Autism Spectrum Disorder In Boys Research Articles

Antipsychotic Medication Adverse Effect on Autistic Patients among Saudi Papulation

Background: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by persistent impairments in social communication and restricted, repetitive patterns of behavior. Pharmacological treatments for the core symptoms of ASD are currently lacking, with existing medications primarily targeting associated symptoms and comorbidities such as irritability and psychiatric conditions. Early implementation of behavioral therapies has shown promise in alleviating core ASD symptoms and improving functional outcomes. Combining behavioral therapies with psychopharmacological monitoring is considered a beneficial approach. Methodology: This cross-sectional study aimed to assess the level of knowledge regarding autism spectrum disorders among general care physicians and psychiatric physicians in a specific region. A self-reported questionnaire, comprising demographic information, understanding of autism, experience with patients with autism, and knowledge-based questions, was administered. The collected data were analyzed using Statistical Package for Social Science (SPSS) software. Results: The study included 286 participants, with 59.1% acknowledging inadequate knowledge of autism spectrum disorders. However, 40.2% reported experience in diagnosing and collaborating with individuals with ASDs. Among the participants, 80.8% were aware of the challenges faced by children with ASDs in social interaction, communication, and behavior, while 61.9% correctly recognized the higher prevalence of ASDs in boys. The study also revealed potential adverse consequences of antipsychotic medication use in individuals with ASDs, including weight increase (67.8%), hyperprolactinemia (29.4%), extrapyramidal symptoms (32.2%), drowsiness (56.1%), and cognitive adverse effects (18.3%). Conclusion: This study highlights a lack of knowledge among healthcare providers regarding Autism Spectrum Disorders (ASDs). This has implications for accurate diagnosis and effective treatment. The study also emphasizes the potential adverse consequences of using antipsychotic medications in individuals with ASDs. Additional education and training are needed to address these knowledge gaps and improve care for individuals with ASDs.

Autism spectrum disorders in boys at a major UK hemophilia center: prevalence and risk factors

BackgroundAutism spectrum disorders (ASDs) are diagnosed by social communication difficulties strong, narrow interests, and repetitive stereotyped behavior. An apparently-elevated prevalence of ASD at a major UK hemophilia center warranted investigation. ObjectivesTo screen boys with hemophilia for difficulties in social communication and executive function and identify the prevalence and risk factors for ASD. MethodsParents of boys with hemophilia aged 5 to 16 years completed the Social Communication Questionnaire, Children’s Communication Checklist, and the Behavior Rating Inventory of executive function. Prevalence and potential risk factors for ASD were evaluated. Boys with an existing diagnosis of ASD did not complete questionnaires, but were included in the prevalence analysis. ResultsNegative scores on all 3 questionnaires were observed for 60 of 79 boys. Positive scores on 1, 2, and 3 questionnaires were seen in 12 of 79, 3 of 79, and 4 of 79 boys, respectively. In addition to the 11 of 214 boys with a prior ASD diagnosis, 3 further boys were diagnosed with ASD, yielding a prevalence of 14 (6.5%) of 214, greater than that of boys in the UK general population. Premature birth was linked to having ASD, but did not fully explain the increased prevalence with more boys born <37 weeks scoring positively on the Social Communications Questionnaire and Children’s Communication Checklist compared with those born at term. ConclusionThis study identified an increased prevalence of ASD at 1 UK hemophilia center. Prematurity was identified as a risk factor but did not fully explain the higher prevalence of ASD. Further investigation in the wider national/global hemophilia communities is warranted to determine whether this is an isolated finding.

Diethylstilbestrol and autism.

