1. Cederlund M, Hagberg B, Gillberg C. {{Asperger syndrome in adolescent and young adult males Interview, self- and parent assessment of social, emotional, and cognitive problems}}. {Res Dev Disabil};2009 (Oct 30)

Descriptive and comparative follow-up studies of young adult males with Asperger syndrome (AS) diagnosed in childhood, using both interview, self- and parent assessment instruments for the study of aspects of emotional well-being, social functioning, and cognitive-practical skills have not been performed in the past. One-hundred males with AS diagnosed in childhood were approached for the assessment using the Asperger Syndrome Diagnostic Interview (ASDI), (personal and parent interview), the Leiter-R-Questionnaires, the Beck Depression Inventory (BDI), and the Dysexecutive Questionnaire (DEX). About 75% of the targeted group participated. The ASDI results came out significantly different at personal vs parent interviews in several key domains. In contrast, the Leiter-R-Questionnaires, showed no significant differences across the individuals with AS and their parents in the scoring of cognitive/social and emotional/adaptive skills. The BDI proved to be an adequate screening instrument for depression in that it correctly identified the vast majority of cases with clinical depression in the AS group. The DEX results suggested an executive function deficit problem profile in males with AS as severe as that reported in groups of individuals with traumatic brain injury and schizophrenia. Interviews (personal and collateral), and self-rating and parent-rating questionnaires all have a role in the comprehensive diagnostic process in AS and other autism spectrum disorders, and could be used as adjuncts when evaluating whether or not individuals meeting diagnostic symptom criteria for the condition have sufficient problems in daily life to warrant a clinical diagnosis of AS.

2. Hardan AY, Pabalan M, Gupta N, Bansal R, Melhem NM, Fedorov S, Keshavan MS, Minshew NJ. {{Corpus callosum volume in children with autism}}. {Psychiatry Res};2009 (Oct 30);174(1):57-61.

The corpus callosum (CC) is the main commissure connecting the cerebral hemispheres. Previous evidence suggests the involvement of the CC in the pathophysiology of autism. However, most studies examined the mid-sagittal area and investigations applying novel methods are warranted. The goal of this investigation is to apply a volumetric method to examine the size of the CC in autism and to identify any association with clinical features. An MRI-based morphometric study of the total CC volume and its seven subdivisions was conducted and involved 22 children with autism (age range 8.1-12.7 years) and 23 healthy, age-matched controls. Reductions in the total volume of the CC and several of its subdivisions were found in the autism sample. Associations were observed between CC structures and clinical features including social deficits, repetitive behaviors, and sensory abnormalities. Volumetric alterations of the CC observed in this investigation are consistent with midsagittal area tracings of decreased CC size in autism. These findings support the aberrant connectivity hypothesis with possible decrease in interhemispheric communications.

3. Ji L, Chauhan A, Brown WT, Chauhan V. {{Increased activities of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase in the frontal cortex and cerebellum of autistic individuals}}. {Life Sci};2009 (Oct 26)

AIMS: Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase are enzymes known to maintain intracellular gradients of ions that are essential for signal transduction. The aim of this study was to compare the activities of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase in postmortem brain samples from the cerebellum and frontal, temporal, parietal, and occipital cortices from autistic and age-matched control subjects. MAIN METHODS: The frozen postmortem tissues from different brain regions of autistic and control subjects were homogenized. The activities of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase were assessed in the brain homogenates by measuring inorganic phosphorus released by the action of Na(+)/K(+)- and Ca(2+)/Mg(2+)-dependent hydrolysis of ATP. KEY FINDINGS: In the cerebellum, the activities of both Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase were significantly increased in the autistic samples compared with their age-matched controls. The activity of Na(+)/K(+)-ATPase but not Ca(2+)/Mg(2+)-ATPase was also significantly increased in the frontal cortex of the autistic samples as compared to the age-matched controls. In contrast, in other regions, i.e., the temporal, parietal and occipital cortices, the activities of these enzymes were similar in autism and control groups. SIGNIFICANCE: The results of this study suggest brain-region specific increases in the activities of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase in autism. Increased activity of these enzymes in the frontal cortex and cerebellum may be due to compensatory responses to increased intracellular calcium concentration in autism. We suggest that altered activities of these enzymes may contribute to abnormal neuronal circuit functioning in autism.

4. Vattikuti S, Chow CC. A {{Computational Model for Cerebral Cortical Dysfunction in Autism Spectrum Disorders}}. {Biol Psychiatry};2009 (Oct 30)

BACKGROUND: Perturbations to the microscopic level balance between synaptic excitation and inhibition and neuron organization in the cerebral cortex are suggested to underlie autism spectrum disorder (ASD) traits. The mechanism linking these perturbations to cognitive behaviors in ASD is unknown. This study strives to bridge this gap by generating clinically testable diagnostic and pharmacological predictions based on the effect of synaptic imbalance and neuron distribution on a computational local circuit model of the cerebral cortex. METHODS: We use a computational microscopic model of the cerebral cortex that incorporates N-methyl-D-aspartate and gamma-aminobutyric acid synaptic kinetics. We employ the model circuit during model tasks similar to visually guided and gap oculomotor saccade tasks and interpret qualitative model predictions of saccade hypometria and dysmetria. We consider the effects of varying the excitatory to inhibitory synaptic balance, neuron density, and neuron clustering in this model. RESULTS: An increase of synaptic excitation over synaptic inhibition results in increased hypometria and dysmetria. Similar effects by either reduced inhibition or increased excitation suggest that a variety of pharmacological compounds can be used for both screening and medical management. On the other hand, any change to the microscopic neuron anatomy that increases the effective maximum distance between excitatory neurons decreases hypometria but has no affect on dysmetria. CONCLUSIONS: Perturbations to a computational model of a local cerebral cortical circuit can account for saccade hypometria and dysmetria reported in ASD studies. This approach may provide a direct link between cerebral cortical function and ASD behaviors.