Genome-wide association identifies genetic variants associated with lentiform nucleus volume in N = 1345 young and elderly subjects

Deficits in lentiform nucleus volume and morphometry are implicated in a number of genetically influenced disorders, including Parkinson's disease, schizophrenia, and ADHD. Here we performed genome-wide searches to discover common genetic variants associated with differences in lentiform nucleus volume in human populations. We assessed structural MRI scans of the brain in two large genotyped samples: the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 706) and the Queensland Twin Imaging Study (QTIM; N = 639). Statistics of association from each cohort were combined meta-analytically using a fixed-effects model to boost power and to reduce the prevalence of false positive findings. We identified a number of associations in and around the flavin-containing monooxygenase (FMO) gene cluster. The most highly associated SNP, rs1795240, was located in the FMO3 gene; after meta-analysis, it showed genome-wide significant evidence of association with lentiform nucleus volume (PMA = 4. 79 × 10-8). This commonly-carried genetic variant accounted for 2. 68 % and 0. 84 % of the trait variability in the ADNI and QTIM samples, respectively, even though the QTIM sample was on average 50 years younger. Pathway enrichment analysis revealed significant contributions of this gene to the cytochrome P450 pathway, which is involved in metabolizing numerous therapeutic drugs for pain, seizures, mania, depression, anxiety, and psychosis. The genetic variants we identified provide replicated, genome-wide significant evidence for the FMO gene cluster's involvement in lentiform nucleus volume differences in human populations.

Sex differences in the human connectome: 4-Tesla high angular resolution diffusion imaging (HARDI) tractography in 234 young adult twins

Cortical connectivity is associated with cognitive and behavioral traits that are thought to vary between sexes. Using high-angular resolution diffusion imaging at 4 Tesla, we scanned 234 young adult twins and siblings (mean age: 23.4 2.0 SD years) with 94 diffusion-encoding directions. We applied a novel Hough transform method to extract fiber tracts throughout the entire brain, based on fields of constant solid angle orientation distribution functions (ODFs). Cortical surfaces were generated from each subject's 3D T1-weighted structural MRI scan, and tracts were aligned to the anatomy. Network analysis revealed the proportions of fibers interconnecting 5 key subregions of the frontal cortex, including connections between hemispheres. We found significant sex differences (147 women/87 men) in the proportions of fibers connecting contralateral superior frontal cortices. Interhemispheric connectivity was greater in women, in line with long-standing theories of hemispheric specialization. These findings may be relevant for ongoing studies of the human connectome.

A commonly carried genetic variant in the delta opioid receptor gene, OPRD1, is associated with smaller regional brain volumes: Replication in elderly and young populations

Delta opioid receptors are implicated in a variety of psychiatric and neurological disorders. These receptors play a key role in the reinforcing properties of drugs of abuse, and polymorphisms in OPRD1 (the gene encoding delta opioid receptors) are associated with drug addiction. Delta opioid receptors are also involved in protecting neurons against hypoxic and ischemic stress. Here, we first examined a large sample of 738 elderly participants with neuroimaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative. We hypothesized that common variants in OPRD1 would be associated with differences in brain structure, particularly in regions relevant to addictive and neurodegenerative disorders. One very common variant (rs678849) predicted differences in regional brain volumes. We replicated the association of this single-nucleotide polymorphism with regional tissue volumes in a large sample of young participants in the Queensland Twin Imaging study. Although the same allele was associated with reduced volumes in both cohorts, the brain regions affected differed between the two samples. In healthy elderly, exploratory analyses suggested that the genotype associated with reduced brain volumes in both cohorts may also predict cerebrospinal fluid levels of neurodegenerative biomarkers, but this requires confirmation. If opiate receptor genetic variants are related to individual differences in brain structure, genotyping of these variants may be helpful when designing clinical trials targeting delta opioid receptors to treat neurological disorders.

Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N1198) using genome-wide search

The caudate is a subcortical brain structure implicated in many common neurological and psychiatric disorders. To identify specific genes associated with variations in caudate volume, structural magnetic resonance imaging and genome-wide genotypes were acquired from two large cohorts, the Alzheimer's Disease NeuroImaging Initiative (ADNI; N=734) and the Brisbane Adolescent/Young Adult Longitudinal Twin Study (BLTS; N=464). In a preliminary analysis of heritability, around 90% of the variation in caudate volume was due to genetic factors. We then conducted genome-wide association to find common variants that contribute to this relatively high heritability. Replicated genetic association was found for the right caudate volume at single-nucleotide polymorphism rs163030 in the ADNI discovery sample (P=2.36 × 10 -6) and in the BLTS replication sample (P=0.012). This genetic variation accounted for 2.79 and 1.61% of the trait variance, respectively. The peak of association was found in and around two genes, WDR41 and PDE8B, involved in dopamine signaling and development. In addition, a previously identified mutation in PDE8B causes a rare autosomal-dominant type of striatal degeneration. Searching across both samples offers a rigorous way to screen for genes consistently influencing brain structure at different stages of life. Variants identified here may be relevant to common disorders affecting the caudate.

‘Appreciate A Mate’ Helping others to feel good about themselves. Safe and Well Online: A report on the development and evaluation of a positive messaging social marketing campaign for young people.

This report describes the Year Two/Campaign Two processes, and articulates findings from the major project components designed to address the challenges noted above (see Figure 1). Three major components comprise the Safe and Well Online project: 1) A participatory design (PD) process involving young people and sector partners (UWS) for; 2) campaign development (Zuni & Digital Arts Network); and 3) a cohort study (University of South Australia) to evaluate campaign effectiveness and attitude and behaviour change. Each sub-study comprehensively considered the ethical requirements of conducting online research with minors. The theoretical and methodological framework for measuring campaign engagement and efficacy (Sub-studies 3, 4 and 5) drew on the Model of Goal Directed Behaviour (MGB) (Perugini & Bagozzi 2001) and Nudge Theory (Thaler & Sunstein, 2008). This report extends the findings and conclusions of the Year One Pilot Study ‘‘Keep it Tame’’ (Spears et.al, 2015), and details the development and evaluation of the second of four Safe and Well Online Campaigns—‘‘Appreciate A Mate’: Helping others feel good about themselves’.

Assessing acculturation over time: A four-year prospective study of Asian American young adults

Acculturation is commonly defined as a dynamic and multidimensional process in which individuals and groups change over time when coming into contact with another culture. Despite the emphasis on acculturation as a process of change over time, few researchers have directly assessed this hypothesis. The current study first identifies and then examines "stable" and "dynamic" dimensions of acculturation within a 4-year prospective study of 433 first- and second-generation Chinese- and Korean-American college students. Separate growth model analyses revealed significant linear change for first-generation students toward greater U.S. acculturation. In comparison, tests of linear and quadratic change for second-generation students were not significant. When stratifying by gender, acculturation increased for women but there was no significant change in acculturation for men. While all students reported increases in alcohol consumption over the study period, changes in acculturation predicted changes in alcohol consumption only for women. Chinese men showed greater increases in alcohol consumption than Korean men but there was no effect for ethnicity among women. There was significant individual variability in the models, which underscores the importance of examining change prospectively through within and between person analyses. The findings highlight the importance of examining acculturation changes over time for different migrant groups with implications for further development of acculturation measures, research methodologies, and health interventions. More prospective research designs of acculturation are needed to examine changes in health behavior and overall adaptation across migrant groups at varying stages of development.

Decisions and actions of distracted drivers at the onset of yellow light

Driving on an approach to a signalized intersection while distracted is relatively risky, as potential vehicular conflicts and resulting angle collisions tend to be relatively more severe compared to other locations. Given the prevalence and importance of this particular scenario, the objective of this study was to examine the decisions and actions of distracted drivers during the onset of yellow lights. Driving simulator data were obtained from a sample of 69 drivers under baseline and handheld cell phone conditions at the University of Iowa – National Advanced Driving Simulator. Explanatory variables included age, gender, cell phone use, distance to stop-line, and speed. Although there is extensive research on drivers’ responses to yellow traffic signals, the examinations have been conducted from a traditional regression-based approach, which do not necessary provide the underlying relations and patterns among the sampled data. In this paper, we exploit the benefits of both classical statistical inference and data mining techniques to identify the a priori relationships among main effects, non-linearities, and interaction effects. Results suggest that the probability of yellow light running increases with the increase in driving speed at the onset of yellow. Both young (18–25 years) and middle-aged (30–45 years) drivers reveal reduced propensity for yellow light running whilst distracted across the entire speed range, exhibiting possible risk compensation during this critical driving situation. The propensity for yellow light running for both distracted male and female older (50–60 years) drivers is significantly higher. Driver experience captured by age interacts with distraction, resulting in their combined effect having slower physiological response and being distracted particularly risky.

