Borderline personality disorder, but not euthymic bipolar disorder, is associated with a failure to sustain reciprocal cooperative behaviour: implications for spectrum models of mood disorders.

BACKGROUND: Borderline personality disorder (BPD) and bipolar disorder (BD) have overlapping clinical presentations and symptoms - sources of persistent clinical confusion. Game-theory can characterize how social function might be sub-optimal in the two disorders and move the field beyond the anecdotal description of clinical history. Here, we tested the hypothesis that BPD and BD can be distinguished on the basis of diminished reciprocal altruism in iterated Prisoner's Dilemma (PD) games. METHOD: Twenty females with BPD, 20 females with euthymic BD and 20 healthy (non-clinical) females, matched for age and cognitive ability, were assessed for Axis-I and personality disorders, and completed psychometric measures of state affect, impulsivity and hostility. Participants completed two iterated PD games and a test of gaze-cueing. RESULTS: In the PD games, BPD participants failed to show statistically stable preferences to cooperate with social partners (playing tit-for-tat) and made significantly fewer cooperative responses compared to BD or controls (ANOVA main effect p = 0.03, post-hoc Tukey p < 0.05 for both comparisons). BPD participants were also less likely to sustain cooperation following experiences involving mutual cooperation than the other groups. Neither BPD nor BD participants demonstrated impairments in shifting visual attention on the basis of other peoples' gaze. CONCLUSIONS: These data indicate that BPD is (selectively) associated with difficulties in establishing, and then maintaining, reciprocal cooperation, involving altruism. These difficulties are not seen in euthymic BD. Our data support the differentiation of BPD from BD and offer fresh insights into the social difficulties experienced by individuals with diagnoses of BPD.

Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis.

OBJECTIVE: An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta-analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view. METHOD: Individual patient and control data were obtained from original authors for 11 measures from four common neuropsychological tests: California or Rey Verbal Learning Task (VLT), Trail Making Test (TMT), Digit Span and/or Wisconsin Card Sorting Task. RESULTS: Impairments were found for all 11 test-measures in the bipolar group after controlling for age, IQ and gender (Ps ≤ 0.001, E.S. = 0.26-0.63). Residual mood symptoms confound this result but cannot account for the effect sizes found. Impairments also seem unrelated to drug treatment. Some test-measures were weakly correlated with illness severity measures suggesting that some impairments may track illness progression. CONCLUSION: This reanalysis supports VLT, Digit Span and TMT as robust measures of cognitive impairments in bipolar disorder patients. The heterogeneity of some test results explains previous differences in meta-analyses. Better controlling for confounds suggests deficits may be smaller than previously reported but should be tracked longitudinally across illness progression and treatment.

Impulsivity modulates performance under response uncertainty in a reaching task.

We sought to explore the interaction of the impulsivity trait with response uncertainty. To this end, we used a reaching task (Pellizzer and Hedges in Exp Brain Res 150:276-289, 2003) where a motor response direction was cued at different levels of uncertainty (1 cue, i.e., no uncertainty, 2 cues or 3 cues). Data from 95 healthy adults (54 F, 41 M) were analysed. Impulsivity was measured using the Barratt Impulsiveness Scale version 11 (BIS-11). Behavioral variables recorded were reaction time (RT), errors of commission (referred to as 'early errors') and errors of precision. Data analysis employed generalised linear mixed models and generalised additive mixed models. For the early errors, there was an interaction of impulsivity with uncertainty and gender, with increased errors for high impulsivity in the one-cue condition for women and the three-cue condition for men. There was no effect of impulsivity on precision errors or RT. However, the analysis of the effect of RT and impulsivity on precision errors showed a different pattern for high versus low impulsives in the high uncertainty (3 cue) condition. In addition, there was a significant early error speed-accuracy trade-off for women, primarily in low uncertainty and a 'reverse' speed-accuracy trade-off for men in high uncertainty. These results extend those of past studies of impulsivity which help define it as a behavioural trait that modulates speed versus accuracy response styles depending on environmental constraints and highlight once more the importance of gender in the interplay of personality and behaviour.

Social and economic costs of gambling problems and related harm among UK military veterans.