It is acknowledged that diethylstilbestrol (DES), a synthetic diphenol with powerful estrogenic properties, causes structural anomalies of the reproductive tract and increases the risk of cancer and genital malformations in children and grandchildren of mothers treated during pregnancy. Conversely, data on DES effects on neurodevelopment and psychiatric disorders in in-utero exposed children and their descendants are rare, especially concerning Autism Spectrum Disorders (ASD). Recent studies presented in this review strengthen the hypothesis that in-utero exposure to DES and also other synthetic estrogens and progestogens, which all are endocrine disruptors, contributes to the pathogenesis of psychiatric disorders, especially ASD. A large epidemiological study in the USA in 2010 reported severe depression in in-utero exposed children (n=1,612), and a French cohort study (n=1,002 in-utero DES exposed children) in 2016 found mainly bipolar disorders, schizophrenia, major depression, suicide attempts, and suicide. Few publications described ASD in in-utero exposed children, mainly a Danish cohort study and a large Chinese epidemiological study. Molecular studies on endocrine disruptors demonstrated the transgenerational induction of diseases and DES epigenetic impact (DNA methylation changes) at two genes implicated in neurodevelopment (ZFP57 and ADAM TS9). We recently described in an informative family, somatic and psychiatric disorders in four generations, particularly ASD in boys of the third and fourth generation. These data show that the principle of precaution must be retained for the protection of future generations: women (pregnant or not) should be extremely vigilant about synthetic hormones.

Particulate matter exposure during pregnancy and infancy and risks of autism spectrum disorder in children: A systematic review and meta-analysis

PurposeThis meta-analysis aimed to clarify the relationship between particulate matter (PM) and autism spectrum disorder (ASD) in detail. MethodsA systematic literature search was performed using eight databases before April 9, 2022. The estimated effects were combined separately according to the PM type. Subgroup analyses were conducted in terms of the study design type, study location, exposure window, birth year, and sex. ResultsPM2.5 was associated with an increased risk of ASD, while PM10 was not. PMc, PM1, and diesel particulate matter (DPM) were also associated with an increased risk of ASD. Specifically, a 10 μg/m3 increase in PM2.5 was associated with a 1.337-fold increased risk of ASD in children, and a 10 μg/m3 increase in PMc and PM1 may increase the risk of ASD by 1.062 and 3.643 times, respectively. PM2.5 exposure may increase the risk of ASD in boys. Exposure to PMc might increase the risk of ASD in children born after the year 2000. The combined results of different PM differed between studies with continuous and non-continuous data for different study design type, study location, and birth year. The sensitive window for PM2.5 exposure to increase the risk of ASD may be from the first, second, and third trimesters to the first year of the postnatal period. Exposure to PMc during pregnancy was significantly associated with ASD. ConclusionExposure to PM2.5 may increase the risk of ASD in boys. Exposure to PM2.5 during the first, second, and third trimesters and postnatally increased the risk of ASD.

Autism spectrum disorders as a risk factor for adolescent self-harm: a retrospective cohort study of 113,286 young people in the UK

BackgroundIndividuals with autism spectrum disorder (ASD) are at particularly high risk of suicide and suicide attempts. Presentation to a hospital with self-harm is one of the strongest risk factors for later suicide. We describe the use of a novel data linkage between routinely collected education data and child and adolescent mental health data to examine whether adolescents with ASD are at higher risk than the general population of presenting to emergency care with self-harm.MethodsA retrospective cohort study was conducted on the population aged 11–17 resident in four South London boroughs between January 2009 and March 2013, attending state secondary schools, identified in the National Pupil Database (NPD). Exposure data on ASD status were derived from the NPD. We used Cox regression to model time to first self-harm presentation to the Emergency Department (ED).ResultsOne thousand twenty adolescents presented to the ED with self-harm, and 763 matched to the NPD. The sample for analysis included 113,286 adolescents (2.2% with ASD). For boys only, there was an increased risk of self-harm associated with ASD (adjusted hazard ratio 2·79, 95% CI 1·40–5·57, P<0·01). Several other factors including school absence, exclusion from school and having been in foster care were also associated with a higher risk of self-harm.ConclusionsThis study provides evidence that ASD in boys, and other educational, social and clinical factors, are risk factors for emergency presentation with self-harm in adolescents. These findings are an important step in developing early recognition and prevention programmes.

Prenatal Androgen Exposure and Traits of Autism Spectrum Disorder in the Offspring: Odense Child Cohort.

