Autism Res Treat
· 2013 · PMID 24151554
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This review identifies mechanisms for altering DNA-histone interactions of cell chromatin to upregulate or downregulate gene expression that could serve as epigenetic targets for therapeutic interventions in autism. DNA...This review identifies mechanisms for altering DNA-histone interactions of cell chromatin to upregulate or downregulate gene expression that could serve as epigenetic targets for therapeutic interventions in autism. DNA methyltransferases (DNMTs) can phosphorylate histone H3 at T6. Aided by protein kinase C β 1, the DNMT lysine-specific demethylase-1 prevents demethylation of H3 at K4. During androgen-receptor-(AR-) dependent gene activation, this sequence may produce AR-dependent gene overactivation which may partly explain the male predominance of autism. AR-dependent gene overactivation in conjunction with a DNMT mechanism for methylating oxytocin receptors could produce high arousal inputs to the amygdala resulting in aberrant socialization, a prime characteristic of autism. Dysregulation of histone methyltransferases and histone deacetylases (HDACs) associated with low activity of methyl CpG binding protein-2 at cytosine-guanine sites in genes may reduce the capacity for condensing chromatin and silencing genes in frontal cortex, a site characterized by decreased cortical interconnectivity in autistic subjects. HDAC1 inhibition can overactivate mRNA transcription, a putative mechanism for the increased number of cerebral cortical columns and local frontal cortex hyperactivity in autistic individuals. These epigenetic mechanisms underlying male predominance, aberrant social interaction, and low functioning frontal cortex may be novel targets for autism prevention and treatment strategies.
Gadad BS, Hewitson L, Young KA
… +1 more, German DC
Autism Res Treat
· 2013 · PMID 24151553
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Autism is a heterogeneous behaviorally defined neurodevelopmental disorder. It is defined by the presence of marked social deficits, specific language abnormalities, and stereotyped repetitive patterns of behavior. Becau...Autism is a heterogeneous behaviorally defined neurodevelopmental disorder. It is defined by the presence of marked social deficits, specific language abnormalities, and stereotyped repetitive patterns of behavior. Because of the variability in the behavioral phenotype of the disorder among patients, the term autism spectrum disorder has been established. In the first part of this review, we provide an overview of neuropathological findings from studies of autism postmortem brains and identify the cerebellum as one of the key brain regions that can play a role in the autism phenotype. We review research findings that indicate possible links between the environment and autism including the role of mercury and immune-related factors. Because both genes and environment can alter the structure of the developing brain in different ways, it is not surprising that there is heterogeneity in the behavioral and neuropathological phenotypes of autism spectrum disorders. Finally, we describe animal models of autism that occur following insertion of different autism-related genes and exposure to environmental factors, highlighting those models which exhibit both autism-like behavior and neuropathology.
Usui S, Senju A, Kikuchi Y
… +4 more, Akechi H, Tojo Y, Osanai H, Hasegawa T
Autism Res Treat
· 2013 · PMID 23970970
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Most previous studies suggest diminished susceptibility to contagious yawning in children with autism spectrum disorder (ASD). However, it could be driven by their atypical attention to the face. To test this hypothesis,...Most previous studies suggest diminished susceptibility to contagious yawning in children with autism spectrum disorder (ASD). However, it could be driven by their atypical attention to the face. To test this hypothesis, children with ASD and typically developing (TD) children were shown yawning and control movies. To ensure participants' attention to the face, an eye tracker controlled the onset of the yawning and control stimuli. Results demonstrated that both TD children and children with ASD yawned more frequently when they watched the yawning stimuli than the control stimuli. It is suggested therefore that the absence of contagious yawning in children with ASD, as reported in previous studies, might relate to their weaker tendency to spontaneously attend to others' faces.
