Better than expected: the gap between self-reported and objective measures of cognitive performance in remitted bipolar disorder

Background: Studies comparing objective and self-reported cognitive functioning as well as influencing factors in individuals with remitted bipolar disorder are scarce and contradictory. Methods: The aim of this study was to compare executive functioning and other objective and self-reported cognitive impairment between 26 individuals with remitted bipolar disorder (15 BD I) and 24 healthy controls using a cross-sectional design. Executive functions were measured by the TAP Go/No-go subtest as well as the Stroop Task. Self-rated functioning was assessed using the Attention Deficit Experience Questionnaire. In addition, possible predictors of self-reported and objective cognitive functioning were examined to perform regression analyses. Results: Individuals with remitted bipolar disorder did not differ significantly in executive functions or other objective cognitive domains from the healthy control group, but showed a significantly lower level of self-reported cognitive functioning and self-esteem. While self-esteem was the strongest predictor in healthy controls for self-reported cognitive functioning, severity of illness and subthreshold depressive mood were the most important predictors in individuals with remitted bipolar disorder. Conclusion: The results once again demonstrate the cognitive heterogeneity in bipolar disorder. In the treatment of cognitive deficits, factors such as subthreshold depressive symptomatology and self-esteem should be focused on in addition to cognitive training in remitted patients

linking goal-directed and model-based behavior

In experimental psychology different experiments have been developed to assess goal–directed as compared to habitual control over instrumental decisions. Similar to animal studies selective devaluation procedures have been used. More recently sequential decision-making tasks have been designed to assess the degree of goal-directed vs. habitual choice behavior in terms of an influential computational theory of model-based compared to model-free behavioral control. As recently suggested, different measurements are thought to reflect the same construct. Yet, there has been no attempt to directly assess the construct validity of these different measurements. In the present study, we used a devaluation paradigm and a sequential decision-making task to address this question of construct validity in a sample of 18 healthy male human participants. Correlational analysis revealed a positive association between model-based choices during sequential decisions and goal-directed behavior after devaluation suggesting a single framework underlying both operationalizations and speaking in favor of construct validity of both measurement approaches. Up to now, this has been merely assumed but never been directly tested in humans

Impact of Long‐Term Alcohol Consumption and Relapse on Genome‐Wide DNA Methylation Changes in Alcohol‐Dependent Subjects: A Longitudinal Study

Background: Genetic factors play an important role in the development and maintenance of alcohol use disorder (AUD). Significant and widespread differences in methylation levels of multiple regions within the genome have been reported between AUD patients and healthy controls in large epigenome-wide association studies (EWASs). Also, within patient populations, methylation changes over time (both during and after withdrawal) have been identified as sensitive indicators for disease activity. The detection of changes in methylation levels is a powerful tool to further explore and understand the biological correlates and underpinnings of AUD. Although there is strong and convincing evidence for differences in methylation of various sites between AUD patients and controls, only few studies assessed changes within patients over longer periods of time while taking into account alcohol consumption, relapse, and abstinence. So far, the longest period assessed as a within-subject design using EWASs was 4 weeks. Methods: Here, we investigated changes in whole-genome methylation levels within a sample of 69 detoxified AUD patients over a period as long as 12 months for the first time, comparing patients that relapsed within the follow-up period to those that remained abstinent. Results: Whole-genome methylation patterns of individual CpG sites over time did not differ between abstinent and relapsing patients. However, there was a negative association between global mean methylation at the 12-month follow-up and alcohol consumption within our sample. Conclusion: Although the present study represents the largest study of methylation levels in a sample of AUD patients with a follow-up period of 1 year and accounting for alcohol consumption and relapse to date, the sample size might still not be large enough to detect genome-wide significant effects. Therefore, large-scale, long-term studies with AUD subjects are needed to determine the utility of DNA methylation for the assessment and monitoring of persons with alcohol use disorders

Disentangling the Roles of Approach, Activation and Valence in Instrumental and Pavlovian Responding

