Psychological and attentional outcomes following acute mindfulness induction among high anxiety individuals: A systematic review and meta-analysis.

BACKGROUND: Training outcomes of mindfulness interventions for anxiety have been extensively researched. Less is known about the acute effects of mindfulness induction and associated mechanisms. This systematic review aimed to identify 1) the effect of mindfulness induction on pre-post measures of state anxiety and attention among adults experiencing high levels of anxiety; and 2) the impact of predictors, mediators and moderators on post-induction changes in anxiety and attention. State distress and mindfulness were included as secondary outcomes. METHODS: A systematic search was conducted in November 2021 in electronic databases using relevant search terms. Five studies (four randomised controlled trials and one non-randomised controlled trial) were included, comprising a total of 277 participants with elevated trait/generalised anxiety. Each study used a brief audio-based mindfulness induction exercise. RESULTS: The meta-analysis indicated mindfulness induction had medium and large effects on state anxiety (k = 3, n = 100, g = -0.60, 95%CI [-1.04, -0.16]; p = .008) and state mindfulness (k = 2, n = 110, g = 0.91, 95%CI [0.52, 1.30], p < .001), respectively, when compared with non-therapeutic control conditions. Furthermore, two studies showed small and moderate effects of mindfulness on state anxiety when compared to therapeutic active controls, but were not pooled in a meta-analysis. While results could not be pooled for attention, there was limited evidence of behavioural improvements on tasks measuring aspects of attention following mindfulness induction. However, one study found an increase in Low Beta to High Beta ratio and a reduction in Beta activity in the Anterior Cingulate Cortex following mindfulness induction. Moreover, another study found aspects of state mindfulness mediated reductions in state anxiety. LIMITATIONS: A small number of studies were included in the review, with high risk of bias and low certainty of evidence present. CONCLUSION: The findings support the use of mindfulness induction to reduce state anxiety in anxious individuals but suggest gains in state mindfulness may be a more realistic expected outcome. Further controlled trials are needed to delineate the relative effects of objectively assessed anxiety outcomes from mindfulness induction in clinically defined samples.

Identification of Streptococcus pneumoniae genes associated with hypothiocyanous acid tolerance through genome-wide screening.

Streptococcus pneumoniae is a commensal bacterium and invasive pathogen that causes millions of deaths worldwide. The pneumococcal vaccine offers limited protection, and the rise of antimicrobial resistance will make treatment increasingly challenging, emphasizing the need for new antipneumococcal strategies. One possibility is to target antioxidant defenses to render S. pneumoniae more susceptible to oxidants produced by the immune system. Human peroxidase enzymes will convert bacterial-derived hydrogen peroxide to hypothiocyanous acid (HOSCN) at sites of colonization and infection. Here, we used saturation transposon mutagenesis and deep sequencing to identify genes that enable S. pneumoniae to tolerate HOSCN. We identified 37 genes associated with S. pneumoniae HOSCN tolerance, including genes involved in metabolism, membrane transport, DNA repair, and oxidant detoxification. Single-gene deletion mutants of the identified antioxidant defense genes sodA, spxB, trxA, and ahpD were generated and their ability to survive HOSCN was assessed. With the exception of ΔahpD, all deletion mutants showed significantly greater sensitivity to HOSCN, validating the result of the genome-wide screen. The activity of hypothiocyanous acid reductase or glutathione reductase, known to be important for S. pneumoniae tolerance of HOSCN, was increased in three of the mutants, highlighting the compensatory potential of antioxidant systems. Double deletion of the gene encoding glutathione reductase and sodA sensitized the bacteria significantly more than single deletion. The HOSCN defense systems identified in this study may be viable targets for novel therapeutics against this deadly pathogen. IMPORTANCE Streptococcus pneumoniae is a human pathogen that causes pneumonia, bacteremia, and meningitis. Vaccination provides protection only against a quarter of the known S. pneumoniae serotypes, and the bacterium is rapidly becoming resistant to antibiotics. As such, new treatments are required. One strategy is to sensitize the bacteria to killing by the immune system. In this study, we performed a genome-wide screen to identify genes that help this bacterium resist oxidative stress exerted by the host at sites of colonization and infection. By identifying a number of critical pneumococcal defense mechanisms, our work provides novel targets for antimicrobial therapy.