Patten E, Ausderau KK, Watson LR
… +1 more, Baranek GT
Autism Res Treat
· 2013 · PMID 23956859
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We sought to examine concurrent and longitudinal associations between sensory response patterns (i.e., hyperresponsiveness, hyporesponsiveness, and sensory seeking) and verbal status of young children with autism spectru...We sought to examine concurrent and longitudinal associations between sensory response patterns (i.e., hyperresponsiveness, hyporesponsiveness, and sensory seeking) and verbal status of young children with autism spectrum disorder (ASD) as a potential factor influencing the development of verbal communication. Seventy-nine children with ASD (verbal, n = 29; nonverbal, n = 50) were assessed using cross-sectional analyses (Study 1), and 14 children with ASD (verbal, n = 6; nonverbal, n = 8) were assessed using prospective longitudinal analyses (Study 2). Data were collected regarding sensory response patterns and verbal ability. Hyporesponsiveness and sensory seeking behaviors were associated with verbal status in both cross-sectional and longitudinal analyses; nonverbal children were more likely to demonstrate higher hyporesponsive and sensory seeking patterns. Hyperresponsiveness did not significantly differ between verbal and nonverbal groups in either design. Sensory hyporesponsiveness and seeking behaviors may be important factors hindering the development of functional verbal communication in children with ASD. Unusual sensory responsiveness can often be observed before the onset of speech and may yield important prognostic capabilities as well as inform early interventions targeting verbal communication or alternative communication options in young children with ASD.
Autism Res Treat
· 2013 · PMID 23862063
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Individuals with autism spectrum disorders (ASD) have impairments in social interaction, communicative capacity, and behavioral flexibility (core triad). Three major cognitive theories (theory of mind deficit, weak centr...Individuals with autism spectrum disorders (ASD) have impairments in social interaction, communicative capacity, and behavioral flexibility (core triad). Three major cognitive theories (theory of mind deficit, weak central coherence, and executive dysfunction) seem to explain many of these impairments. Currently, however, the empathizing-systemizing (a newer version of the theory of mind deficit account) and mnesic imbalance theories are the only ones that attempt to explain all these core triadic symptoms of ASD On the other hand, theory of mind deficit in empathizing-systemizing theory is the most influential account for ASD, but its counterpart in the mnesic imbalance theory, faulty procedural memory, seems to occur earlier in development; consequently, this might be a better solution to the problem of the etiology of ASD, if it truly meets the precedence criterion. Hence, in the present paper I review the reasoning in favor of the theory of mind deficit but with a new interpretation based on the mnesic imbalance theory, which posits that faulty procedural memory causes deficits in several cognitive skills, resulting in poor performance in theory of mind tasks.
Lopata C, Smith RA, Volker MA
… +3 more, Thomeer ML, Lee GK, McDonald CA
Autism Res Treat
· 2013 · PMID 23819048
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Adaptive behavior rating scales are frequently used to gather information on the adaptive functioning of children with high-functioning autism spectrum disorders (HFASDs), yet little is known about the extent to which th...Adaptive behavior rating scales are frequently used to gather information on the adaptive functioning of children with high-functioning autism spectrum disorders (HFASDs), yet little is known about the extent to which these measures yield comparable results. This study was conducted to (a) document the parent-rated VABS-II, BASC-2, and ABAS-II adaptive behavior profiles of 6- to 11-year-olds with HFASDs (including relative strengths and weaknesses); (b) examine the extent to which these measures yielded similar scores on comparable scales; and (c) assess potential discrepancies between cognitive ability and adaptive behavior across the measures. All three adaptive measures revealed significant deficits overall for the sample, with the VABS-II and ABAS-II indicating relative weaknesses in social skills and strengths in academic-related skills. Cross-measure comparisons indicated significant differences in the absolute magnitude of scores. In general, the VABS-II yielded significantly higher scores than the BASC-2 and ABAS-II. However, the VABS-II and ABAS-II yielded scores that did not significantly differ for adaptive social skills which is a critical area to assess for children with HFASDs. Results also indicated significant discrepancies between the children's average IQ score and their scores on the adaptive domains and composites of the three adaptive measures.