INTRODUCTION: Military veterans are at heightened risk of problem gambling. Little is known about the costs of problem gambling and related harm among United Kingdom (UK) Armed Forces (AF) veterans. We investigated the social and economic costs of gambling among a large sample of veterans through differences in healthcare and social service resource use compared with age-matched and gender-matched non-veterans from the UK AF Veterans' Health and Gambling Study. METHODS: An online survey measured sociodemographic characteristics, gambling experience and problem severity, mental health and healthcare resource utilisation. Healthcare provider, personal social service and societal costs were estimated as total adjusted mean costs and utility, with cost-consequence analysis of a single timepoint. RESULTS: Veterans in our sample had higher healthcare, social service and societal costs and lower utility. Veterans had greater contacts with the criminal justice system, received more social service benefits, had more lost work hours and greater accrued debt. A cost difference of £590 (95% CI -£1016 to -£163) was evident between veterans with scores indicating problem gambling and those reporting no problems. Costs varied by problem gambling status. CONCLUSIONS: Our sample of UK AF veterans has higher healthcare, social service and societal costs than non-veterans. Veterans experiencing problem gambling are more costly but have no reduction in quality of life.

A correlation-based predictor for pair-association in ionic liquids.

Pair association in Ionic Liquids is an important quantity that affects many of their physical and chemical properties. However, the association constant is a complex function of the component ions as well as of the solvent environment, and no single theory can compute or predict it with quantitative accuracy. In this work we analyze infinite-dilution association data from a number of recent conductance measurements, and develop a linear model correlating the association constant with two relevant interaction energies, i.e., (1) the dielectrically screened Coulomb attraction and hydrogen bonding between ion-pairs, and (2) the ion solvation energy, which in turn takes into account solvent-specific interactions like hydrogen-bond acidity/basicity and hydrophobic/hydrophilic interactions. The results reveal the unique nature of water as a solvent in that it affects ionic association in ways qualitatively different from other common solvents.

Omega-3 fatty acids (fish-oil) and depression-related cognition in healthy volunteers.

Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation may be beneficial in the treatment of several psychiatric disorders, including depression. A small number of studies have suggested that there may also be cognitive and mood effects in healthy samples. The purpose of the present study was to investigate the effects of n-3 PUFA on depression-relevant cognitive functioning in healthy individuals. Fifty-four healthy university students were randomized to receive either n-3 PUFA supplements or placebo for 4 weeks in a double-blind design. The test battery included measures of cognitive reactivity, attention, response inhibition, facial emotion recognition, memory and risky decision-making. Results showed few effects of n-3 PUFAs on cognition and mood states. The n-3 PUFA group made fewer risk-averse decisions than the placebo group. This difference appeared only in non-normative trials of the decision-making test, and was not accompanied by increased impulsiveness. N-3 PUFAs improved scores on the control/perfectionism scale of the cognitive reactivity measure. No effects were found on the other cognitive tasks and no consistent effects on mood were observed. The present findings indicate that n-3 PUFA supplementation may have a selective effect on risky decision making in healthy volunteers, which is unrelated to impulsiveness.

Hypergolic zeolitic imidazolate frameworks (ZIFs) as next-generation solid fuels: Unlocking the latent energetic behavior of ZIFs.

Hypergolic materials, capable of spontaneous ignition upon contact with an external oxidizer, are of critical importance as fuels and propellants in aerospace applications (e.g., rockets and spacecraft). Currently used hypergolic fuels are highly energetic, toxic, and carcinogenic hydrazine derivatives, inspiring the search for cleaner and safer hypergols. Here, we demonstrate the first strategy to design hypergolic behavior within a metal-organic framework (MOF) platform, by using simple "trigger" functionalities to unlock the latent and generally not recognized energetic properties of zeolitic imidazolate frameworks, a popular class of MOFs. The herein presented six hypergolic MOFs, based on zinc, cobalt, and cadmium, illustrate a uniquely modular platform to develop hypergols free of highly energetic or carcinogenic components, in which varying the metal and linker components enables the modulation of ignition and combustion properties, resulting in excellent hypergolic response evident by ultrashort ignition delays as low as 2 ms.

