Psychiatric symptoms and expression of glucocorticoid receptor gene in cocaine users: A longitudinal study.

BACKGROUND: Chronic cocaine users (CU) display reduced peripheral expression of the glucocorticoid receptor gene (NR3C1), which is potentially involved in stress-related psychiatric symptoms frequently occurring in CU. However, it is unknown whether psychiatric symptoms and lower NR3C1 expression are related to each other and whether reduction of drug consumption reverse them. METHOD: At baseline, NR3C1 mRNA expression was measured in 68 recreational CU, 30 dependent CU, and 68 stimulant-naïve controls. Additionally, the Revised Symptom Checklist (SCL-90R) and the Barratt Impulsiveness Scale (BIS) were assessed. At a one-year follow-up, the association between change in NR3C1 expression and psychiatric symptoms was examined in 48 stimulant-naïve controls, 19 CU who increased and 19 CU who decreased their consumption. At both test sessions, cocaine concentrations in hair samples were determined. Mixed-effects models were used to investigate how changes in drug use intensity affect severity of psychiatric symptoms and NR3C1 expression over time. RESULTS: At baseline, recreational and dependent CU displayed elevated impulsivity and considerable symptom burden across most of the SCL-90R subscales. Time-group interaction effects were found for several impulsivity scores, SCL-90R Global Severity Index, Paranoid Thoughts, and Depression subscales as well as for NR3C1 expression. Pairwise comparisons showed that decreasing CU specifically improved in these SCL-90R subscales, while their NR3C1 expression was adapted. Finally, changes in NR3C1 expression were negatively correlated with changes in impulsivity but not SCL-90R scores. CONCLUSION: Our findings suggest that NR3C1 expression changes and some psychiatric symptoms are reversible upon reduction of cocaine intake, thus favouring abstinence-oriented treatment approaches.

Substance related disorders are associated with impaired valuation of delayed gratification and feedback processing: A multilevel meta-analysis and meta-regression.

Across numerous studies, individuals with substance use disorders (SUDs) differed from non-using controls regarding valuation of delayed gratification and feedback processing. However, it remains unclear whether the magnitude of the effect sizes is different across these two cognitive processes and how specific SUDs as well as demographic and clinical moderators influence these effects. In this study we thus performed multilevel linear mixed-effects meta-analyses and meta-regressions to examine the effects of SUDs on the Delay Discounting Task (DD) and on the Iowa Gambling Task (IGT). We found a moderate to large effect for SUD on both, the IGT and DD. While the effect on the DD was generalized to all substance classes, a smaller effect for cannabis-related disorder when compared to other SUDs was found with regard to the IGT. Early onset of substance use and psychiatric comorbidities were associated with stronger effects on the DD. Our findings suggest that feedback processing is more vulnerable to specific substance effects, while valuation of delayed gratification depends more on developmental and clinical factors.

Sensitivity to gains during risky decision-making differentiates chronic cocaine users from stimulant-naïve controls.

BACKGROUND: Chronic cocaine use has been consistently associated with decision-making impairments that contribute to the development and maintenance of drug-taking. However, the underlying cognitive processes of risk-seeking behaviours observed in chronic cocaine users (CU) have so far remained unclear. Here we therefore tested whether CU differ from stimulant-naïve controls in their sensitivity to gain, loss, and probability of loss information when making decisions under risk. METHOD: A sample of 96 participants (56 CU and 40 controls) performed the no-feedback version of the Columbia Card Task, designed to assess risk-taking in relation to gain, loss, and probability of loss information. Additionally, cognitive performance and impulsivity were determined. Current and recent substance use was objectively assessed by toxicological urine and hair analysis. RESULTS: Compared to controls, CU showed increased risk-seeking in unfavourable decision scenarios in which the loss probability was high and the returns were low, and a tendency for increased risk aversion in more favourable decision scenarios. In comparison to controls, CU were less sensitive to gain, but similarly sensitive to loss and probability of loss information. Further analysis revealed that individual differences in sensitivity to loss and probability of loss information were related to cognitive performance and impulsivity. CONCLUSION: Reduced sensitivity to gains in people with CU may contribute to their propensity for making risky decisions. While these alterations in gain sensitivity might directly relate to cocaine use per se, the individual psychopathological profile of CU might moderate sensitivity to loss information.

Executive functions rehabilitation for schizophrenia: a critical systematic review.

BACKGROUND: Consistent evidences suggest that poor functional outcomes in schizophrenia are associated with deficits in executive functions (EF). As result cognitive training, remediation and/or rehabilitation (CR) programs have been developed and many theories, methods and approaches have emerged in support of them. This article presents a systematic review of randomized controlled trials (RCT), including EF rehabilitation interventions, with a focus on methodological issues and evidences of EF improvements. METHOD: Electronic databases (Medline, Web of Science, PsycINFO and Embase) were searched for articles on schizophrenia, EF and cognitive rehabilitation terms. The methodological quality of each article was measured by 5-point JADAD scale. RESULTS: A total of 184 articles were initially identified, but after exclusion criteria, 30 RCT remained in this review. A proportion of 23% of studies scored higher than 4 points in JADAD scale, 40% scored 3 points, 33% scored 2 points and one study scored only 1 point. The average length of interventions was approximately 80 h distributed around 3.42 h/week. CONCLUSION: The reviewed articles corroborate the literature pointing that CR could be a promising therapeutic option for cognitive deficits in schizophrenia. In general, CR could improve cognitive domains and social adjustment either using computerized or paper-and-pencil programs. Additionally, CR combined with cognitive behavioral therapy and/or group sessions is particularly effective. In this paper, we also speculated and discussed optimal doses of treatment and the differences regarding modalities and approaches.