Genetic and molecular biology of autism spectrum disorder among Middle East population: a review.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disease, characterized by impaired social communication, executive dysfunction, and abnormal perceptual processing. It is more frequent among males. All of these clinical manifestations are associated with atypical neural development. Various genetic and environmental risk factors are involved in the etiology of autism. Genetic assessment is essential for the early detection and intervention which can improve social communications and reduce abnormal behaviors. Although, there is a noticeable ASD incidence in Middle East countries, there is still a lack of knowledge about the genetic and molecular biology of ASD among this population to introduce efficient diagnostic and prognostic methods. MAIN BODY: In the present review, we have summarized all of the genes which have been associated with ASD progression among Middle East population. We have also categorized the reported genes based on their cell and molecular functions. CONCLUSIONS: This review clarifies the genetic and molecular biology of ASD among Middle East population and paves the way of introducing an efficient population based panel of genetic markers for the early detection and management of ASD in Middle East countries.

A Preliminary Epidemiologic Study of Social (Pragmatic) Communication Disorder Relative to Autism Spectrum Disorder and Developmental Disability Without Social Communication Deficits.

The goal of this preliminary investigation was to compare demographic and clinical characteristics in a sample of children with likely Social (Pragmatic) Communication Disorder (SCD) (N = 117) to those in children with possible (N = 118) and some (N = 126) SCD traits, other developmental delay (DD) (N = 91) and autism spectrum disorder (ASD) (N = 642). We used data from the Study to Explore Early Development (SEED), a multi-site case-control study. Items reflecting SCD DSM-5 criteria were selected from an autism diagnostic measure, with SCD categories identified by creating quartiles. Our results suggest that SCD may fall along a continuum involving elevated deficits (in comparison to DD with no SCD) in social communication and restricted and repetitive behavior that do not reach the clinical threshold for ASD.

Pragmatic language dysfunction in systemic lupus erythematosus patients: Results from a single center Italian study.

BACKGROUND: Cognitive impairment (CI) in systemic lupus erythematosus (SLE) is a frequent neuropsychiatric manifestation affecting several domains, even in apparently asymptomatic patients. Current research revealed that the typical CI pattern affects frontal-subcortical circuit and thus executive functions. The impairment of non-literal language or pragmatic language (PL), including metaphors, idioms, inferences or irony has been well described in several conditions such as autism disorders, Parkinson's disease, brain injury and even in earlier phases of neurodegenerative processes. Even if PL neuro-anatomy remains controversial, correlation between executive dysfunctions and non-literal language involvement has been reported both in traumatic injury and mild cognitive impairment patients. Nonetheless, no specific study has been performed to evaluate PL impairment in SLE patients so far. OBJECTIVES: We aimed at assessing the PL domain in a Italian monocentric SLE cohort in comparison to healthy controls, matched to age and education, through a specific battery, the batteria sul linguaggio dell'emisfero destro (BLED). Secondly, we focused attention on possible correlations between CI and clinical and laboratory SLE-related features. METHODS: Forty adult patients affected by SLE, according to the American College of Rheumatology (ACR) criteria, and thirty healthy subjects were enrolled consecutively in this cross-sectional study. The protocol included complete physical examination, extensive clinical and laboratory data collection (comprehensive of demographics, past medical history, co-morbidities, disease activity, chronic damage evaluation, previous and concomitant treatments) and cognitive assessment for five different domains: memory, attention, pragmatic language, executive and visuospatial functions. Self-reported scale for anxiety and depression were performed to exclude the influence of mood disorders on cognitive dysfunction. RESULTS: We studied 40 Caucasian SLE patients [male (M)/ female (F) 3/37; mean±standard deviation (SD) age 45.9±10.1 years, mean±SD disease duration 120.8±81.2 months] and 30 healthy subjects (M/F 9/21; mean±SD age 41.3±13 years). According to the low level of disease activity and damage (mean±SD Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 1.3±2.3, mean±SD Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI) of 0.2±0.5), only 30% of patients was on glucocorticoid treatment at the study entry. PL was the most compromised domain in terms of Mean Domain Z scores. As for the Domain Cognitive Dysfunction score, a deficit of PL was observed in 45% of patients and was significantly more prevalent than memory, executive and visuospatial functions impairment (P = 0.0002, P = 0.0002 and P<0.000001, respectively). According to Global Cognitive Dysfunction score, 25% of patients experienced a mild impairment and 7.5% a moderate one. Anti-phospholipid antibodies positivity was significantly associated with memory impairment (P<0.0005), whereas the presence of other neuropsychiatric events was associated with executive dysfunctions (P<0.05); no further significant association nor correlation were identified. CONCLUSION: In this study we evaluated for the first time PL in SLE patients finding a dysfunction in almost half of patients. The dysfunction of PL was significantly more frequent than the other domains assessed.

