1. Chechi T, Siyahian S, Thairu L, Hagerman R, Lozano R. {{Participation of underrepresented minority children in clinical trials for Fragile X syndrome and other neurodevelopmental disorders}}. {Intractable Rare Dis Res}. 2014; 3(4): 147-52.
The purpose of this study was to identify demographic data, motivational factors and barriers for participation in clinical trials (CTs) at the University of California Davis, MIND Institute. We conducted a cross-sectional survey in 100 participants (81 females and 19 males). The participants had high education levels (only 2% had not completed high school), a mean age of 44 years (SD +/- 9.899) and had at least one child with a neurodevelopmental disorder. The diagnosis of Fragile X syndrome (FXS) had a significant association with past participation in CTs (p < 0.001). A statistical significance for age of diagnosis and participation in CTs was also found (z = -2.01, p = 0.045). The motivating factors were to help find cures/treatments for neurodevelopmental disorders and to relieve symptoms related to child’s diagnosis. Factors explaining lack of participation, unwillingness to participate or unsure of participation were: lack of information/knowledge about the trials, time commitment to participation (screening, appointments, assessments, laboratory tests, etc.) and low annual household income. These results show that a portion of underrepresented minorities (URM) not participating in CTs are willing to participate and suggests that reducing barriers, particularly lack of knowledge/information and time commitment to trials are needed to improve recruitment.
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2. Craig F, Lamanna AL, Margari F, Matera E, Simone M, Margari L. {{Overlap Between Autism Spectrum Disorders and Attention Deficit Hyperactivity Disorder: Searching for Distinctive/Common Clinical Features}}. {Autism Res}. 2015.
Recent studies support several overlapping traits between autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD), assuming the existence of a combined phenotype. The aim of our study was to evaluate the common or distinctive clinical features between ASD and ADHD in order to identify possible different phenotypes that could have a clinical value. We enrolled 181 subjects divided into four diagnostic groups: ADHD group, ASD group, ASD+ADHD group (that met diagnostic criteria for both ASD and ADHD), and control group. Intelligent quotient (IQ), emotional and behavior problems, ADHD symptoms, ASD symptoms, and adaptive behaviors were investigated through the following test: Wechsler Intelligence Scale for Children, Wechsler Preschool and Primary Scale of Intelligence or Leiter International Performances Scale Revised, Child Behavior Checklist, Conners’ Rating Scales-Revised, SNAP-IV Rating Scale, the Social Communication Questionnaire, Vineland Adaptive Behavior Scales. The ASD+ADHD group differs from ADHD or ASD in some domains such as lower IQ mean level and a higher autistic symptoms severity. However, the ASD+ADHD group shares inattention and hyperactivity deficit and some emotional and behavior problems with the ADHD group, while it shares adaptive behavior impairment with ASD group. These findings provide a new understanding of clinical manifestation of ASD+ADHD phenotype, they may also inform a novel treatment target. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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3. Davis JM, Finke EH. {{The Experience of Military Families with Children with Autism Spectrum Disorders During Relocation and Separation}}. {J Autism Dev Disord}. 2015.
Military families with a child with autism spectrum disorder (ASD) are underrepresented in the literature. In order to provide appropriate services, research must be done to determine the needs of these families. A qualitative methodology was used to interview military spouses with children with ASD about their experiences with therapeutic services. Overall, results indicate military families with a child with ASD experience challenges associated with both the military lifestyle and having a child with special needs. Due to their membership in two groups prone to support limitations and therapeutic service accessibility issues, military families with a child with ASD may be at additional risk for high levels of stress and difficulty obtaining and maintaining ASD related services.
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4. Diez-Juan M, Schneider A, Phillips T, Lozano R, Tassone F, Solomon M, Hagerman RJ. {{Parent-delivered touchscreen intervention for children with fragile X syndrome}}. {Intractable Rare Dis Res}. 2014; 3(4): 166-77.
