Investigating the increased risk of schizophrenia and bipolar disorders in relatives of ADHD probands using colocalization analysis of common genetic variants.

BACKGROUND: Relatives of ADHD probands are known to be at increased risk of schizophrenia and bipolar disorder, suggesting shared genetic factors. In this study, we aim to identify shared common risk variants (i.e., Single-Nucleotide Polymorphisms, SNPs) between ADHD and schizophrenia, and between ADHD and bipolar disorder. METHODS: With the summary data from three GWAS, one on ADHD (20,183 cases with ADHD and 35,191 controls), another on schizophrenia (76,755 cases with schizophrenia and 243,649 controls) and another on bipolar disorder (41,917 cases with bipolar disorder and 371,549 controls), we used colocalization analysis to identify SNPs shared by ADHD and schizophrenia, and SNPs shared by ADHD and bipolar disorder. Functional genomic analyses were then conducted on these two sets of shared common genetic variants. RESULTS: We found that three of the 12 SNPs associated with ADHD colocalized with schizophrenia SNPs and one of the 12 SNPs associated with ADHD colocalized with bipolar disorder. Only 0.4% of the SNPs associated with schizophrenia (2 out of 431) and 2.3% of the SNPs associated with bipolar disorder (2 out of 86), colocalized with ADHD SNPs. Some genes mapped to these shared genetic variants (SCN2A and UNC5D) are involved in the development of the nervous system. CONCLUSIONS: Using colocalization analysis, the present study uncovers shared genetic variants associated with ADHD and schizophrenia as well as ADHD and bipolar disorder, and may at least partially explain the increased risk of schizophrenia and bipolar disorder in relatives of ADHD probands.

Association of difficulties in motor skills with longitudinal changes in social skills in children with autism spectrum disorder: findings from the ELENA French Cohort.

Developmental coordination disorder is a frequently co-occurring condition with autism spectrum disorder (ASD). Several cross-sectional studies have reported that children with difficulties in motor skills have a higher severity of ASD symptoms. This study aims to examine the association of difficulties in motor skills with longitudinal changes in social skills in children with ASD. Participants were drawn from the ELENA cohort, a French longitudinal cohort of children with ASD. Motor skills were assessed using the Movement Assessment Battery for Children at baseline, while social skills were measured using the Autism Diagnostic Observation Schedule (ADOS-2) and the Vineland Adaptive Behavior Scales (VABS-II) at both the baseline and a follow-up assessment conducted 3 years later. A composite score of social skills was created at baseline and at both time points. Linear regression models were performed to assess the association between difficulties in motor skills and changes in social skills, considering potential confounders such as IQ, age, and gender. The sample included 162 children with ASD. Children with difficulties in global motor skills (N = 114) showed less favorable trajectories in social skills compared to those without motor difficulties. The results were consistent when examining the ADOS-2 and the VABS-II separately. This study provides evidence for the negative impact of difficulties in motor skills on the longitudinal development of social skills in children with ASD. Interventions targeting motor difficulties may have broader benefits, extending beyond motor function to improve socialization.

Barriers and facilitators to achieving employment in mainstream settings in adults with autism spectrum disorder without intellectual developmental disorders: A scoping review.

Autistic people without Intellectual Developmental Disorders (IDD) have a significantly lower employment rate compared to the general population even though employment favors social integration and quality of life. AIMS: To examine the barriers and facilitators to employability in mainstream settings for autistic adults without intellectual disability. METHODS: Following the scoping review guidelines, we searched the Cochrane, PubMed and PsycINFO databases for references published between 01/01/2000 to 01/08/2023. RESULTS: A review of the 44 identified articles suggests the existence of multiple individual and environmental factors influencing job access and retention. CONCLUSIONS: This is the first review to assess the facilitators and barriers to employment support for autistic people without intellectual disability. The results underline the need for studying strategies to promote access to employment and job retention for autistic people. Future research should explore the mediating and moderating factors leading to the improvement of employability of autistic people WIDD.

Predictors of an earlier diagnosis of Autism Spectrum Disorder in children and adolescents: a systematic review (1987-2017).

Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder in which the first signs generally emerge at approximately 12 months of age but its diagnosis is feasible only from the age of 18 months. According to the literature, the average age of diagnosis ranges from 2.7 to 7.2 years, which raises the question of factors associated with early diagnosis as a condition for early intervention. In this systematic review, we aim to identify clinical, social, and environmental factors associated with the age at which the diagnosis of ASD is confirmed in children. A literature search was performed in the Pubmed, Web of Sciences, PsycInfo, and Cochrane databases. Among the 530 publications identified, 50 were selected according to the inclusion criteria. This review focuses on studies conducted in 21 countries using data collected over a period from 1987 to 2017. These studies were published before December 31st, 2019. The results suggest that the diagnosis of ASD occurs earlier if there is a delay in social communication or the presence of intellectual disability. There is a low level of evidence concerning associations between the age at diagnosis and sex, race, parental education, or socioeconomic status and accessibility to health care. Further studies using large and well-characterized data sets are needed to simultaneously explore clinical and socio-environmental factors involved in early diagnosis.

Burnout among direct support workers of adults with autism spectrum disorder and intellectual disability.

BACKGROUND: Direct support workers (DSWs) accompany adults with autism spectrum disorder (ASD) and intellectual disability (ID) in residential care homes. Such DSWs, without specialised ASD training, are exposed to chronic stress linked to supporting ASD-ID clients and must adjust by coping strategies adapted to the needs of the residents. Nevertheless, difficulties adjusting constitute a burnout risk for DSWs, characterised by high levels of emotional exhaustion, depersonalisation and loss of a sense of personal accomplishment. We aimed to describe the burnout of DSWs who support adults with ASD-ID and to identify personal variables (experience and specialised training for ASD) and transactional variables (perceived stress and coping strategies) that could predict and mediate burnout. METHOD: In total, 125 DSWs accompanying ASD-ID adults on a daily basis were included. Each participant answered four questionnaires measuring burnout, sociodemographic and professional variables, coping strategies and perceived stress. RESULTS: Five per cent of DSWs were in a state of burnout. Eighteen, six and fifty-nine per cent showed high average scores of emotional exhaustion, depersonalisation and loss of a sense of personal accomplishment, respectively. Being older, specialised training in ASD, stress perceived as a challenge and problem-focused coping strategies were associated with low levels of depersonalisation and loss of a sense of personal accomplishment. CONCLUSIONS: Understanding the burnout process of ASD-ID DSWs may require the assessment of the organisational characteristics linked to the quality of life of the DSWs and the recognition of their specific needs when facing difficulties. The necessary ASD-focused training and support depends on an appraisal that would be individualised to adult ASD-ID DSWs.

Perceptions of parents of the impact of autism spectrum disorder on their quality of life and correlates: comparison between mothers and fathers.

PURPOSE: To compare mothers and fathers perceptions of the impact of autism spectrum disorder on their Quality of Life (QoL), we used the Parental-Developmental Disorders-Quality of Life scale (Par-DD-QoL). METHOD: The perception of QoL of mothers and fathers was compared for 130 pairs of parents of children with ASD and the associated variables were investigated. RESULTS: Mothers perceived a significantly greater impact of ASD on their QoL than fathers. Parents perceived a higher impact of ASD on global QoL when their child's adaptive skills were low and when the level of aberrant behaviors was high. More precisely, the perception of QoL by the mothers was negatively associated with their child's internalized disorders, whereas the perception of QoL by the fathers was negatively associated with their child's externalized disorders. Neither the mothers' nor the fathers' perception of the impact on QoL was associated with their children's age or the severity of their autistic symptoms. Some parental factors, such as being members of a family association, having benefited from training in ASD and having experienced a disruption in professional activity were associated with a greater impact on their QoL. CONCLUSION: Our finding that the perceived impact of ASD on QoL differed between mothers and fathers argues for individualized psychosocial support. Moreover, the strong correlation between the child's clinical characteristics and the perception by parents of a higher impact of ASD on QoL should be seen as red flag concerning the needs of the parents in terms of social and educational support. TRIAL REGISTRATION NUMBER: NCT02625116 (October 2015).

Group-based educational interventions in adolescents and young adults with ASD without ID: a systematic review focusing on the transition to adulthood.