Relationship between attentional bias and stimulus control: An observational study of real-world eating patterns.

BACKGROUND: Attentional bias towards food related stimuli has been proposed as a potential target for dieting intervention, however the evidence supporting a relationship between attentional bias and food intake is mixed. Theory holds that food related attentional bias should be positively associated with measures of stimulus-controlled eating, and that implicit processes such as impulsivity moderate this association. The aim of the present study was to examine whether the proposed relationship between food-related attentional bias and stimulus control exists, and whether it is moderated by impulsivity. METHOD: A community sample of 68 participants completed a food-related attentional bias task and impulsiveness scale during a laboratory visit, after which they recorded their real-world eating in real-time over 14 days using Ecological Momentary Assessment (EMA). During this time, participants also responded to 4-5 randomly timed assessments per day. Food outlet presence (e.g., fast food restaurants, cafes, corner stores etc.) was assessed during both eating and non-eating assessments. EMA data was then used to determine levels of stimulus controlled eating for each participant. FINDINGS: Substantial variation was seen in both our measure of both food-related attentional bias (Range: 33.9 to 80.0) and in the degree to which the participant's eating could be categorised as being under stimulus control (Range: 0.50 to 0.93). However, food-related attentional bias scores were not a significant independent predictor of stimulus control and nor was this relationship moderated by impulsivity. CONCLUSION: Contrary to theoretical predictions, we found no evidence that of an association between attentional bias, impulsivity, and stimulus control. More work is needed to better understand the implicit processes underlying eating behaviour in the real-world.

Psychological Outcomes and Mechanisms of Mindfulness-Based Training for Generalised Anxiety Disorder: A Systematic Review and Meta-Analysis.

This systematic review aimed to identify 1) the effect of mindfulness training on pre-post measures of anxiety and attention among adults experiencing high levels of generalised anxiety; and 2) the impact of predictors, mediators and moderators on post-intervention changes in anxiety or attention. Trait mindfulness and distress measures were included as secondary outcomes. A systematic search was conducted in November 2021 in electronic databases using relevant search terms. Eight articles comprising four independent studies were included (N = 334). All studies included participants diagnosed with generalised anxiety disorder (GAD) who participated in an 8-week manualised program. The meta-analysis indicated that mindfulness training had a large effect on anxiety symptoms (g = -1.92, 95%CI[-3.44, -0.40]) when compared to inactive (i.e., care as usual, waitlist) or non-specified (i.e., condition not defined) controls. However, a significant effect was not found when compared to active controls. Effects for depression, worry and trait mindfulness did not reach statistical significance, despite small-large effect sizes favouring mindfulness compared to inactive/non-specified controls. Our narrative review found evidence that changes in aspects of trait mindfulness mediate anxiety reduction following mindfulness training. However, a small number of studies were available for inclusion in the review, with high risk of bias and low certainty of evidence present. Overall, the findings support the use of mindfulness training programs for GAD and indicate mechanisms that may differ from those involved in other cognitive therapy approaches. Further RCTs with evidence-based controls are needed to clarify techniques most beneficial for generalised anxiety to support individually tailored treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-023-04695-x.

A Tn-seq Screen of Streptococcus pneumoniae Uncovers DNA Repair as the Major Pathway for Desiccation Tolerance and Transmission.