The use of touchscreen applications for the iPad((R)) allows children with disabilities to improve their personal autonomy and quality of life. In light of this emerging literature and our clinical experience with toddlers and children with Fragile X syndrome (FXS), a randomized clinical trial pilot study was conducted of whether an interactive iPad((R))-based parent training program was efficacious for both individuals with FXS and autism spectrum disorder aged 2-to-12 compared to wait-listed controls. As a second goal, we assessed the difference between direct person-to-person therapy vs. online therapy sessions through telehealth. In this case series report it is presented preliminary results of four individuals with FXS enrolled in the study and described the innovative experience including qualitative and quantitative data analysis. Furthermore, we provide professionals with specific guidelines about the use of touchscreen devices as in-home learning tools and parent training strategies to actively involve families in educational treatments in conjunction with clinical guidance.
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5. Hagerman R, Lozano R, Schneider A. {{Translational research guided by animal studies in Fragile X Disorders}}. {Intractable Rare Dis Res}. 2014; 3(4): 100.
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6. Hanson AC, Hagerman RJ. {{Serotonin dysregulation in Fragile X Syndrome: implications for treatment}}. {Intractable Rare Dis Res}. 2014; 3(4): 110-7.
Fragile X Syndrome (FXS) is a trinucleotide repeat disorder that results in the silencing of the Fragile X Mental Retardation 1 gene (FMR1), leading to a lack of the FMR1 protein (FMRP). FMRP is an mRNA-binding protein that regulates the translation of hundreds of mRNAs important for synaptic plasticity. Several of these pathways have been identified and have guided the development of targeted treatments for FXS. Here we present evidence that serotonin is dysregulated in FXS and treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline may be beneficial for individuals with FXS, particularly in early childhood.
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7. Kazdoba TM, Leach PT, Silverman JL, Crawley JN. {{Modeling fragile X syndrome in the Fmr1 knockout mouse}}. {Intractable Rare Dis Res}. 2014; 3(4): 118-33.
Fragile X Syndrome (FXS) is a commonly inherited form of intellectual disability and one of the leading genetic causes for autism spectrum disorder. Clinical symptoms of FXS can include impaired cognition, anxiety, hyperactivity, social phobia, and repetitive behaviors. FXS is caused by a CGG repeat mutation which expands a region on the X chromosome containing the FMR1 gene. In FXS, a full mutation (> 200 repeats) leads to hypermethylation of FMR1, an epigenetic mechanism that effectively silences FMR1 gene expression and reduces levels of the FMR1 gene product, fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that is important for the regulation of protein expression. In an effort to further understand how loss of FMR1 and FMRP contribute to FXS symptomology, several FXS animal models have been created. The most well characterized rodent model is the Fmr1 knockout (KO) mouse, which lacks FMRP protein due to a disruption in its Fmr1 gene. Here, we review the behavioral phenotyping of the Fmr1 KO mouse to date, and discuss the clinical relevance of this mouse model to the human FXS condition. While much remains to be learned about FXS, the Fmr1 KO mouse is a valuable tool for understanding the repercussions of functional loss of FMRP and assessing the efficacy of pharmacological compounds in ameliorating the molecular and behavioral phenotypes relevant to FXS.
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8. Lozano R, Rosero CA, Hagerman RJ. {{Fragile X spectrum disorders}}. {Intractable Rare Dis Res}. 2014; 3(4): 134-46.
The fragile X mental retardation 1 gene (FMR1), which codes for the fragile X mental retardation 1 protein (FMRP), is located at Xp27.3. The normal allele of the FMR1 gene typically has 5 to 40 CGG repeats in the 5′ untranslated region; abnormal alleles of dynamic mutations include the full mutation (> 200 CGG repeats), premutation (55-200 CGG repeats) and the gray zone mutation (45-54 CGG repeats). Premutation carriers are common in the general population with approximately 1 in 130-250 females and 1 in 250-810 males, whereas the full mutation and Fragile X syndrome (FXS) occur in approximately 1 in 4000 to 1 in 7000. FMR1 mutations account for a variety of phenotypes including the most common monogenetic cause of inherited intellectual disability (ID) and autism (FXS), the most common genetic form of ovarian failure, the fragile X-associated primary ovarian insufficiency (FXPOI, premutation); and fragile X-associated tremor/ataxia syndrome (FXTAS, premutation). The premutation can also cause developmental problems including ASD and ADHD especially in boys and psychopathology including anxiety and depression in children and adults. Some premutation carriers can have a deficit of FMRP and some unmethylated full mutation individuals can have elevated FMR1 mRNA that is considered a premutation problem. Therefore the term « Fragile X Spectrum Disorder » (FXSD) should be used to include the wide range of overlapping phenotypes observed in affected individuals with FMR1 mutations. In this review we focus on the phenotypes and genotypes of children with FXSD.