Fetal androgen exposure may be associated with autism spectrum disorder (ASD). We studied 1777 mother-child pairs in the prospective Odense Child Cohort. Prenatal androgen exposure was assessed by maternal 3rd trimester testosterone concentrations, maternal polycystic ovary syndrome (PCOS), and 3months offspring anogenital distance. ASD traits were assessed at age 3years with the ASD-symptom scale of the Child Behavior Checklist for ages 1½-5years. Maternal testosterone was positively associated with traits of ASD in boys (p < 0.05). Maternal PCOS was associated with increased offspring ASD traits (p = 0.046), but became non-significant after excluding parental psychiatric diagnosis. Offspring anogenital distance was not linked to ASD traits. Higher prevalence of ASD in boys could be linked to higher susceptibility to fetal androgen exposure.

Preterm or Early Term Birth and Risk of Autism.

Preterm birth has been linked with increased risk of autism spectrum disorder (ASD); however, potential causality, sex-specific differences, and association with early term birth are unclear. We examined whether preterm and early term birth are associated with ASD in a large population-based cohort. A national cohort study was conducted of all 4 061 795 singleton infants born in Sweden during 1973-2013 who survived to age 1 year, who were followed-up for ASD identified from nationwide outpatient and inpatient diagnoses through 2015. Poisson regression was used to determine prevalence ratios for ASD associated with gestational age at birth, adjusting for confounders. Cosibling analyses were used to assess the influence of unmeasured shared familial (genetic and/or environmental) factors. ASD prevalences by gestational age at birth were 6.1% for extremely preterm (22-27 weeks), 2.6% for very to moderate preterm (28-33 weeks), 1.9% for late preterm (34-36 weeks), 2.1% for all preterm (<37 weeks), 1.6% for early term (37-38 weeks), and 1.4% for term (39-41 weeks). The adjusted prevalence ratios comparing extremely preterm, all preterm, or early term versus term, respectively, were 3.72 (95% confidence interval, 3.27-4.23), 1.35 (1.30-1.40), and 1.11 (1.08-1.13) among boys and 4.19 (3.45-5.09), 1.53 (1.45-1.62), and 1.16 (1.12-1.20) among girls (P < .001 for each). These associations were only slightly attenuated after controlling for shared familial factors. In this national cohort, preterm and early term birth were associated with increased risk of ASD in boys and girls. These associations were largely independent of covariates and shared familial factors, consistent with a potential causal relationship.

Blood biomarker discovery for autism spectrum disorder: A proteomic analysis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, or activities. Given the lack of specific pharmacological therapy for ASD and the clinical heterogeneity of the disorder, current biomarker research efforts are geared mainly toward identifying markers for determining ASD risk or for assisting with a diagnosis. A wide range of putative biological markers for ASD is currently being investigated. Proteomic analyses indicate that the levels of many proteins in plasma/serum are altered in ASD, suggesting that a panel of proteins may provide a blood biomarker for ASD. Serum samples from 76 boys with ASD and 78 typically developing (TD) boys, 18 months-8 years of age, were analyzed to identify possible early biological markers for ASD. Proteomic analysis of serum was performed using SomaLogic’s SOMAScanTM assay 1.3K platform. A total of 1,125 proteins were analyzed. There were 86 downregulated proteins and 52 upregulated proteins in ASD (FDR < 0.05). Combining three different algorithms, we found a panel of 9 proteins that identified ASD with an area under the curve (AUC) = 0.8599±0.0640, with specificity and sensitivity of 0.8217±0.1178 and 0.835±0.1176, respectively. All 9 proteins were significantly different in ASD compared with TD boys, and were significantly correlated with ASD severity as measured by ADOS total scores. Using machine learning methods, a panel of serum proteins was identified that may be useful as a blood biomarker for ASD in boys. Further verification of the protein biomarker panel with independent test sets is warranted.

