Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: The PULSES trial.

BACKGROUND: Primary adrenal insufficiency (PAI) mortality and morbidity remain unacceptably high, possibly arising as glucocorticoid replacement does not replicate natural physiology. A pulsatile subcutaneous pump can closely replicate cortisol's circadian and ultradian rhythm. OBJECTIVES: To assess the effect of pump therapy on quality of life, mood, functional neuroimaging, behavioural/cognitive responses, sleep and metabolism. METHODS: A 6-week randomised, crossover, double-blinded and placebo-controlled feasibility study of usual dose hydrocortisone in PAI administered as either pulsed subcutaneous or standard care in Bristol, United Kingdom (ISRCTN67193733). Participants were stratified by adrenal insufficiency type. All participants who received study drugs are included in the analysis. The primary outcome, the facial expression recognition task (FERT), occurred at week 6. RESULTS: Between December 2014 and 2017, 22 participants were recruited - 20 completed both arms, and 21 were analysed. The pump was well-tolerated. No change was seen in the FERT primary outcome; however, there were subjective improvements in fatigue and mood. Additionally, functional magnetic resonance imaging revealed differential neural processing to emotional cues and visual stimulation. Region of interest analysis identified the left amygdala and insula, key glucocorticoid-sensitive regions involved in emotional ambiguity. FERT post hoc analysis confirmed this response. There were four serious adverse events (AE): three intercurrent illnesses requiring hospitalisation (1/3, 33.3% pump) and a planned procedure (1/1, 100% pump). There was a small number of expected AEs: infusion site bruising/itching (3/5, 60% pump), intercurrent illness requiring extra (3/7, 42% pump) and no extra (4/6, 66% pump) steroid. CONCLUSIONS: These findings support the administration of hormone therapy that mimics physiology.

Polydrug Use Typologies of Regular Ecstasy Users Visiting Electronic Dance Music Events: A Latent Class Analysis.

INTRODUCTION: Polydrug use patterns among young adults using ecstasy vary, as well as their willingness to change them. Polydrug use patterns are likely associated with different adverse health outcomes. It is unknown whether polydrug use patterns of young adults who use ecstasy are similar in different countries. This study aims to identify and compare polydrug use patterns and willingness to change them of young adults that use ecstasy in the United Kingdom (UK) and the Netherlands (NL), two countries with a high prevalence of ecstasy use and a large electronic dance music (EDM) scene. METHODS: The data from the online cross-sectional Electronic Music Scene Survey were used in a latent class analysis. The binary indicators used in the estimation were past-year substance use of 21 different substances. The sample consisted of young adult ecstasy users that regularly visit EDM events (age 18-34). RESULTS: A total of 1,077 respondents from the UK (age M = 23.1) and 1,178 from the NL (age M = 23.7) that regularly visit EDM events were included in the analyses. In both countries, three polydrug use patterns of ecstasy users were identified based on Bayesian Information Criterion fit indices: a traditional polydrug use class (UK: 28%; NL: 40%), a stimulant and ketamine polydrug use class (UK: 48%; NL: 52%), and an extensive polydrug use class (UK: 24%; NL: 8%) characterized by substantial use of stimulants, depressant, and psychedelic substances. Overall, young adults that used ecstasy in the UK consumed 3,4-methylenedioxymeth-amphetamine (MDMA) more often as powder/crystalline and at higher dosages compared to young adults in the NL who preferred MDMA tablets. Regardless of polydrug class or country, most respondents indicated that they had the intention to reduce but not quit their use. CONCLUSION: In both countries, structurally similar polydrug use patterns among young adults that use ecstasy were found, while the use frequencies of individual substances and preferred MDMA form varied between the countries.

[Hepatitis C in prisons : Treatment and barriers to the elimination goals of the United Nations]. / Hepatitis C in Haftanstalten : Behandlung und Barrieren auf dem Weg zu den Eliminierungszielen der Vereinten Nationen.