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9. Manning C, Charman T, Pellicano E. {{Brief Report: Coherent Motion Processing in Autism: Is Dot Lifetime an Important Parameter?}}. {J Autism Dev Disord}. 2015.
Contrasting reports of reduced and intact sensitivity to coherent motion in autistic individuals may be attributable to stimulus parameters. Here, we investigated whether dot lifetime contributes to elevated thresholds in children with autism. We presented a standard motion coherence task to 31 children with autism and 31 typical children, with both limited and unlimited lifetime conditions. Overall, children had higher thresholds in the limited lifetime condition than in the unlimited lifetime condition. However, children with autism were affected by this manipulation to the same extent as typical children and were equally sensitive to coherent motion. Our results suggest that dot lifetime is not a critical stimulus parameter and speak against pervasive difficulties in coherent motion perception in children with autism.
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10. Muzar Z, Adams PE, Schneider A, Hagerman RJ, Lozano R. {{Addictive substances may induce a rapid neurological deterioration in fragile X-associated tremor ataxia syndrome: A report of two cases}}. {Intractable Rare Dis Res}. 2014; 3(4): 162-5.
A debilitating late-onset disorder of the premutation in the FMR1 gene is the neurodegenerative disorder fragile X-associated tremor ataxia syndrome (FXTAS). We report two patients with FXTAS who have a history of substance abuse (opiates, alcohol, and cocaine) which may have exacerbated their rapid neurological deterioration with FXTAS. There has been no case report regarding the role of substance abuse in onset, progression, and severity of FXTAS symptoms. However, research has shown that substance abuse can have a negative impact on several neurodegenerative diseases, and we propose that in these cases, substance abuse contributed to a faster progression of FXTAS as well as exacerbated white matter disease.
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11. Muzar Z, Lozano R. {{Current research, diagnosis, and treatment of fragile X-associated tremor/ataxia syndrome}}. {Intractable Rare Dis Res}. 2014; 3(4): 101-9.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is caused by a premutation CGG-repeat expansion in the 5’UTR of the fragile X mental retardation 1 (FMR1) gene. The classical clinical manifestations include tremor, cerebellar ataxia, cognitive decline and psychiatric disorders. Other less frequent features are peripheral neuropathy and autonomic dysfunction. Cognitive decline, a form of frontal subcortical dementia, memory loss and executive function deficits are also characteristics of this disorder. In this review, we present an expansion of recommendations for genetic testing for adults with suspected premutation disorders and provide an update of the clinical, radiological and molecular research of FXTAS, as well as the current research in the treatment for this intractable complex neurodegenerative genetic disorder.
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12. Ou JJ, Shi LJ, Xun GL, Chen C, Wu RR, Luo XR, Zhang FY, Zhao JP. {{Employment and financial burden of families with preschool children diagnosed with autism spectrum disorders in urban China: results from a descriptive study}}. {BMC Psychiatry}. 2015; 15(1): 3.
BackgroundAutism spectrum disorder (ASD) affects many aspects of family life, such as social and economic burden. Little investigation of this phenomenon has been carried out in China. We designed this study to evaluate the employment and financial burdens of families with ASD-diagnosed preschoolers.MethodsFour hundred and fifty-nine nuclear families of children with ASD, 418 with some other disability (OD) and 424 with typically developing (TD) children were recruited for this study. Employment and financial burdens of families were evaluated using a structured questionnaire; logistic regression was used to examine differences in job change measures by group, and ordinal logistic regression was used to investigate the association between household income and group.ResultsFifty-eight percent of families with ASD children and 19% of families with OD children reported that childcare problems had greatly affected their employment decisions, compared with 9% of families with TD children (p inverted question mark< inverted question mark0.001). Age of child, parental education and parental age notwithstanding, having a child with ASD and having a child with OD were both associated with increased odds of reporting that childcare greatly interfered with employment (ASD, OR: 15.936; OD, OR: 2.502; all p inverted question mark< inverted question mark0.001) and decreased the odds of living in a higher-income household (ASD, estimate inverted question mark= inverted question mark-1.271; OD, estimate inverted question mark= inverted question mark-0.569; all p inverted question mark< inverted question mark0.001). The average loss of annual income associated with having a child with ASD was Chinese RenMinBi (RMB) 44,077 ($7,226), compared with RMB 20,788 ($3,408) for families of OD children.ConclusionsASD is associated with severe employment and financial burdens, much more than for OD, in families with preschool children.