Investigating the neurocognitive deficits associated with chronic drug misuse.

Cognitive deficits associated with the chronic abuse of drugs have important theoretical and clinical significance: such deficits reflect changes to the underlying cortical, sub-cortical and neuromodulatory mechanisms that underpin cognition, and also interfere directly with rehabilitative programs. Recent investigations have been made into the neuropsychology of chronic abuse of cannabis, stimulants and opiates. It is suggested that future progress in this area, involving developing advances in brain-imaging and neuropharmacology, will capitalize on experimental demonstrations of specific patterns of impairments in decision-making, attention and memory function.

Choosing between small, likely rewards and large, unlikely rewards activates inferior and orbital prefrontal cortex.

Patients sustaining lesions of the orbital prefrontal cortex (PFC) exhibit marked impairments in the performance of laboratory-based gambling, or risk-taking, tasks, suggesting that this part of the human PFC contributes to decision-making cognition. However, to date, little is known about the particular regions of the orbital cortex that participate in this function. In the present study, eight healthy volunteers were scanned, using H(2)(15)0 PET technology, while performing a novel computerized risk-taking task. The task involved predicting which of two mutually exclusive outcomes would occur, but critically, the larger reward (and penalty) was associated with choice of the least likely outcome, whereas the smallest reward (and penalty) was associated with choice of the most likely outcome. Resolving these "conflicting" decisions was associated with three distinct foci of regional cerebral blood flow increase within the right inferior and orbital PFC: laterally, in the anterior part of the middle frontal gyrus [Brodmann area 10 (BA 10)], medially, in the orbital gyrus (BA 11), and posteriorly, in the anterior portion of the inferior frontal gyrus (BA 47). By contrast, increases in the degree of conflict inherent in these decisions was associated with only limited changes in activity within orbital PFC and the anterior cingulate cortex. These results suggest that decision making recruits neural activity from multiple regions of the inferior PFC that receive information from a diverse set of cortical and limbic inputs, and that the contribution of the orbitofrontal regions may involve processing changes in reward-related information.

The acute effect of alcohol on decision making in social drinkers.

RATIONALE: Many studies have reported the long-term adverse effects of alcohol on executive cognitive function in chronic alcohol abusers, yet little research has investigated the acute effects of alcohol in social drinkers. Studies on acute effects report alcohol-induced deficits on tasks that require executive cognitive processes, with alcohol acting to increase preservative errors and reduce planning. AIM: The present investigation examines the acute effects of a moderate dose of alcohol on a decision-making task that involves participants making a forced choice between two simultaneously presented binary-outcome gambles. METHODS: Alcohol (0.6 g/kg) or placebo was administered to 32 social drinkers. Participants completed the task, making a total of 80 decisions about gambles that varied in the magnitude of expected gains, losses and the probability with which these outcomes were delivered. Participants also chose between gambles probing identified non-normative biases in human decision making, namely, risk aversion for choosing between gains and risk seeking for choosing between losses. RESULTS: All participants picked the experimental gamble more frequently when the probability of winning was high vs low, when the gains were large vs small and when the losses were small vs large; the alcohol group had an impaired ability to factor in the magnitude of gains and the likelihood of winning when the losses were large. Deliberation time did not differ between the groups. CONCLUSION: These data suggest that alcohol given acutely impairs risky decision making. In particular, alcohol impairs one's ability to alter responding in light of changing prospective rewards in order to make favourable decisions.

The effects of a branched chain amino acid mixture supplemented with tryptophan on biochemical indices of neurotransmitter function and decision-making.

