1. Arnevik EA, Helverschou SB. {{Autism Spectrum Disorder and Co-occurring Substance Use Disorder – A Systematic Review}}. {Subst Abuse}. 2016; 10: 69-75.
OBJECTIVE: Patients with co-occurring autism spectrum disorders (ASD) and substance use disorder (SUD) require special attention from clinical services. Screening for this co-occurrence is not generally an integral part of routine clinical assessments, and failure to identify and understand this group of patients may contribute to a worsening of their symptoms and/or an increase in drug abuse. Thus, there is a need to review the evidence base on patients with co-occurring ASD and SUD in order to enhance clinical practice and future research. METHODS: We reviewed all identified papers on patients with co-occurring ASD and SUD. The focus of the review was on epidemiology, patient characteristics, function of drug use, and the effect of current interventions. RESULTS: A total of 18 papers were included in the analysis. Eleven papers were based on epidemiological studies, although only one study reported the prevalence of ASD in an SUD population. Two papers explored the role of personality, three papers studied subgroups of individuals serving prison for violent or sexual crimes, and one paper explored the function of drugs in the ASD patient group. There were no studies testing specific treatment interventions. CONCLUSIONS: In most of the treatment settings studied, there were relatively few patients with co-occurring ASD and SUD, but due to differences in study samples it was difficult to establish a general prevalence rate. The one consistent finding was the lack of focused treatment studies. There is clearly a need for research on interventions that take account of the special needs of this patient group.
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2. Cellot G, Maggi L, Di Castro MA, Catalano M, Migliore R, Migliore M, Scattoni ML, Calamandrei G, Cherubini E. {{Premature changes in neuronal excitability account for hippocampal network impairment and autistic-like behavior in neonatal BTBR T+tf/J mice}}. {Sci Rep}. 2016; 6: 31696.
Coherent network oscillations (GDPs), generated in the immature hippocampus by the synergistic action of GABA and glutamate, both depolarizing and excitatory, play a key role in the construction of neuronal circuits. In particular, GDPs-associated calcium transients act as coincident detectors for enhancing synaptic efficacy at emerging GABAergic and glutamatergic synapses. Here, we show that, immediately after birth, in the CA3 hippocampal region of the BTBR T+tf/J mouse, an animal model of idiopathic autism, GDPs are severely impaired. This effect was associated with an increased GABAergic neurotransmission and a reduced neuronal excitability. In spite its depolarizing action on CA3 pyramidal cells (in single channel experiments EGABA was positive to Em), GABA exerted at the network level an inhibitory effect as demonstrated by isoguvacine-induced reduction of neuronal firing. We implemented a computational model in which experimental findings could be interpreted as the result of two competing effects: a reduction of the intrinsic excitability of CA3 principal cells and a reduction of the shunting activity in GABAergic interneurons projecting to principal cells. It is therefore likely that premature changes in neuronal excitability within selective hippocampal circuits of BTBR mice lead to GDPs dysfunction and behavioral deficits reminiscent of those found in autistic patients.
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3. Cheng N, Khanbabaei M, Murari K, Rho JM. {{Disruption of visual circuit formation and refinement in a mouse model of autism}}. {Autism Res}. 2016.
Aberrant connectivity is believed to contribute to the pathophysiology of autism spectrum disorder (ASD). Recent neuroimaging studies have increasingly identified such impairments in patients with ASD, including alterations in sensory systems. However, the cellular substrates and molecular underpinnings of disrupted connectivity remain poorly understood. Utilizing eye-specific segregation in the dorsal lateral geniculate nucleus (dLGN) as a model system, we investigated the formation and refinement of precise patterning of synaptic connections in the BTBR T + tf/J (BTBR) mouse model of ASD. We found that at the neonatal stage, the shape of the dLGN occupied by retinal afferents was altered in the BTBR group compared to C57BL/6J (B6) animals. Notably, the degree of overlap between the ipsi- and contralateral afferents was significantly greater in the BTBR mice. Moreover, these abnormalities continued into mature stage in the BTBR animals, suggesting persistent deficits rather than delayed maturation of axonal refinement. Together, these results indicate disrupted connectivity at the synaptic patterning level in the BTBR mice, suggesting that in general, altered neural circuitry may contribute to autistic behaviours seen in this animal model. In addition, these data are consistent with the notion that lower-level, primary processing mechanisms contribute to altered visual perception in ASD. Autism Res 2016. (c) 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
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4. Deserno MK, Borsboom D, Begeer S, Geurts HM. {{Multicausal systems ask for multicausal approaches: A network perspective on subjective well-being in individuals with autism spectrum disorder}}. {Autism}. 2016.
