Association of the cannabinoid receptor gene (CNR1) with ADHD and post-traumatic stress disorder.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder affecting some 5-10% of children and 4-5% of adults. The cannabinoid receptor gene (CNR1) is a positional candidate gene due to its location near an identified ADHD linkage peak on chromosome 6, its role in stress and dopamine regulation, its association with other psychiatric disorders that co-occur with ADHD, and its function in learning and memory. We tested SNP variants at the CNR1 gene in two independent samples-an unselected adolescent sample from Northern Finland, and a family-based sample of trios (an ADHD child and their parents).

Sensing array for coherence analysis of modulated aquatic chemical plumes.

Here we show that an array of sensors can provide information about the spatial and temporal distribution of chemicals in liquid turbulent plumes. Planar laser induced fluorescence (PLIF) and amperometric sensor arrays were used to record signals from modulated chemical plumes released into a recirculating flume. Coherence analysis was applied to extract the frequency components contained in the sensor response.

Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene.

Autism is a genetically complex neurodevelopmental syndrome in which language deficits are a core feature. We describe results from two complimentary approaches used to identify risk variants on chromosome 7 that likely contribute to the etiology of autism. A two-stage association study tested 2758 SNPs across a 10 Mb 7q35 language-related autism QTL in AGRE (Autism Genetic Resource Exchange) trios and found significant association with Contactin Associated Protein-Like 2 (CNTNAP2), a strong a priori candidate.

Mitochondrial dysfunction, oxidative stress, and apoptosis revealed by proteomic and transcriptomic analyses of the striata in two mouse models of Parkinson's disease.

The molecular mechanisms underlying the changes in the nigrostriatal pathway in Parkinson's disease (PD) are not completely understood. Here, we use mass spectrometry and microarrays to study the proteomic and transcriptomic changes in the striatum of two mouse models of PD, induced by the distinct neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Proteomic analyses resulted in the identification and relative quantification of 912 proteins with two or more unique peptides and 86 proteins with significant abundance changes following neurotoxin treatment.

Profound metabolic acidosis and oxoprolinuria in an adult.

Introduction: Profound metabolic acidosis in critically ill adults sometimes remains unexplained despite extensive evaluation.

Case Report: A 58-year-old female presented in a confused state to the emergency department; she had been confused for several days. Laboratory evaluation revealed a high anion gap metabolic acidosis and modestly elevated acetaminophen level.

A quantitative trait locus for variation in dopamine metabolism mapped in a primate model using reference sequences from related species.

Non-human primates (NHP) provide crucial research models. Their strong similarities to humans make them particularly valuable for understanding complex behavioral traits and brain structure and function. We report here the genetic mapping of an NHP nervous system biologic trait, the cerebrospinal fluid (CSF) concentration of the dopamine metabolite homovanillic acid (HVA), in an extended inbred vervet monkey (Chlorocebus aethiops sabaeus) pedigree.

Pediatric major trauma: an approach to evaluation and management.

Trauma is the leading cause of death in children nationwide. Proper management of the pediatric trauma patient involves many of the components contained within standard trauma protocols. By paying strict attention to the anatomical and physiological differences in the pediatric population, clinicians will be assured the best possible outcomes.

Exfoliation syndrome: prevalence and inheritance in a subisolate of the Finnish population.

Purpose: To estimate the prevalence of pseudoexfoliation syndrome or exfoliation syndrome (ES) in a cross-sectional study and during a long-term follow-up, and to analyse how ES has been inherited in a large pedigree on an isolated population of Kökar island in southern Finland.

Methods: In a population-based study conducted between 1960 and 1962, a comprehensive ophthalmological examination was performed on 595 subjects (85% of the population). From then until 2002, 965 subjects were examined at least once.

Anesthetic-like modulation of a gamma-aminobutyric acid type A, strychnine-sensitive glycine, and N-methyl-d-aspartate receptors by coreleased neurotransmitters.

Introduction: A mechanism of anesthesia has recently been proposed which predicts that coreleased neurotransmitters may modulate neurotransmitter receptors for which they are not the native agonist in a manner similar to anesthetics.

Methods: We tested this prediction by applying acetylcholine to a NR1/NR2A N-methyl-d-aspartate receptor, glycine to a wild-type alpha(1)beta(2) and anesthetic-resistant alpha(1)(S270I)beta(2) gamma-amino-butyric acid (GABA) type A receptor, and GABA to a homomeric alpha(1) wild type and anesthetic-resistant alpha(1) S267I glycine receptor. Receptors were expressed in Xenopus laevis oocytes and studied using two-electrode voltage clamping.

The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in Mexican-Americans.

The hypothesis that brain-derived neurotrophic factor (BDNF) is involved in the pathogenesis of major depression is supported by several research findings; however, genetic studies assessing the relationship between BDNF and psychiatric disorders have produced conflicting results. We examined the effect of a BDNF polymorphism on depression susceptibility in Mexican-Americans. The single nucleotide polymorphism (Val66Met), which has been shown to have functional and behavioral effects, was genotyped in 284 depressed participants and 331 controls, showing association with depression (P=0.

A quantitative trait locus analysis of social responsiveness in multiplex autism families.

Objective: Autism is a complex genetic disorder with a highly heterogeneous phenotype defined by repetitive behaviors, language deficits, and problems with reciprocal social interactions. The authors present the first genome-wide scan for a social endophenotype in autism using the Social Responsiveness Scale, which provides a quantitative measure of autistic-like behavior, primarily focused on social relatedness.

