Decision making as a predictor of first ecstasy use: a prospective study

Ecstasy (+/- 3,4-methylenedioxymethamphetamine) is a widely used recreational drug that may damage the serotonin system and may entail neuropsychological dysfunctions. Few studies investigated predictors for ecstasy use. Self-reported impulsivity does not predict the initiation of ecstasy use; the question is if neuropsychological indicators of impulsivity can predict first ecstasy use. This study tested the hypothesis that a neuropsychological indicator of impulsivity predicts initiation of ecstasy use. Decision-making strategy and decision-making reaction times were examined with the Iowa Gambling Task in 149 ecstasy-naive subjects. The performance of 59 subjects who initiated ecstasy use during a mean follow-up period of 18 months (range, 11-26) was compared with the performance of 90 subjects that remained ecstasy-naive. Significant differences in decision-making strategy between female future ecstasy users and female persistent ecstasy-naive subjects were found. In addition, the gap between decision-making reaction time after advantageous choices and reaction time after disadvantageous choices was smaller in future ecstasy users than in persistent ecstasy-naives. Decision-making strategy on a gambling task was predictive for future use of ecstasy in female subjects. Differences in decision-making time between future ecstasy users and persistent ecstasy-naives may point to lower punishment sensitivity or higher impulsivity in future ecstasy users. Because differences were small, the clinical relevance is questionabl

Corporate governance for sustainability : Statement

The current model of corporate governance needs reform. There is mounting evidence that the practices of shareholder primacy drive company directors and executives to adopt the same short time horizon as financial markets. Pressure to meet the demands of the financial markets drives stock buybacks, excessive dividends and a failure to invest in productive capabilities. The result is a ‘tragedy of the horizon’, with corporations and their shareholders failing to consider environmental, social or even their own, long-term, economic sustainability. With less than a decade left to address the threat of climate change, and with consensus emerging that businesses need to be held accountable for their contribution, it is time to act and reform corporate governance in the EU. The statement puts forward specific recommendations to clarify the obligations of company boards and directors and make corporate governance practice significantly more sustainable and focused on the long term

Behavioural characterization of neuregulin 1 type I overexpressing transgenic mice.

Neuregulin 1 (NRG1) is a pleiotropic growth factor involved in diverse aspects of brain development and function. In schizophrenia, expression of the NRG1 type I isoform is selectively increased. However, virtually nothing is known about the roles of this isoform in brain. We have studied transgenic mice overexpressing type I NRG1(NRG1type 1-tg) using a series of behavioural tests. NRG1(type 1-tg) mice have a tremor, are impaired on the accelerating rotarod, and have reduced prepulse inhibition in the context of an increased baseline startle response. There is no overall anxiety or activity phenotype, although female NRG(1type 1-tg) mice show mild increases in anxiety on some measures. The pattern of results shows both similarities and differences to those reported in hypomorphic NRG1 mice, and may be relevant for interpreting the increased NRG1 type I expression observed in schizophrenia

Altered hippocampal gene expression and structure in transgenic mice overexpressing neuregulin 1 (Nrg1) type I

Transgenic mice overexpressing the type I isoform of neuregulin 1 (Nrg1; NRG1) have alterations in hippocampal gamma oscillations and an age-emergent deficit in hippocampus-dependent spatial working memory. Here, we examined the molecular and morphological correlates of these findings. Microarrays showed over 100 hippocampal transcripts differentially expressed in Nrg1tg-type I mice, with enrichment of genes related to neuromodulation and, in older mice, of genes involved in inflammation and immunity. Nrg1tg-type I mice had an enlarged hippocampus with a widened dentate gyrus. The results show that Nrg1 type I impacts on hippocampal gene expression and structure in a multifaceted and partly age-related way, complementing the evidence implicating Nrg1 signaling in aspects of hippocampal function. The findings are also relevant to the possible role of NRG1 signaling in the pathophysiology of schizophrenia or other disorders affecting this brain region

Serotonin Modulates Sensitivity to Reward and Negative Feedback in a Probabilistic Reversal Learning Task in Rats

Depressed patients show cognitive deficits that may depend on an abnormal reaction to positive and negative feedback. The precise neurochemical mechanisms responsible for such cognitive abnormalities have not yet been clearly characterized, although serotoninergic dysfunction is frequently associated with depression. In three experiments described here, we investigated the effects of different manipulations of central serotonin (5-hydroxytryptamine, 5-HT) levels in rats performing a probabilistic reversal learning task that measures response to feedback. Increasing or decreasing 5-HT tone differentially affected behavioral indices of cognitive flexibility (reversals completed), reward sensitivity (win-stay), and reaction to negative feedback (lose-shift). A single low dose of the selective serotonin reuptake inhibitor citalopram (1 mg/kg) resulted in fewer reversals completed and increased lose-shift behavior. By contrast, a single higher dose of citalopram (10 mg/kg) exerted the opposite effect on both measures. Repeated (5 mg/kg, daily, 7 days) and subchronic (10 mg/kg, b.i.d., 5 days) administration of citalopram increased the number of reversals completed by the animals and increased the frequency of win-stay behavior, whereas global 5-HT depletion had the opposite effect on both indices. These results show that boosting 5-HT neurotransmission decreases negative feedback sensitivity and increases reward (positive feedback) sensitivity, whereas reducing it has the opposite effect. However, these effects depend on the nature of the manipulation used: acute manipulations of the 5-HT system modulate negative feedback sensitivity, whereas long-lasting treatments specifically affect reward sensitivity. These results parallel some of the findings in humans on effects of 5-HT manipulations and are relevant to hypotheses of altered response to feedback in depression