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13. Perrone-McGovern K, Simon-Dack S, Niccolai L. {{Prenatal and Perinatal Factors Related to Autism, IQ, and Adaptive Functioning}}. {J Genet Psychol}. 2015: 1-10.
ABSTRACT This study focused on prenatal and perinatal factors related to autism spectrum disorder (ASD). The authors hypothesized that mothers who exposed their infants to intrauterine toxicity or who had complications with labor or delivery would be more likely to give birth to individuals with lower IQ scores, higher scores on a measure of ASD, and lower scores on a measure of adaptive functioning. This clinical sample consisted of 33 children who presented for neuropsychological assessment with symptoms of ASD. Results indicated that individuals with a history of intrauterine toxicity had lower IQ scores than individuals who did not have a history of intrauterine toxicity. However, no significant effects were found for intrauterine toxicity and ASD or adaptive functioning. Results indicated that individuals with a history of complications during labor and delivery had lower IQ scores, higher scores on a measure of ASD, and lower scores on a measure of adaptive functioning. Findings may lend support to the oxidative stress theory of ASD.
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14. Schneider I, Regenbogen C, Kohn N, Zepf FD, Bubenzer-Busch S, Schneider F, Gur RC, Habel U. {{Reduced Responsiveness to Social Provocation in Autism Spectrum Disorder}}. {Autism Res}. 2015.
Deficits in emotion processing and social interaction are prominent symptoms of autism spectrum disorder (ASD). ASD has also been associated with aggressive tendencies towards self and others. The prevalence of aggressive behavior in this disorder, its etiology and its impact on social life are still unclear. This study investigated behavioral and physiological effects of social provocation in patients with ASD and healthy controls. We used a modified Taylor Aggression Paradigm in 24 high-functioning patients with ASD and 24 healthy controls. Participants were instructed to play against a fictitious human opponent. Money withdrawals toward the participant represented provocation and money deduction by the participant denoted aggressive behavior. Throughout the measurement, electrodermal activity (EDA) was recorded. Healthy controls showed higher aggressive responses to high provocation compared to low provocation, which demonstrated the effectiveness of the used procedure in eliciting aggression. Patients’ responses were not influenced by the level of social provocation, although in both groups aggression was higher after lost compared to won trials. Physiologically, controls showed fewer but higher EDA amplitudes when responding aggressively, whereas patients displayed the opposite pattern of more but lower EDA amplitudes. The modified Taylor Aggression Paradigm successfully elicited aggression and revealed different behavioral and neurophysiological responses in patients and healthy controls. Patients’ aggressive behavior as well as their physiological responses were less modulated by level of provocation compared to controls. Therapeutic attempts for patients might concentrate on improving empathic abilities and the understanding of social situations, including provocation and aggressive behavior. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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15. Yang CJ, Liu CL, Sang B, Zhu XM, Du YJ. {{The combined role of serotonin and interleukin-6 as biomarker for autism}}. {Neuroscience}. 2015; 284: 290-6.
Autism is a severe neurodevelopmental disorder characterized by impairments in social interaction and repetitive behaviors. Diagnosis of autism is currently phenotype based with no reliable laboratory test available to assist clinicians. It has been shown that dysfunction of serotonin (5-HT) and interleukin-6 (IL-6) are involved in autism. The goal of this study was to evaluate the combined role of 5-HT and IL-6 as potential biomarkers for autism. The whole blood concentration of 5-HT and plasma concentration of IL-6 of individuals with autism were significantly elevated compared with the control group, and the concentration of 5-HT and IL-6 had positive correlations with the severity of autism. The results of receiver operating characteristic (ROC) analysis indicated that the combination of 5-HT and IL-6 produced the best sensitivity and specificity for diagnosis of autism. Therefore, the present study has revealed a simple clinical method with great potential for assisting the diagnosis of autism.
