Autism spectrum disorder and Coffin-Siris syndrome-Case report.

Introduction: Autism spectrum disorders (ASDs) are a group of developmental disorders characterized by deficits in social communicative skills and the occurrence of repetitive and/or stereotyped behaviors. Coffin-Siris syndrome (CSS) is classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degrees, distinctive facial features, hypotonia, hirsutism/hypertrichosis, and sparse scalp hair. In this study, we present a detailed description of autistic traits in a boy diagnosed with CSS and further discuss their genetic backgrounds. Case description: An 8-year-old boy with ASD, congenital anomalies, and neurological problems had been diagnosed with Coffin-Siris syndrome after genetic testing. Genetic testing revealed a heterozygous de novo pathogenic variant (class 5) c.1638_1647del in the ARID1B gene that is causative of Coffin-Siris syndrome but also other intellectual disability (ID)-related disorders, including autism. Tests that preceded the diagnoses, as well as congenital anomalies and developmental issues, were further described in an attempt to better present his phenotype. Conclusion: Both autism and ARID1B-related disorders are on a spectrum. This report points out the importance and necessity of further research regarding the genetic backgrounds of these disorders to understand their complex etiology.

Internal Consistency of the Serbian Translation of the Stanford Social Dimensions Scale and Association to Strengths and Difficulties Questionnaire Scores in Male and Female Individuals on the Autism Spectrum and Non-autistic Individuals.

We aimed to evaluate the internal consistency of Stanford Social Dimensions Scale (SSDS) translated to Serbian and to test it against the Strengths and Difficulties Questionnaire (SDQ). The sample consisted of 200 patients (32% ASD) of the Institute of Mental Health in Belgrade, Serbia (68 females, 132 males, Mage=9.61, SDage=4.06). Internal consistency coefficients were within good/acceptable range for Social Motivation, Affiliation, Recognition and Unusual Approach subscales and below acceptable for Expressive Social Communication subscale. The non-autistic group scored higher on all subscales compared to the ASD group. All SSDS subscales positively correlated with SDQ Prosocial Behaviors scale. The SSDS is a valuable instrument for accessing sociobehavioral phenotype in both individuals on the autism spectrum and non-autistic individuals.

How are parental practices and attitudes towards corporal punishment related to child academic, developmental, or psychological-emotional dysfunctioning?

Corporal punishment (CP) is a widely spread disciplining practice among parents and caregivers globally. Our paper aimed to explore the relationship between the parental attitudes towards CP, expected outcomes of CP, and parenting practices on one hand, with the reported dysfunctions of their children, on the other. Additionally, we aimed to explore the relationship between the use of CP and the reported academic, developmental, and psychological-emotional dysfunctions of their children. The present study involved a nationally representative sample of 1186 parents in Serbia, who had at least one child aged 0-18 years at the moment of interviewing. The parents filled out a series of questionnaires on their attitudes towards CP, expectations of CP outcomes, and their parental practices. Findings indicate that parents that report having a child with dysfunctions have positive attitudes towards CP and expect positive outcomes of CP. These parents also report using more CP as a disciplining method, as well as other harsh disciplining practices. We also identified parental positive expectations of CP, use of physical assault, psychological aggression, neglect as significant predictors of reported child dysfunctions severity. Having all the results in mind, we can assume that children with health-related and school-related issues might be at potential risk of further maltreatment.

Positive Effects of the Caregiver Skill Training Program on Children With Developmental Disabilities: Experiences From Serbia.

