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Decision-making plays a pivotal role in daily life as impairments in processes underlying decision-making often lead to an inability to make profitable long-term decisions. As a case in point, pathological gamblers continue gambling despite the fact that this disrupts their personal, professional or financial life. The prevalence of pathological gambling will likely increase in the coming years due to expanding possibilities of on-line gambling through the Internet and increasing liberal attitudes towards gambling. It therefore represents a growing concern for society. Both human and animal studies rapidly advance our knowledge on brain-behaviour processes relevant for understanding normal and pathological gambling behaviour. Here, we review in humans and animals three features of pathological gambling which hitherto have received relatively little attention: (1) sex differences in (the development of) pathological gambling, (2) adolescence as a (putative) sensitive period for (developing) pathological gambling and (3) avenues for improving ecological validity of research tools. Based on these issues we also discuss how research in humans and animals may be brought in line to maximize translational research opportunities., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Corticosteroid hormones, released after stress, are known to change neuronal activity in two time-domains: within minutes via non-genomic pathways and with a delay of >1 h through pathways involving transcriptional regulation. Recent evidence in rodents and humans indicates that these two modes of corticosteroid action differently affect cognitive tasks. Here, we investigated whether reward-based decision-making, in a rat model of the Iowa Gambling Task (rIGT), is also differently altered by rapid versus delayed actions of corticosterone. We targeted the rapid and delayed time domain by injecting corticosterone (CORT, 1 mg/kg, s.c.) at 30 min (rapid) or 180 min (delayed) respectively prior to behavioural testing, during the final 3 days of the behavioural paradigm. In saline treated rats, the number of visits to the disadvantageous arm decreased over trial blocks, whilst this was attenuated when CORT was administered 30 min before testing. This attenuation was associated with a significantly increased c-Fos expression in the lateral orbitofrontal cortex and insular cortex, and a trend for an increase in the infralimbic cortex. The rapid corticosteroid effect contrasted with treatment 180 min before testing, where the number of visits to the disadvantageous arm as well as c-Fos labelling was not affected. These findings indicate that rapid corticosteroid actions impair reward-based decision-making., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Psycho-genetic studies have revealed a role for the brain serotonin system in gambling proneness and poor decision-making. We assessed whether manipulation of brain serotonin levels in rats affected performance in operant-based tasks for decision-making and gambling proneness. Male Wistar rats were exposed to an l-tryptophan (TRP) deficient diet (0.0 g/kg; T- group) or to a control, l-tryptophan containing diet (2.8 g/kg; T+ group). The same rats were tested for decision-making performance in the rodent Iowa Gambling Task (rIGT) using home-cage operant panels, and subsequently for gambling proneness in a Probabilistic Delivery Task (rPDT) using classic Skinnerboxes. At sacrifice, monoamines and metabolites were evaluated with HPLC analysis, confirming a drastically reduced serotonin synthesis, as well as altered dopamine turnover in the prefrontal cortex of T- rats. As expected, control rats (T+) progressively chose the option with the best long-term payoff in the rIGT, and also shifted from "Large & Luck-Linked" (LLL) to "Small & Sure" (SS) reinforcers in the rPDT. In contrast, depleted animals (T-) exhibited a weaker improvement of performance in the rIGT and maintained a sub-optimal attraction for LLL reinforcer in the rPDT. Comparing individual performances in both tests, we found a significant correlation between the two tasks in control (T+) but not in depleted (T-) rats. The present study revealed that (1) brain 5-HT depletion leads to poor decision-making and to gambling proneness; (2) the relationship between these two traits, shown in the control group, was disrupted in 5-HT depleted rats. The data are discussed in terms of changes within forebrain loops involved in cognitive and motivational/affective processes., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Excessive levels of trait anxiety are a risk factor for psychiatric conditions, including anxiety disorders and substance abuse. High trait anxiety has been associated with altered cognitive functioning, in particular with an attentional bias towards aversive stimuli. Decision-making is a crucial aspect of cognitive functioning that relies on the correct processing and control of emotional stimuli. Interestingly, anxiety and decision-making share underlying neural substrates, involving cortico-limbic pathways, including the amygdala, striatum and medial and dorsolateral prefrontal cortices. In the present study, we investigated the relationship between trait anxiety, measured by the State-Trait Anxiety Inventory, and complex decision-making, measured by the Iowa Gambling Task, in healthy male and female volunteers. The main focus of this study was the inclusion of gender as a discriminative factor. Indeed, we found distinct gender-specific effects of trait anxiety: in men, both low and high anxiety groups showed impaired decision-making compared to medium anxiety individuals, whereas in women only high anxiety individuals performed poorly. Furthermore, anxiety affected decision-making in men early in the task, i.e. the exploration phase, as opposed to an effect on performance in women during the second part of the test, i.e. the exploitation phase. These findings were related to different profiles of trait anxiety in men and women, and were independent of performance in the Wisconsin Card Sorting Test and cortisol levels. Our data show gender-specific effects of trait anxiety on emotional decision-making. We suggest gender-specific endophenotypes of anxiety to exist, that differentially affect cognitive functioning., (2010 Elsevier Ltd. All rights reserved.)

