1. de Krom M, Staal WG, Ophoff RA, Hendriks J, Buitelaar J, Franke B, de Jonge MV, Bolton P, Collier D, Curran S, van Engeland H, van Ree JM. A {{Common Variant in DRD3 Receptor Is Associated with Autism Spectrum Disorder}}. {Biol Psychiatry};2008 (Dec 4)
BACKGROUND: The presence of specific and common genetic etiologies for autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) was investigated for 132 candidate genes in a two-stage design-association study. METHODS: 1,536 single nucleotide polymorphisms (SNPs) covering these candidate genes were tested in ASD (n = 144) and ADHD (n = 110) patients and control subjects (n = 404) from The Netherlands. A second stage was performed with those SNPs from Stage I reaching a significance threshold for association of p < .01 in an independent sample of ASD patients (n = 128) and controls (n = 124) from the United Kingdom and a Dutch ADHD (n = 150) and control (n = 149) sample. RESULTS: No shared association was found between ASD and ADHD. However, in the first and second ASD samples and in a joint statistical analysis, a significant association between SNP rs167771 located in the DRD3 gene was found (joint analysis uncorrected: p = 3.11 x 10(-6); corrected for multiple testing and potential stratification: p = .00162). CONCLUSIONS: The DRD3 gene is related to stereotyped behavior, liability to side effects of antipsychotic medication, and movement disorders and may therefore have important clinical implications for ASD.
2. Gomarus HK, Wijers AA, Minderaa RB, Althaus M. {{Do children with ADHD and/or PDD-NOS differ in reactivity of alpha/theta ERD/ERS to manipulations of cognitive load and stimulus relevance?}} {Clin Neurophysiol};2008 (Dec 4)
OBJECTIVE: We examined whether the method of event-related (de-)synchronization (ERD/ERS) revealed differential effects of selective attention and working memory load in children (8-11 years) with pervasive developmental disorder – not otherwise specified (PDD-NOS) or attention-deficit/hyperactivity disorder (ADHD). METHODS: Fifteen healthy controls and three equally large groups of children with symptoms of PDD-NOS, ADHD or both (PDD/HD) performed a visual selective memory search task. The EEG was recorded from which occipital alpha and frontal theta were derived. RESULTS: The effects of the overall task manipulations of task load, relevance and target/nontarget were clearly present in the overall analyses of alpha and theta ERD/ERS. However, no significant differences with respect to these manipulations existed between any of the subject groups. CONCLUSIONS: The results supply no evidence for a distinction in information processing abilities of selective attention and working memory as reflected by alpha and theta ERD/ERS between children diagnosed with either ADHD, PDD-NOS or healthy controls. SIGNIFICANCE: Alpha and theta ERD/ERS are sensitive to manipulations of task load, relevance and target/nontarget, but supply no additional information on possible group differences in comparison to the more frequently used method of event-related potentials.
3. Mehler MF, Purpura DP. {{Autism, fever, epigenetics and the locus coeruleus}}. {Brain Res Rev};2008 (Nov 24)
Some children with autism spectrum disorders (ASD) exhibit improved behaviors and enhanced communication during febrile episodes. We hypothesize that febrigenesis and the behavioral-state changes associated with fever in autism depend upon selective normalization of key components of a functionally impaired locus coeruleus-noradrenergic (LC-NA) system. We posit that autistic behaviors result from developmental dysregulation of LC-NA system specification and neural network deployment and modulation linked to the core behavioral features of autism. Fever transiently restores the modulatory functions of the LC-NA system and ameliorates autistic behaviors. Fever-induced reversibility of autism suggests preserved functional integrity of widespread neural networks subserving the LC-NA system and specifically the subsystems involved in mediating the cognitive and behavioral repertoires compromised in ASD. Alterations of complex gene-environmental interactions and associated epigenetic mechanisms during seminal developmental critical periods are viewed as instrumental in LC-NA dysregulation as emphasized by the timing and severity of prenatal maternal stressors on autism prevalence. Our hypothesis has implications for a rational approach to further interrogate the interdisciplinary etiology of ASD and for designing novel biological detection systems and therapeutic agents that target the LC-NA system’s diverse network of pre- and postsynaptic receptors, intracellular signaling pathways and dynamic epigenetic remodeling processes involved in their regulation and functional plasticity.