Background: Intervention programs for children with developmental disabilities increasingly target caregiver training to implement effective strategies for child development. Research conducted in different countries shows that the Caregiver Skills Training Program (CST) developed by the World Health Organization and Autism Speaks could also be a recommended intervention. Methods: The pre-pilot phase included seven, and the pilot phase included 29 families of children with developmental disabilities trained to implement the intervention program. The caregivers were asked to complete the Autism Treatment Evaluation Checklist at the beginning and at the end of the program. Results: In the pre-pilot phase, the Wilcoxon signed-rank test determined a statistically significant improvement in Speech, Language and Communication (z = -2.99, p < 0.05) and Health/Physical/Behavior (z = -2.375, p < 0.05) after caregiver participation in the training program. In the pilot phase, the paired t-test also determined a statistically significant improvement in Speech, Language and Communication between the first (M = 24.52, SD = 5.57) and the second testing (M = 25.66, SD = 6.11), t(28) = -2.29, p < 0.05, as well as a significant improvement between the first (M = 36.62; SD = 7.15) and the second testing (M = 35.38; SD = 5.91), t(28) = 2.11, p < 0.05 in Health/Physical/Behavior. Eta squared values (0.16 and 0.14) indicate that the intervention effect was significant. No differences were determined in Sociability and Sensory/Cognitive Awareness between the first and the second testing. Conclusion: The initial results of the Caregiver Skills Training Program are encouraging. For this program to be recommended as an evidence-based intervention, further research should be conducted on larger samples, controlling possible intervening variables.

Mental Health, Alcohol and Substance Use of Refugee Youth.

This study aims to explore the prevalence of alcohol and substance use among young refugees along with the indicators of experienced psychological difficulties. It is based on a sample of 184 children and adolescents aged 11-18 years old, residing at two refugee centers in the Republic of Serbia. Out of 184 participants, the majority was male (N = 155; 84.29%). More than a half of participants (53.3%) displayed significant symptoms of PTSD. 50% consume energy drinks, 28% use tobacco; 13% use alcohol; 4.6% use marijuana; 1.7% use LSD, amphetamines, glue, tranquilizers and cocaine. Female respondents were more frequently expressing emotional difficulties (p < 0.05) while male participants were more frequent users of alcohol or substances (p < 0.01). Younger children were more frequently expressing symptoms of hyperactivity and prosocial behavior, while they were less frequently using substances. There is also a significant negative correlation between the years of education and individual proneness to substance use. Furthermore, those who resided in a greater number of refugee camps were found to experience greater levels of emotional and behavioral difficulties and face a greater risk of physical abuse. The burden of migration increases proneness to substance use, as a consequence of scarce coping resources and the stress of adjusting. Migrants are vulnerable to substance use, since some of them have commonly witnessed and/or personally experienced pre-and post-migration stress and trauma, including loss of homes and livelihoods, violence, torture and family separation. Preventive programs need to focus on the problem of alcohol and substance use among this vulnerable population.

Mental health in the second year of the COVID-19 pandemic: protocol for a nationally representative multilevel survey in Serbia.

INTRODUCTION: The COVID-19 pandemic is likely to have a prolonged impact on mental health (MH); however, the long-term MH effects of the COVID-19 pandemic remain unknown. The Serbian national survey-CoV2Soul.RS-was launched to document the MH status of the Serbian population following the COVID-19 pandemic and to contribute to an international evidence base about MH prevalence rates during different phases of the pandemic. METHODS AND ANALYSIS: This cross-sectional study was designed to collect a nationally representative sample (N=1200; age 18-65 years; estimated start/end-June/November 2021) using multistage probabilistic household sampling. Trained staff will conduct in-person diagnostic interviews. A battery of self-report instruments will be administered to assess the quality of life (QoL), general distress and associated protective and harmful psychological and societal factors. Analyses will be conducted to delineate the prevalence rates of MH disorders, how MH conditions and QoL vary with respect to sociodemographic variables, personality, health status and traumatic events during the COVID-19 pandemic, and to test how these relations depend on geographical region. Moreover, this study was designed to explore mechanisms linking personality and the perception of pandemic consequences and associated distress. Prevalence rates of MH disorders will be calculated using descriptive statistics. For additional analyses, we will use correlations, analysis of variance and regression analyses. The hierarchical structure of the data will be explored using multilevel random coefficient modelling. Structural equation modelling will be used to investigate the indirect effects of personality on distress through relevant variables. ETHICS AND DISSEMINATION: Ethical Committees of the Faculty of Medicine (1322-VII/31) and Faculty of Philosophy in Belgrade (02-33/273) and Faculty of Philosophy in Novi Sad (05-27, br.893/1) approved the protocol. Only respondents able to provide informed consent will participate in the study. Research reports will be submitted to peer-reviewed journals and the results will be placed on the website www.cov2soul.rs to be available to funders, researchers, policy-makers and interested laypeople, and will be advertised through social media. TRIAL REGISTRATION NUMBER: NCT04896983.