Autism Res Treat
· 2013 · PMID 23762552
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The Autism Spectrum Quotient is used to assess autistic spectrum traits in intellectually competent adults in both the general population and the autism spectrum community. While the autism spectrum Quotient has been val...The Autism Spectrum Quotient is used to assess autistic spectrum traits in intellectually competent adults in both the general population and the autism spectrum community. While the autism spectrum Quotient has been validated in several different cultures, to date no study has assessed the psychometrics of the Autism Spectrum Quotient on an Australian population. The purpose of this study was to assess the psychometrics of the autism spectrum Quotient in an Australian sample of both typically developing individuals (n = 128) and individuals with autism spectrum disorder (n = 104). The results revealed that the internal consistency and the test-retest reliability were satisfactory; individuals with autism spectrum disorder scored higher on total Autism Spectrum Quotient score and its subscales than typically developing individuals; however, gender differences were not apparent on total score. Possible cultural differences may explain some of the psychometric variations found. The results of this analysis revealed that the Autism Spectrum Quotient was a reliable instrument for investigating variation in autistic symptomology in both typically developing and Autism Spectrum Disorders populations within an Australian population.
Apicella F, Chericoni N, Costanzo V
… +4 more, Baldini S, Billeci L, Cohen D, Muratori F
Autism Res Treat
· 2013 · PMID 23762551
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From early infancy onwards, young children appear motivated to engage reciprocally with others and share psychological states during dyadic interactions. Although poor reciprocity is one of the defining features of autis...From early infancy onwards, young children appear motivated to engage reciprocally with others and share psychological states during dyadic interactions. Although poor reciprocity is one of the defining features of autism spectrum disorders (ASDs), few studies have focused on the direct assessment of real-life reciprocal behavior; consequently, our knowledge of the nature and the development of this core feature of autism is still limited. In this study, we describe the phenomenon of reciprocity in infant-caregiver interaction by analyzing family movies taken during the first year of life of 10 infants with ASD and 9 infants with typical development (TD). We analyzed reciprocal behaviors by means of a coding scheme developed for this purpose (caregiver-infant reciprocity scale (CIRS)). Infants with ASD displayed less motor activity during the first semester and subsequently fewer vocalizations, compared to TD infants. Caregivers of ASD infants showed in the second semester shorter periods of involvement and a reduction of affectionate touch. These results suggest that from the first months of life a nonsynchronic motor-vocal pattern may interfere in different ways with the development of reciprocity in the primary relationship between infants later diagnosed with ASD and their caregivers.
Lopata C, Toomey JA, Fox JD
… +3 more, Thomeer ML, Volker MA, Lee GK
Autism Res Treat
· 2013 · PMID 23762550
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This study examined (1) the prevalence of psychotropic medication use for a sample of children with high-functioning autism spectrum disorders (HFASDs), (2) the extent to which psychotropic agents were linked to targeted...This study examined (1) the prevalence of psychotropic medication use for a sample of children with high-functioning autism spectrum disorders (HFASDs), (2) the extent to which psychotropic agents were linked to targeted symptoms, and (3) predictors of psychotropic use. A total of 115 children, ages 6-13, with HFASDs who were enrolled in psychosocial treatment trials were included in this study. Parents completed extensive background and rating forms prior to treatment that included data on demographic characteristics, child health, child medication use, and child ASD-related symptoms. Results indicated that 33% (n = 38) of the sample was taking psychotropic medication with the most common being stimulants (25%; n = 29), antidepressants (10%; n = 12), and neuroleptics (6%; n = 7). All children taking stimulants had target symptoms that were appropriate for stimulant medication, whereas 57% of those taking neuroleptics and 42% of those taking antidepressants did not have targeted symptoms consistent with the medication. Logistic regression for the major psychotropic drug categories indicated that lower IQ was a significant predictor of increased antidepressant and neuroleptic use. A higher level of ASD-related symptoms was related to the likelihood of stimulant use.