Examining signs of driver sleepiness, usage of sleepiness countermeasures and the associations with sleepy driving behaviours and individual factors

The impairing effect from sleepiness is a major contributor to road crashes. The ability of a sleepy driver to perceive their level of sleepiness is an important consideration for road safety as well as the type of sleepiness countermeasure used by drivers as some sleepiness countermeasures are more effective than others. The aims of the current study were to determine the extent that the signs of driver sleepiness were associated with sleepy driving behaviours, as well as determining which individual factors (demographic, work, driving, and sleep-related factors) were associated with using a roadside or in-vehicle sleepiness countermeasure. A sample of 1518 Australian drivers from the Australian State of New South Wales and the neighbouring Australian Capital Territory took part in the study. The participants’ experiences with the signs of sleepiness were reasonably extensive. A number of the early signs of sleepiness (e.g., yawning, frequent eye blinks) were related with continuing to drive while sleepy, with the more advanced signs of sleepiness (e.g., difficulty keeping eyes open, dreamlike state of consciousness) associated with having a sleep-related close call. The individual factors associated with using a roadside sleepiness countermeasure included age (being older), education (tertiary level), difficulties getting to sleep, not continuing to drive while sleepy, and having experienced many signs of sleepiness. The results suggest that these participants have a reasonable awareness and experience with the signs of driver sleepiness. Factors related to previous experiences with sleepiness were associated with implementing a roadside countermeasure. Nonetheless, the high proportions of drivers performing sleepy driving behaviours, suggest that concerted efforts are needed with road safety campaigns regarding the dangers of driving while sleepy.

Young drivers’ responses to anti-speeding advertisements: Comparison of self-report and objective measures of persuasive processing and outcomes

Objective Self-report measures are typically used to assess the effectiveness of road safety advertisements. However, psychophysiological measures of persuasive processing (i.e., skin conductance response [SCR]) and objective driving measures of persuasive outcomes (i.e., in-vehicle GPS devices) may provide further insights into the effectiveness of these advertisements. This study aimed to explore the persuasive processing and outcomes of two anti-speeding advertisements by incorporating both self-report and objective measures of speeding behaviour. In addition, this study aimed to compare the findings derived from these different measurement approaches. Methods Young drivers (N = 20, Mage = 21.01 years) viewed either a positive or negative emotion-based anti-speeding television advertisement. Whilst viewing the advertisement, SCR activity was measured to assess ad-evoked arousal responses. The RoadScout® GPS device was then installed into participants’ vehicles for one week to measure on-road speed-related driving behaviour. Self-report measures assessed persuasive processing (emotional and arousal responses) and actual driving behaviour. Results There was general correspondence between the self-report measures of arousal and the SCR and between the self-report measure of actual driving behaviour and the objective driving data (as assessed via the GPS devices). Conclusions This study provides insights into how psychophysiological and GPS devices could be used as objective measures in conjunction with self-report measures to further understand the persuasive processes and outcomes of emotion-based anti-speeding advertisements.

Does Social Anxiety and Bullying Victimization Create Loneliness in Young People?

Loneliness is a distressing, complex, universal phenomena. This chapter focuses on loneliness in children and adolescents, specifically examining research on the relationship between young people’s social anxiety and loneliness and the role of bullying victimisation and loneliness. It answers the question does social anxiety and bullying victimization create loneliness in young people. It was found from a review of the literature that all three concepts are distinct yet inextricably intertwined as antecedents and consequences of each other. The constructs are bi-directional, often forming a feedback loop or negative cycle. In addition these variables can also be mediating and moderating variables. Implications for interventions are discussed.

