1. Ciuladaite Z, Kasnauskiene J, Cimbalistiene L, Preiksaitiene E, Patsalis PC, Kucinskas V. {{Mental retardation and autism associated with recurrent 16p11.2 microdeletion: incomplete penetrance and variable expressivity}}. {J Appl Genet}. 2011.
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2. Green SA, Ben-Sasson A, Soto TW, Carter AS. {{Anxiety and Sensory Over-Responsivity in Toddlers with Autism Spectrum Disorders: Bidirectional Effects Across Time}}. {J Autism Dev Disord}. 2011.
This report focuses on the emergence of and bidirectional effects between anxiety and sensory over-responsivity (SOR) in toddlers with autism spectrum disorders (ASD). Participants were 149 toddlers with ASD and their mothers, assessed at 2 annual time points. A cross-lag analysis showed that anxiety symptoms increased over time while SOR remained relatively stable. SOR positively predicted changes in anxiety over and above child age, autism symptom severity, NVDQ, and maternal anxiety, but anxiety did not predict changes in SOR. Results suggest that SOR emerges earlier than anxiety, and predicts later development of anxiety.
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3. Hamlin A, Liu Y, Nguyen DV, Tassone F, Zhang L, Hagerman RJ. {{Sleep apnea in fragile X premutation carriers with and without FXTAS}}. {Am J Med Genet B Neuropsychiatr Genet}. 2011.
This report seeks to establish the prevalence of sleep apnea in patients with the fragile X mental retardation 1 (FMR1) premutation with and without fragile X-associated tremor/ataxia syndrome (FXTAS) and to determine any correlation between CGG repeat and FMR1 mRNA levels with sleep apnea prevalence. Demographic and medical data from 430 (229 males, 201 females) participants were used in this analysis. Participants included premutation carriers with (n = 118) and without FXTAS (n = 174) as well as controls without the premutation (n = 123). Logistic regression models were employed to estimate the odds ratio of sleep apnea relative to controls, adjusted for age and gender, and also to examine potential association with CGG size and FMR1 mRNA expression level. The observed proportion of sleep apnea in premutation carriers with and without FXTAS and controls are 31.4% (37/118), 8.6% (15/174), and 13.8% (17/123), respectively. The adjusted odds of sleep apnea for premutation carriers with FXTAS is about 3.4 times that compared to controls (odds ratio, OR = 3.4, 95% confidence interval (CI) 1.8-7.4; P = 0.001), and similarly relative to premutation carriers without FXTAS (OR = 2.9, 95% CI 1.2-6.9; P = 0.014). The risk of sleep apnea was not different between controls and premutation carriers without FXTAS. The presence of sleep apnea is not associated with CGG repeat numbers nor FMR1 mRNA expression level among premutation carriers. Our data supports a higher prevalence and risk of sleep apnea in patients with FXTAS. We recommend that all patients diagnosed with FXTAS be screened for sleep apnea given the negative and perhaps accelerative impact sleep apnea may have on their FXTAS progression. (c) 2011 Wiley-Liss, Inc.
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4. Johnson N, Frenn M, Feetham S, Simpson P. {{Autism spectrum disorder: Parenting stress, family functioning and health-related quality of life}}. {Fam Syst Health}. 2011; 29(3): 232-52.
The prevalence of Autism Spectrum Disorder (ASD) is 1 in 110 persons in the U.S. Both parents of children with ASD are under stress that may impact their health-related quality of life (HRQL) (physical and mental health). The purpose of the current study was to explore the relationship of parenting stress, support from family functioning and the HRQL (physical and mental health) of both parents. Female (n = 64) and male (n = 64) parents of children with ASD completed Web-based surveys examining parenting stress, family functioning, and physical and mental health. Results of a Wilcoxon signed-ranks test showed that female parent discrepant (D) scores between « what is » and « should be » family functioning were significantly larger than male parents, p = .002. Results of stepwise linear regression for the male-female partners showed that (1) higher female caregiving stress was related to lower female physical health (p < .001), (2) a higher discrepancy score in family functioning predicted lower mental health (p < .001), accounting for 31% of the variance for females and (3) male parent personal and family life stress (p < .001) and family functioning discrepant (D) score (p < .001) predicted poor mental health, with the discrepancy score accounting for 35% of the variance. These findings suggest that there may be differences in mothers’ and fathers’ perceptions and expectations about family functioning and this difference needs to be explored and applied when working with families of children with ASD. (PsycINFO Database Record (c) 2011 APA, all rights reserved).
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5. Kana RK, Murdaugh DL, Libero LE, Pennick MR, Wadsworth HM, Deshpande R, Hu CP. {{Probing the brain in autism using FMRI and diffusion tensor imaging}}. {J Vis Exp}. 2011; (55).