Given the heterogeneity of autism spectrum disorder, an important limitation of much autism spectrum disorder research is that outcome measures are statistically modeled as separate dependent variables. Often, their multivariate structure is either ignored or treated as a nuisance. This study aims to lift this limitation by applying network analysis to explicate the multivariate pattern of risk and success factors for subjective well-being in autism spectrum disorder. We estimated a network structure for 27 potential factors in 2341 individuals with autism spectrum disorder to assess the centrality of specific life domains and their importance for well-being. The data included both self- and proxy-reported information. We identified social satisfaction and societal contribution as the strongest direct paths to subjective well-being. The results suggest that an important contribution to well-being lies in resources that allow the individual to engage in social relations, which influence well-being directly. Factors most important in determining the network’s structure include self-reported IQ, living situation, level of daily activity, and happiness. Number of family members with autism spectrum disorder and openness about one’s diagnosis are least important of all factors for subjective well-being. These types of results can serve as a roadmap for interventions directed at improving the well-being of individuals with autism spectrum disorder.
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5. Faroy M, Meiri G, Arbelle S. {{[DSM-5 AND AUTISM: DIAGNOSTIC CHANGES AND CLINICAL IMPLICATIONS IN EARLY CHILDHOOD]}}. {Harefuah}. 2016; 155(5): 291-5, 322.
Autistic spectrum disorders (ASDs) are characterized by significant disability in interpersonal communication, social interactions and patterns of unusual behavior. In recent decades the worldwide prevalence of ASDs is rising almost exponentially, without a clear known etiological explanation. Until recently, ASDs were defined by the American Manual of Psychiatric Diagnoses: The DSM-IV-TR, under one conceptual umbrella of « Pervasive Developmental Disorders » (PDD). Under this category, there were five separate diagnoses. The DSM-5 eliminated the separate,diagnoses and created one continuum (Autism Spectrum Disorder = ASD). By this definition, the symptomatic manifestation was reduced and the criteria for diagnosis are fixed for the entire spectrum. The differences between individuals are expressed in the levels of severity rated. Studies evaluating the transition from PDD to ASD, found an increase in the specificity of the diagnosis and its potential ability to distinguish between clinical and non-clinical populations. Alongside the increase in consistency and stability, there is a decrease in sensitivity, and about a quarter of the children who were previously diagnosed with PDD are not diagnosed as such, due to a failure to meet all the necessary symptoms. These changes especially affect the clinical diagnosis of young children as their symptomatic manifestation is not yet clear and distinct enough due to their age and maturation processes. This article discusses the clinical implications of these findings and demonstrates it from a case report.
6. Glod M, Riby DM, Honey E, Rodgers J. {{Sensory atypicalities in dyads of children with autism spectrum disorder (ASD) and their parents}}. {Autism Res}. 2016.
Sensory atypicalities are a common feature of autism spectrum disorder (ASD). To date, the relationship between sensory atypicalities in dyads of children with ASD and their parents has not been investigated. Exploring these relationships can contribute to an understanding of how phenotypic profiles may be inherited, and the extent to which familial factors might contribute towards children’s sensory profiles and constitute an aspect of the broader autism phenotype (BAP). Parents of 44 children with ASD and 30 typically developing (TD) children, aged between 3 and 14 years, participated. Information about children’s sensory experiences was collected through parent report using the Sensory Profile questionnaire. Information about parental sensory experiences was collected via self-report using the Adolescent/Adult Sensory Profile. Parents of children with ASD had significantly higher scores than parents of TD children in relation to low registration, over responsivity, and taste/smell sensory processing. Similar levels of agreement were obtained within ASD and TD parent-child dyads on a number of sensory atypicalities; nevertheless significant correlations were found between parents and children in ASD families but not TD dyads for sensation avoiding and auditory, visual, and vestibular sensory processing. The findings suggest that there are similarities in sensory processing profiles between parents and their children in both ASD and TD dyads. Familial sensory processing factors are likely to contribute towards the BAP. Further work is needed to explore genetic and environmental influences on the developmental pathways of the sensory atypicalities in ASD. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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7. Hadjkacem I, Ayadi H, Turki M, Yaich S, Khemekhem K, Walha A, Cherif L, Moalla Y, Ghribi F. {{Prenatal, perinatal and postnatal factors associated with autism spectrum disorder}}. {J Pediatr (Rio J)}. 2016.