RATIONALE: We have previously shown that a 60-g mixture of branched chain amino acids (BCAAs) lowers the plasma availability of the catecholamine precursors tyrosine (TYR) and phenylalanine (PHE) and produces biochemical and neuropsychological changes consistent with impaired dopamine neurotransmission. However, the BCAA mixture also lowers the ratio of tryptophan (TRP) to BCAA which could impair brain serotonin function. OBJECTIVES: To determine the biochemical and neuropsychological effects of a BCAA mixture supplemented with TRP. METHODS: We studied 32 healthy volunteers who were randomly and blindly allocated to either a single administration of amino acid mixture (60 g BCAA and 2 g TRP) or placebo. We carried out venous sampling to measure plasma levels of amino acids and performed selected cognitive tasks sensitive to monoamine manipulation 5 h after mixture ingestion. RESULTS: Relative to placebo, the BCAA/TRP mixture substantially lowered the ratio of TYR+PHE:BCAA and increased plasma prolactin. The ratio of TRP:BCAA was also lowered but to a lesser extent. The BCAA/TRP mixture produced significant changes in a task of decision-making where volunteers showed reduced discrimination between gambles with large and small losses. CONCLUSIONS: A 62 g BCAA/TRP mixture decreases the availability of TYR and PHE for brain catecholamine synthesis and increases plasma prolactin consistent with lowered brain dopamine function. Addition of 2 g TRP to the 60 g BCAA mixture does not prevent a reduction of the ratio TRP:BCAA relative to placebo. The effects of the BCAA/TRP mixture on decision-making suggest a general action of dopamine pathways on the processing of emotional information in risky choice, including punishment-related cues, consistent with suggestions that dopamine mechanisms mediate behavioural responses to aversive as well as appetitive stimuli in instrumental conditioning.

Manipulation of ionic liquid anion-solute-antisolvent interactions for the purification of acetaminophen.

Hydrogen bond donating cosolvents have been shown to significantly reduce the solubility of acetaminophen (AAP) in ionic liquids containing the acetate anion. Reduced solubility arises from competition for solvation by the acetate anion and can be used for the design of advanced separation techniques, illustrated by the crystallization of AAP.

Discrimination, reversal, and shift learning in Huntington's disease: mechanisms of impaired response selection.

In a series of three experiments, we investigated different aspects of response selection in early-stage clinically symptomatic Huntington's disease (HD) patients in the context of discrimination learning. A series of structurally related response selection tasks involving discrimination, reversal, and shift learning were employed. In Experiment 1, the mechanisms of our previously reported [37] finding of impaired extra-dimensional shift learning were explored. The results suggested that impaired shift learning in HD is a result of perseverative responding. In Experiment 2, performance on a concurrent-pair (CP) discrimination and reversal task was examined. HD patients showed no deficits in CP discrimination learning or reversal. In Experiment 3, the performance of HD patients on a probabilistic discrimination and reversal task was examined. HD patients were impaired in the learning of a probabilistic discrimination, and also its reversal. This reversal deficit was again the result of perseverative responding. In addition, there was a strong correlation between HD patients' activities of daily living scores and reversal errors. The result are consistent with current theories of the role of the basal ganglia in cognition, and suggest specific impairments in response selection mechanisms in HD, in particular, in overcoming selection biases based on prior reinforcement.

Neural systems engaged by planning: a PET study of the Tower of London task.

The functional anatomy of planning was investigated using the Tower of London task. Activation was observed in a distributed network of cortical areas incorporating prefrontal, cingulate, premotor, parietal and occipital cortices. Activation in corresponding areas has been observed in visuospatial working memory tasks with the exception of the rostral prefrontal cortex. This area may be identified with the executive components of planning comprising response selection and evaluation. Enhanced neural activity in both this rostral prefrontal area and the visuospatial working memory system was associated with increased task difficulty.

Impaired planning but intact decision making in early Huntington's disease: implications for specific fronto-striatal pathology.

Previous neuropsychological data have suggested that deficits in early Huntington's disease (HD) include executive impairments, which often are linked with frontal-lobe dysfunction. This study sought to investigate the profile of cognitive deficits using two computerised tasks whose performance is known to rely on intact functions of separate areas of the prefrontal cortex. Twenty patients with early HD and 20 matched controls were given the one-touch Tower of London, a stringent measure of visuo-spatial planning, and a decision making task, which involved selecting and gambling on outcomes on the basis of their differing probabilities. Patients were significantly less accurate than controls on the planning test, which is sensitive to frontal lobe lesions and is strongly associated with the dorsolateral prefrontal cortex in functional imaging studies. On the decision making task, patients were unimpaired on the quality of their decision making, in contrast to previous reports of impairment on this task in patients with ventromedial prefrontal cortex lesions. This dissociation of performance is discussed in terms of the usual path of progression of HD through the striatum and the resultant pattern of disruption of the functioning of the different cortico-striatal functional loops.

