1. Angelidou A, Francis K, Vasiadi M, Alysandratos KD, Zhang B, Theoharides A, Lykouras L, Sideri K, Kalogeromitros D, Theoharides TC. {{Neurotensin is increased in serum of young children with autistic disorder}}. {J Neuroinflammation} (Aug 23);7(1):48.
ABSTRACT: Autism spectrum disorders (ASD) are a group of pervasive neurodevelopmental disorders diagnosed in early childhood. They are associated with a set of « core symptoms » that include disabilities in social interaction skills, verbal and non-verbal communication, as well as repetitive and stereotypic behaviors. There is no definite pathogenetic mechanism or diagnostic tests. Many children with ASD also have « allergic-like » symptoms, but test negative implying mast cell activation by non-allergic triggers. We measured by Milliplex arrays serum levels of 3 neuropeptides that could stimulate mast cells in children with autistic disorder (n=19; 16 males and 3 females; mean age 3.0 +/- 0.4 years) and healthy, unrelated controls (n=16; 13 males and 3 females; mean age 3 +/- 1.2 years). Only neurotensin (NT) was significantly increased from 60.5 +/- 6.0 pg/ml in controls to 105.6 +/- 12.4 pg/ml in autistic disorder (p=0.004). There was no statistically significant difference in the serum levels of beta-endorphin or substance P (SP). NT could stimulate immune cells, especially mast cells, and/or have direct effects on brain inflammation and ASD.
2. Gadow KD, Devincent CJ, Olvet DM, Pisarevskaya V, Hatchwell E. {{Association of DRD4 polymorphism with severity of oppositional defiant disorder, separation anxiety disorder and repetitive behaviors in children with autism spectrum disorder}}. {Eur J Neurosci} (Aug 22)
Abstract The objective was to examine whether a common polymorphism in the dopamine D4 receptor gene (DRD4) might be a potential biomarker for behavioral variation within the autism spectrum disorder clinical phenotype. Children (N = 66) were evaluated with a validated mother- and teacher-completed DSM-IV-referenced rating scale. Partial eta-squared (etap(2)) was used to gauge the magnitude of group differences: 0.01-0.06 = small, 0.06-0.14 = moderate and > 0.14 = large. Children who were 7-repeat allele carriers had more severe oppositional defiant disorder behaviors according to mothers’ (etap(2) = 0.10) and teachers’ (etap(2) = 0.06) ratings than noncarriers, but the latter was marginally significant (P = 0.07). Children who were 7-repeat allele carriers also obtained more severe maternal ratings of tics (etap(2) = 0.07) and obsessions-compulsions (etap(2) = 0.08). Findings for maternal ratings of separation anxiety were marginally significant (P = 0.08, etap(2) = 0.05). Analyses of combined DRD4 and dopamine transporter gene (DAT1) genotypes approached significance (P = 0.05) for teachers’ ratings of oppositional behavior and mothers’ ratings of tics. DRD4 allelic variation may be a prognostic biomarker for challenging behaviors in children with autism spectrum disorder, but these exploratory findings remain tentative pending replication with larger independent samples.
3. Hall SS, Lightbody AA, Hirt M, Rezvani A, Reiss AL. {{Autism in Fragile X Syndrome: A Category Mistake?}}. {J Am Acad Child Adolesc Psychiatry} (Sep);49(9):921-933.
OBJECTIVE: Many investigators now routinely classify children with fragile X syndrome (FXS) according to whether or not they also meet diagnostic criteria for autism. To determine whether this classification is appropriate, we examined the profiles of autistic behaviors shown by boys and girls with FXS. METHOD: Individuals with FXS, aged 5 to 25 years, were assessed on two established measures of autism, the Social Communication Questionnaire (SCQ) and the Autism Diagnostic Observation Schedule (ADOS). RESULTS: We found that 35.1% of boys and 4.3% of girls with FXS scored in the « autism » category on both instruments. Analysis of the symptom profile indicated that both boys and girls with FXS showed lower rates of impairment on communication and reciprocal social interaction items than the reference autism samples on the measures. Furthermore, a regression model showed that IQ was significantly negatively associated with the SCQ total score in both boys and girls with FXS, when controlling for age, medication use, and FMRP levels. CONCLUSIONS: These data suggest that there are significant differences in the profile of social and communicative symptomatology in FXS compared with individuals diagnosed with idiopathic autism. Given these differences, the implementation of standard autism interventions for individuals with FXS may not be optimal. Maintaining the conceptual distinction between FXS (an established biological disease) and idiopathic autism (a phenomenologically defined behavioral disorder) may also facilitate the development of more targeted and thus effective interventions for individuals with FXS in the future.
4. Hartley SL, Barker ET, Seltzer MM, Floyd F, Greenberg J, Orsmond G, Bolt D. {{The relative risk and timing of divorce in families of children with an autism spectrum disorder}}. {J Fam Psychol} (Aug);24(4):449-457.
We compared the occurrence and timing of divorce in 391 parents of children with an autism spectrum disorder (ASD) and a matched representative sample of parents of children without disabilities using a survival analysis. Parents of children with an ASD had a higher rate of divorce than the comparison group (23.5% vs. 13.8%). The rate of divorce remained high throughout the son’s or daughter’s childhood, adolescence, and early adulthood for parents of children with an ASD, whereas it decreased following the son’s or daughter’s childhood (after about age 8 years) in the comparison group. Younger maternal age when the child with ASD was born and having the child born later in the birth order were positively predictive of divorce for parents of children with an ASD. Findings have implications for interventions focused on ameliorating ongoing and long-term marital strains for parents of children with an ASD. (PsycINFO Database Record (c) 2010 APA, all rights reserved).
