Spatial attentional bias as a marker of genetic risk, symptom severity, and stimulant response in ADHD

Attention-deficit hyperactivity disorder (ADHD) is a heritable childhood onset disorder that is marked by variability at multiple levels including clinical presentation, cognitive profile, and response to stimulant medications. It has been suggested that this variability may reflect etiological differences, particularly, at the level of underlying genetics. This study examined whether an attentional phenotype-spatial attentional bias could serve as a marker of symptom severity, genetic risk, and stimulant response in ADHD. A total of 96 children and adolescents with ADHD were assessed on the Landmark Task, which is a sensitive measure of spatial attentional bias. All children were genotyped for polymorphisms (30 untranslated (UTR) and intron 8 variable number of tandem repeats (VNTRs)) of the dopamine transporter gene (DAT1). Spatial attentional bias correlated with ADHD symptom levels and varied according to DAT1 genotype. Children who were homozygous for the 10-repeat allele of the DAT1 30-UTR VNTR displayed a rightward attentional bias and had higher symptom levels compared to those with the low-risk genotype. A total of 26 of these children who were medication naive performed the Landmark Task at baseline and then again after 6 weeks of stimulant medication. Left-sided inattention (rightward bias) at baseline was associated with an enhanced response to stimulants at 6 weeks. Moreover, changes in spatial bias with stimulant medications, varied as a function of DAT1 genotype. This study suggests an attentional phenotype that relates to symptom severity and genetic risk for ADHD, and may have utility in predicting stimulant response in ADHD.

Attentional bias to food-related visual cues: is there a role in obesity?

The incentive sensitisation model of obesity suggests that modification of the dopaminergic associated reward systems in the brain may result in increased awareness of food-related visual cues present in the current food environment. Having a heightened awareness of these visual food cues may impact on food choices and eating behaviours with those being most aware of or demonstrating greater attention to food-related stimuli potentially being at greater risk of overeating and subsequent weight gain. To date, research related to attentional responses to visual food cues has been both limited and conflicting. Such inconsistent findings may in part be explained by the use of different methodological approaches to measure attentional bias and the impact of other factors such as hunger levels, energy density of visual food cues and individual eating style traits that may influence visual attention to food-related cues outside of weight status alone. This review examines the various methodologies employed to measure attentional bias with a particular focus on the role that attentional processing of food-related visual cues may have in obesity. Based on the findings of this review, it appears that it may be too early to clarify the role visual attention to food-related cues may have in obesity. Results however highlight the importance of considering the most appropriate methodology to use when measuring attentional bias and the characteristics of the study populations targeted while interpreting results to date and in designing future studies.

Obsessive-compulsive symptoms and attentional bias: An eye-tracking methodology

Background and objectives: Cognitive models suggest that attentional biases are integral in the maintenance of obsessive-compulsive symptoms (OCS). Such biases have been established experimentally in anxiety disorders; however, the evidence is unclear in Obsessive Compulsive disorder (OCD). In the present study, an eye-tracking methodology was employed to explore attentional biases in relation to OCS.
Methods: A convenience sample of 85 community volunteers was assessed on OCS using the Yale-Brown Obsessive Compulsive Scale-self report. Participants completed an eye-tracking paradigm where they were exposed to OCD, Aversive and Neutral visual stimuli. Indices of attentional bias were derived from the eye-tracking data.
Results: Simple linear regressions were performed with OCS severity as the predictor and eye-tracking measures of the different attentional biases for each of the three stimuli types were the criterion variables. Findings revealed that OCS severity moderately predicted greater frequency and duration of fixations on OCD stimuli, which reflect the maintenance attentional bias. No significant results were found in support of other biases.
Limitations: Interpretations based on a non-clinical sample limit the generalisability of the conclusions, although use of such samples in OCD research has been found to be comparable to clinical populations. Future research would include both clinical and sub-clinical participants.
Conclusions: Results provide some support for the theory of maintained attention in OCD attentional biases, as opposed to vigilance theory. Individuals with greater OCS do not orient to OCD stimuli any faster than individuals with lower OCS, but once a threat is identified, these individuals allocate more attention to OCS-relevant stimuli.