There is a growing number of young people, diagnosed with an autism-spectrum disorder (ASD), transitioning to adulthood. Among this number, individuals without an intellectual disability have significant adaptive deficits and need individualized care and support services to better target vocational, social, and educational prospects and outcomes. Group-based interventions, including patient education, social-skills training, and cognitive-behavioral therapy, are widely used in clinical settings to improve the daily life and prospects of ASD individuals facing the challenge of transitioning to adulthood. We performed a systematic review of studies concerning the efficiency of group-based educational interventions with a focus on the transition to adulthood for young, ASD individuals without intellectual disability (ID). As a result of this systematic search, 21 studies out of 163 were found to be eligible for inclusion. We observed considerable heterogeneity across the studies, in terms of effect sizes and intervention design, delivery, and the comparison of controls. Strong evidence was found in favor of social-skills training and cognitive-behavioral therapy interventions. Professionals should consider group-based psychoeducational intervention to be an appropriate and relevant service for young subjects with ASD without ID transitioning to adulthood. Further research is needed on larger samples using multicentric designs to validate efficacy before generalization.

A longitudinal exploratory study of changes in sensory processing in children with ASD from the ELENA cohort.

Atypical sensory processing (SP) is a diagnostic criterion of autism spectrum disorder (ASD). However, little is known about its course during development. In this exploratory longitudinal study, we aimed to investigate the course of SP among children with ASD and identify clinical variables associated with changes. We used a subsample of 51 children with confirmed ASD, aged from 3 to 10 years, recruited from the ELENA cohort. SP was assessed using the Sensory Profile questionnaire at baseline and three years later. Our preliminary results highlight the heterogeneity of the evolution of SP during the children's development and the existence of three subgroups based on the course of SP (improvement, stable, and worsening). In addition, the children's adaptive skills and maladaptive behaviors were related to the course of SP. These results could be confirmed in future studies with a larger sample size using a longitudinal approach to capture individual variability in SP. In addition, our results highlight the importance of accounting for temporal changes in the sensory needs of individuals with ASD in clinical practice.

Sensory processing related to attention in children with ASD, ADHD, or typical development: results from the ELENA cohort.

Autism-spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are early neurodevelopmental conditions that share clinical characteristics, raising important issues in clinical diagnosis. We aimed to compare (1) sensory processing in four groups of children: ASD alone, ASD + ADHD, ADHD alone, and typical development (TD) and (2) the association between sensory processing and attention in the three groups with neurodevelopmental disorders. Our sample included 120 children aged from 6 to 12 years divided into four groups: ASD alone (N = 43), ASD + ADHD (N = 18), ADHD alone (N = 28), and TD (N = 31). Atypical sensory processing was more frequent in ASD and/or ADHD than in TD, without a significant difference between ASD and ADHD. However, the variance analysis of attention problems revealed differences between the ADHD and ASD groups. Thus, the rate of atypical sensory processing was comparable between the ASD and ADHD groups, suggesting that further studies are needed to explore atypical SP in all neurodevelopmental disorders.

Is there a dysbiosis in individuals with a neurodevelopmental disorder compared to controls over the course of development? A systematic review.

Many scientific papers reported that an unbalanced gut microbiota could lead to or worsen neurodevelopmental disorders (NDD). A dysbiosis may then be observed in the course of development and mark a dysfunction within what is called the gut-brain axis. The aim of this systematic review is to investigate potential evidence of dysbiosis in children and young adults with NDD compared to controls. Using the PRISMA guidelines we systematically reviewed studies that compared the gut microbiota in NDD participants (with an age inferior to thirty) to the gut microbiota of controls, regardless of the data analysis methods used. The MEDLINE, Scopus and PsycINFO databases were searched up to September 2018. 31 studies with a total sample size of 3002 ASD (Autism Spectrum Disorder) and 84 ADHD (Attention Deficit Hyperactivity Disorder) participants were included in this systematic review. Independent data extraction and quality assessment were conducted. The quality of the studies was rated from low to high. Population characterization and experimental methods were highly heterogeneous in terms of the data available, selection of criteria, and dysbiosis measurement. A dysbiosis was reported in 28 studies in terms of either diversity, bacterial composition or metabolome dysfunction. Due to heterogeneity, a quantitative synthesis was not applicable. In this paper, we discuss the different biases to understand the complexity of microbiota and neurodevelopmental disorders to provide leads for future cohort studies looking to answer the questions raised by the trillions of microorganisms that inhabit key body niches.

Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies.

With depression being the psychiatric disorder incurring the largest societal costs in developed countries, there is a need to gather evidence on the role of nutrition in depression, to help develop recommendations and guide future psychiatric health care. The aim of this systematic review was to synthesize the link between diet quality, measured using a range of predefined indices, and depressive outcomes. Medline, Embase and PsychInfo were searched up to 31st May 2018 for studies that examined adherence to a healthy diet in relation to depressive symptoms or clinical depression. Where possible, estimates were pooled using random effect meta-analysis with stratification by observational study design and dietary score. A total of 20 longitudinal and 21 cross-sectional studies were included. These studies utilized an array of dietary measures, including: different measures of adherence to the Mediterranean diet, the Healthy Eating Index (HEI) and Alternative HEI (AHEI), the Dietary Approaches to Stop Hypertension, and the Dietary Inflammatory Index. The most compelling evidence was found for the Mediterranean diet and incident depression, with a combined relative risk estimate of highest vs. lowest adherence category from four longitudinal studies of 0.67 (95% CI 0.55-0.82). A lower Dietary Inflammatory Index was also associated with lower depression incidence in four longitudinal studies (relative risk 0.76; 95% CI: 0.63-0.92). There were fewer longitudinal studies using other indices, but they and cross-sectional evidence also suggest an inverse association between healthy diet and depression (e.g., relative risk 0.65; 95% CI 0.50-0.84 for HEI/AHEI). To conclude, adhering to a healthy diet, in particular a traditional Mediterranean diet, or avoiding a pro-inflammatory diet appears to confer some protection against depression in observational studies. This provides a reasonable evidence base to assess the role of dietary interventions to prevent depression. This systematic review was registered in the PROSPERO International Prospective Register of Systematic Reviews under the number CRD42017080579.

Correction: Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies.

This article was originally published under standard licence, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the paper have been modified accordingly.

Associations between long-term adherence to healthy diet and recurrent depressive symptoms in Whitehall II Study.

PURPOSE: We examined whether long-term adherence to three diet quality scores-the Alternative Healthy Eating Index-2010 (AHEI-2010), Dietary Approach to Stop Hypertension (DASH) and  transformed-Mediterranean Diet Score (tMDS), Alternative Healthy Eating Index-2010 (AHEI-2010) and Dietary Approach to Stop Hypertension (DASH) is associated with the risk of recurrent depressive symptoms. METHODS: Analyses were conducted on a sample of 4949 men and women from the Whitehall II study. Diet scores were calculated using data collected from food frequency questionnaires repeated over 11 years of exposure (1991/1993-2002/2004). Recurrence of depressive symptoms was defined when participants reported at least two episodes of depressive symptoms (assessed by Center for Epidemiologic Studies Depression Scale and use of antidepressants) over the four phases of follow-up (2002/04-2015/16). RESULTS: After adjustment for potential cofounders, higher scores on AHEI-2010, DASH and tMDS at the end of the exposure period were associated with lower risk of recurrent depressive symptoms over the 13-year follow-up. Repeat measures of dietary history showed that participants who maintained a high AHEI-2010 score over the 11-year exposure period had a 19% (OR 0.81, 95% CI 0.65-1.00) lower odds of recurrent depressive symptoms compared to those who maintained a low AHEI score. Participants whose AHEI-2010 score decreased over time had a 1.34-fold increased odds (95% CI 1.02-1.75) of developing recurrent depressive symptoms compared to those maintaining a high AHEI-2010. No robust associations were observed for long-term tMDS and DASH. CONCLUSION: Our findings suggest that long-term adherence to healthy diet defined by Alternative Healthy Eating Index-2010 confers protection against recurrent depressive symptoms.

Pesticides used in Europe and autism spectrum disorder risk: can novel exposure hypotheses be formulated beyond organophosphates, organochlorines, pyrethroids and carbamates? - A systematic review.