BACKGROUND: Despite general advances in the treatment of people with hepatitis C in Germany, it is unclear to what extent this also applies to specific key populations, such as prisoners. METHODS: In a short survey conducted in June 2021, the ministries of justice in the federal states were asked about data collection and diagnostic methods as well as the prevalence of infections caused by the hepatitis C virus (HCV) and HCV treatment among prisoners in Germany. In addition, expert interviews were conducted regarding HCV treatment barriers and missed opportunities in prisons. RESULTS: It is evident that there is no complete and comprehensive data collection within the ministries of justice. Prevention measures, such as opiate substitution therapy in prison, are available in all participating federal states. More specific offers and measures (e.g., razor and syringe exchange) are only found in a few cases and are sometimes subject to a charge. Experts point out that although treatment in prison generally complies with the equivalence principle: it is more difficult to reach the target group. CONCLUSIONS: Comprehensive education and counselling on HCV treatment, consistent HCV testing and treatment, and preventive measures to avoid (re-)infection are important for successful HCV elimination in prisons.

Substance Use and Attendance Motives of Electronic Dance Music (EDM) Event Attendees: A Survey Study.

EDM event attendees are a high-risk population for substance use and associated adverse effects. The aim of this study was to examine substance use at EDM events, focusing on associations between attendance motives and substance use. Sociodemographic characteristics, event specifics, past-year use, and attendance motives were assessed through an online survey. Participants were 1345 Belgian EDM event attendees (69.44% male, Mage = 22.63, SDage = 4.03). Ecstasy/MDMA/Molly (52.28%), other synthetic hallucinogens (53.68%), ketamine (42.13%), amphetamines (40.45%), and alkyl nitrites (poppers) (32.76%) were most frequently used at festivals/outdoor parties/raves. In nightclubs, cocaine (32.29%) was shown to be prevalent as well, while other synthetic hallucinogens (15.79%) were less often consumed. At events with a more private character, cannabis (68.88%) and magic mushrooms (66.44%) were most frequently used. Aside from alcohol (47.76%), substance use in pubs/bars was negligible. Overall enjoyment was demonstrated to be the key attendance motive, which was succeeded by those relating to music and socialization. A wide range of motives proved to be more important to users (e.g., dance, exploration, escapism, excitement, alcohol, drugs) than non-users, while some were associated with the use of particular substances. The prevalence of substance use was shown to be dependent on the specifics of the setting. Moreover, the idea of a three-dimensional classification of the most principal motives for music event attendance was supported. Finally, correlations were estimated between attendance motives and substance use as well as specific substances. Results could enable more tailored approaches in prevention and harm reduction efforts as well as event management strategies.

Is approving esketamine as an antidepressant for treatment resistant depression associated with recreational use and risk perception of ketamine? Results from a longitudinal and cross-sectional survey in nightlife attendees.

BACKGROUND: Esketamine was licensed for use in treatment resistant depression by the European Medicines Agency in December 2019. It is unclear whether this new approval has lowered the risk perception of recreational ketamine use. This is important given a recent increase in recreational ketamine use. METHODS: This study expanded on an existing longitudinal online study of the nightlife scene, by adding an additional longitudinal assessment as well as a new cross-sectional sample. Participants had to be aged 18-34 years, reside in the UK and have attended at least 6 electronic music events in the past year. The likelihood of increasing recreational ketamine use due to the approval, attitudes towards and risk perception of medical ketamine use and experiences resulting from recreational ketamine use were collected after the approval. Changes in ketamine use and frequency were assessed longitudinally before and after the approval. RESULTS: The overall sample size was 2415: 414 longitudinal (57% retention rate) and 2001 new cross-sectional participants. The majority indicated no change in their likelihood of using recreational ketamine due to the approval of esketamine (87%). Longitudinal participants did not indicate an increase in past 12 month use or frequency after the approval. Only one-third of participants reported being aware of the approval. Participants previously aware showed greater overall support for medical use of ketamine than participants previously unaware of the change. However, an equally high risk was assigned to the recreational use of ketamine in both groups. Ketamine users indicated both increases as well as decreases in depression and anxiety as a result of ketamine use. CONCLUSION: The introduction of esketamine as an antidepressant was not associated with a change in the risk perception of recreational ketamine use in most participants, nor was it longitudinally associated with increased use. Potential negative effects of recreational ketamine use on mental health, as users in this sample reported, should be clearly communicated when discussing the benefits of (es-) ketamine in a therapeutic context.

Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder.

OBJECTIVE: Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol education as a therapy control. METHODS: In a double-blind placebo-controlled phase 2 clinical trial, 96 patients with severe alcohol use disorder were randomly assigned to one of four conditions: 1) three weekly ketamine infusions (0.8 mg/kg i.v. over 40 minutes) plus psychological therapy, 2) three saline infusions plus psychological therapy, 3) three ketamine infusions plus alcohol education, or 4) three saline infusions plus alcohol education. The primary outcomes were self-reported percentage of days abstinent and confirmed alcohol relapse at 6-month follow-up. RESULTS: Ninety-six participants (35 women; mean age, 44.07 years [SD=10.59]) were included in the intention-to-treat analysis. The treatment was well tolerated, and no serious adverse events were associated with the study drug. Although confidence intervals were wide, consistent with a proof-of-concept study, there were a significantly greater number of days abstinent from alcohol in the ketamine group compared with the placebo group at 6-month follow-up (mean difference=10.1%, 95% CI=1.1, 19.0), with the greatest reduction in the ketamine plus therapy group compared with the saline plus education group (15.9%, 95% CI=3.8, 28.1). There was no significant difference in relapse rate between the ketamine and placebo groups. CONCLUSIONS: This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at 6-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment.

Drug Use Changes at the Individual Level: Results from a Longitudinal, Multisite Survey in Young Europeans Frequenting the Nightlife Scene.

BACKGROUND: Monitoring emerging trends in the increasingly dynamic European drug market is vital; however, information on change at the individual level is scarce. In the current study, we investigated changes in drug use over 12 months in European nightlife attendees. METHOD: In this longitudinal online survey, changes in substances used, use frequency in continued users, and relative initiation of use at follow-up were assessed for 20 different substances. To take part, participants had to be aged 18-34 years; be from Belgium, Italy, the Netherlands, Sweden, or the UK; and have attended at least 6 electronic music events in the past 12 months at baseline. Of 8,045 volunteers at baseline, 2,897 completed the survey at both time points (36% follow-up rate), in 2017 and 2018. RESULTS: The number of people using ketamine increased by 21% (p < 0.001), and logarithmized frequency of use in those continuing use increased by 15% (p < 0.001; 95% CI: 0.07-0.23). 4-Fluoroamphetamine use decreased by 27% (p < 0.001), and logarithmized frequency of use in continuing users decreased by 15% (p < 0.001, 95% CI: -0.48 to -0.23). The drugs with the greatest proportion of relative initiation at follow-up were synthetic cannabinoids (73%, N = 30), mephedrone (44%, N = 18), alkyl nitrites (42%, N = 147), synthetic dissociatives (41%, N = 15), and prescription opioids (40%, N = 48). CONCLUSIONS: In this European nightlife sample, ketamine was found to have the biggest increase in the past 12 months, which occurred alongside an increase in frequency of use in continuing users. The patterns of uptake and discontinuation of alkyl nitrates, novel psychoactive substances, and prescription opioids provide new information that has not been captured by existing cross-sectional surveys. These findings demonstrate the importance of longitudinal assessments of drug use and highlight the dynamic nature of the European drug landscape.

"This Is Something That Changed My Life": A Qualitative Study of Patients' Experiences in a Clinical Trial of Ketamine Treatment for Alcohol Use Disorders.