Autism Res Treat
· 2013 · PMID 23533752
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Autism, a neurodevelopmental disorder that affects boys more than girls, is often associated with altered levels of monoamines (serotonin and catecholamines), especially elevated serotonin levels. The monoamines act as b...Autism, a neurodevelopmental disorder that affects boys more than girls, is often associated with altered levels of monoamines (serotonin and catecholamines), especially elevated serotonin levels. The monoamines act as both neurotransmitters and signaling molecules in the gastrointestinal and immune systems. The evidence related to monoamine metabolism may be summarized as follows: (i) monoamine neurotransmitters are enzymatically degraded/inactivated by three mechanisms: oxidative deamination, methylation, and sulfation. The latter two are limited by the supply of methyl groups and sulfate, respectively. (ii) A decrease in methylation- and sulfation-mediated monoamine inactivation can be compensated by an increase in the oxidative deamination catalyzed by monoamine oxidase, an X-linked enzyme exhibiting higher activity in females than in males. (iii) Vitamins can, on one hand, facilitate the synthesis of monoamine neurotransmitters and, on the other hand, inhibit their inactivation by competing for methylation and sulfation. Therefore, we postulate that excess multivitamin feeding in early infancy, which has become very popular over the past few decades, may be a potential risk factor for disturbed monoamine metabolism. In this paper, we will focus on the relationship between excess multivitamin exposure and the inactivation/degradation of monoamine neurotransmitters and its possible role in the development of autism.
Murphy ER, Foss-Feig J, Kenworthy L
… +2 more, Gaillard WD, Vaidya CJ
Autism Res Treat
· 2012 · PMID 23326662
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We examined functional connectivity of the amygdala in preadolescent children with Autism Spectrum Disorders (ASDs) during spontaneous attention to eye-gaze in emotional faces. Children responded to a target word ("LEFT/...We examined functional connectivity of the amygdala in preadolescent children with Autism Spectrum Disorders (ASDs) during spontaneous attention to eye-gaze in emotional faces. Children responded to a target word ("LEFT/RIGHT") printed on angry or fearful faces looking in a direction that was congruent, incongruent, or neutral with the target word. Despite being irrelevant to the task, gaze-direction facilitated (Congruent > Neutral) or interfered with (Incongruent > Congruent) performance in both groups. Despite similar behavioral performance, amygdala-connectivity was atypical and more widespread in children with ASD. In control children, the amygdala was more strongly connected with an emotional cognitive control region (subgenual cingulate) during interference, while during facilitation, no regions showed greater amygdala connectivity than in ASD children. In contrast, in children with ASD the amygdala was more strongly connected to salience and cognitive control regions (posterior and dorsal cingulate) during facilitation and with regions involved in gaze processing (superior temporal sulcus), cognitive control (inferior frontal gyrus), and processing of viscerally salient information (pregenual cingulate, anterior insula, and thalamus) during interference. These findings showing more widespread connectivity of the amygdala extend past findings of atypical functional anatomy of eye-gaze processing in children with ASD and challenge views of general underconnectivity in ASD.
Lofthouse N, Hendren R, Hurt E
… +2 more, Arnold LE, Butter E
Autism Res Treat
· 2012 · PMID 23243505
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Given the severe and chronic problems associated with Autism Spectrum Disorders (ASD) and the limitations of available treatments, there exists a large public health need for additional interventions. As more parents are...Given the severe and chronic problems associated with Autism Spectrum Disorders (ASD) and the limitations of available treatments, there exists a large public health need for additional interventions. As more parents are inquiring about complementary and alternative treatments (CATs), both parents and practitioners require up-to-date information about them and whether and how to integrate them into treatment. After presenting data on CAT usage patterns for ASD, we review 13 ingestible (i.e., orally administered) and 6 noningestible (i.e., externally administered) CATs for ASD. For each CAT we briefly describe its definition; rationale for use; current research support, limitations, and future directions; safety issues; and whether we currently recommend, not recommend, or find it acceptable for the treatment of ASD. We conclude this paper with recommendations for future research and ten clinical recommendations for practitioners.
