Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of approximately 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

The antihypertensive drug pindolol attenuates long-term but not short-term binge-like ethanol consumption in mice

Alcohol dependence is a debilitating disorder with current therapies displaying limited efficacy and/or compliance. Consequently, there is a critical need for improved pharmacotherapeutic strategies to manage alcohol use disorders (AUDs). Previous studies have shown that the development of alcohol dependence involves repeated cycles of binge-like ethanol intake and abstinence. Therefore, we used a model of binge-ethanol consumption (drinking-in-the-dark) in mice to test the effects of compounds known to modify the activity of neurotransmitters implicated in alcohol addiction. From this, we have identified the FDA-approved antihypertensive drug pindolol, as a potential candidate for the management of AUDs. We show that the efficacy of pindolol to reduce ethanol consumption is enhanced following long-term (12-weeks) binge-ethanol intake, compared to short-term (4-weeks) intake. Furthermore, pindolol had no effect on locomotor activity or consumption of the natural reward sucrose. Because pindolol acts as a dual beta-adrenergic antagonist and 5-HT1A/1B partial agonist, we examined its effect on spontaneous synaptic activity in the basolateral amygdala (BLA), a brain region densely innervated by serotonin- and norepinephrine-containing fibres. Pindolol increased spontaneous excitatory post-synaptic current frequency in BLA principal neurons from long-term ethanol consuming mice but not naïve mice. Additionally, this effect was blocked by the 5-HT1A/1B receptor antagonist methiothepin, suggesting that altered serotonergic activity in the BLA may contribute to the efficacy of pindolol to reduce ethanol intake following long-term exposure. Although further mechanistic investigations are required, this study demonstrates the potential of pindolol as a new treatment option for AUDs that can be fast-tracked into human clinical studies.

Cointegration and causal relationships between energy consumption and output: Assessing the evidence from Australia

In this paper, we describe our investigation of the cointegration and causal relationships between energy consumption and economic output in Australia over a period of five decades. The framework used in this paper is the single-sector aggregate production function, which is the first comprehensive approach used in an Australian study of this type to include energy, capital and labour as separate inputs of production. The empirical evidence points to a cointegration relationship between energy and output and implies that energy is an important variable in the cointegration space, as are conventional inputs capital and labour. We also find some evidence of bidirectional causality between GDP and energy use. Although the evidence of causality from energy use to GDP was relatively weak when using the thermal aggregate of energy use, once energy consumption was adjusted for energy quality, we found strong evidence of Granger causality from energy use to GDP in Australia over the investigated period. The results are robust, irrespective of the assumptions of linear trends in the cointegration models, and are applicable for different econometric approaches.

Consumers' perceptions and attitudes towards firms' green marketing initiatives: How do they influence green consumption?

This thesis examines green marketing and green consumption behaviours addressing limited understandings about how consumers interpret their green consumption behaviour in their everyday lives; what motivates people to purchase green products, and what barriers exist to this behaviour. Findings reveal that enhancing green consumption through green marketing depends on consumers' enthusiasm to engage in green practices and green behavioural influences. The research supports the need for qualitative research to provide rich insights into relationships between consumer behaviour, green marketing and green consumption and builds a stronger knowledge foundation by introducing social practice theory into the marketing discipline.

A relational approach to direct mail consumption

- Purpose This paper aims to investigate how direct mail consumption contributes to brand relationship quality. Store flyers and other direct mailings continue to play a significant role in many companies’ communication strategies. Research on this topic predominantly investigates driving store traffic and sales. Less is known regarding the consumer side, such as the value that consumers may derive from the consumption of direct mailings and the effects of such a value on brand relationship quality. To address this limitation, this paper tests a causal model of the contribution of direct mail value to brand commitment, drawing on a value framework that integrates social theory of engagement regimes and literature on experiential customer value. - Design/methodology/approach The empirical work of this paper is based on a rigorous four-study mixed methods design, involving qualitative study, confirmatory factor analysis and partial least squares structural modeling. - Findings The authors develop two second-order formatively designed scales – familiar value and planned value scales – that illustrate the role of engagement regimes in consumer behavior. Although both types of value contribute equally to direct mail attachment, they exert contrasting effects on other mediational consumer responses, such as reading and gratitude. Finally, the proposed theoretical model appears to be robust in predicting customers’ brand commitment. - Research limitations/implications This study provides new insights into the research on consumer value and brand relational communication. - Originality/value This study is the first to consider consumer benefits from the social perspective of engagement regimes.

Prolonged consumption of sucrose in a binge-like manner, alters the morphology of medium spiny neurons in the nucleus accumbens shell

The modern diet has become highly sweetened, resulting in unprecedented levels of sugar consumption, particularly among adolescents. While chronic long-term sugar intake is known to contribute to the development of metabolic disorders including obesity and type II diabetes, little is known regarding the direct consequences of long-term, binge-like sugar consumption on the brain. Because sugar can cause the release of dopamine in the nucleus accumbens (NAc) similarly to drugs of abuse, we investigated changes in the morphology of neurons in this brain region following short- (4 weeks) and long-term (12 weeks) binge-like sucrose consumption using an intermittent two-bottle choice paradigm. We used Golgi-Cox staining to impregnate medium spiny neurons (MSNs) from the NAc core and shell of short- and long-term sucrose consuming rats and compared these to age-matched water controls. We show that prolonged binge-like sucrose consumption significantly decreased the total dendritic length of NAc shell MSNs compared to age-matched control rats. We also found that the restructuring of these neurons resulted primarily from reduced distal dendritic complexity. Conversely, we observed increased spine densities at the distal branch orders of NAc shell MSNs from long-term sucrose consuming rats. Combined, these results highlight the neuronal effects of prolonged binge-like intake of sucrose on NAc shell MSN morphology.

The pulling power of chocolate: Effects of approach-avoidance training on approach bias and consumption

Previous research has shown that action tendencies to approach alcohol may be modified using computerized ApproacheAvoidance Task (AAT), and that this impacted on subsequent consumption. A recent paper in this journal (Becker, Jostman, Wiers, & Holland, 2015) failed to show significant training effects for food in three studies: Nor did it find effects on subsequent consumption. However, avoidance training to high calorie foods was tested against a control rather than Approach training. The present study used a more comparable paradigm to the alcohol studies. It randomly assigned 90 participants to ‘approach’ or ‘avoid’ chocolate images on the AAT, and then asked them to taste and rate chocolates. A significant interaction of condition and time showed that training to avoid chocolate resulted in faster avoidance responses to chocolate images, compared with training to approach it. Consistent with Becker et al.'s Study 3, no effect was found on amounts of chocolate consumed, although a newly published study in this journal (Schumacher, Kemps, & Tiggemann, 2016) did do so. The collective evidence does not as yet provide solid basis for the application of AAT training to reduction of problematic food consumption, although clinical trials have yet to be conducted.