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

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

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData Availability Statement: Due to ethical concerns, the research data supporting this publication are not publicly available.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.Medical Research Council (MRC)Society for the Study of AddictionUniversity of Exete

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

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

Behavioral 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 used a quantitative measure. Studies were combined in a random effects meta-analysis.RESULTS: We included 42 acute abstinence studies and 13 cessation studies were included. There was evidence for an effect of abstinence on delay discounting [d = 0.26, 95% CI 0.07 to 0.45, p = 0.005], response inhibition [d = 0.48, 95% CI 0.26 to 0.70, p &lt; 0.001], mental arithmetic [d = 0.38, 95% CI 0.06 to 0.70, p = 0.018], and recognition memory [d = 0.46, 95% CI 0.23 to 0.70, p &lt; 0.001]. In contrast performance on the Stroop [d =0 .17, 95% CI -0.17 to 0.51, p = 0.333] and smoking Stroop [d = 0.03, 95% CI -0.11 to 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 to 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.</p

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

ObjectivesIt 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.MethodsAn 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 naive 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.ResultsThe 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%).ConclusionsThis study supports the utility of the EFT for the detection of feigned adult ADHD.</p

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.</p

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

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

The Underlying Mechanisms of the Laterality Judgement Task

A vast amount of research suggests that making laterality judgments about left and right body parts is achieved by an embodied mental rotation process. Therefore the laterality judgment task has been extensively used in the last decade in order to investigate properties of motor imagery and furthermore to assess clinical populations concerning their motor imagery abilities. Nevertheless it is still not sufficiently clear in which way the decision is actually derived. In this study the predictions of two models concerning this issue are tested. Firstly the two- stage model which assumes a decision based on initial rapid visual recognition and furthermore the recently proposed hand- binding model according to which it is not motor imagery but a multisensory integrative process that underlies the laterality decision. A forced laterality judgment task, in which participants were only given a very short amount of time to respond was implemented in order to investigate specific predictions of the two models. The analysis could not find further evidence for the hand- binding model, whereas none of the findings contradicted the predictions of the two- stage model