Background: The therapeutic benefits of ketamine have been demonstrated for a variety of psychiatric disorders. However, the role of ketamine induced psychoactive experiences in mediating the therapeutic effects is unclear. Despite the growing quantitative research on the efficacy of ketamine treatment, very few studies examined participant experiences of ketamine infusions in a treatment setting. Aims: The current study aimed to examine participant experiences of ketamine infusions and how these relate to therapeutic mechanisms in a clinical trial setting. Methods: We conducted semi-structured interviews with 12 participants who received up to three ketamine infusions (0.8 mg/kg) as part of a Phase II double blind, randomised controlled trial. The interviews explored participants' acute experiences of ketamine infusions, experiences of psychotherapy/education, and the lasting effects of the trial. The interviews were transcribed verbatim and analysed using thematic analysis. Results: Six key themes were identified. (1) Participants reported multifaceted motivations for trial participation. (2) The set and setting was found to be influential in determining acute ketamine experiences. The acute ketamine experiences included: (3) the inherent contradictions of the experience (e.g., dissociation vs feelings of connection), (4) rapidly fluctuating and changing experiences, (5) meaningful, mystical and spiritual experiences. Finally, the final theme (6) relates to the transformational effects of the infusions and the trial. Conclusion: Provided in a supportive and professional environment, ketamine treatment led to a significant change in relationship with alcohol. Ketamine induced ego dissolution and dissociation were reported to be related to the transformational effects on relationship with alcohol. The extent to which the acute psychoactive effects of ketamine mediate therapeutic effects on drinking outcomes remain to be investigated in the trial data. The acute effects of ketamine reported by our participants transcend its traditional conceptualisation as a "dissociative anaesthetic"; therefore, we suggest the development or use of new measures alongside ketamine infusions to fully capture the spectrum of these effects which may be crucial in its therapeutic and transformative effects.

Illicit Drug Use and Associated Problems in the Nightlife Scene: A Potential Setting for Prevention.

Illicit drug use is prevalent in the nightlife scene, especially at electronic dance music (EDM) events. The aim of the present study was to investigate illicit drug use patterns and consequences of drug use among frequent visitors of EDM events. Young adults (18-34 years old) who had visited at least six EDM events in Sweden during the past year participated in a web-based survey on drug use patterns and its consequences. Fifty-nine percent of participants had used illicit drugs during the past year, most often cannabis followed by ecstasy, cocaine, and amphetamine. Nightlife venues were identified as the main setting for the use of central stimulants, while cannabis was mostly used at home. Frequent alcohol and tobacco use was associated with illicit drug use. The most prevalent negative consequences of drug use were related to mental health, such as impairments in mood, sleep, and memory problems, but physical manifestations were also reported, such as palpitations and collapsing. These findings confirm that drug use is prevalent and associated with negative health effects among EDM nightlife attendees. The nightlife scene is a setting with promising potential to reach a high-risk target group with illicit drug use prevention interventions.

Glucocorticoid ultradian rhythmicity differentially regulates mood and resting state networks in the human brain: A randomised controlled clinical trial.

Adrenal glucocorticoid secretion into the systematic circulation is characterised by a complex rhythm, composed of the diurnal variation, formed by changes in pulse amplitude of an underlying ultradian rhythm of short duration hormonal pulses. To elucidate the potential neurobiological significance of glucocorticoid pulsatility in man, we have conducted a randomised, double-blind, placebo-controlled, three-way crossover clinical trial on 15 healthy volunteers, investigating the impact of different glucocorticoid rhythms on measures of mood and neural activity under resting conditions by recruiting functional neuroimaging, computerised behavioural tests and ecological momentary assessments. Endogenous glucocorticoid biosynthesis was pharmacologically suppressed, and plasma levels of corticosteroid restored by hydrocortisone replacement in three different regimes, either mimicking the normal ultradian and circadian profile of the hormone, or retaining the normal circadian but abolishing the ultradian rhythm of the hormone, or by our current best oral replacement regime which results in a suboptimal circadian and ultradian rhythm. Our results indicate that changes in the temporal mode of glucocorticoid replacement impact (i) the morning levels of self-perceived vigour, fatigue and concentration, (ii) the diurnal pattern of mood variation, (iii) the within-network functional connectivity of various large-scale resting state networks of the human brain, (iv) the functional connectivity of the default-mode, salience and executive control networks with glucocorticoid-sensitive nodes of the corticolimbic system, and (v) the functional relationship between mood variation and underlying neural networks. The findings indicate that the pattern of the ultradian glucocorticoid rhythm could affect cognitive psychophysiology under non-stressful conditions and opens new pathways for our understanding on the neuropsychological effects of cortisol pulsatility with relevance to the goal of optimising glucocorticoid replacement strategies.