Autism Res Treat
· 2012 · PMID 23227334
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Although there is consensus that parents should be involved in interventions designed for young children with autism spectrum disorder (ASD), parent participation alone does not ensure consistent, generalized gains in ch...Although there is consensus that parents should be involved in interventions designed for young children with autism spectrum disorder (ASD), parent participation alone does not ensure consistent, generalized gains in children's development. Barriers such as costly intervention, time-intensive sessions, and family life may prevent parents from using the intervention at home. Telehealth integrates communication technologies to provide health-related services at a distance. A 12 one-hour per week parent intervention program was tested using telehealth delivery with nine families with ASD. The goal was to examine its feasibility and acceptance for promoting child learning throughout families' daily play and caretaking interactions at home. Parents became skilled at using teachable moments to promote children's spontaneous language and imitation skills and were pleased with the support and ease of telehealth learning. Preliminary results suggest the potential of technology for helping parents understand and use early intervention practices more often in their daily interactions with children.
Stahmer AC, Suhrheinrich J, Reed S
… +1 more, Schreibman L
Autism Res Treat
· 2012 · PMID 23209896
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Several evidence-based practices (EBPs) have been identified as efficacious for the education of students with autism spectrum disorders (ASD). However, effectiveness research has rarely been conducted in schools and tea...Several evidence-based practices (EBPs) have been identified as efficacious for the education of students with autism spectrum disorders (ASD). However, effectiveness research has rarely been conducted in schools and teachers express skepticism about the clinical utility of EBPs for the classroom. Innovative methods are needed to optimally adapt EBPs for community use. This study utilizes qualitative methods to identify perceived benefits and barriers of classroom implementation of a specific EBP for ASD, Pivotal Response Training (PRT). Teachers' perspectives on the components of PRT, use of PRT as a classroom intervention strategy, and barriers to the use of PRT were identified through guided discussion. Teachers found PRT valuable; however, they also found some components challenging. Specific teacher recommendations for adaptation and resource development are discussed. This process of obtaining qualitative feedback from frontline practitioners provides a generalizable model for researchers to collaborate with teachers to optimally promote EBPs for classroom use.
Autism Res Treat
· 2012 · PMID 23193469
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Research suggests that self-injurious behavior (SIB) is related to social deficits and cooccurring problem behaviors in children and adolescents with autism spectrum disorder. A sample of 95 participants with ASD was ass...Research suggests that self-injurious behavior (SIB) is related to social deficits and cooccurring problem behaviors in children and adolescents with autism spectrum disorder. A sample of 95 participants with ASD was assessed on presence and frequency of SIB (Behavior Problems Inventory), social deficits (the Matson Evaluation of Social Skills with Youngsters-II) and cooccurring problem behaviors (ASD-Comorbidity-Child version). A model was created and tested to explain the relationship between these variables. Results showed that the model was acceptable in presenting the relationships between these variables. This information could be used to help predict which individuals are at risk of developing further cooccurring behavioral problems and determine risk markers for the development of social deficits.
Reaven J, Blakeley-Smith A, Leuthe E
… +2 more, Moody E, Hepburn S
Autism Res Treat
· 2012 · PMID 23091719
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Adolescents with high-functioning autism spectrum disorders (ASDs) are at high risk for developing psychiatric symptoms, with anxiety disorders among the most commonly cooccurring. Cognitive behavior therapies (CBTs) are...Adolescents with high-functioning autism spectrum disorders (ASDs) are at high risk for developing psychiatric symptoms, with anxiety disorders among the most commonly cooccurring. Cognitive behavior therapies (CBTs) are considered the best practice for treating anxiety in the general population. Modified CBT approaches for youth with high-functioning ASD and anxiety have resulted in significant reductions in anxiety following intervention. The purpose of the present study was to develop an intervention for treating anxiety in adolescents with ASD based on a CBT program designed for school-aged children. The Facing Your Fears-Adolescent Version (FYF-A) program was developed; feasibility and acceptability data were obtained, along with initial efficacy of the intervention. Twenty-four adolescents, aged 13-18, completed the FYF-A intervention. Results indicated significant reductions in anxiety severity and interference posttreatment, with low rates of anxiety maintained at 3-month follow-up. In addition, nearly 46% of teen participants met criteria for a positive treatment response on primary diagnosis following the intervention. Initial findings from the current study are encouraging and suggest that modified group CBT for adolescents with high-functioning ASD may be effective in reducing anxiety symptoms. Limitations include small sample size and lack of control group. Future directions are discussed.