Sex-specific effects of prenatal valproic acid exposure on sociability and neuroinflammation: Relevance for susceptibility and resilience in autism

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with an incidence four times higher in boys than in girls. By analyzing the effect of sex in a mouse model of ASD, we were able to identify immune alterations that could underlie this sex bias.Pregnant mice were injected subcutaneously with 600 mg/kg of valproic acid (VPA) or saline at gestational day 12.5. Their male and female offspring were evaluated in a social interaction test at adulthood, and only male VPA mice showed reduced sociability levels and a lack of preference for the social stimulus over a novel object. We then analyzed the corticosterone (CORT) response to an inflammatory stimulus, as a measure of the hypothalamus-pituitary-adrenal (HPA) function, and the neuroinflammatory state in adult and young animals. Adult VPA males exhibited increased basal CORT levels, while VPA females showed levels comparable to controls. As male mice showed a blunted CORT response at PD21 when compared to female mice, we propose that this early dimorphism could explain the different effects of VPA on HPA function. In addition, prenatal VPA exposure resulted in altered astroglial and microglial cell density levels in the cerebellum and dentate gyrus of adult mice. These neuroinflammatory effects were more pronounced in females than males, and appeared at early developmental stages. Hence, these postnatal glial density differences could underlie the behavioral alterations observed in adulthood, when only males show a social deficit.Our work contributes to the understanding of biological mechanisms affected by VPA on male and female rodents and shed light on the study of possible resilience mechanisms in the female population and/or susceptibility to ASD in boys.

Prenatal Stress, Maternal Immune Dysregulation, and Their Association With Autism Spectrum Disorders.

While genetic factors are a major etiological contributor to autism spectrum disorder (ASD), evidence also supports a role for environmental factors. Herein, we will discuss two such factors that have been associated with a significant proportion of ASD risk: prenatal stress exposure and maternal immune dysregulation, and how sex and gender relate to these factors. Recent evidence suggests that maternal stress susceptibility interacts with prenatal stress exposure to affect offspring neurodevelopment. Additionally, understanding of the impact of maternal immune dysfunction on ASD has recently been advanced by recognition of specific fetal brain proteins targeted by maternal autoantibodies, and identification of unique mid-gestational maternal immune profiles. Animal models have been developed to explore pathophysiology targeting both of these factors, with limited sex-specific effects observed. While prenatal stress and maternal immune dysregulation are associated with ASD, most cases of these prenatal exposures do not result in ASD, suggesting interaction with multiple other risks. We are beginning to understand the behavioral, pharmacopathological, and epigenetic effects related to these interactions, as well as potential mitigating factors. Sex differences of these risks have been understudied but are crucial for understanding the higher prevalence of ASD in boys. Continued growth in understanding of these mechanisms may ultimately allow for the identification of multiple potential points for prevention or intervention, and for a personalized medicine approach for this subset of environmental-associated ASD cases.

Clinical Features of Children With Autism Who Passed 18-Month Screening.

We compared sex-stratified developmental and temperamental profiles at 18 months in children screening negative for autism spectrum disorder (ASD) on the Modified Checklist for Autism in Toddlers (M-CHAT) but later receiving diagnoses of ASD (false-negative group) versus those without later ASD diagnoses (true-negative group). We included 68 197 screen-negative cases from the Norwegian Mother and Child Cohort Study (49.1% girls). Children were screened by using the 6 critical items of the M-CHAT at 18 months. Groups were compared on domains of the Ages and Stages Questionnaire and the Emotionality Activity Sociability Temperament Survey. Despite passing M-CHAT screening at 18 months, children in the false-negative group exhibited delays in social, communication, and motor skills compared with the true-negative group. Differences were more pronounced in girls. However, with regard to shyness, boys in the false-negative group were rated as more shy than their true-negative counterparts, but girls in the false-negative group were rated as less shy than their counterparts in the true-negative group. This is the first study to reveal that children who pass M-CHAT screening at 18 months and are later diagnosed with ASD exhibit delays in core social and communication areas as well as fine motor skills at 18 months. Differences appeared to be more pronounced in girls. With these findings, we underscore the need to enhance the understanding of early markers of ASD in boys and girls, as well as factors affecting parental report on early delays and abnormalities, to improve the sensitivity of screening instruments.