OBJECTIVE: To identify prenatal, perinatal and postnatal risk factors in children with autism spectrum disorder (ASD) by comparing them to their siblings without autistic disorders. METHOD: The present study is cross sectional and comparative. It was conducted over a period of three months (July-September 2014). It included 101 children: 50 ASD’s children diagnosed according to DSM-5 criteria and 51 unaffected siblings. The severity of ASD was assessed by the CARS. RESULTS: Our study revealed a higher prevalence of prenatal, perinatal and postnatal factors in children with ASD in comparison with unaffected siblings. It showed also a significant association between perinatal and postnatal factors and ASD (respectively p=0.03 and p=0.042). In this group, perinatal factors were mainly as type of suffering acute fetal (26% of cases), long duration of delivery and prematurity (18% of cases for each factor), while postnatal factors were represented principally by respiratory infections (24%). As for parental factors, no correlation was found between advanced age of parents at the moment of the conception and ASD. Likewise, no correlation was observed between the severity of ASD and different factors. After logistic regression, the risk factors retained for autism in the final model were: male gender, prenatal urinary tract infection, acute fetal distress, difficult labor and respiratory infection. CONCLUSIONS: The present survey confirms the high prevalence of prenatal, perinatal and postnatal factors in children with ASD and suggests the intervention of some of these factors (acute fetal distress and difficult labor, among others), as determinant variables for the genesis of ASD.
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8. Hayward BE, Zhou Y, Kumari D, Usdin K. {{A Set of Assays for the Comprehensive Analysis of FMR1 Alleles in the Fragile X-Related Disorders}}. {J Mol Diagn}. 2016; 18(5): 762-74.
The diagnosis and study of the fragile X-related disorders is complicated by the difficulty of amplifying the long CGG/CCG-repeat tracts that are responsible for disease pathology, the potential presence of AGG interruptions within the repeat tract that can ameliorate expansion risk, the occurrence of variable DNA methylation that modulates disease severity, and the high frequency of mosaicism for both repeat number and methylation status. These factors complicate patient risk assessment. In addition, the variability in these parameters that is seen when patient cells are grown in culture requires their frequent monitoring to ensure reproducible results in a research setting. Many existing assays have the limited ability to amplify long alleles, particularly in a mixture of different allele sizes. Others are better at this, but are too expensive for routine use in most laboratories or for newborn screening programs and use reagents that are proprietary. We describe herein a set of assays to routinely evaluate all of these important parameters in a time- and cost-effective way.
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9. Heinicke MR, Carr JE, Pence ST, Zias DR, Valentino AL, Falligant JM. {{Assessing the efficacy of pictorial preference assessments for children with developmental disabilities}}. {J Appl Behav Anal}. 2016.
Past research has demonstrated that pictorial preference assessments can predict subsequent reinforcement effects for individuals with developmental disabilities only when access to the selected stimulus is provided contingent on a pictorial selection. The purpose of the present investigation was to assess more comprehensively the feasibility of the pictorial format with children with developmental disabilities. In Experiment 1, prerequisite skill assessments were conducted, and the role of a contingent reinforcer was assessed by comparing the results from the pictorial assessment without contingent access to a reinforcer assessment. If contingent access was found to be necessary, the effects of schedule thinning were evaluated to determine whether a pictorial format could be made more practical in Experiment 2. The pictorial format without contingent access was successful with only some participants. However, schedule thinning was found to be an effective method to establish conditioned reinforcement properties for pictorial stimuli to create a more practical assessment for a subset of participants.
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10. Hens K, Peeters H, Dierickx K. {{Genetic testing and counseling in the case of an autism diagnosis: A caregivers perspective}}. {Eur J Med Genet}. 2016; 59(9): 452-8.
The search for genes that can explain the development of autism is ongoing. At the same time, genetic counselling and genetic testing can be offered to families with a child diagnosed with autism. However, given the complexity of autism, both with respect to its aetiology as well as with respect to its heterogeneity, such genetic counselling and testing raises specific ethical questions regarding the aim and scope. In order to map these questions and opinions we interviewed 15 Belgian autism professionals. We found that they believed that genetic counselling and genetic testing have certain benefits for families confronted with an autism diagnosis, but also that direct benefit to the child is limited to those cases where a genetic finding offers a certain prognosis and intervention plan. In cases where autism is the result of a syndrome or a known genetic variant that is associated with other health problems, detection can also enable prevention of these health issues. Benefits of genetic testing, such as relief of guilt and reproductive choice, are primarily benefits to the parents, although indirectly they may affect the wellbeing of the person diagnosed. These benefits are associated with ethical questions.