5. Kron M, Muller M. {{Impaired Hippocampal Ca 2+ Homeostasis and Concomitant K + Channel Dysfunction In a Mouse Model of Rett Syndrome During Anoxia}}. {Neuroscience} (Aug 20)
MeCP2 deficiency causes Rett syndrome (RTT), a neurodevelopmental disorder characterized by severe cognitive impairment, synaptic dysfunction, and hyperexcitability. Previously we reported that the hippocampus of MeCP2-deficient mice ( Mecp2(-/y)), a mouse model for RTT, is more susceptible to hypoxia. To identify the underlying mechanisms we now focused on the anoxic responses of wildtype (WT) and Mecp2(-/y) CA1 neurons in acute hippocampal slices. Intracellular recordings revealed that Mecp2(-/y) neurons show only reduced or no hyperpolarizations early during cyanide-induced anoxia, suggesting K(+) channel dysfunction. Blocking K(ATP)- and BK-channels did not affect the early anoxic hyperpolarization in either genotype. However, blocking Ca(2+) release from the endoplasmic reticulum almost abolished the anoxic hyperpolarizations in Mecp2(-/y) neurons. Single-channel recordings confirmed that neither K(ATP)- nor BK-channels are the sole mediators of the early anoxic hyperpolarization. Instead, anoxia Ca(2+)-dependently activated various small/intermediate-conductance K(+) channels in WT neurons, which was less evident in Mecp2(-/y) neurons. Yet, pharmacologically increasing the Ca(2+) sensitivity of small/intermediate-conductance K(Ca) channels fully restored the anoxic hyperpolarization in Mecp2(-/y) neurons. Furthermore, Ca(2+) imaging unveiled lower intracellular Ca(2+) levels in resting Mecp2(-/y) neurons and reduced anoxic Ca(2+) transients with diminished Ca(2+) release from intracellular stores. In conclusion, the enhanced hypoxia susceptibility of Mecp2(-/y) hippocampus is primarily associated with disturbed Ca(2+) homeostasis and diminished Ca(2+) rises during anoxia. This secondarily attenuates the activation of K(Ca) channels and thereby increases the hypoxia susceptibility of Mecp2-(/y) neuronal networks. Since cytosolic Ca(2+) levels also determine neuronal excitability and synaptic plasticity, Ca(2+) homeostasis may constitute a promising target for pharmacotherapy in RTT.
6. Le Guen T, Bahi-Buisson N, Nectoux J, Boddaert N, Fichou Y, Diebold B, Desguerre I, Raqbi F, Daire VC, Chelly J, Bienvenu T. {{A FOXG1 mutation in a boy with congenital variant of Rett syndrome}}. {Neurogenetics} (Aug 24)
Mutations in the FOXG1 gene have been shown to cause congenital variant of Rett syndrome. To date, point mutations have been reported only in female patients. We screened the entire coding region of the gene for mutations in 50 boys with congenital encephalopathy, postnatal microcephaly, and complex movement disorders, a clinical picture very similar to that described in girls with FOXG1 mutations. We found one boy carrying the de novo c.256_257dupC frameshift mutation. He presented the association of postnatal microcephaly, severe axial dystonia with severe feeding difficulties with protruding tongue movements during the first year of life that subsequently evolved into dyskinetic movement disorders with hand stereotypies. In contrast to his severe motor impairment, he developed nonverbal communication skills and relative good eye contact. Brain MRI showed frontal gyral simplification with dramatic myelination delay most prominent in both frontal lobes. Altogether the presentation in this male patient is highly reminiscent of that observed in FOXG1-mutated females with the congenital variant of Rett syndrome. This new case confirms the prediction that congenital variant of Rett syndrome should be found also in males, with the characteristic hallmarks consisting of postnatal microcephaly, dyskinetic movement disorder with Rett-like features, i.e., hand stereotypies, and frontal gyral simplification with myelination delay. FOXG1 screening should be considered in individuals with these clinical features.
7. Maras K, Bowler DM. {{Brief Report: Schema Consistent Misinformation Effects in Eyewitnesses with Autism Spectrum Disorder}}. {J Autism Dev Disord} (Aug 24)
A number of studies have demonstrated schema-related misinformation effects in typical individuals, but no research to date has examined this with witnesses with autism spectrum disorder (ASD), despite their impaired ability to generate core elements that define everyday events. After witnessing slides depicting a bank robbery, 16 adults with ASD and 16 matched comparison individuals were exposed to post-event misinformation that was either schema typical or atypical. Consistent with previous work, the comparison group went onto report more schema typical misinformation than atypical misinformation. However, so too did the ASD group, suggesting that individuals with ASD do have understanding of the causal links between events, persons and actions, an important finding from both theoretical and applied perspectives.
8. Woodbury-Smith MR, Boyd K, Szatmari P. {{Autism spectrum disorders, schizophrenia and diagnostic confusion}}. {J Psychiatry Neurosci} (Sep);35(5):360.