BACKGROUND: A growing body of evidences suggests an association between early exposure to organophosphates (OPs), organochlorines (OCs), pyrethroids or carbamates and autism spectrum disorder (ASD). However, there are limited data about the other pesticide groups, especially in Europe. OBJECTIVES: Based on a systematic review, we aimed to assess the influence of neuro- and thyrotoxic agricultural and domestic pesticides (other than OPs, OCs, pyrethroids and carbamates) authorized in Europe on risk of ASD in children or ASD behavioral phenotypes in rodents. METHODS: Pesticides were initially identified in the Hazardous Substances Data Bank. 20 currently used (10 pesticide groups) were retained based on the higher exposure potential. Epidemiological (children) and in vivo (rodents) studies were identified through PubMed, Web of Science and TOXLINE, without restriction of publication date or country (last update: November 2019). The risk of bias and level of evidence were also assessed. This systematic review is registered at the International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42019145384). RESULTS: In total, two epidemiological and 15 in vivo studies were retained, focusing on the azole, neonicotinoid, phenylpyrazole and phosphonoglycine pesticide groups. No study was conducted in Europe. Glyphosate, imidacloprid, clothianidin, myclobutanil, acetamiprid, tebuconazole, thiabendazole and fipronil, globally reported an association with an increased risk of ASD in children and/or ASD behavioral phenotypes in rodents. In children, glyphosate and myclobutanil showed a "moderate level of evidence" in their association with ASD, whereas imidacloprid showed an "inadequate level of evidence". In rodents, clothianidin, imidacloprid and glyphosate showed a "high level of evidence" in their association with altered behavioral, learning and memory skills. CONCLUSION: In the framework of environmental risk factors of ASD, novel hypotheses can be formulated about early exposure to eight pesticides. Glyphosate presented the most salient level of evidence. Given their neuro- and thyrotoxic properties, additional studies are needed for the 12 other pesticides not yet studied as potential ASD risk factors according to our inclusion criteria.

Association of Borderline Intellectual Functioning and Adverse Childhood Experience with adult psychiatric morbidity. Findings from a British birth cohort.

BACKGROUND: To examine whether Borderline Intellectual Functioning (BIF) and Adverse Childhood Experiences independently predict adult psychiatric morbidity. METHODS: We performed a secondary analysis of longitudinal data derived from the 1970 British Birth Cohort Study to examine whether BIF and Adverse Childhood Experiences independently predict adult mental distress as measured by the Malaise Inventory. Factor analysis was used to derive a proxy measure of IQ from cognitive testing at age 10 or 5. Variables that could be indicators of exposure to Adverse Childhood Experiences were identified and grouped into health related and socio-economic related adversity. RESULTS: Children with BIF were significantly more likely than their peers to have been exposed to Adverse Childhood Experiences (BIF mean 5.90, non-BIF mean 3.19; Mann-Whitney z = 31.74, p < 0.001). As adults, participants with BIF were significantly more likely to score above the cut-off on the Malaise Inventory. We found statistically significant relationships between the number of socio-economic Adverse Childhood Experiences and poorer adult psychiatric morbidity (r range 0.104-0.141, all p < 001). At all ages the indirect mediating effects of Adverse Childhood Experiences were significantly related to adult psychiatric morbidity. CONCLUSIONS: The relationship between BIF and adult psychiatric morbidity appears to be partially mediated by exposure to Adverse Childhood Experiences. Where possible, targeting Adverse Childhood Experiences through early detection, prevention and interventions may improve psychiatric morbidity in this population group.

Coping strategies of parents of children with autism spectrum disorder: a systematic review.

To deal with stress, parents of children with ASD use coping strategies that help to tackle the challenging situations of raising their child. This systematic review examines parental coping strategy's questionnaires, factors which influence these coping strategies, interactions between these strategies and perceived stress and their impact on parental quality of life. According to PRISMA guidelines, an electronic search was conducted on Medline, PsycInfo and Eric: 156 articles were identified and 11 studies were selected. Many types of self-reported questionnaires were used to assess parental coping strategies. Studies highlighted that parents of a child with ASD used more avoidance strategies and less social support-seeking strategies than those of typical children. Furthermore, problem-focused coping protects parental stress and quality of life, that on the contrary, emotion-focused coping is a risk factor for alteration. Our systematic review illustrates the need to adapt psychoeducational interventions for parents of children with ASD.

