = .009). CONCLUSION: The prevalence of ADHD in this study was one of the highest prevalence reported. The factors associated with ADHD may have diagnostic and therapeutic implications.

[Prevalence of specific learning disorders in a cohort of children with school failure]. / Prévalence des troubles spécifiques des apprentissages dans une cohort d'enfants en difficultiés scolaries.

BACKGROUND: Specific learning disorders (SLD) are poorly known and studied in Tunisia. A National research project on their prevalence was launched recently. Aim of this study was to estimate prevalence of SLD in a cohort of children with school failure. METHODS: Cross-sectional descriptive study with a population of 287 First and Third grade Primary School students, screened by their teachers as facing learning problems through a systematic screening process based on achievement and behavior. Multidisciplinary assessment consisted in general medical examination, child psychiatry, child neurology, speech therapy and psychology (cognitive). 180 students have been assessed. RESULTS: Prevalence of SLD over study population was 32%, which gives a general population prevalence 6.4%. Most common SLDs were dyslexia and dyscalculia. Most of children with SLD came from disadvantaged social groups. CONCLUSION: Despite methodological limitations, this first study on SLD sheds some light on their prevalence in Tunisian students, and opens perspectives for future more focused studies and interventions for their management in Tunisia.