Method: A nonparametric quantitative genome scan was performed using the Social Responsiveness Scale in a cohort of about 100 families with two or more autistic probands from the Autism Genetic Resource Exchange to identify autism loci.

High density SNP association study of a major autism linkage region on chromosome 17.

A region on chromosome 17 has recently been highlighted as linked to autism (MIM[209850]) in multiple studies and evidence has accumulated suggesting that male-only families (those families that have produced only affected males) provide the major contribution to linkage at this locus. In an attempt to comprehensively test for association of common variants to autism within the region on chromosome 17 defined in Stone et al. (Stone, J.

Association of a common complement receptor 2 haplotype with increased risk of systemic lupus erythematosus.

A genomic region on distal mouse chromosome 1 and its syntenic human counterpart 1q23-42 show strong evidence of harboring lupus susceptibility genes. We found evidence of linkage at 1q32.2 in a targeted genome scan of 1q21-43 in 126 lupus multiplex families containing 151 affected sibpairs (nonparametric linkage score 2.

Offering to share: how to put heads together in autism neuroimaging.

Data sharing in autism neuroimaging presents scientific, technical, and social obstacles. We outline the desiderata for a data-sharing scheme that combines imaging with other measures of phenotype and with genetics, defines requirements for comparability of derived data and recommendations for raw data, outlines a core protocol including multispectral structural and diffusion-tensor imaging and optional extensions, provides for the collection of prospective, confound-free normative data, and extends sharing and collaborative development not only to data but to the analytical tools and methods applied to these data. A theme in these requirements is the need to preserve creative approaches and risk-taking within individual laboratories at the same time as common standards are provided for these laboratories to build on.

Weighted variance FBAT: a powerful method for including covariates in FBAT analyses.

The family-based association test (FBAT), an extension of transmission/disequilibrium test, capitalizes on linkage disequilibrium to assess the association of genetic markers and traits in nuclear families. It does not permit a formal inclusion of covariates, although an offset under the FBAT -o option allows for an overall trait-intercept adjustment. The PBAT software provides additional features and permits the inclusion of covariates in the FBAT test statistic, but does not account for the parental genotype information when the traits are adjusted for the covariates.

Mapping autism risk loci using genetic linkage and chromosomal rearrangements.

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families.

Partial duplication at AZFc on the Y chromosome is a risk factor for impaired spermatogenesis in Han Chinese in Taiwan.

The Azoospermia Factor c (AZFc) region on the Y chromosome long arm is one of the least stable regions in the human genome. It consists almost entirely of very long repeats and is prone to rearrangement. Numerous structures at AZFc have been identified, and some of them have been reported to be associated with male infertility.

Central corneal thickness and visual field loss in fellow eyes of patients with open-angle glaucoma.

Purpose: To determine the relationship of central corneal thickness (CCT) and visual field loss between fellow eyes in primary open-angle glaucoma.

Design: Retrospective, observational case series.

Methods: Records review of glaucoma patients seen at local Veterans Administration eye clinic.

Phosphodiesterase genes are associated with susceptibility to major depression and antidepressant treatment response.

Cyclic nucleotide phosphodiesterases (PDEs) constitute a family of enzymes that degrade cAMP and cGMP. Intracellular cyclic nucleotide levels increase in response to extracellular stimulation by hormones, neurotransmitters, or growth factors and are down-regulated through hydrolysis catalyzed by PDEs, which are therefore candidate therapeutic targets. cAMP is a second messenger implicated in learning, memory, and mood, and cGMP modulates nervous system processes that are controlled by the nitric oxide (NO)/cGMP pathway.

Meta-analysis of genome-wide linkage studies of systemic lupus erythematosus.

A genetic contribution to the development of systemic lupus erythematosus (SLE) is well established. Several genome-wide linkage scans have identified a number of putative susceptibility loci for SLE, some of which have been replicated in independent samples. This study aimed to identify the regions showing the most consistent evidence for linkage by applying the genome scan meta-analysis (GSMA) method.

Heritability and genetic loci of fatty liver in familial combined hyperlipidemia.

VLDL overproduction, a process that is driven by an excess amount of hepatic fat, is a well-documented feature of familial combined hyperlipidemia (FCHL). The aims of this study were to investigate whether fatty liver, measured with ultrasound and as plasma alanine aminotransferase (ALT) levels, develops against a genetic background in FCHL and to identify chromosomal loci that are linked to these traits. In total, 157 FCHL family members and 20 spouses participated in this study.

Stratification based on language-related endophenotypes in autism: attempt to replicate reported linkage.

The identification of autism susceptibility genes has been hampered by phenotypic heterogeneity of autism, among other factors. However, the use of endophenotypes has shown preliminary success in reducing heterogeneity and identifying potential autism-related susceptibility regions. To further explore the utility of using language-related endophenotypes, we performed linkage analysis on multiplex autism families stratified according to delayed expressive speech and also assessed the extent to which parental phenotype information would aid in identifying regions of linkage.

Learning from the U.S. National Assessment of Climate Change Impacts.

The U.S. National Assessment of the Potential Consequences of Climate Variability and Change was a federally coordinated nationwide effort that involved thousands of experts and stakeholders.