Identification of disrupted AUTS2 and EPHA6 genes by array painting in a patient carrying a de novo balanced translocation t(3;7) with intellectual disability and neurodevelopment disorder.

Intellectual disability (ID) is a frequent feature but is highly clinically and genetically heterogeneous. The establishment of the precise diagnosis in patients with ID is challenging due to this heterogeneity but crucial for genetic counseling and appropriate care for the patients. Among the etiologies of patients with ID, apparently balanced de novo rearrangements represent 0.6%. Several mechanisms explain the ID in patients with apparently balanced de novo rearrangement. Among them, disruption of a disease gene at the breakpoint, is frequently evoked. In this context, technologies recently developed are used to characterize precisely such chromosomal rearrangements. Here, we report the case of a boy with ID, facial features and autistic behavior who is carrying a de novo balanced reciprocal translocation t(3;7)(q11.2;q11.22)dn. Using microarray analysis, array painting (AP) technology combined with molecular study, we have identified the interruption of the autism susceptibility candidate 2 gene (AUTS2) and EPH receptor A6 gene (EPHA6). We consider that the disruption of AUTS2 explains the phenotype of the patient; the exact role of EPHA6 in human pathology is not well defined. Based on the observation of recurrent germinal and somatic translocations involving AUTS2 and the molecular environment content, we put forward the hypothesis that the likely chromosomal mechanism responsible for the translocation could be due either to replicative stress or to recombination-based mechanisms.

Impact of autism in adolescents on parental quality of life.

PURPOSE: To study the impact of autism spectrum disorders (ASDs) on parental quality of life (QoL) at adolescence using the parental-developmental disorders-quality of life scale (Par-DD-QoL). METHODS: One hundred and fifty-two mothers of adolescents with ASD completed Par-DD-QoL. This scale assesses the following dimensions: emotional, daily disturbance and global QoL. This cross-sectional study uses a subset of data collected at the final time of a follow-up study (EpiTED cohort). RESULTS: A polytomic regression identified an increase in aberrant behavior scores as the major independent risk factor for parental QoL. The identified protective factors were the increase in daily living, communication and object cognition scores and a higher number of siblings. CONCLUSIONS: Those results suggest that there is a negative effect of externalizing behaviors and a protective effect of adaptive skills, communication and object cognition on parental QoL. Study limitations and implications are discussed.

Effectiveness of CO-OP group intervention for children with developmental coordination disorder: single-case experimental design study protocol.

INTRODUCTION: With the Cognitive Orientation to daily Occupational Performance (CO-OP) approach, children with developmental coordination disorder learn to use a problem-solving strategy to deal with their motor difficulties and perform daily activities of their choice. Therapists use guided discovery to enable children to find their own solutions. Although CO-OP is recommended in a group setting, studies are needed to support its effectiveness. METHODS AND ANALYSIS: A single-case study design with multiple baselines across participants and four systematic replications will be used. In each of the five groups, four children (aged 8-12 years) will be randomly included at the baseline. The baseline includes 5-8 measurements, and the CO-OP intervention stage is comprised of 10 sessions. The follow-up stage includes five measurements. Prior to baseline, each child in each of the five groups will choose five activities of which three will be carried out during the intervention sessions. Children's performance in each of these activities will be scored using the Performance Quality Rating Scale (PQRS) as the main measure. Three secondary measures will be collected: perceived activity performance using the Canadian Occupational Performance Measure, quality of life using the Kidscreen-27 and spontaneous motor rhythm using a computerised typing task. Graphed data will be analysed visually at the individual level with the Visual Aid Implying an Objective Rule (VAIOR) protocol which provides a colour code based on the level and trend of two consecutive phases, facilitating an objective visual analysis. Statistics will be performed for PQRS scores at the individual level and at the group level. ETHICS AND DISSEMINATION: The protocol has been approved by the Comité de protection des personnes Sud-Est I (CPP 2021070) and the Comité d'éthique de la recherche avec les êtres humains de l'Université du Québec à Trois-Rivières (CER-22-294-07.03). Results will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT05231486.