1. Enriquez-Barreto L, Morales M. {{The PI3K signaling pathway as a pharmacological target in Autism related disorders and Schizophrenia}}. {Mol Cell Ther};2016;4:2.
This review is focused in PI3K’s involvement in two widespread mental disorders: Autism and Schizophrenia. A large body of evidence points to synaptic dysfunction as a cause of these diseases, either during the initial phases of brain synaptic circuit’s development or later modulating synaptic function and plasticity. Autism related disorders and Schizophrenia are complex genetic conditions in which the identification of gene markers has proved difficult, although the existence of single-gene mutations with a high prevalence in both diseases offers insight into the role of the PI3K signaling pathway. In the brain, components of the PI3K pathway regulate synaptic formation and plasticity; thus, disruption of this pathway leads to synapse dysfunction and pathological behaviors. Here, we recapitulate recent evidences that demonstrate the imbalance of several PI3K elements as leading causes of Autism and Schizophrenia, together with the plausible new pharmacological paths targeting this signaling pathway.
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2. Guven-Ozkan T, Busto GU, Schutte SS, Cervantes-Sandoval I, O’Dowd DK, Davis RL. {{MiR-980 Is a Memory Suppressor MicroRNA that Regulates the Autism-Susceptibility Gene A2bp1}}. {Cell Rep};2016 (Feb 10)
MicroRNAs have been associated with many different biological functions, but little is known about their roles in conditioned behavior. We demonstrate that Drosophila miR-980 is a memory suppressor gene functioning in multiple regions of the adult brain. Memory acquisition and stability were both increased by miR-980 inhibition. Whole cell recordings and functional imaging experiments indicated that miR-980 regulates neuronal excitability. We identified the autism susceptibility gene, A2bp1, as an mRNA target for miR-980. A2bp1 levels varied inversely with miR-980 expression; memory performance was directly related to A2bp1 levels. In addition, A2bp1 knockdown reversed the memory gains produced by miR-980 inhibition, consistent with A2bp1 being a downstream target of miR-980 responsible for the memory phenotypes. Our results indicate that miR-980 represses A2bp1 expression to tune the excitable state of neurons, and the overall state of excitability translates to memory impairment or improvement.
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3. Kim KN, Kwon HJ, Hong YC. {{Low-level lead exposure and autistic behaviors in school-age children}}. {Neurotoxicology};2016 (Feb 11)
INTRODUCTION: The association between lead exposure and autism spectrum disorder is inconclusive. We hypothesized an association between higher blood lead concentrations and more autistic behaviors, including impaired social interactions and communication, stereotypical behaviors, and restricted interests, among school-age children. METHODS: Data from 2473 Korean children aged 7-8 years who had no prior history of developmental disorders were analyzed. Two follow-up surveys were conducted biennially until the children reached 11-12 years of age. Blood lead concentrations were measured at every survey, and autistic behaviors were evaluated at 11-12 years of age using the Autism Spectrum Screening Questionnaire (ASSQ) and Social Responsiveness Scale (SRS). The associations of blood lead concentration with ASSQ and SRS scores were analyzed using negative binomial, logistic, and linear regression models. RESULTS: Blood lead concentrations at 7-8 years of age (geometric mean: 1.64 mug/dL), but not at 9-10 and 11-12 years of age, were associated with more autistic behaviors at 11-12 years of age, according to the ASSQ (beta = 0.151; 95% confidence interval [CI]: 0.061, 0.242) and SRS (beta = 2.489; 95% CI: 1.378, 3.600). SRS subscale analysis also revealed associations between blood lead concentrations and social awareness, cognition, communication, motivation, and mannerisms. CONCLUSION: Even low blood lead concentrations at 7-8 years of age are associated with more autistic behaviors at 11-12 years of age, underscoring the need for continued efforts to reduce lead exposure.
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4. Kind LS, van Gemert-Schriks MC, Elhorst JH. {{[Autism-friendly dental care]}}. {Ned Tijdschr Tandheelkd};2016 (Feb);123(2):73-77.
Autism Spectrum Disorder (ASD) occurs in approximately 1% of the Dutch population. Among the group of patients with this disorder, there is a substantial diversity regarding skills, intelligence and treatability. However, there are also common characteristics; people with ASD often have difficulty with social interaction, communication, and exhibit typical patterns of behaviour. Therefore, problems may arise in the various areas of development, such as language development and responding to sensory stimuli. Dental practitioners will also be confronted with individuals with ASD. Care can be significantly improved, considering that negative experiences and dental anxiety are widespread at this time.
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5. Smith J, Rho JM, Teskey GC. {{Ketogenic diet restores aberrant cortical motor maps and excitation-to-inhibition imbalance in the BTBR mouse model of autism spectrum disorder}}. {Behav Brain Res};2016 (Feb 11)
Autism spectrum disorder (ASD) is an increasingly prevalent neurodevelopmental disorder characterized by deficits in sociability and communication, and restricted and/or repetitive motor behaviors. Amongst the diverse hypotheses regarding the pathophysiology of ASD, one possibility is that there is increased neuronal excitation, leading to alterations in sensory processing, functional integration and behavior. Meanwhile, the high-fat, low-carbohydrate ketogenic diet (KD), traditionally used in the treatment of medically intractable epilepsy, has already been shown to reduce autistic behaviors in both humans and in rodent models of ASD. While the mechanisms underlying these effects remain unclear, we hypothesized that this dietary approach might shift the balance of excitation and inhibition towards more normal levels of inhibition. Using high-resolution intracortical microstimulation, we investigated basal sensorimotor excitation/inhibition in the BTBR T+Itprtf/J (BTBR) mouse model of ASD and tested whether the KD restores the balance of excitation/inhibition. We found that BTBR mice had lower movement thresholds and larger motor maps indicative of higher excitation/inhibition compared to C57BL/6J (B6) controls, and that the KD reversed both these abnormalities. Collectively, our results afford a greater understanding of cortical excitation/inhibition balance in ASD and may help expedite the development of therapeutic approaches aimed at improving functional outcomes in this disorder.
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6. Yousefi N, Dadgar H, Mohammadi MR, Jalilevand N, Keyhani MR, Mehri A. {{The Validity and Reliability of Autism Behavior Checklist in Iran}}. {Iran J Psychiatry};2015 (Jun);10(3):144-149.
OBJECTIVES: The aim of this study was to evaluate the psychometric features of the Persian version of the Autism Behavior Checklist (ABC). METHOD: The International Quality of Life Assessment (IQOLA) approach was used to translate the English ABC into Persian. A total sample of 184 parents of children including 114 children with autism disorder (mean age =7.21, SD =1.65) and 70 typically developing children (mean age = 6.82, SD =1.75) completed the ABC. Internal consistency, test-retest reliability, concurrent and discriminant validity, and cut-off score were assessed. RESULTS: The results of this study revealed that the Persian version of the ABC has an acceptable degree of internal consistency (.73). Test-retest comparisons using interclass correlation confirmed the instrument’s time stability (.83). The instrument’s concurrent validity with Gilliam Autism Rating Scale (GARS) was verified; the correlation between total scores was .94. In the discriminant validity, the autism group had significantly higher scores compared to the normal group. Receiver Operating Characteristic (ROC) analysis revealed that individuals with total scores below 25 are less likely to be in the autism group. CONCLUSION: The Persian version of the ABC can be used as an initial screening tool in clinical contexts.