Cognitive inhibition and interference in dissociative indentity disorder: the effects of anxiety on specific executive functions:The effects of anxiety on specific executive functions

Using an experimentally based, computer-presented task, this study assessed cognitive inhibition and interference in individuals from the dissociative identity disorder (DID; n=12), generalized anxiety disorder (GAD; n=12) and non-clinical (n=12) populations. Participants were assessed in a neutral and emotionally negative (anxiety provoking) context, manipulated by experimental instructions and word stimuli. The DID sample displayed effective cognitive inhibition in the neutral but not the anxious context. The GAD sample displayed the opposite findings. However, the interaction between group and context failed to reach significance. There was no indication of an attentional bias to non-schema specific negative words in any sample. Results are discussed in terms of the potential benefit of weakened cognitive inhibition during anxious arousal in dissociative individuals.

Nonconservative dynamics in long atomic wires

The effect of nonconservative current-induced forces on the ions in a defect-free metallic nanowire is investigated using both steady-state calculations and dynamical simulations. Nonconservative forces were found to have a major influence on the ion dynamics in these systems, but their role in increasing the kinetic energy of the ions decreases with increasing system length. The results illustrate the importance of nonconservative effects in short nanowires and the scaling of these effects with system size. The dependence on bias and ion mass can be understood with the help of a simple pen and paper model. This material highlights the benefit of simple preliminary steady-state calculations in anticipating aspects of brute-force dynamical simulations, and provides rule of thumb criteria for the design of stable quantum wires.

Length matters:Keeping atomic wires in check

Dynamical effects of non-conservative forces in long, defect free atomic wires are investigated. Current flow through these wires is simulated and we find that during the initial transient, the kinetic energies of the ions are contained in a small number of phonon modes, closely clustered in frequency. These phonon modes correspond to the waterwheel modes determined from preliminary static calculations. The static calculations allow one to predict the appearance of non-conservative effects in advance of the more expensive real-time simulations. The ion kinetic energy redistributes across the band as non-conservative forces reach a steady state with electronic factional forces. The typical ion kinetic energy is found to decrease with system length, increase with atomic mass, and its dependence on bias, mass and length is supported with a pen and paper model. This paper highlights the importance of non-conservative forces in current carrying devices and provides criteria for the design of stable atomic wires.

Externalizing and attentional behaviors in children of depressed mothers treated with a selective serotonin reuptake inhibitor antidepressant during pregnancy

To evaluate attentional and activity behaviors in 4-year-olds following prenatal selective serotonin reuptake inhibitor (SSRI) exposure.

Polymorphims in the Interferon-y/Interleukin 26 Gene Region Contribute to Sex Bias in Susceptibility to Rheumatoid Arthritis

Objective:

To determine whether polymorphisms in the interferon-? (IFN?)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA).

Methods:

Four microsatellite markers, located in a 118-kb interval that contains both the IFN? and IL-26 genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction–based fragment analysis.

Results:

Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with RA in women (corrected P [Pcorr] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32–0.78; P = 0.002, Pcorr = 0.03) but not in men with RA.

Conclusion:

Our results demonstrate that common polymorphisms in the IFN?/IL-26 gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis.

Polymorphisms in SLC6A4, PAH, GABRB3, and MAOB and modification of psychotic disorder features

We tested four genes [phenylalanine hydroxylase (PAH), the serotonin transporter (SLC6A4), monoamine oxidase B (MAOB), and the gamma-aminobutyric acid A receptor beta-3 subunit (GABRB3)] for their impact on five schizophrenia symptom factors: delusions, hallucinations, mania, depression, and negative symptoms. In a 90 family subset of the Irish Study of High Density Schizophrenia Families, the PAH 232 bp microsatellite allele demonstrated significant association with the delusions factor using both QTDT (F = 8.0, p = .031) and QPDTPHASE (chi-square = 12.54, p = .028). Also, a significant association between the GABRB3 191 bp allele and the hallucinations factor was detected using QPDTPHASE (chi-square 15.51, p = .030), but not QTDT (chi-square = 2.07, p = .560). (C) 2009 Elsevier B.V. All rights reserved.

