1. Good P. {{Does Fever Relieve Autistic Behavior by Improving Brain Blood Flow?}}. {Neuropsychol Rev};2011 (Jan 20)

2. Hussman JP, Chung RH, Griswold AJ, Jaworkski JM, Salyakina D, Ma D, Konidari I, Whitehead PL, Vance JM, Martin ER, Cuccaro ML, Gilbert JR, Haines JL, Pericak-Vance MA. {{A noise-reduction GWAS analysis implicates altered regulation of neurite outgrowth and guidance in autism}}. {Mol Autism};2011 (Jan 19);2(1):1.

ABSTRACT: BACKGROUND: Genome-wide Association Studies (GWAS) have proved invaluable for the identification of disease susceptibility genes. However, the prioritization of candidate genes and regions for follow-up studies often proves difficult due to false-positive associations caused by statistical noise and multiple-testing. In order to address this issue, we propose the novel GWAS noise reduction (GWAS-NR) method as a way to increase the power to detect true associations in GWAS, particularly in complex diseases such as autism. METHODS: GWAS-NR utilizes a linear filter to identify genomic regions demonstrating correlation among association signals in multiple datasets. We used computer simulations to assess the ability of GWAS-NR to detect association against the commonly used joint analysis and Fisher’s methods. Furthermore, we applied GWAS-NR to a family-based autism GWAS of 597 families and a second existing autism GWAS of 696 families from the Autism Genetic Resource Exchange (AGRE) to arrive at a compendium of autism candidate genes. These genes were manually annotated and classified by a literature review and functional grouping in order to reveal biological pathways which might contribute to autism aetiology. RESULTS: Computer simulations indicate that GWAS-NR achieves a significantly higher classification rate for true positive association signals than either the joint analysis or Fisher’s methods and that it can also achieve this when there is imperfect marker overlap across datasets or when the closest disease-related polymorphism is not directly typed. In two autism datasets, GWAS-NR analysis resulted in 1535 significant linkage disequilibrium (LD) blocks overlapping 431 unique reference sequencing (RefSeq) genes. Moreover, we identified the nearest RefSeq gene to the non-gene overlapping LD blocks, producing a final candidate set of 860 genes. Functional categorization of these implicated genes indicates that a significant proportion of them cooperate in a coherent pathway that regulates the directional protrusion of axons and dendrites to their appropriate synaptic targets. CONCLUSIONS: As statistical noise is likely to particularly affect studies of complex disorders, where genetic heterogeneity or interaction between genes may confound the ability to detect association, GWAS-NR offers a powerful method for prioritizing regions for follow-up studies. Applying this method to autism datasets, GWAS-NR analysis indicates that a large subset of genes involved in the outgrowth and guidance of axons and dendrites is implicated in the aetiology of autism.

3. Oberman LM, Horvath JC, Pascual-Leone A. {{TMS: Using the Theta-Burst Protocol to Explore Mechasnism of Plasticity in Individuals with Fragile X Syndrome and Autism}}. {J Vis Exp};2010 (46)

Fragile X Syndrome (FXS), also known as Martin-Bell Syndrome, is a genetic abnormality found on the X chromosome.(1,2) Individuals suffering from FXS display abnormalities in the expression of FMR1 – a protein required for typical, healthy neural development.(3) Recent data has suggested that the loss of this protein can cause the cortex to be hyperexcitable thereby affecting overall patterns of neural plasticity.(4,5) In addition, Fragile X shows a strong comorbidity with autism: in fact, 30% of children with FXS are diagnosed with autism, and 2 – 5% of autistic children suffer from FXS.(6) Transcranial Magnetic Stimulation (a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability via the application of localized magnetic field pulses (7,8)) represents a unique method of exploring plasticity and the manifestations of FXS within affected individuals. More specifically, Theta-Burst Stimulation (TBS), a specific stimulatory protocol shown to modulate cortical plasticity for a duration up to 30 minutes after stimulation cessation in healthy populations, has already proven an efficacious tool in the exploration of abnormal plasticity.(9,10) Recent studies have shown the effects of TBS last considerably longer in individuals on the autistic spectrum – up to 90 minutes.(11) This extended effect-duration suggests an underlying abnormality in the brain’s natural plasticity state in autistic individuals – similar to the hyperexcitability induced by Fragile X Syndrome. In this experiment, utilizing single-pulse motor-evoked potentials (MEPs) as our benchmark, we will explore the effects of both intermittent and continuous TBS on cortical plasticity in individuals suffering from FXS and individuals on the Autistic Spectrum.

4. Reichelt AC, Rodgers RJ, Clapcote SJ. {{The role of neurexins in schizophrenia and autistic spectrum disorder}}. {Neuropharmacology};2011 (Jan 21)

Schizophrenia and autistic spectrum disorder (ASD) are common, chronic mental conditions with both genetic and environmental components to their aetiology. The identification of genes influencing susceptibility to these disorders offers a rational route towards a clearer understanding of the neurobiology, and with this the prospect of treatment and prevention strategies tailored towards the remediation of the altered pathways. Copy number variants (CNVs) underlie many serious illnesses, including neurological and neurodevelopmental syndromes. Recent studies assessing copy number variation in ASD and schizophrenia have repeatedly observed heterozygous deletions eliminating exons of the neurexin-1alpha gene (but not the neurexin-1beta gene) in patients with ASD and schizophrenia. The neurexins are synaptic adhesion proteins that are known to play a key role in synaptic formation and maintenance. The functional significance of the recurrent deletion is poorly understood, but the availability of mice with deletion of the promoter and first exon of neurexin-1alpha provides direct access to the biological effects of neurexin-1alpha disruption on phenotypes relevant to ASD and schizophrenia. We review the evidence for the role of neurexin-1alpha in schizophrenia and ASD, and consider how genetic disruption of neurexin-1alpha may underpin the neuropathology contributing to these distinct neurodevelopmental disorders.

5. Wachtel LE, Jaffe R, Kellner CH. {{Electroconvulsive therapy for psychotropic-refractory bipolar affective disorder and severe self-injury and aggression in an 11-year-old autistic boy}}. {Eur Child Adolesc Psychiatry};2011 (Jan 21)

We report the successful use of electroconvulsive therapy in a 11-year-old boy with autism and a 4-year history of psychotropic-resistant bipolar affective disorder associated with dangerous episodes of self-injurious and aggressive behaviors placing his caregivers and himself at significant safety risk. Extensive behavioral and medication interventions in both inpatient and outpatient settings had been ineffective, and the boy was at risk for acute physical injury and restrictive out-of-home placement. An acute course of eight bilateral electroconvulsive therapies resulted in significant mood stabilization and significant improvement of self-injury and aggression. Maintenance electroconvulsive therapy and psychotropic interventions were then pursued.