Postnatal behavioral and inflammatory alterations in female pups prenatally exposed to valproic acid

In Autism Spectrum Disorders (ASD), a bias to a higher incidence in boys than in girls has been reported. With the aim to identify biological mechanisms acting in female animals that could underlie this bias, we used an extensively validated mouse model of ASD: the prenatal exposure to valproic acid (VPA). We found postnatal behavioral alterations in female VPA pups: a longer latency in righting reflex at postnatal day (P) 3, and a delay in the acquisition of the acoustic startle response. We also analyzed the density of glial cells in the prefrontal cortex, hippocampus and cerebellum, in VPA and control animals. Female VPA pups showed alterations in the density of astrocytes and microglial cells between P21 and P42, with specific dynamics in each brain region. We also found a decrease in histone 3 acetylation in the cerebellum of female VPA pups at P14, suggesting that the changes in glial cell density could be due to alterations in the epigenetic developmental program. Finally, no differences in maternal behavior were found. Our results show that female VPA pups exhibit behavioral and inflammatory alterations postnatally, although they have been reported to have normal levels of sociability in adulthood. With our work, we contribute to the understanding of biological mechanisms underlying different effects of VPA on male and female rodents, and we hope to help elucidate whether there are factors increasing susceptibility to ASD in boys and/or resilience in girls.

Are there two different neural pathways for gender differences in autism spectrum disorders? – A pilot study

Many studies have described sex differences in the prevalence of autism spectrum disorders (ASD) which was diagnosed four times more often in boys than in girls. However, there is no unified conclusion about why gender differences exist in ASD. Several theories attempt to elaborate why ASD in boys is more prevalent than that in girls including extreme male brain, failure of accurate diagnosis, endocrinologic mechanism effecting brain development and genetics explanation. Based on previous studies we hypothesize that there may be two different neural pathways existed in boys and girls with ASD. Using de novo copy number variations (CNVs) from boys and girls with ASD, we tested the genes contained in de novo CNVs from boys and girls with ASD by a web database. Two significant different neural pathways were identified. It indicated that a different combination of genes in the neural pathways may be responsible for sex difference of ASD. Then it is favorable to the judgment of the prognosis and influence on the treatment.

Increased prevalence of seizures in boys who were probands with the FMR1 premutation and co-morbid autism spectrum disorder

Seizures are a common co-occurring condition in those with fragile X syndrome (FXS), and in those with idiopathic autism spectrum disorder (ASD). Seizures are also associated with ASD in those with FXS. However, little is known about the rate of seizures and how commonly these problems co-occur with ASD in boys with the FMR1 premutation. We, therefore, determined the prevalence of seizures and ASD in boys with the FMR1 premutation compared with their sibling counterparts and population prevalence estimates. Fifty premutation boys who presented as clinical probands (N=25), or non-probands (identified by cascade testing after the proband was found) (N=25), and 32 non-carrier controls were enrolled. History of seizures was documented and ASD was diagnosed by standardized measures followed by a team consensus of ASD diagnosis. Seizures (28%) and ASD (68%) were more prevalent in probands compared with non-probands (0 and 28%), controls (0 and 0%), and population estimates (1 and 1.7%). Seizures occurred more frequently in those with the premutation and co-morbid ASD particularly in probands compared with those with the premutation alone (25 vs. 3.85%, p=0.045). Although cognitive and adaptive functioning in non-probands were similar to controls, non-probands were more likely to meet the diagnosis of ASD than controls (28 vs. 0%, p<0.0001). In conclusion, seizures were relatively more common in premutation carriers who presented clinically as probands of the family and seizures were commonly associated with ASD in these boys. Therefore, boys with the premutation, particularly if they are probands should be assessed carefully for both ASD and seizures.