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11. Johnson BP, Lum JA, Rinehart NJ, Fielding J. {{Ocular motor disturbances in autism spectrum disorders: Systematic review and comprehensive meta-analysis}}. {Neurosci Biobehav Rev}. 2016; 69: 260-79.
There has been considerable focus placed on how individuals with autism spectrum disorder (ASD) visually perceive and attend to social information, such as facial expressions or social gaze. The role of eye movements is inextricable from visual perception, however this aspect is often overlooked. We performed a series of meta-analyses based on data from 28 studies of eye movements in ASD to determine whether there is evidence for ocular motor dysfunction in ASD. Tasks assessed included visually-guided saccade tasks, gap/overlap, anti-saccade, pursuit tasks and ocular fixation. These analyses revealed evidence for ocular motor dysfunction in ASD, specifically relating to saccade dysmetria, difficulty inhibiting saccades and impaired tracking of moving targets. However there was no evidence for deficits relating to initiating eye movements, or engaging and disengaging from simple visual targets. Characterizing ocular motor abnormalities in ASD may provide insight into the functional integrity of brain networks in ASD across development, and assist our understanding of visual and social attention in ASD.
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12. Lu H, Ash RT, He L, Kee SE, Wang W, Yu D, Hao S, Meng X, Ure K, Ito-Ishida A, Tang B, Sun Y, Ji D, Tang J, Arenkiel BR, Smirnakis SM, Zoghbi HY. {{Loss and Gain of MeCP2 Cause Similar Hippocampal Circuit Dysfunction that Is Rescued by Deep Brain Stimulation in a Rett Syndrome Mouse Model}}. {Neuron}. 2016; 91(4): 739-47.
Loss- and gain-of-function mutations in methyl-CpG-binding protein 2 (MECP2) underlie two distinct neurological syndromes with strikingly similar features, but the synaptic and circuit-level changes mediating these shared features are undefined. Here we report three novel signs of neural circuit dysfunction in three mouse models of MECP2 disorders (constitutive Mecp2 null, mosaic Mecp2(+/-), and MECP2 duplication): abnormally elevated synchrony in the firing activity of hippocampal CA1 pyramidal neurons, an impaired homeostatic response to perturbations of excitatory-inhibitory balance, and decreased excitatory synaptic response in inhibitory neurons. Conditional mutagenesis studies revealed that MeCP2 dysfunction in excitatory neurons mediated elevated synchrony at baseline, while MeCP2 dysfunction in inhibitory neurons increased susceptibility to hypersynchronization in response to perturbations. Chronic forniceal deep brain stimulation (DBS), recently shown to rescue hippocampus-dependent learning and memory in Mecp2(+/-) (Rett) mice, also rescued all three features of hippocampal circuit dysfunction in these mice.
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13. Mychasiuk R, Rho JM. {{Genetic modifications associated with ketogenic diet treatment in the BTBRT+Tf/J mouse model of autism spectrum disorder}}. {Autism Res}. 2016.
Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder characterized by hallmark behavioral features. The spectrum of disorders that fall within the ASD umbrella encompass a distinct but overlapping symptom complex that likely results from an array of molecular and genetic aberrations rather than a single genetic mutation. The ketogenic diet (KD) is a high-fat low-carbohydrate anti-seizure and neuroprotective diet that has demonstrated efficacy in the treatment of ASD-like behaviors in animal and human studies. We investigated changes in mRNA and gene expression in the BTBR mouse model of ASD that may contribute to the behavioral phenotype. In addition, we sought to examine changes in gene expression following KD treatment in BTBR mice. Despite significant behavioral abnormalities, expression changes in BTBR mice did not differ substantially from controls; only 33 genes were differentially expressed in the temporal cortex, and 48 in the hippocampus. Examination of these differentially expressed genes suggested deficits in the stress response and in neuronal signaling/communication. After treatment with the KD, both brain regions demonstrated improvements in ASD deficits associated with myelin formation and white matter development. Although our study supports many of the previously known impairments associated with ASD, such as excessive myelin formation and impaired GABAergic transmission, the RNAseq data and pathway analysis utilized here identified new therapeutic targets for analysis, such as Vitamin D pathways and cAMP signaling. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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14. Qasem H, Al-Ayadhi L, El-Ansary A. {{Cysteinyl leukotriene correlated with 8-isoprostane levels as predictive biomarkers for sensory dysfunction in autism}}. {Lipids Health Dis}. 2016; 15: 130.