Determinants of quality of life among individuals seeking mental health care after termination of state of emergency due to the coronavirus disease 2019 pandemic.

ABSTRACT: Prompted by the need to measure the impact of the coronavirus disease 2019 on main areas of quality of life related to mental health (MH), the COV-19-impact on quality of life (COV19-QoL) scale has been developed recently. We measured how patients seeking face-to-face MH care perceived the coronavirus disease 2019 impact on QoL and how socio-demographic factors, stress, and personality contributed to QoL in this diagnostically diverse population.Patients aged 18 to 65 years (n = 251) who came for the first time to the outpatient units during the 6-week index-period (May 21-July 1, 2020) were included. The cross-sectional assessment involved sociodemographic variables, working diagnosis, personality traits (7-dimension model, including HEXACO and DELTA), stress (list of threatening experiences and proximity to virus), and COV19-QoL.The perceived impact of the pandemic on QoL was above the theoretical mean of a 5-point scale (COV19-Qol = 3.1 ±â€Š1.2). No association between total COV19-QoL score, sociodemographic parameters, and working diagnoses was found in the present sample. After testing whether positional (threatening experiences), or dispositional (personality) factors were predominant in the perceived impact of COV-19 on QoL, significant predictors of the outcome were personality traits Disintegration (B = 0.52; P < .01) and Emotionality (B = 0.18; P < .05).It seems that pervasiveness and uncertainty of the pandemic threat triggers-especially in those high on Disintegration trait-a chain of mental events with the decrease of QoL as a final result. Present findings could be used to establish a profile of MH help seeking population in relation to this biological disaster, and to further explore QoL and personality in different contexts.

Glutathione S-Transferase Polymorphisms and Clinical Characteristics in Autism Spectrum Disorders.

Background: Autism spectrum disorders (ASD) are a heterogeneous group of developmental disorders, with different levels of symptoms, functioning, and comorbidities. Recent findings suggested that oxidative stress and genetic variability in glutathione S-transferases (GSTs) might increase the risk of ASD development. We aimed to determine whether GST polymorphisms influence the severity of symptoms as well as the cognitive and adaptive abilities in children with ASD. Methods: The sample included 113 ASD cases. All participants were genotyped for GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms. The clinical characteristics were determined with Autism Diagnostic Interview-Revised (ADI-R) in all of the participants. In non-verbal participants, we explored the adaptive functioning using the Vineland Adaptive Behavior Scale II, while in verbal participants, we used the Wechsler Abbreviated Scale of Intelligence (WASI). Results: It was shown that the GSTA1 * CC genotype was a predictor of a lower non-verbal communication impairment as well as of a lower chance of having seizures during life. GSTM1-active genotype predicted a higher adaptive functioning. The predictive effect of GSTA1, GSTM1, and GSTT1 genotype was moderated by exposure during pregnancy (maternal smoking and medication). The GSTP1 * IleIle genotype was significantly associated to a better cognitive functioning in children with ASD. Conclusion: Besides the complex gene-environment interaction for the specific risk of developing ASD, there is also a possible complexity of interactions between genetic and environmental factors influencing the level of symptoms and impairment in people with ASD. Detoxification and antioxidant enzymes, such as GSTA1, might contribute to the core of this complexity.

A Genetics-First Approach to Dissecting the Heterogeneity of Autism: Phenotypic Comparison of Autism Risk Copy Number Variants.

OBJECTIVE: Certain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships. METHODS: This international study included 547 individuals (mean age, 12.3 years [SD=4.2], 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years [SD=4.9], 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview-Revised and IQ testing. RESULTS: The four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%-97% of the variance, depending on the trait), whereas variability between groups was low (1%-21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits. CONCLUSIONS: Many CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant.

Dopamine in Autism Spectrum Disorders-Focus on D2/D3 Partial Agonists and Their Possible Use in Treatment.