Newly emerging theories suggest that the brain does not function as a cohesive unit in autism, and this discordance is reflected in the behavioral symptoms displayed by individuals with autism. While structural neuroimaging findings have provided some insights into brain abnormalities in autism, the consistency of such findings is questionable. Functional neuroimaging, on the other hand, has been more fruitful in this regard because autism is a disorder of dynamic processing and allows examination of communication between cortical networks, which appears to be where the underlying problem occurs in autism. Functional connectivity is defined as the temporal correlation of spatially separate neurological events1. Findings from a number of recent fMRI studies have supported the idea that there is weaker coordination between different parts of the brain that should be working together to accomplish complex social or language problems(2,3,4,5,6). One of the mysteries of autism is the coexistence of deficits in several domains along with relatively intact, sometimes enhanced, abilities. Such complex manifestation of autism calls for a global and comprehensive examination of the disorder at the neural level. A compelling recent account of the brain functioning in autism, the cortical underconnectivity theory,(2,7) provides an integrating framework for the neurobiological bases of autism. The cortical underconnectivity theory of autism suggests that any language, social, or psychological function that is dependent on the integration of multiple brain regions is susceptible to disruption as the processing demand increases. In autism, the underfunctioning of integrative circuitry in the brain may cause widespread underconnectivity. In other words, people with autism may interpret information in a piecemeal fashion at the expense of the whole. Since cortical underconnectivity among brain regions, especially the frontal cortex and more posterior areas (3,6), has now been relatively well established, we can begin to further understand brain connectivity as a critical component of autism symptomatology. A logical next step in this direction is to examine the anatomical connections that may mediate the functional connections mentioned above. Diffusion Tensor Imaging (DTI) is a relatively novel neuroimaging technique that helps probe the diffusion of water in the brain to infer the integrity of white matter fibers. In this technique, water diffusion in the brain is examined in several directions using diffusion gradients. While functional connectivity provides information about the synchronization of brain activation across different brain areas during a task or during rest, DTI helps in understanding the underlying axonal organization which may facilitate the cross-talk among brain areas. This paper will describe these techniques as valuable tools in understanding the brain in autism and the challenges involved in this line of research.
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6. Paluszkiewicz SM, Martin BS, Huntsman MM. {{Fragile X Syndrome: The GABAergic System and Circuit Dysfunction}}. {Dev Neurosci}. 2011.
Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by intellectual disability, sensory hypersensitivity, and high incidences of autism spectrum disorders and epilepsy. These phenotypes are suggestive of defects in neural circuit development and imbalances in excitatory glutamatergic and inhibitory GABAergic neurotransmission. While alterations in excitatory synapse function and plasticity are well-established in Fmr1 knockout (KO) mouse models of FXS, a number of recent electrophysiological and molecular studies now identify prominent defects in inhibitory GABAergic transmission in behaviorally relevant forebrain regions such as the amygdala, cortex, and hippocampus. In this review, we summarize evidence for GABAergic system dysfunction in FXS patients and Fmr1 KO mouse models alike. We then discuss some of the known developmental roles of GABAergic signaling, as well as the development and refinement of GABAergic synapses as a framework for understanding potential causes of mature circuit dysfunction. Finally, we highlight the GABAergic system as a relevant target for the treatment of FXS.
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7. Pina-Camacho L, Villero S, Fraguas D, Boada L, Janssen J, Navas-Sanchez FJ, Mayoral M, Llorente C, Arango C, Parellada M. {{Autism Spectrum Disorder: Does Neuroimaging Support the DSM-5 Proposal for a Symptom Dyad? A Systematic Review of Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging Studies}}. {J Autism Dev Disord}. 2011.
A systematic review of 208 studies comprising functional magnetic resonance imaging and diffusion tensor imaging data in patients with ‘autism spectrum disorder’ (ASD) was conducted, in order to determine whether these data support the forthcoming DSM-5 proposal of a social communication and behavioral symptom dyad. Studies consistently reported abnormal function and structure of fronto-temporal and limbic networks with social and pragmatic language deficits, of temporo-parieto-occipital networks with syntactic-semantic language deficits, and of fronto-striato-cerebellar networks with repetitive behaviors and restricted interests in ASD patients. Therefore, this review partially supports the DSM-5 proposal for the ASD dyad.
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8. Veenstra-Vanderweele J, Blakely RD. {{Networking in Autism: Leveraging Genetic, Biomarker and Model System Findings in the Search for New Treatments}}. {Neuropsychopharmacology}. 2011.
Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder affecting approximately 1% of children. ASD is defined by core symptoms in two domains: negative symptoms of impairment in social and communication function, and positive symptoms of restricted and repetitive behaviors. Available treatments are inadequate for treating both core symptoms and associated conditions. Twin studies indicate that ASD susceptibility has a large heritable component. Genetic studies have identified promising leads, with converging insights emerging from single-gene disorders that bear ASD features, with particular interest in mammalian target of rapamycin (mTOR)-linked synaptic plasticity mechanisms. Mouse models of these disorders are revealing not only opportunities to model behavioral perturbations across species, but also evidence of postnatal rescue of brain and behavioral phenotypes. An intense search for ASD biomarkers has consistently pointed to elevated platelet serotonin (5-HT) levels and a surge in brain growth in the first 2 years of life. Following a review of the diversity of ASD phenotypes and its genetic origins and biomarkers, we discuss opportunities for translation of these findings into novel ASD treatments, focusing on mTor- and 5-HT-signaling pathways, and their possible intersection. Paralleling the progress made in understanding the root causes of rare genetic syndromes that affect cognitive development, we anticipate progress in models systems using bona fide ASD-associated molecular changes that have the potential to accelerate the development of ASD diagnostics and therapeutics.Neuropsychopharmacology Reviews advance online publication, 21 September 2011; doi:10.1038/npp.2011.185.
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9. Walsh P, Elsabbagh M, Bolton P, Singh I. {{In search of biomarkers for autism: scientific, social and ethical challenges}}. {Nat Rev Neurosci}. 2011; 12(10): 603-12.
There is widespread hope that the discovery of valid biomarkers for autism will both reveal the causes of autism and enable earlier and more targeted methods for diagnosis and intervention. However, growing enthusiasm about recent advances in this area of autism research needs to be tempered by an awareness of the major scientific challenges and the important social and ethical concerns arising from the development of biomarkers and their clinical application. Collaborative approaches involving scientists and other stakeholders must combine the search for valid, clinically useful autism biomarkers with efforts to ensure that individuals with autism and their families are treated with respect and understanding.