"How do online and offline sampling compare in a multinational study of drug use and nightlife behaviour?"

BACKGROUND: Online sampling is widely used to recruit hard to reach samples such as drug users at nightlife events. We conducted the first study comparing differences in demographics, drug use and nightlife behaviour between an online sample of young adults engaging with the European nightlife scene, and an offline sample recruited at nightclubs and festivals in Europe. METHODS: Online participants who attended at least six nightlife events in the past 12 months were recruited using social media advertising (May-November 2017). Offline participants were recruited at nightclubs and festivals using a random intercept method (May-November 2017). Samples were compared with respect to age, gender, past year use of alcohol, cannabis, cocaine, ecstasy/MDMA and amphetamines, and past year attendance at nightclubs, licensed festivals, illegal festivals, pubs and house-parties. RESULTS: 6153 online and 3529 offline participants were recruited. When adjusting for differences in age and gender, online participants were less likely to have used each drug and to have attended illegal festivals, pubs and house-parties in the past 12 months. The online sample also used each drug and attended each venue, with the exception of nightclubs, less frequently on average than offline participants. Adjusted odds ratios (range 0.37 to 1.39) and regression coefficients (range -0.84 to 0.07) indicate that the majority of observed differences between the samples were of a small effect size. CONCLUSIONS: Estimates of drug use and nightlife engagement are more conservative when using online sampling compared to venue based sampling. Observed differences were generally small in effect, indicating good overall representativeness when using online sampling in the European nightlife scene.

Ketamine as a mental health treatment: Are acute psychoactive effects associated with outcomes? A systematic review.

Esketamine was recently licensed by the US Food and Drug Administration (FDA) and European Drug Agency (EDA) for use in treatment resistant depression (TRD), and further research indicates ketamine as a possible treatment in other mental health conditions. While the underlying mechanisms remain unclear, it has been hypothesised that ketamine's acute psychoactive effects may be associated with psychiatric treatment efficacy. We systematically reviewed the evidence for this association. The databases Medline, Embase and PsychInfo were searched up to June 2019. Studies were included if they enrolled adults with a psychiatric diagnosis, assessed acute psychoactive effects using a quantitative measure, and reported on the relationship between acute effects and treatment outcome. We included 21 studies, involving 891 patients. Seventeen studies assessed patients with depression (TRD [k = 14]), three assessed substance use disorders, and one assessed social anxiety disorder. Overall, 41 associations were assessed, of which 26 % were significant. The studies reviewed displayed great variability in terms of methodology and quality of reporting. The most commonly assessed effect was dissociation, measured by the CADSS. Our results suggest that the CADSS total is not consistently associated with antidepressant outcomes. Apart from this, the current literature is too limited to draw definite conclusions on the presence of an association between acute psychoactive effects and mental health outcomes. The field would benefit from consistently employing a priori hypotheses, more transparent reporting and sufficiently powered statistical analyses. Furthermore, the use of a broader range of assessments tools of acute psychoactive effects during ketamine administration would be beneficial.

The development and validation of a human screening model of tobacco abstinence.

INTRODUCTION: Given the low efficacy of smoking cessation methods, an experimental medicine model indicating smoking abstinence would be of great benefit to the development of new treatments. Hence the sensitivity of cognitive tasks and ambulatory craving measures to smoking abstinence were investigated. METHODS: Cognitive tasks and ambulatory ratings of craving were assessed for sensitivity to acute abstinence (experiment 1), and nicotine replacement therapy administration (NRT) (experiment 2). RESULTS: In experiment 1 go/no-go performance was improved (Mean Difference [MD] -0.99, 95% CI: -1.90 to -0.08) and craving was lower (Regression Coefficient [RC] -33.39, 95% CI: -39.96 to -26.82) in satiated compared with abstinent smokers. There was no clear evidence that N-back (MD 0.64, 95% CI: -0.42 to 2.51), delay discounting (MD 0.01, 95% CI: 0.001 to 0.005) or dot probe performance (MD 0.61, 95% CI: -0.87 to 1.54) were sensitive to acute abstinence. In experiment 2 go/no-go performance was improved (MD 1.12, 95% CI: 0.16-2.08) and craving was lower (RC -18.59, 95% CI: -24.63 to -12.55) smokers abstinent overnight receiving NRT compared with placebo. There was no clear evidence that N-back (MD -0.25, 95% CI: -1.45 to 0.94), delay discounting (MD 0.01, 95% CI: -0.002 to 0.004) or dot probe performance (MD -0.49, 95% CI: -1.61 to -0.64) were sensitive to NRT. CONCLUSIONS: Findings from two experiments converge to suggest that abstinence in smokers reliably increases ambulatory craving assessments and, to a lesser extent, decreases go/no-go task performance. These findings can be utilized in the development of an experimental medicine model to test novel treatments for smoking cessation.

Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal.

BACKGROUND AND AIMS: Cannabidiol (CBD), a non-intoxicating cannabinoid found in cannabis, may be a promising novel smoking cessation treatment due to its anxiolytic properties, minimal side effects and research showing that it may modify drug cue salience. We used an experimental medicine approach with dependent cigarette smokers to investigate if (1) overnight nicotine abstinence, compared with satiety, will produce greater attentional bias (AB), higher pleasantness ratings of cigarette-related stimuli and increased craving and withdrawal; and (2) CBD in comparison to placebo, would attenuate AB, pleasantness of cigarette-related stimuli, craving and withdrawal and not produce any side effects. DESIGN: Randomized, double-blind cross-over study with a fixed satiated session followed by two overnight abstinent sessions. SETTING: UK laboratory. PARTICIPANTS: Thirty non-treatment-seeking, dependent cigarette smokers recruited from the community. INTERVENTION AND COMPARATOR: 800 mg oral CBD, or matched placebo (PBO) in a counterbalanced order MEASUREMENTS: AB to pictorial tobacco cues was recorded using a visual probe task and an explicit rating task. Withdrawal, craving, side effects, heart rate and blood pressure were assessed repeatedly. FINDINGS: When participants received PBO, tobacco abstinence increased AB (P = 0.001, d = 0.789) compared with satiety. However, CBD reversed this effect, such that automatic AB was directed away from cigarette cues (P = 0.007, d = 0.704) and no longer differed from satiety (P = 0.82). Compared with PBO, CBD also reduced explicit pleasantness of cigarette images (P = 0.011; d = 0.514). Craving (Bayes factor = 7.08) and withdrawal (Bayes factor = 6.95) were unaffected by CBD, but greater in abstinence compared with satiety. Systolic blood pressure decreased under CBD during abstinence. CONCLUSIONS: A single 800-mg oral dose of cannabidiol reduced the salience and pleasantness of cigarette cues, compared with placebo, after overnight cigarette abstinence in dependent smokers. Cannabidiol did not influence tobacco craving or withdrawal or any subjectively rated side effects.

The Association of Cigarette Smoking With Depression and Anxiety: A Systematic Review.

BACKGROUND: Many studies report a positive association between smoking and mental illness. However, the literature remains mixed regarding the direction of this association. We therefore conducted a systematic review evaluating the association of smoking and depression and/or anxiety in longitudinal studies. METHODS: Studies were identified by searching PubMed, Scopus, and Web of Science and were included if they: (1) used human participants, (2) were longitudinal, (3) reported primary data, (4) had smoking as an exposure and depression and/or anxiety as an outcome, or (5) had depression and/or anxiety as the exposure and smoking as an outcome. RESULTS: Outcomes from 148 studies were categorized into: smoking onset, smoking status, smoking heaviness, tobacco dependence, and smoking trajectory. The results for each category varied substantially, with evidence for positive associations in both directions (smoking to later mental health and mental health to later smoking) as well as null findings. Overall, nearly half the studies reported that baseline depression/anxiety was associated with some type of later smoking behavior, while over a third found evidence that a smoking exposure was associated with later depression/anxiety. However, there were few studies directly supporting a bidirectional model of smoking and anxiety, and very few studies reporting null results. CONCLUSIONS: The literature on the prospective association between smoking and depression and anxiety is inconsistent in terms of the direction of association most strongly supported. This suggests the need for future studies that employ different methodologies, such as Mendelian randomization (MR), which will allow us to draw stronger causal inferences. IMPLICATIONS: We systematically reviewed longitudinal studies on the association of different aspects of smoking behavior with depression and anxiety. The results varied considerably, with evidence for smoking both associated with subsequent depression and anxiety, and vice versa. Few studies supported a bidirectional relationship, or reported null results, and no clear patterns by gender, ethnicity, clinical status, length to follow-up, or diagnostic test. Suggesting that despite advantages of longitudinal studies, they cannot alone provide strong evidence of causality. Therefore, future studies investigating this association should employ different methods allowing for stronger causal inferences to be made, such as MR.