Hard-wired, Pavlovian, responses elicited by predictions of rewards and punishments exert significant benevolent and malevolent influences over instrumentally-appropriate actions. These influences come in two main groups, defined along anatomical, pharmacological, behavioural and functional lines. Investigations of the influences have so far concentrated on the groups as a whole; here we take the critical step of looking inside each group, using a detailed reinforcement learning model to distinguish effects to do with value, specific actions, and general activation or inhibition. We show a high degree of sophistication in Pavlovian influences, with appetitive Pavlovian stimuli specifically promoting approach and inhibiting withdrawal, and aversive Pavlovian stimuli promoting withdrawal and inhibiting approach. These influences account for differences in the instrumental performance of approach and withdrawal behaviours. Finally, although losses are as informative as gains, we find that subjects neglect losses in their instrumental learning. Our findings argue for a view of the Pavlovian system as a constraint or prior, facilitating learning by alleviating computational costs that come with increased flexibility

Association between DRD2/ANKK1 TaqIA Allele Status and Striatal Dopamine D2/3 Receptor Availability in Alcohol Use Disorder

Background: The association between blunted dopaminergic neurotransmission and alcohol use disorder (AUD) is well-known. In particular, the impairment of postsynaptic dopamine 2 and 3 receptors (DRD2/3) in the ventral and dorsal striatum during the development and maintenance of alcohol addiction has been investigated in several positron emission tomography (PET) studies. However, it is unclear whether these changes are the result of adaptation or genetic predisposition. Methods: Here we investigated the association between DRD2/ankyrin repeat and kinase domain-containing 1 (ANKK1) TaqIA allele (rs1800497) status and striatal DRD2/3 availability measured by 18F-fallypride PET in 12 AUD patients and 17 sex-matched healthy controls. Age and smoking status were included as covariates. Results: Contrary to our expectations, TaqIA allele status was not associated with striatal DRD2/3 availability in either group and there was no significant difference between groups, possibly due to the relatively small sample size (N = 29). Conclusions: Nonetheless, this is the first in vivo study investigating the relationship between dopamine receptor availability and genetic factors in AUD. The pitfalls of assessing such relationships in a relatively small sample are discussed. Clinical Trial Registration: The published analysis is an additional, post hoc analysis to the preregistered trial with clinical trial number NCT01679145 available on https://clinical - trials.gov/ct2/show/NCT01679145

Exploring the volatile composition of comets C/2012 F6 (Lemmon) and C/2012 S1 (ISON) with ALMA

Comets formed in the outer and cold parts of the disk which eventually evolved into our Solar System. Assuming that the comets have undergone no major processing, studying their composition provides insight in the pristine composition of the Solar Nebula. We derive production rates for a number of volatile coma species and explore how molecular line ratios can help constrain the uncertainties of these rates. We analyse observations obtained with the Atacama Large Millimetre/Submillimetre Array of the volatile composition of the comae of comets C/2012 F6 (Lemmon) and C/2012 S1 (ISON) at heliocentric distances of ~1.45 AU and ~0.56 AU, respectively. Assuming a Haser profile with constant outflow velocity, we model the line intensity of each transition using a 3D radiative transfer code and derive molecular production rates and parent scale lengths. We report the first detection of CS in comet ISON obtained with the ALMA array and derive a parent scale length for CS of ~200 km. Due to the high spatial resolution of ALMA, resulting in a synthesised beam with a size slightly smaller than the derived parent scale length, we are able to tentatively identify CS as a daughter species, i.e., a species produced in the coma and/or sublimated from icy grains, rather than a parent species. In addition we report the detection of several CH3OH transitions and confirm the previously reported detections of HCN, HNC and H2CO as well as dust in the coma of each comet, and report 3sigma upper limits for HCO+. We derive molecular production rates relative to water of 0.2% for CS, 0.06-0.1% for HCN, 0.003-0.05% for HNC, 0.1-0.2% for H2CO and 0.5-1.0% for CH3OH, and show that the modelling uncertainties due to unknown collision rates and kinematic temperatures are modest and can be mitigated by available observations of different transitions of HCN.Comment: 10 pages, 4 figures, 2 tables. Accepted for publication in A&