BACKGROUND: Autism is a neurodevelopmental disorder that clinically presented as cognitive deficits, social impairments and sensory dysfunction. An increasing body of evidence has shown that oxidative stress and inflammation are involved in the pathophysiology of autism. Recording biomarkers as measure of the severity of autistic features might help in understanding the pathophysiology of autism. METHODS: This study investigates the plasma levels of 8-isoprostane and Cysteinyl leukotrienes (CysLTs) in 44 autistic children and 40 healthy controls. The recruited autistic patients were assessed for behavior, cognitive and sensory deficits by using different autism severity rating scales, including the Childhood Autism Rating Scales (CARS), Social responsiveness scale (SRS) and Short Sensory Profile (SSP). Receiver Operating Characteristics analysis (ROC) of the obtained data was performed to measure the predictive value of 8-isoprostane and Cysteinyl leukotrienes (CysLTs) as oxidative stress- related parameters. Pearson’s correlations between the measured parameters was also performed. RESULTS: The concentrations of 8-isoprostane and CysLTs in autistic patients were significantly higher than those in controls. While cognitive and social impairments did not show any significant differences, the SSP results were strongly correlated with the levels of both of the biomarkers assessed. However, autistic children showed improvements in oxidative stress status (as determined by 8-isoprostane levels) at increasing ages. CONCLUSION: This study indicates that 8-isoprostane and CysLTs can be used as markers for the early recognition of autistic patients through sensory deficits phenotypes which might help early intervention.
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15. Riikonen R. {{Treatment of autistic spectrum disorder with insulin-like growth factors}}. {Eur J Paediatr Neurol}. 2016.
There are no treatments for the core symptoms of autistic spectrum disorder (ASD), but there is now more knowledge on emerging mechanisms and on mechanism-based therapies. In autism there are altered synapses: genes affected are commonly related to synaptic and immune function. Dysregulation of activity-dependent signaling networks may have a key role the etiology of autism. There is an over-activation of IGF-AKT-mTor in autism spectrum disorders. Morphological and electro-physiological defects of the cerebellum are linked to system-wide ASD-like behavior defects. The molecular basis for a cerebellar contribution has been demonstrated in a mouse model. These have led to a potential mechanism-based use of drug targets and mouse models. Neurotrophic factors are potential candidates for the treatment. Insulin-like growth factor-1 (IGF-1) is altered in autism. It reduces neuro-inflammation: by causing changes of cytokines such as IL-6 and microglial function. IGF-1 reduces the defects in the synapse. It alleviates NMDA-induced neurotoxicity via the IGF-AKT-mTor pathway in microglia. IGF-1 may rescue function in Rett syndrome and ASD caused by changes of the SCHANK3 gene. There are recently pilot studies of the treatment of Rett syndrome and of SCHANK3 gene deficiency syndromes. The FDA has granted Orphan drug designations for Fragile X syndrome, SCHANK3 gene deficiency syndrome and Rett syndrome.
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16. Sharpley CF, Bitsika V, Agnew LL, Andronicos NM. {{Is daily replication necessary when sampling cortisol concentrations in association studies of children with autism spectrum disorder? A systematic review and discussion paper}}. {Rev Neurosci}. 2016.
Salivary cortisol may be used as a biomarker of stress and anxiety in children with an autism spectrum disorder (ASD). Some suggestions have been made that the measurement of cortisol needs to be undertaken by repeated days’ observations to ensure reliability of the data obtained. These requirements are discussed in regard to 14 studies of the test-retest agreement and stability in cortisol data across repeated daily measurements. Results of those studies almost universally fail to support the argument for repeated daily measurements of cortisol. Implications for the research protocols of studies using cortisol as an index of stress in children with ASD are discussed.
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17. Smith AD, Kenny L, Rudnicka A, Briscoe J, Pellicano E. {{Drawing Firmer Conclusions: Autistic Children Show No Evidence of a Local Processing Bias in a Controlled Copying Task}}. {J Autism Dev Disord}. 2016.
Drawing tasks are frequently used to test competing theories of visuospatial skills in autism. Yet, methodological differences between studies have led to inconsistent findings. To distinguish between accounts based on local bias or global deficit, we present a simple task that has previously revealed dissociable local/global impairments in neuropsychological patients. Autistic and typical children copied corner elements, arranged in a square configuration. Grouping cues were manipulated to test whether global properties affected the accuracy of reproduction. All children were similarly affected by these manipulations. There was no group difference in the reproduction of local elements, although global accuracy was negatively related to better local processing for autistic children. These data speak against influential theories of visuospatial differences in autism.