The Development of an Embedded Figures Test for the Detection of Feigned Attention Deficit Hyperactivity Disorder in Adulthood.

OBJECTIVES: It has been shown that an increasing number of adults deliberately feign attention deficit hyperactivity disorder (ADHD), which demonstrates the need for new tests designed to detect feigned ADHD. METHODS: An Embedded Figures Test (EFT) was developed for the detection of feigned ADHD in adulthood. EFT performance of 51 adults with ADHD was compared to the performance of 52 matched healthy individuals, as well as to 268 undergraduate students who were randomly allocated in a simulation design to one of four experimental conditions, i.e. a control group, a naïve simulation group, a symptom-coached simulation group or a test-coached simulation group. Furthermore, an independent sample of 11 adults with ADHD as well as a sample of 17 clinicians experienced in the work with adults with ADHD were assessed for further validation of the EFT. RESULTS: The EFT was relatively easy to perform for both patients with ADHD and healthy comparisons as shown by low error rates and non-significant group differences. However, simulation groups differed from patients with ADHD by significant and large effects. An EFT index for the prediction of feigned ADHD was derived based on logistic regression coefficients. Receiver Operating Characteristics (ROC) demonstrated good classification accuracy of feigned ADHD relative to ADHD (AUC = 94.8%), i.e. high sensitivity (88%) and specificity (90%). CONCLUSIONS: This study supports the utility of the EFT for the detection of feigned adult ADHD.

Behavioural tasks sensitive to acute abstinence and predictive of smoking cessation success: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Performance on cognitive tasks may be sensitive to acute smoking abstinence and may also predict whether quit attempts fail. Our aim was to conduct a systematic review and meta-analysis to identify cognitive tasks sensitive to acute abstinence and predictive of smoking cessation success. METHODS: Embase, Medline, PsycInfo and Web of Science were searched up to March 2016. Studies were included if they enrolled adults and assessed smoking using a quantitative measure. Studies were combined in a random effects meta-analysis. RESULTS: We included 42 acute abstinence studies and 13 cessation studies. There was evidence for an effect of abstinence on delay discounting [d = 0.26, 95% confidence interval (CI) = 0.07-0.45, P = 0.005], response inhibition (d = 0.48, 95% CI = 0.26-0.70, P < 0.001), mental arithmetic (d = 0.38, 95% CI = 0.06-0.70, P = 0.018), and recognition memory (d = 0.46, 95% CI = 0.23-0.70, P < 0.001). In contrast, performance on the Stroop (d = 0 .17, 95% CI = -0.17-0.51, P = 0.333) and smoking Stroop (d = 0.03, 95% CI = -0.11-0.17, P = 0.675) task was not influenced by abstinence. We found only weak evidence for an effect of acute abstinence on dot probe task performance (d = 0.15, 95% CI = -0.01-0.32, P = 0.072). The design of the cessation studies was too heterogeneous to permit meta-analysis. CONCLUSIONS: Compared with satiated smokers, acutely abstinent smokers display higher delay discounting, lower response inhibition, impaired arithmetic and recognition memory performance. However, reaction-time measures of cognitive bias appear to be unaffected by acute tobacco abstinence. Conclusions about cognitive tasks that predict smoking cessation success were limited by methodological inconsistencies.