The association between complement component 2/complement factor B polymorphisms and age-related macular degeneration: A HuGE review and meta-analysis

The authors performed a systematic review of the association of complement component 2(C2)/complement factor B (CFB) gene polymorphisms with age-related macular degeneration (AMD). In total, data from 19 studies published between 2006 and 2011 were pooled for 4 polymorphisms: rs9332739 and rs547154 in the C2 gene and rs4151667 and rs641153 in the CFB gene. Data extraction and assessments for risk of bias were independently performed by 2 reviewers. Allele frequencies and allele and genotypic effects were pooled. Heterogeneity and publication bias were explored. Pooled minor allele frequencies for all 4 SNPs were between 4.7% and 9.6% for all polymorphisms, except for an Indian population in which the C allele at rs9332739 was the major allele. For the C2 polymorphisms, the minor C allele at rs9332739 and the minor T allele at rs547154 carried estimated relative risks (odds ratios) of 0.55 (95% confidence interval (CI): 0.46, 0.65) and 0.47 (95% CI: 0.39, 0.57), respectively. For the CFB polymorphisms, the minor A alleles at rs4151667 and rs614153 carried estimated risks of 0.54 (95% CI: 0.45, 0.64) and 0.41 (95% CI: 0.34, 0.51), respectively. These allele effects contributed to an absolute lowering of the risk of all AMD in Caucasian populations by 2.0%-6.0%. This meta-analysis provides a robust estimate of the protective association of C2/CFB with AMD.

Clinical features of psychotic disorders and polymorphisms in HT2A, DRD2, DRD4, SLC6A3 (DAT1), and BDNF:a family based association study

Schizophrenia is clinically heterogeneous and multidimensional, but it is not known whether this is due to etiological heterogeneity. Previous studies have not consistently reported association between any specific polymorphisms and clinical features of schizophrenia, and have primarily used case-control designs. We tested for the presence of association between clinical features and polymorphisms in the genes for the serotonin 2A receptor (HT2A), dopamine receptor types 2 and 4, dopamine transporter (SLC6A3), and brain-derived neurotrophic factor (BDNF). Two hundred seventy pedigrees were ascertained on the basis of having two or more members with schizophrenia or poor outcome schizoaffective disorder. Diagnoses were made using a structured interview based on the SCID. All patients were rated on the major symptoms of schizophrenia scale (MSSS), integrating clinical and course features throughout the course of illness. Factor analysis revealed positive, negative, and affective symptom factors. The program QTDT was used to implement a family-based test of association for quantitative traits, controlling for age and sex. We found suggestive evidence of association between the His452Tyr polymorphism in HT2A and affective symptoms (P = 0.02), the 172-bp allele of BDNF and negative symptoms (P = 0.04), and the 480-bp allele in SLC6A3 (= DAT1) and negative symptoms (P = 0.04). As total of 19 alleles were tested, we cannot rule out false positives. However, given prior evidence of involvement of the proteins encoded by these genes in psychopathology, our results suggest that more attention should be focused on the impact of these alleles on clinical features of schizophrenia.

Novel Panel Cointegration Tests Emending for Cross-Section Dependence with N Fixed

In this paper, we propose new cointegration tests for single equations and panels. Inboth cases, the asymptotic distributions of the tests, which are derived with N fixed andT → ∞, are shown to be standard normals. The effects of serial correlation and crosssectionaldependence are mopped out via long-run variances. An effective bias correctionis derived which is shown to work well in finite samples; particularly when N is smallerthan T. Our panel tests are robust to possible cointegration across units.

Alcohol attention bias in adolescent social drinkers: an eye tracking study

Rationale
Previous research on attention bias in nondependent social drinkers has focused on adult samples with limited focus on the presence of attention bias for alcohol cues in adolescent social drinkers.
Objectives
The aim of this study was to examine the presence of alcohol attention bias in adolescents and the relationship of this cognitive bias to alcohol use and alcohol-related expectancies.
Methods
Attention bias in adolescent social drinkers and abstainers was measured using an eye tracker during exposure to alcohol and neutral cues. Questionnaires measured alcohol use and explicit alcohol expectancies.
Results
Adolescent social drinkers spent significantly more time fixating to alcohol stimuli compared to controls. Total fixation time to alcohol stimuli varied in accordance with level of alcohol consumption and was significantly associated with more positive alcohol expectancies. No evidence for automatic orienting to alcohol stimuli was found in adolescent social drinkers.
Conclusion
Attention bias in adolescent social drinkers appears to be underpinned by controlled attention suggesting that whilst participants in this study displayed alcohol attention bias comparable to that reported in adult studies, the bias has not developed to the point of automaticity. Initial fixations appeared to be driven by alternative attentional processes which are discussed further.