Do repeated rumble strip hits improve driver alertness?

Driving while sleepy is associated with increased crash risk. Rumble strips are designed to alert a sleepy or inattentive driver when they deviate outside their driving lane. The current study sought to examine the effects of repeated rumble strip hits on levels of physiological and subjective sleepiness as well as simulated driving performance. In total, 36 regular shift workers drove a high-fidelity moving base simulator on a simulated road with rumble strips installed at the shoulder and centre line after a working a full night shift. The results show that on average, the first rumble strip occurred after 20 minutes of driving, with subsequent hits occurring 10 minutes later, with the last three occurring approximately every 5 minutes thereafter. Specifically, it was found that the first rumble strip hit reduced physiological sleepiness; however, subsequent hits did not increase alertness. Moreover, the results also demonstrate that increased subjective sleepiness levels, via the Karolinska Sleepiness Scale, were associated with a greater probability of hitting a rumble strip. The present results suggest that sleepiness is very resilient to even strongly arousing stimuli, with physiologicl and subjective sleepiness increasing over the duration of the drive, despite the interference by rumble strips.

Measuring, understanding and reducing psychotic-like experiences (PLEs) in young people

Using large community samples, an existing screening instrument for unusual beliefs and perceptual experiences was refined, and a current version of the lifetime measure was developed and tested. Importantly, high scores on the instruments were associated with psychological distress and suicide risk. Acceptability testing of a web treatment was also undertaken. Routine use of the screening instrument and web program in health services may improve identification and support of young people at risk of distress and serious psychological disorder.

Parenting and the behavior problems of young children with an intellectual disability: Concurrent and longitudinal relationships in a population-based study

We examined parenting behaviors, and their association with concurrent and later child behavior problems. Children with an intellectual disability (ID) were identified from a UK birth cohort (N  =  516 at age 5). Compared to parents of children without an ID, parents of children with an ID used discipline less frequently, but reported a more negative relationship with their child. Among children with an ID, discipline, and home atmosphere had no long-term association with behavior problems, whereas relationship quality did: closer relationships were associated with fewer concurrent and later child behavior problems. Increased parent-child conflict was associated with greater concurrent and later behavior problems. Parenting programs in ID could target parent-child relationship quality as a potential mediator of behavioral improvements in children.

Spatiotemporal pattern of bacillary dysentery in China from 1990 to 2009: What is the driver behind?

BACKGROUND Little is known about the spatiotemporal pattern of bacillary dysentery (BD) in China. This study assessed the geographic distribution and seasonality of BD in China over the past two decades. METHODS Data on monthly BD cases in 31 provinces of China from January 1990 to December 2009 obtained from Chinese Center for Disease Control and Prevention, and data on demographic and geographic factors, as well as climatic factors, were compiled. The spatial distributions of BD in the four periods across different provinces were mapped, and heat maps were created to present the seasonality of BD by geography. A cosinor function combined with Poisson regression was used to quantify the seasonal parameters of BD, and a regression analysis was conducted to identify the potential drivers of morbidity and seasonality of BD. RESULTS Although most regions of China have experienced considerable declines in BD morbidity over the past two decades, Beijing and Ningxia still had high BD morbidity in 2009. BD morbidity decreased more slowly in North-west China than other regions. BD in China mainly peaked from July to September, with heterogeneity in peak time between regions. Relative humidity was associated with BD morbidity and peak time, and latitude was the major predictor of BD amplitude. CONCLUSIONS The transmission of BD was heterogeneous in China. Improved sanitation and hygiene in North-west China, and better access to clean water and food in the big floating population in some metropolises could be the focus of future preventive interventions against BD. BD control efforts should put more emphasis on those dry areas in summer.

What triggers problem recognition? An exploration on young Australian male problematic online gamers

Help-seeking is a complex decision-making process that first begins with problem recognition. However, little is understood about the conceptualisation of the helpseeking process and the triggers of problem recognition. This research proposes the use of the Critical Incident Technique (CIT) to examine and classify incidents that serve as key triggers of problem recognition among young Australian male problematic online gamers. The research provides a classification of five different types of triggers that will aid social marketers into developing effective early detection, prevention and treatment focused social marketing interventions.