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18. Tabolacci E, Palumbo F, Nobile V, Neri G. {{Transcriptional Reactivation of the FMR1 Gene. A Possible Approach to the Treatment of the Fragile X Syndrome}}. {Genes (Basel)}. 2016; 7(8).
Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability, caused by CGG expansion over 200 repeats (full mutation, FM) at the 5′ untranslated region (UTR) of the fragile X mental retardation 1 (FMR1) gene and subsequent DNA methylation of the promoter region, accompanied by additional epigenetic histone modifications that result in a block of transcription and absence of the fragile X mental retardation protein (FMRP). The lack of FMRP, involved in multiple aspects of mRNA metabolism in the brain, is thought to be the direct cause of the FXS phenotype. Restoration of FMR1 transcription and FMRP production can be obtained in vitro by treating FXS lymphoblastoid cell lines with the demethylating agent 5-azadeoxycytidine, demonstrating that DNA methylation is key to FMR1 inactivation. This concept is strengthened by the existence of rare male carriers of a FM, who are unable to methylate the FMR1 promoter. These individuals produce limited amounts of FMRP and are of normal intelligence. Their inability to methylate the FMR1 promoter, whose cause is not yet fully elucidated, rescues them from manifesting the FXS. These observations demonstrate that a therapeutic approach to FXS based on the pharmacological reactivation of the FMR1 gene is conceptually tenable and worthy of being further pursued.
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19. Tylee DS, Espinoza AJ, Hess JL, Tahir MA, McCoy SY, Rim JK, Dhimal T, Cohen OS, Glatt SJ. {{RNA sequencing of transformed lymphoblastoid cells from siblings discordant for autism spectrum disorders reveals transcriptomic and functional alterations: Evidence for sex-specific effects}}. {Autism Res}. 2016.
Genome-wide expression studies of samples derived from individuals with autism spectrum disorder (ASD) and their unaffected siblings have been widely used to shed light on transcriptomic differences associated with this condition. Females have historically been under-represented in ASD genomic studies. Emerging evidence from studies of structural genetic variants and peripheral biomarkers suggest that sex-differences may exist in the biological correlates of ASD. Relatively few studies have explicitly examined whether sex-differences exist in the transcriptomic signature of ASD. The present study quantified genome-wide expression values by performing RNA sequencing on transformed lymphoblastoid cell lines and identified transcripts differentially expressed between same-sex, proximal-aged sibling pairs. We found that performing separate analyses for each sex improved our ability to detect ASD-related transcriptomic differences; we observed a larger number of dysregulated genes within our smaller set of female samples (n = 12 sibling pairs), as compared with the set of male samples (n = 24 sibling pairs), with small, but statistically significant overlap between the sexes. Permutation-based gene-set analyses and weighted gene co-expression network analyses also supported the idea that the transcriptomic signature of ASD may differ between males and females. We discuss our findings in the context of the relevant literature, underscoring the need for future ASD studies to explicitly account for differences between the sexes. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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20. Zhao F, Qiao L, Shi F, Yap PT, Shen D. {{Feature fusion via hierarchical supervised local CCA for diagnosis of autism spectrum disorder}}. {Brain Imaging Behav}. 2016.
Early diagnosis of autism spectrum disorder (ASD) is critical for timely medical intervention, for improving patient quality of life, and for reducing the financial burden borne by the society. A key issue in neuroimaging-based ASD diagnosis is the identification of discriminating features and then fusing them to produce accurate diagnosis. In this paper, we propose a novel framework for fusing complementary and discriminating features from different imaging modalities. Specifically, we integrate the Fisher discriminant criterion and local correlation information into the canonical correlation analysis (CCA) framework, giving a new feature fusion method, called Supervised Local CCA (SL-CCA), which caters specifically to local and global multimodal features. To alleviate the neighborhood selection problem associated with SL-CCA, we further propose a hierarchical SL-CCA (HSL-CCA), by performing SL-CCA with the gradually varying neighborhood sizes. Extensive experiments on the multimodal ABIDE database show that the proposed method achieves superior performance. In addition, based on feature weight analysis, we found that only a few specific brain regions play active roles in ASD diagnosis. These brain regions include the putamen, precuneus, and orbitofrontal cortex, which are highly associated with human emotional modulation and memory formation. These finding are consistent with the behavioral phenotype of ASD.