Pavlovian-to-Instrumental Transfer in Alcohol Dependence: A Pilot Study

This publication is with permission of the rights owner freely accessible due to an alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping ongoing thought and behavior. The influence of pavlovian stimuli on ongoing behavior is paradigmatically measured by pavlovian-to-instrumental transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced PIT. Methods: Thirty-two recently detoxified alcohol-dependent patients and 32 age- and gender-matched healthy controls performed a PIT task with instrumental go/no-go approach behaviors. The task involved both pavlovian stimuli associated with monetary rewards and losses, and images of drinks. Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect, and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs. Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol-dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.Peer Reviewe

Better than expected: the gap between self-reported and objective measures of cognitive performance in remitted bipolar disorder

BackgroundStudies comparing objective and self-reported cognitive functioning as well as influencing factors in individuals with remitted bipolar disorder are scarce and contradictory.MethodsThe aim of this study was to compare executive functioning and other objective and self-reported cognitive impairment between 26 individuals with remitted bipolar disorder (15 BD I) and 24 healthy controls using a cross-sectional design. Executive functions were measured by the TAP Go/No-go subtest as well as the Stroop Task. Self-rated functioning was assessed using the Attention Deficit Experience Questionnaire. In addition, possible predictors of self-reported and objective cognitive functioning were examined to perform regression analyses.ResultsIndividuals with remitted bipolar disorder did not differ significantly in executive functions or other objective cognitive domains from the healthy control group, but showed a significantly lower level of self-reported cognitive functioning and self-esteem. While self-esteem was the strongest predictor in healthy controls for self-reported cognitive functioning, severity of illness and subthreshold depressive mood were the most important predictors in individuals with remitted bipolar disorder.ConclusionThe results once again demonstrate the cognitive heterogeneity in bipolar disorder. In the treatment of cognitive deficits, factors such as subthreshold depressive symptomatology and self-esteem should be focused on in addition to cognitive training in remitted patients

Association of the OPRM1 A118G polymorphism and Pavlovian-to-instrumental transfer: Clinical relevance for alcohol dependence

Background: Pavlovian-to-instrumental transfer (PIT) quantifies the extent to which a stimulus that has been associated with reward or punishment alters operant behaviour. In alcohol dependence (AD), the PIT effect serves as a paradigmatic model of cue-induced relapse. Preclinical studies have suggested a critical role of the opioid system in modulating Pavlovian–instrumental interactions. The A118G polymorphism of the OPRM1 gene affects opioid receptor availability and function. Furthermore, this polymorphism interacts with cue-induced approach behaviour and is a potential biomarker for pharmacological treatment response in AD. In this study, we tested whether the OPRM1 polymorphism is associated with the PIT effect and relapse in AD. Methods: Using a PIT task, we examined three independent samples: young healthy subjects ( N = 161), detoxified alcohol-dependent patients ( N = 186) and age-matched healthy controls ( N = 105). We used data from a larger study designed to assess the role of learning mechanisms in the development and maintenance of AD. Subjects were genotyped for the A118G (rs1799971) polymorphism of the OPRM1 gene. Relapse was assessed after three months. Results: In all three samples, participants with the minor OPRM1 G-Allele (G+ carriers) showed increased expression of the PIT effect in the absence of learning differences. Relapse was not associated with the OPRM1 polymorphism. Instead, G+ carriers displaying increased PIT effects were particularly prone to relapse. Conclusion: These results support a role for the opioid system in incentive salience motivation. Furthermore, they inform a mechanistic model of aberrant salience processing and are in line with the pharmacological potential of opioid receptor targets in the treatment of AD