Predictors of Pragmatic Communication in School-Age Siblings of Children with ASD and Low-Risk Controls.

Little empirical evidence exists about school-age pragmatic communication or predictors in siblings at heightened familial risk for ASD (HR) and low-risk (LR) controls. The Pragmatic Rating Scale-School-Age (Landa unpublished) was scored for 49 HR siblings and 18 LR controls at 8-12 years. Social-communication and language measures were collected between 14 and 36 months. At 36-months, siblings were classified as ASD (HR-ASD, n = 15), broad autism phenotype (HR-BAP, n = 19), or typically developing (HR-TD, n = 15). Results revealed a pragmatic continuum with significantly better scores for HR-TD than HR-BAP or HR-ASD, and HR-BAP than HR-ASD. Per regression models including all participants, 14-month joint attention initiations predicted school-age pragmatic communication, as did 24-month social-communication and expressive language scores. Early joint attention, social-communication, and language abilities contribute to later pragmatic functioning.

Co-occurrence of communication disorder and psychiatric disorders in maltreated children and adolescents: relationship with global functioning

Objective: To study the co-occurrence of psychiatric disorders (PD) and communication disorders (CD) and their relationship with global functioning in maltreated children and adolescents. Methods: The sample comprised 143 maltreated children and adolescents (55.8% male). All underwent clinical communication and psychiatric evaluations, as well as global functioning assessment using the Children’s Global Assessment Scale (C-GAS). Results: Four groups emerged from evaluation: Group 1 (n=7, 4.9%) did not exhibit any disorders; Group 2 (n=26, 18.2%) exhibited PD; Group 3 (n=34, 23.8%) exhibited CD; and Group 4 (n=76, 53.1%) exhibited both PD and CD on evaluation. Significant differences in global functioning scores were found between G1 and G2, G1 and G4, G2 and G4, and G3 and G4, with the highest C-GAS scores found in G1 and the lowest in G4. Conclusion: Rates of PD and CD are high in this maltreated population. The presence of PD has a major impact on C-GAS score, and the simultaneous presence of CD increases the already impaired function of PD. Demonstration of the additive effects of PD and CD on youth functioning suggests that professionals should be alert to the presence of both disorders to better act preventively and therapeutically in a high-risk population.

Co-occurrence of communication disorder and psychiatric disorders in maltreated children and adolescents: relationship with global functioning.

OBJECTIVE: To study the co-occurrence of psychiatric disorders (PD) and communication disorders (CD) and their relationship with global functioning in maltreated children and adolescents. METHODS: The sample comprised 143 maltreated children and adolescents (55.8% male). All underwent clinical communication and psychiatric evaluations, as well as global functioning assessment using the Children's Global Assessment Scale (C-GAS). RESULTS: Four groups emerged from evaluation: Group 1 (n=7, 4.9%) did not exhibit any disorders; Group 2 (n=26, 18.2%) exhibited PD; Group 3 (n=34, 23.8%) exhibited CD; and Group 4 (n=76, 53.1%) exhibited both PD and CD on evaluation. Significant differences in global functioning scores were found between G1 and G2, G1 and G4, G2 and G4, and G3 and G4, with the highest C-GAS scores found in G1 and the lowest in G4. CONCLUSION: Rates of PD and CD are high in this maltreated population. The presence of PD has a major impact on C-GAS score, and the simultaneous presence of CD increases the already impaired function of PD. Demonstration of the additive effects of PD and CD on youth functioning suggests that professionals should be alert to the presence of both disorders to better act preventively and therapeutically in a high-risk population.

Family history interview of a broad phenotype in specific language impairment and matched controls.

The aim was to study a broader phenotype of language-related diagnoses and problems in three generations of relatives of children with specific language impairment (SLI). Our study is based on a family history interview of the parents of 59 children with SLI and of 100 matched control children, exploring the prevalence of problems related to language, reading, attention, school achievement and social communication as well as diagnoses such as attention-deficit hyperactivity disorder (ADHD), autism, Asperger syndrome, dyslexia, mental retardation, cleft palate and stuttering. The results show a spectrum of language-related problems in families of SLI children. In all three generations of SLI relatives, we found significantly higher prevalence rates of language, literacy and social communication problems. The risk of one or both parents having language-related diagnoses or problems was approximately six times higher for the children with SLI (85%) than for the control children (13%) (odds ratio = 37.2). We did not find a significantly higher prevalence of the diagnoses ADHD, autism or Asperger syndrome in the relatives of the children with SLI. However, significantly more parents of the children with SLI had problems with attention/hyperactivity when compared with the parents of controls. Our findings suggest common underlying mechanisms for problems with language, literacy and social communication, and possibly also for attention/hyperactivity symptoms.