Yi L, Liu Y, Li Y
… +3 more, Fan Y, Huang D, Gao D
Autism Res Treat
· 2012 · PMID 23050145
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Impaired cognitive flexibility in children with autism spectrum disorder (ASD) has been reported in previous literature. The present study explored ASD children's visual scanning patterns during the Dimensional Change Ca...Impaired cognitive flexibility in children with autism spectrum disorder (ASD) has been reported in previous literature. The present study explored ASD children's visual scanning patterns during the Dimensional Change Card Sorting (DCCS) task using eye-tracking technique. ASD and typical developing (TD) children completed the standardized DCCS procedure on the computer while their eye movements were tracked. Behavioral results confirmed previous findings on ASD children's deficits in executive function. ASD children's visual scanning patterns also showed some specific underlying processes in the DCCS task compared to TD children. For example, ASD children looked shorter at the correct card in the postswitch phase and spent longer time at blank areas than TD children did. ASD children did not show a bias to the color dimension as TD children did. The correlations between the behavioral performance and eye moments were also discussed.
Autism Res Treat
· 2012 · PMID 22997574
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Autism affects 1 : 88 children in the United States. Familial history of autoimmune disease, autoantibodies in the serum of mothers when there is more than one autistic offspring, and neuroglial response in CSF and brain...Autism affects 1 : 88 children in the United States. Familial history of autoimmune disease, autoantibodies in the serum of mothers when there is more than one autistic offspring, and neuroglial response in CSF and brain tissue in autistic patients suggest an immunological variable may be associated with this condition. Lenalidomide has the potential to invoke changes in TNF-α with less toxicity than thalidomide. This pilot study evaluated lenalidomide at reduction of TNF-α and improvement of behavior and language in children with autism with elevated TNF-α. Subjects with elevated TNF-α were given 2.5 mgs lenalidomide daily for 12-weeks. Pharmacodynamics and safety was evaluated. Changes in language and autistic behaviors after six and twelve weeks were measured. Although statistical significance was not achieved for most measures, there were trends toward improvement. After 6-weeks, mean receptive language increased: 60.67 ± 12.06 to 65.00 ± 15.10 (P = 0.11) and symptoms of autism decreased (40.75 ± 5.96 versus 38.67 ± 7.90, P = 0.068). After 12-weeks, CSF-TNF-α declined 57% ± 25% from 80.5 ± 41.03 to 38.0 ± 31.27 (P = 0.068). Serum TNF-α declined 57% (92.50 ± 68.92 to 40.25 ± 44.53 (P = 0.048). This study suggests that lenalidomide is tolerated as a treatment by children with autism and should be further studied as a potential agent for cytockine inflammation.
Autism Res Treat
· 2012 · PMID 22937260
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Autism is a chronic neurodevelopmental disorder of unknown cause that affects approximately 1-3 percent of children and four times more boys than girls. Its prevalence is global and its social impact is devastating. In a...Autism is a chronic neurodevelopmental disorder of unknown cause that affects approximately 1-3 percent of children and four times more boys than girls. Its prevalence is global and its social impact is devastating. In autism, the brain is unable to process sensory information normally. Instead, simple stimuli from the outside world are experienced as overwhelmingly intense and strain the emotional centers of the brain. A stress response to the incoming information is initiated that destabilizes cognitive networks and short-circuits adequate behavioral output. As a result, the child is unable to respond adequately to stimulation and initiate social behavior towards family, friends, and peers. In addition, these children typically face immune-digestive disorders that heighten social fears, anxieties, and internal conflicts. While it is critical to treat the physical symptoms, it is equally vital to offer an evidence-based holistic solution that harmonizes both their emotional and physical well-being as they move from childhood into adult life. Here, we summarize evidence from clinical studies and neuroscience research that suggests that an approach built on yogic principles and meditative tools is worth pursuing. Desired outcomes include relief of clinical symptoms of the disease, greater relaxation, and facilitated expression of feelings and skills, as well as improved family and social quality of life.