Autism spectrum disorders (ASD) are a group of disorders characterized by impairment in social communication and repetitive and stereotyped behaviors. ASD etiology is very complex, including the effect of both genetic and environmental factors. So far, no specific treatment for the core symptoms of ASD has been developed, although attempts have been made for the treatment of repetitive behavior. The pharmacological treatment is aimed at treating non-specific symptoms such as irritability and aggression. Recent studies pointed out to the possible role of altered dopamine signaling in mesocorticolimbic and nigrostriatal circuits in ASD. In addition, several research pointed out to the association of dopamine receptors polymorphism and ASD, specifically repetitive and stereotyped behavior. In this paper, we will provide a review of the studies regarding dopamine signaling in ASD, existing data on the effects of D2/D3 partial agonists in ASD, possible implications regarding their individual receptor profiles, and future perspectives of their possible use in ASD treatment.

Autism Spectrum Disorders and Perinatal Complications-Is Oxidative Stress the Connection?

Background: Autism spectrum disorders (ASD) are complex psychiatric disorders, with gene environment interaction being in the basis of their etiology. The association of perinatal complications and ASD is well established. Recent findings suggested that oxidative stress and polymorphism in genes encoding antioxidant enzymes might be involved in the development of ASD. Glutathione transferases (GSTs) have an important role in the antioxidant defense system. We aimed to establish whether the predictive effects of prenatal and perinatal complications (as possible oxidative stress inducers) on ASD risk are dependent on GST polymorphisms. Methods: The study included 113 ASD cases and 114 age- and sex group-matched healthy controls. All participants were genotyped for GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms. The questionnaire regarding prenatal and perinatal risk factors and complications was administered for all the subjects in the study. Results: The evaluated perinatal complications as a group significantly increased the risk of ASD [odds ratio (OR) = 9.415; p = 0.000], as well as individual perinatal complications, such as prematurity (OR = 11.42; p = 0.001), neonatal jaundice (OR = 8.774; p = 0.000), respiratory distress syndrome (OR = 4.835; p = 0.047), and the use of any medication during pregnancy (OR = 2.413; p = 0.03). In logistic regression model, adding GST genotypes did not modify the significant effects found for prematurity and neonatal jaundice as risk factors in ASD. However, there was a significant interaction of GST genotype with medication use during pregnancy and the use of tocolytics during pregnancy, which was predictive of ASD risk only in carriers of GSTM1-null, as opposed to carriers of GSTM1-active genotype. Conclusion: Specific perinatal complications may be significant risk factors for ASD. GSTM1 genotype may serve as a moderator of the effect of some prenatal factors on the risk of ASD such as using medication during pregnancy. It may be speculated that different oxidative stress-related genetic and environmental factors could lead to development of ASD. Apart from etiological mechanisms, possible therapeutic implications in ASD are also discussed.

Interaction of glutathione S-transferase polymorphisms and tobacco smoking during pregnancy in susceptibility to autism spectrum disorders.

Autism spectrum disorders (ASD) are a group of complex psychiatric disorders, with a proposed gene-environment interaction in their etiology. One mechanism that could explain both the genetic and environmental component is oxidative stress. The aim of our study was to investigate the potential role of common polymorphisms in genes for glutathione transferase A1, M1, T1 and P1 in susceptibility to ASD. We also aimed to explore the possible oxidative stress - specific gene-environment interaction, regarding GST polymorphisms, maternal smoking tobacco during pregnancy (TSDP) and the risk of ASD. This case-control study included 113 children with ASD and 114 age and sex-matched controls. The diagnosis was made based on ICD-10 criteria and verified by Autism Diagnostic Interview - Revised (ADI-R). We investigated GSTA1, GSTM1, GSTP1 and GSTT1 genotypes and explored their individual and combined effects in individuals with ASD. Individual effect of GST genotypes was shown for GSTM1 active genotype decreasing the risk of ASD (OR = 0.554, 95%CI: 0.313-0.983, p = 0.044), and for GSTA1 CC genotype, increasing susceptibility to ASD (OR = 4.132, 95%CI: 1.219-14.012, p = 0.023); the significance was lost when genotype-genotype interactions were added into the logistic regression model. The combination of GSTM1 active and GSTT1 active genotype decreased the risk of ASD (OR = 0.126, 95%CI: 0.029-0.547, p = 0.006), as well as combination of GSTT1 active and GSTP1 llelle (OR = 0.170, 95%CI: 0.029-0.992, p = 0.049). Increased risk of ASD was observed if combination of GSTM1 active and GSTP1 llelle was present (OR = 11.088, 95%CI: 1.745-70.456, p = 0.011). The effect of TSDP was not significant for the risk of ASD, neither individually, nor in interaction with specific GST genotypes. Specific combination of GST genotypes might be associated with susceptibility to ASD, while it appears that maternal smoking during pregnancy does not increase the risk of ASD.