Acutely elevated levels of cortisol are associated with euphoria and reward-like properties related to sensation-seeking behaviour. Thus, acute stress and elevated levels of cortisol may promote risk-taking behaviour. High cortisol responders are more sensitive to immediate rewards than low cortisol responders. In this study we therefore tested whether acute stress in male and female subjects, induced by the Trier Social Stress Test (TSST), affects decision-making as measured by the Iowa Gambling Task (IGT) and to what extent this is related to cortisol reactivity. Control subjects did not receive the stress manipulation. We specifically predict that high responders show risk-taking behaviour in the IGT compared to low responders and controls. The data show that the more (salivary) cortisol levels are elevated after the TSST the poorer the subsequent performance in the IGT in male subjects. In female subjects an inverse relationship between cortisol levels and IGT performance is observed: slightly elevated levels of cortisol after the TSST improve IGT performance, while highly elevated levels decrease IGT performance. Thus, acute stress as induced by the TSST affects decision-making behaviour of men and women differently and cortisol reactivity is associated with decision-making performance.

Poor decision-making is inherent to several psychiatric conditions for which a genetic basis may exist. We previously showed that healthy female volunteers homozygous for the short allele (s/s) of the serotonin transporter length polymorphic region (5-HTTLPR) chose more often cards from disadvantageous decks in the Iowa Gambling Task (IGT), which measures decision-making, than long (l) allele carriers. The 5-HTTLPR and catechol-O-methyltransferase (COMT) Val(158) Met polymorphism affect the same set of neuronal structures. Therefore, we explored the effect of the (COMT) Val(158) Met polymorphism on IGT performance and its interaction with the 5-HTTLPR in the same subjects in this study. We observed that subjects homozygous for methionine (Met/Met) chose more disadvantageously than subjects homozygous for valine (Val/Val). s/s-Met/Met-subjects appeared to show the poorest IGT performance of all possible combinations of 5-HTTLPR and COMT allelic variants. Using the Expectancy-Valence model, no differences were found for the three different 5-HTTLPR or COMT genotypes regarding (i) attention to wins versus losses, (ii) updating rate, or (iii) response consistency. However, subjects with at least one Met-allele were paying more attention to wins than subjects with no Met-alleles. We discuss whether a common neuronal mechanism relates to s- and Met-allele-related deficits in updating and/or processing of choice outcome to guide subsequent choices in this gamble-based test.

Decision-making plays an important role in everyday life and is often disturbed in psychiatric conditions affected by the common human serotonin transporter promoter length polymorphism (5-HTTLPR). This raises the hypothesis that decision-making is modulated by the serotonergic system, but currently it is unclear how the 5-HTTLPR affects central serotonergic functioning. We tested healthy human volunteers genotyped for the 5-HTTLPR in the Iowa Gambling Task (IGT), which is one of the most frequently used neuropsychological tasks to assess decision-making. Furthermore, we tested female homozygous (SERT(-/-)) and heterozygous (SERT(+/-)) serotonin transporter knockout rats in a rodent version of the IGT. Women homozygous for the short (s) allele of the 5-HTTLPR were found to choose more disadvantageously than women homozygous for the long allele of the 5-HTTLPR as the IGT progressed. In the rat, SERT(-/-) and SERT(+/-) were associated with advantageous decision-making compared to SERT(+/+) as the IGT progressed. Combining the human and rat observations, we show that SERT dosage affects the maintenance of a once established choice option, irrespective of the choice (advantageous or disadvantageous) that has been made. We postulate that the SERT-mediated effects relate to deficits in the processing of choice outcome to guide subsequent choices in this gamble-based test, and that SERT(-/-) and SERT(+/-) rodent models in combination with studies in humans can be used to provide insight in the modulatory effects of 5-HTTLPR.

In a previous cross-sectional study of mirror self-recognition involving 92 chimpanzees, Povinelli et al. [Journal of Comparative Psychology 107 (1993) 347] reported a peak in the proportion of animals exhibiting self-recognition in the adolescent/young adult sample (8-15 years), with 75% being classified as positive. In contrast, only 26% of the older animals (16-39 years) were classified as positive, suggesting a marked decline in self-recognition in middle to late adulthood. In the present study, all of the chimpanzees from the 8-15-year-old group in the Povinelli et al. study (n=12) were again tested for self-recognition, 8 years later. Using the same criteria, 67% of the animals were classified the same. Although a higher proportion of the adult animals in this study (50%) exhibited self-recognition than would be inferred on the basis of the previous study (25%), all changes in self-recognition status were in the negative direction. These results show that mirror self-recognition is a highly stable trait in many chimpanzees, but may be subject to decline with age. Connections with human research are briefly discussed.