Sex differences in the evaluation and diagnosis of autism spectrum disorders among children

Background One of the most consistent features of the autism spectrum disorders (ASDs) is the predominance among males, with approximately four males to every female. We sought to examine sex differences among children who met case definition for ASD in a large, population-based cohort with respect to age at first developmental evaluation, age of diagnosis, influence of cognitive impairment on these outcomes, and sex-specific behavioral characteristics. Methods We conducted a secondary analysis of data collected for a population-based study of the prevalence of ASD. The sample comprised 2,568 children born in 1994 who met the case definition of ASD as established by the Autism and Developmental Disabilities Monitoring (ADDM) Network for ASD surveillance. Children who had a history of developmental disability and behavioral features consistent with the DSM-IV-TR criteria for autistic disorder, Asperger's disorder, and Pervasive Developmental Disorder–Not Otherwise Specified in existing evaluation records were classified as ASD cases via two paths: streamlined and nonstreamlined. Streamlined reviews were conducted if there was an ASD diagnosis documented in the records. Data were collected in 13 sites across the United States through the ADDM Network, funded by the Centers for Disease Control and Prevention. Results Males constituted 81% of the sample. There were no differences by sex in average age at first evaluation or average age of diagnosis among those with an existing documented chart diagnosis of an ASD. Girls were less likely than boys to have a documented diagnosis (odds ratio [OR] = 0.76, p = .004). This analysis was adjusted for cognitive impairment status. In the logistic model, with the interaction term for sex and cognitive impairment, girls with IQ of 70 or less were less likely than boys with IQ of 70 or less to have a documented diagnosis (OR = 0.70, 95% confidence interval [CI] = 0.50-0.97, p = .035). Boys with IQ greater than 70 were less likely than boys with IQ of 70 or less to have a documented diagnosis (OR = 0.60, 95% CI = 0.49-0.74, p < .001). This finding (less likely to have a documented diagnosis) was also true for girls with IQ greater than 70 (OR = 0.45, 95% CI = 0.32-0.66, p < .001). Girls were more likely to have notations of seizure-like behavior ( p < .001). Boys were more likely to have notations of hyperactivity or a short attention span and aggressive behavior ( p < .01). Conclusions Girls, especially those without cognitive impairment, may be formally identified at a later age than boys. This may delay referral for early intervention. Community education efforts should alert clinicians and parents to the potential of ASDs in boys and girls.

Editorial: Why a diversity of methods are required to understand childhood disorders

Editorial: Why a diversity of methods are required to understand childhood disorders

Association of the DAO and DAOA gene polymorphisms with autism spectrum disorders in boys in Korea: A preliminary study

We examined the association of autism spectrum disorders (ASD) with polymorphisms in the DAO and DAOA genes. The sample comprised 57 children with ASD, 47 complete trios, and 83 healthy controls in Korea. Although the transmission disequilibrium test showed no association, a population-based case-control study showed significant associations between the rs3918346 and rs3825251 SNPs of the DAO gene and boys with ASD.

Autism spectrum disorder in Fragile X syndrome: Differential contribution of adaptive socialization and social withdrawal

The present study extends our previous work on characterizing the profile of social behavior abnormalities in boys with Fragile X (FraX) and autism spectrum disorder (ASD) using clinically oriented behavioral rating scales and standardized instruments. The goal was to further distinguish behavioral parameters contributing to the diagnostic classification of FraX + ASD. The study design included two cohorts of boys with FraX (3-8 years), a larger main cohort for cross-sectional analyses (n = 56, 24 with ASD), and a longitudinal subset (n = 30, 11 with ASD) of the main cohort with up to 3 yearly observations. The focus was on the relative contribution of delayed adaptive socialization and social withdrawal, including item components of their corresponding rating instruments, to the diagnosis of ASD in boys with FraX. Using a combination of regression analyses, we demonstrated that: (1) as delayed socialization, social withdrawal is also a correlate of FraX + ASD; (2) items of social withdrawal scales representing avoidance were the main predictors of ASD status, particularly in older boys; (3) adaptive socialization skills reflecting rules of social behavior and recognition and labeling of emotions, linked to verbal reasoning abilities, were selectively associated with FraX + ASD; (4) adaptive socialization is the primary determinant over time of ASD status in boys with FraX; and (5) integrated adaptive socialization-social withdrawal models allow the identification of distinctive FraX + ASD subgroups. Altogether, our findings suggest that two distinct but interrelated social behavior abnormalities, one linked to impaired cognitive processes (delayed socialization) and the second one to disturbance in limbic circuits (avoidance), play a role in the development of ASD in boys with FraX.