Probabilistic learning and reversal deficits in patients with Parkinson's disease or frontal or temporal lobe lesions: possible adverse effects of dopaminergic medication.

Three groups of patients with Parkinson's disease (PD) - mild, unmedicated (UPD), mild, medicated (MPD) and severe, medicated (SPD) - and patients with lesions of the frontal lobe (FLL) or temporal lobe (TLL) were compared with matched controls on the learning and reversal of probabilistic and two-pair concurrent colour discriminations. Both of the cortical lesion groups showed reversal deficits, with no increase in perseverative responding. The UPD group, although impaired on a spatial recognition task, showed intact discrimination learning and reversal; the MPD and SPD patients showed non-perseverative reversal impairments on both reversal tasks. Two hypotheses - based on disease severity and possible deleterious effects of medication - are offered to explain the reversal impairments of the PD patients and the results are discussed in terms of the role of dopamine in reward-based learning.

Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms.

We used a novel computerized decision-making task to compare the decision-making behavior of chronic amphetamine abusers, chronic opiate abusers, and patients with focal lesions of orbital prefrontal cortex (PFC) or dorsolateral/medial PFC. We also assessed the effects of reducing central 5-hydroxytryptamine (5-HT) activity using a tryptophan-depleting amino acid drink in normal volunteers. Chronic amphetamine abusers showed suboptimal decisions (correlated with years of abuse), and deliberated for significantly longer before making their choices. The opiate abusers exhibited only the second of these behavioral changes. Importantly, both sub-optimal choices and increased deliberation times were evident in the patients with damage to orbitofrontal PFC but not other sectors of PFC. Qualitatively, the performance of the subjects with lowered plasma tryptophan was similar to that associated with amphetamine abuse, consistent with recent reports of depleted 5-HT in the orbital regions of PFC of methamphetamine abusers. Overall, these data suggest that chronic amphetamine abusers show similar decision-making deficits to those seen after focal damage to orbitofrontal PFC. These deficits may reflect altered neuromodulation of the orbitofrontal PFC and interconnected limbic-striatal systems by both the ascending 5-HT and mesocortical dopamine (DA) projections.

Copyrine alkaloids: synthesis, spectroscopic characterization, and antimycotic/antimycobacterial activity of A- and B-ring-functionalized sampangines.

Several A- and B-ring-substituted sampangines were synthesized and evaluated for antifungal and antimycobacterial activity against AIDS-related opportunistic infection pathogens. Electrophilic halogenation provided a channel for structural elaboration of the sampangine B-ring at position 4, while the synthesis of A-ring 3-substituted sampangines and benzo[4,5]sampangine (24) were achieved from the corresponding functionalized cleistopholines. Two-dimensional NMR spectroscopy was used to rigorously characterize the A- and B-ring substituent patterns. Structure-activity relationship studies revealed the activity of the sampangines was enhanced by the presence of a substituent at position 3 or by a 4,5-benzo group.

Lesions of the medial and lateral striatum in the rat produce differential deficits in attentional performance.

Excitotoxic lesions of the medial frontal cortex and anterior cingulate cortex in rats have been shown to produce dissociable impairments on a reaction time visual attention (5-choice) task. Because these cortical areas project to the medial striatal region, the authors predicted similar deficits after lesions of this striatal area compared with the lateral area. Compared with sham-operated controls, rats with quinolinic acid-induced medial striatal lesions showed all the behavioral changes associated with medial frontal cortex and anterior cingulate cortex lesions. In contrast, lateral striatal lesions produced profound disturbances in the performance of the task. Control tests showed little evidence of gross deficits in either group of rats in terms of motivation, locomotor function, or Pavlovian appetitive conditioning. These data suggest that the medial and lateral striatum have contrasting roles in the control of instrumental responding related to the primary sources of their cortical innervation.