Streptococcus pneumoniae is an opportunistic pathogen that is a common cause of serious invasive diseases such as pneumonia, bacteremia, meningitis, and otitis media. Transmission of this bacterium has classically been thought to occur through inhalation of respiratory droplets and direct contact with nasal secretions. However, the demonstration that S. pneumoniae is desiccation tolerant and, therefore, environmentally stable for extended periods of time opens up the possibility that this pathogen is also transmitted via contaminated surfaces (fomites). To better understand the molecular mechanisms that enable S. pneumoniae to survive periods of desiccation, we performed a high-throughput transposon sequencing (Tn-seq) screen in search of genetic determinants of desiccation tolerance. We identified 42 genes whose disruption reduced desiccation tolerance and 45 genes that enhanced desiccation tolerance. The nucleotide excision repair pathway was the most enriched category in our Tn-seq results, and we found that additional DNA repair pathways are required for desiccation tolerance, demonstrating the importance of maintaining genome integrity after desiccation. Deletion of the nucleotide excision repair gene uvrA resulted in a delay in transmission between infant mice, indicating a correlation between desiccation tolerance and pneumococcal transmssion. Understanding the molecular mechanisms that enable pneumococcal persistence in the environment may enable targeting of these pathways to prevent fomite transmission, thereby preventing the establishment of new colonization and any resulting invasive disease.

Khat withdrawal symptoms among chronic khat users following a quit attempt: An ecological momentary assessment study.

Research reports show increased prevalence of habitual khat chewing among various parts of the community in Ethiopia. Some users experience problems controlling their use; withdrawal symptoms may be adding to difficulties with reducing or ceasing use. We aimed to describe the nature and the time course of any withdrawal syndrome in relation to the cessation of khat use over the first 2 weeks of a quit attempt. Fifty-nine participants between the ages of 18 and 35 and who have already chewed ≥1 bundle of khat in their life with a chewing frequency of ≥3 days per week were recruited from Adama Science and Technology University campus. Participants were predominantly male (n = 45, 75%) and had the mean age of 24.8 years (range = 20-32; SD = 2.8). Participants used smart phones to monitor withdrawal symptoms and cravings. The total assessments were divided in to 3 prequit and 14 postquit days. The development of withdrawal symptoms was evident, and all withdrawal symptoms followed similar overall patterns, with salient elevations after the quit day and curvatures around the first week of postquit period. Depression, craving, nervousness, tiredness, restlessness, poor motivation, irritability, and negative affect substantially increased and reached peak on the first week around Day 7 and remained higher compared with the level at baseline indicating the persistence and severity of these symptoms over time. In addition, craving, irritability, and restlessness had significantly reverted to their baseline level during the second week of the postquit duration. We have demonstrated low rates of success during unaided quite attempts from khat and that the withdrawal syndrome is not trivial. Interventions are necessary to support individuals during the period of increased symptoms of dysphoria and to reduce the risk of relapse. (PsycINFO Database Record

Transcription and translation of the sigG gene is tuned for proper execution of the switch from early to late gene expression in the developing Bacillus subtilis spore.

A cascade of alternative sigma factors directs developmental gene expression during spore formation by the bacterium Bacillus subtilis. As the spore develops, a tightly regulated switch occurs in which the early-acting sigma factor σF is replaced by the late-acting sigma factor σG. The gene encoding σG (sigG) is transcribed by σF and by σG itself in an autoregulatory loop; yet σG activity is not detected until σF-dependent gene expression is complete. This separation in σF and σG activities has been suggested to be due at least in part to a poorly understood intercellular checkpoint pathway that delays sigG expression by σF. Here we report the results of a careful examination of sigG expression during sporulation. Unexpectedly, our findings argue against the existence of a regulatory mechanism to delay sigG transcription by σF and instead support a model in which sigG is transcribed by σF with normal timing, but at levels that are very low. This low-level expression of sigG is the consequence of several intrinsic features of the sigG regulatory and coding sequence-promoter spacing, secondary structure potential of the mRNA, and start codon identity-that dampen its transcription and translation. Especially notable is the presence of a conserved hairpin in the 5' leader sequence of the sigG mRNA that occludes the ribosome-binding site, reducing translation by up to 4-fold. Finally, we demonstrate that misexpression of sigG from regulatory and coding sequences lacking these features triggers premature σG activity in the forespore during sporulation, as well as inappropriate σG activity during vegetative growth. Altogether, these data indicate that transcription and translation of the sigG gene is tuned to prevent vegetative expression of σG and to ensure the precise timing of the switch from σF to σG in the developing spore.

Using the Severity of Dependence Scale to screen for DSM-5 khat use disorder.