Autism Spectrum Disorders and Attention-Deficit/Hyperactivity Disorder in Boys with the Fragile X Premutation

Fragile X syndrome (FXS) is caused by a full mutation expansion (>200 CGG repeats) in the FMR1 gene that results in a deficiency of the fragile X mental retardation protein. Although most individuals with the premutation (55-200 CGG repeats) are considered unaffected by FXS, recent case studies have documented children with the premutation who have cognitive deficits, behavioral problems, and/or autism spectrum disorders. The objective of this study was to compare the prevalence of autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) symptoms in boys with the premutation who presented as probands, in brothers with the premutation who did not present as probands, and in normal brothers of premutation and/or full mutation carriers. Participants included 43 male children: 14 probands who presented to clinic, 13 nonprobands who were identified through cascade testing (routine genetic testing of family members after identification of a proband) and confirmed to have the premutation, and a control group of 16 male siblings of individuals with the fragile X premutation or full mutation who were negative for the FMR1 mutation. Participants came from 1 of 2 collaborative sites: University of California, Davis and La Trobe University in Australia. Parents completed the Conners' Global Index-Parent Version for assessing symptoms of ADHD and the Social Communication Questionnaire (SCQ) for identifying symptoms of ASD. Children who were in the ASD range on the SCQ (n = 13) underwent further evaluation with either the Autism Diagnostic Observation Schedule-Generic (n = 10) or the Autism Diagnostic Interview-Revised (n = 3). A final diagnosis of ASD included clinical assessment utilizing DSM-IV-TR criteria in addition to the standardized assessments. There was a higher rate of ASD in boys with the premutation presenting as probands (p < 0.001) or nonprobands (p < .04) compared with sibling controls without the premutation. In addition, probands had a significant increase in ADHD symptoms compared with controls (p < .0001). Of the probands, 93% had symptoms of ADHD and 79% had ASD. In the nonproband premutation group, 38% had symptoms of ADHD and 8% had ASD. Thirteen percent of sibling controls had symptoms of ADHD and none had ASD. IQ scores were similar in all 3 groups (p = .13), but the use of psychotropic medications was significantly higher in probands with the premutation compared with that in controls (p < .0001). Developmental problems have been observed in premutation carriers, particularly those who present clinically with behavioral difficulties. Although this study is based on a small sample size, it suggests that premutation carriers, even those who do not present clinically, may be at increased risk for an ASD and/or symptoms of ADHD. If the premutation is identified through cascade testing, then further assessment should be carried out for symptoms of ADHD, social deficits, or learning disabilities.

Association of Duchenne Muscular Dystrophy With Autism Spectrum Disorder

We hypothesize that Duchenne muscular dystrophy and autism spectrum disorder/pervasive developmental disorder co-occur with a greater than random frequency. In this study, we set out to reject the hypothesis that Duchenne muscular dystrophy and autism spectrum disorder/pervasive developmental disorder co-occur no more often than expected by chance. Two index cases and six additional boys with concomitant Duchenne muscular dystrophy and autism spectrum disorder were identified in a muscular dystrophy clinic that approximates the total number of Duchenne muscular dystrophy boys (158) in the state of Massachusetts. The rate of prevalence (6 of 158) was compared with the prevalence rate of autism spectrum disorder in boys in the general population (1.6 in 1,000). We rejected the hypothesis that Duchenne muscular dystrophy and autism spectrum disorder co-occurrence was likely to be explained by chance (P = .006). We identify a previously unrecognized association of Duchenne muscular dystrophy with autism spectrum disorder. Further work might elucidate the level of association between these two conditions, either at the genetic or at the protein level, and might clarify, at least partially, the neurobiologic mechanisms associated with autism spectrum disorder.