4. Montag C, Schubert F, Heinz A, Gallinat J. {{Prefrontal cortex glutamate correlates with mental perspective-taking}}. {PLoS ONE};2008;3(12):e3890.
BACKGROUND: Dysfunctions in theory of mind and empathic abilities have been suggested as core symptoms in major psychiatric disorders including schizophrenia and autism. Since self monitoring, perspective taking and empathy have been linked to prefrontal (PFC) and anterior cingulate cortex (ACC) function, neurotransmitter variations in these areas may account for normal and pathological variations of these functions. Converging evidence indicates an essential role of glutamatergic neurotransmission in psychiatric diseases with pronounced deficits in empathy. However, the role of the glutamate system for different dimensions of empathy has not been investigated so far. METHODOLOGY/PRINCIPAL FINDINGS: Absolute concentrations of cerebral glutamate in the ACC, left dorsolateral PFC and left hippocampus were determined by 3-tesla proton magnetic resonance spectroscopy (1H-MRS) in 17 healthy individuals. Three dimensions of empathy were estimated by a self-rating questionnaire, the Interpersonal Reactivity Index (IRI). Linear regression analysis showed that dorsolateral PFC glutamate concentration was predicted by IRI factor « perspective taking » (T = -2.710, p = 0.018; adjusted alpha-level of 0.017, Bonferroni) but not by « empathic concern » or « personal distress ». No significant relationship between IRI subscores and the glutamate levels in the ACC or left hippocampus was detected. CONCLUSIONS/SIGNIFICANCE: This is the first study to investigate the role of the glutamate system for dimensions of theory of mind and empathy. Results are in line with recent concepts that executive top-down control of behavior is mediated by prefrontal glutamatergic projections. This is a preliminary finding that needs a replication in an independent sample.
5. Monteggia LM, Kavalali ET. {{Rett Syndrome and the Impact of MeCP2 Associated Transcriptional Mechanisms on Neurotransmission}}. {Biol Psychiatry};2008 (Dec 4)
Subtle alterations in synaptic function contribute to the pathophysiology associated with several neuropsychiatric diseases. Modifications in synaptic vesicle trafficking can cause frequency-dependent changes in neurotransmission, alter information coding in neural circuits, and affect long-term plasticity. Rett syndrome, a neurodevelopmental disorder that arises from mutations in the methyl-CpG-binding protein-2 (MeCP2) gene, is a salient example for such a disease state in which synaptic transmission-in particular, spontaneous neurotransmission and short-term synaptic plasticity, have been altered. MeCP2 is widely believed to be a transcriptional repressor that silences methylated genes. Recent studies have identified synaptic deficits associated with the loss of MeCP2 in several brain regions, including the hippocampus. These findings suggest a synaptic basis for neurological symptoms associated with Rett syndrome and suggest an important role for transcriptional repression in the regulation of neurotransmission. These studies also highlight the importance of histone deacetylation and DNA methylation, two key epigenetic mechanisms in controlling synaptic function. These mechanisms are essential for chromatin remodeling in neurons as well as for repression of gene activation by MeCP2 and related methyl-binding proteins. Future work focusing on the regulation of DNA methylation and histone deacetylation by synaptic activity and how these epigenetic alterations affect neurotransmission will be critical to elucidate the mechanisms underlying Rett syndrome. In addition, this work will also help delineate a key pathway that regulates properties of neurotransmission in the central nervous system that may underlie additional neuropsychiatric disorders.
6. Rapin I, Goldman S. {{The Brazilian CARS: a standardized screening tool for autism}}. {J Pediatr} (Rio J);2008 (Nov-Dec);84(6):473-475.
