1. Giza J, Urbanski MJ, Prestori F, Bandyopadhyay B, Yam A, Friedrich V, Kelley K, D’Angelo E, Goldfarb M. {{Behavioral and cerebellar transmission deficits in mice lacking the autism-linked gene islet brain-2}}. {J Neurosci};2010 (Nov 3);30(44):14805-14816.
Deletion of the human SHANK3 gene near the terminus of chromosome 22q is associated with Phelan-McDermid syndrome and autism spectrum disorders. Nearly all such deletions also span the tightly linked IB2 gene. We show here that IB2 protein is broadly expressed in the brain and is highly enriched within postsynaptic densities. Experimental disruption of the IB2 gene in mice reduces AMPA and enhances NMDA receptor-mediated glutamatergic transmission in cerebellum, changes the morphology of Purkinje cell dendritic arbors, and induces motor and cognitive deficits suggesting an autism phenotype. These findings support a role for human IB2 mutation as a contributing genetic factor in Chr22qter-associated cognitive disorders.
2. Hall HR, Graff JC. {{Parenting challenges in families of children with autism: a pilot study}}. {Issues Compr Pediatr Nurs};2010;33(4):187-204.
A pilot study was conducted using a focus group interview with parents of children with autism to provide parents with the opportunity to express their concerns related to parenting a child with autism and to discuss strategies parents can use to manage these challenges. Parents’ desire and need for information related to autism is evident. Parents’ identified supports and resources in need of expansion and development to assist with their child’s needs. These findings support previous research with families communicating a need for partnership with healthcare providers. Nurses are often the first contact with children with autism and their families; they can support the partnership between parents and healthcare professionals. Using the Double ABCX Model of family behavior as the conceptual framework, a study investigating the findings of this pilot study has been completed.
3. Scott-Van Zeeland AA, Abrahams BS, Alvarez-Retuerto AI, Sonnenblick LI, Rudie JD, Ghahremani D, Mumford JA, Poldrack RA, Dapretto M, Geschwind DH, Bookheimer SY. {{Altered Functional Connectivity in Frontal Lobe Circuits Is Associated with Variation in the Autism Risk Gene CNTNAP2}}. {Sci Transl Med};2010 (Nov 3);2(56):56ra80.
Genetic studies are rapidly identifying variants that shape risk for disorders of human cognition, but the question of how such variants predispose to neuropsychiatric disease remains. Noninvasive human brain imaging allows assessment of the brain in vivo, and the combination of genetics and imaging phenotypes remains one of the only ways to explore functional genotype-phenotype associations in human brain. Common variants in contactin-associated protein-like 2 (CNTNAP2), a neurexin superfamily member, have been associated with several allied neurodevelopmental disorders, including autism and specific language impairment, and CNTNAP2 is highly expressed in frontal lobe circuits in the developing human brain. Using functional neuroimaging, we have demonstrated a relationship between frontal lobar connectivity and common genetic variants in CNTNAP2. These data provide a mechanistic link between specific genetic risk for neurodevelopmental disorders and empirical data implicating dysfunction of long-range connections within the frontal lobe in autism. The convergence between genetic findings and cognitive-behavioral models of autism provides evidence that genetic variation at CNTNAP2 predisposes to diseases such as autism in part through modulation of frontal lobe connectivity.
4. Wiggins JL, Peltier SJ, Ashinoff S, Weng SJ, Carrasco M, Welsh RC, Lord C, Monk CS. {{Using a Self-Organizing Map Algorithm to Detect Age-Related Changes in Functional Connectivity During Rest in Autism Spectrum Disorders}}. {Brain Res};2010 (Oct 31)
Healthy individuals show robust functional connectivity during rest, which is stronger in adults than in children. Connectivity occurs between the posterior and anterior portions of the default network, a group of structures active in the absence of a task, including the posterior cingulate cortex and the superior frontal gyrus. Previous studies found weaker posterior-anterior connectivity in the default network in adults and adolescents with autism spectrum disorders (ASD). However, these studies used small a priori regions of interest (« seeds ») to calculate connectivity. Since seed location for all participants was chosen based on controls’ brains, these studies’ analyses are more tailored to controls than individuals with ASD. An alternative is to use a data-driven approach, such as self-organizing maps (SOM), to create a reference for each participant to calculate connectivity. We used individualized resting-state clusters identified by an SOM algorithm to corroborate previous findings of weaker posterior-anterior connectivity in the ASD group and examine age-related changes in the ASD and control groups. Thirty-nine adolescents with ASD and 41 controls underwent a 10-minute, eyes-open, resting state functional MRI scan. The SOM analysis revealed that adolescents with ASD versus controls have weaker connectivity between the posterior hub of the default network and the right superior frontal gyrus. Additionally, controls have larger increases in connectivity with age compared to the ASD group. These findings indicate that SOM is a complementary method for calculating connectivity in a clinical population. Additionally, adolescents with ASD have a different developmental trajectory of the default network compared to controls.
5. Zikopoulos B, Barbas H. {{Changes in prefrontal axons may disrupt the network in autism}}. {J Neurosci};2010 (Nov 3);30(44):14595-14609.
Neural communication is disrupted in autism by unknown mechanisms. Here, we examined whether in autism there are changes in axons, which are the conduit for neural communication. We investigated single axons and their ultrastructure in the white matter of postmortem human brain tissue below the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and lateral prefrontal cortex (LPFC), which are associated with attention, social interactions, and emotions, and have been consistently implicated in the pathology of autism. Area-specific changes below ACC (area 32) included a decrease in the largest axons that communicate over long distances. In addition, below ACC there was overexpression of the growth-associated protein 43 kDa accompanied by excessive number of thin axons that link neighboring areas. In OFC (area 11), axons had decreased myelin thickness. Axon features below LPFC (area 46) appeared to be unaffected, but the altered white matter composition below ACC and OFC changed the relationships among all prefrontal areas examined, and could indirectly affect LPFC function. These findings provide a mechanism for disconnection of long-distance pathways, excessive connections between neighboring areas, and inefficiency in pathways for emotions, and may help explain why individuals with autism do not adequately shift attention, engage in repetitive behavior, and avoid social interactions. These changes below specific prefrontal areas appear to be linked through a cascade of developmental events affecting axon growth and guidance, and suggest targeting the associated signaling pathways for therapeutic interventions in autism.