Epilepsy and interictal epileptiform activity in patients with autism spectrum disorders.

PURPOSE: The purpose of this study was to determine the prevalence of epilepsy and subclinical epileptiform abnormalities in children with autism spectrum disorder (ASD), and to investigate its effects on core autistic symptoms and adaptive behavior skills. METHODS: Patients with diagnosis of ASD who met full criteria on Autism Diagnostic Interview-Revised (ADI-R) were included in the study. Adaptive behavior skills were assessed by Vineland Adaptive Behavior Scale-II (VABS-II). Clinical assessment for epilepsy and video electroencephalography (EEG) (v-EEG) examinations during wakefulness and/or sleep were prospectively performed in all patients. RESULTS: A total of 112 patients with diagnosis of ASD of mean age 6.58 ±â€¯3.72 were included in the study. Based on clinical and v-EEG assessments, three groups of patients were defined: 1) patients with epilepsy (n = 17; 15.2%); 2) patients with epileptiform discharges in absence of clinical seizures (n = 14; 12.5%); 3) patients without epilepsy and without epileptiform discharges (n = 81; 72.3%). There were no significant differences between three groups of patients on ADI-R subscores. Speech development was also not significantly related to epilepsy. There was a slight tendency of the VABS-II motor skills score to be higher in the group of patients with autism without clinical diagnosis of epilepsy and without subclinical epileptiform discharges (p < 0.05) in comparison with the two other groups. According to this tendency, we might claim that patients with higher scores on motor skills could have 0.88 times lower odds for having epileptiform EEG activity. CONCLUSIONS: According to our results, we were not able to detect differences in the ADI-R between the three populations with ASD, all with unknown etiology. Epilepsy, as well as subclinical epileptic discharges, showed small effects on Motor Skills in patients with autism, and had no effect on adaptive behavior Communication/Socialization/Daily Living Skills.

Perceptions on Support, Challenges and Needs among Parents of Children with Autism: the Serbian Experience.

BACKGROUND: Autism spectrum disorders (ASD) significantly impact lives of affected individuals and their families. They confront daunting challenges and multiple demands in their daily life, when compared to parents of children with other disabilities or parents of typically developing children. SUBJECTS AND METHODS: Participants completed The Caregiver Needs Survey, the survey intended for parents or primary caregivers of children with a diagnosis of ASD. During the study, 231 parents were interviewed; 167 mothers and 64 fathers. Parents were recruited from the patient database comprised of families from the two largest cities in Serbia. All of them were contacted before the study, either via phone or at the child's regular check-in visit. RESULTS: Over 90 percent of the parents reported that additional support at schools, home, and improved relationships with service providers are necessary and important. The most important challenges related to care were child's communication difficulties, social interaction difficulties, and problems with daily living skills. The significant predictors of lower overall satisfaction were parent's higher education, having a first concern related to problems of the child's interaction with others or playing alone, and parent frustration with accessing services in the past 12 months. Greater overall satisfaction, on the other hand, was related to having an in-school tutor training or assistance in managing child's needs or implementing treatments, and having primary care doctor or pediatrician as a source of information on autism. CONCLUSIONS: Future efforts to develop ASD-related policies and services should also take the following into consideration: the low level of awareness among caregivers and health care providers about the early signs of autism; disparities in access to services; educational problems and significant levels of dissatisfaction with the overall care and stigma.