OBJECTIVE: This study aimed to determine the efficacy of the Severity of Dependence Scale (SDS) as a screening tool for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-defined khat use disorder. METHODS: Cross-sectional, purposive sample of past-year khat consumers aged 16 and above were recruited from khat markets and cafes from university and general community in Adama, Ethiopia. Participants self-completed a survey comprising current substance use disorder. RESULTS: The SDS formed a unifactorial structure, consistent with the dependence construct. Almost three quarters (73%) of the sample were identified as experiencing Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition khat use disorder. The SDS demonstrated excellent discrimination (area under the curve = 0.92) and an optimal cut-off as a score of 3 or greater, with sensitivity of 81% and specificity of 96%. This classification validly identified a group with more frequent and higher dose khat use than participants that did not screen positive. CONCLUSION: Although khat is a mild stimulant, there is clear evidence that some consumers are both concerned with their use and experience problems associated with their use. Consistent with its application for other drugs, the SDS is a brief and simple screening tool that appears to validly identify individuals experiencing a khat use disorder syndrome and experiencing high rates of adverse consequences in association with use.

Stopping khat use: Predictors of success in an unaided quit attempt.

INTRODUCTION AND AIMS: Despite the adverse effects of khat use and chewers interest in cessation, there are few studies that have reported on the outcome of khat cessation attempts, and limited resources available for potential quitters. We used electronic diaries to monitor the outcomes of an unassisted quit attempt among daily and near daily khat consumers, and examine predictors of success. DESIGN AND METHODS: Sixty participants between the ages of 18 and 35 years who regularly chewed khat and who were attempting to quit were purposively recruited from an Ethiopian University campus. Real-time prospective daily recording of khat use was obtained for an average of 10 days prior to quit day (range 6-13) and 28 post-quit days (range 9-31), using an electronic diary. RESULTS: Almost all (95%) achieved initial abstinence. Of these, 80% reached at least seven continuous days of abstinence; 7% maintained continuous abstinence for 28 days post-quit. While 93% lapsed (average 11 days post-quit, SD = 7), only a smaller proportion relapsed (41%: chewed for at least three consecutive days after at least 5 days of abstinence). No demographic factors were predictive of successful abstinence. DISCUSSION AND CONCLUSIONS: Regular khat chewers have difficulties in maintaining abstinence despite having motivation and desire to quit. This implies that treatment aids may be needed to assist chewers' in their quit attempts. Controlled experimental trial through the use of available low cost quit aids and behavioural resources is crucial in order to increase success rates for those seeking to desist from khat use.

Verbal Learning and Memory in Cannabis and Alcohol Users: An Event-Related Potential Investigation.

Aims: Long-term heavy use of cannabis and alcohol are known to be associated with memory impairments. In this study, we used event-related potentials to examine verbal learning and memory processing in a commonly used behavioral task. Method: We conducted two studies: first, a small pilot study of adolescent males, comprising 13 Drug-Naive Controls (DNC), 12 heavy drinkers (HD) and 8 cannabis users (CU). Second, a larger study of young adults, comprising 45 DNC (20 female), 39 HD (16 female), and 20 CU (9 female). In both studies, participants completed a modified verbal learning task (the Rey Auditory Verbal Learning Test, RAVLT) while brain electrical activity was recorded. ERPs were calculated for words which were subsequently remembered vs. those which were not remembered, and for presentations of learnt words, previously seen words, and new words in a subsequent recognition test. Pre-planned principal components analyses (PCA) were used to quantify the ERP components in these recall and recognition phases separately for each study. Results: Memory performance overall was slightly lower than published norms using the standardized RAVLT delivery, but was generally similar and showed the expected changes over trials. Few differences in performance were observed between groups; a notable exception was markedly poorer delayed recall in HD relative to DNC (Study 2). PCA identified components expected from prior research using other memory tasks. At encoding, there were no between-group differences in the usual P2 recall effect (larger for recalled than not-recalled words). However, alcohol-related differences were observed in a larger P540 (indexing recollection) in HD than DNC, and cannabis-related differences were observed in a smaller N340 (indexing familiarity) and a lack of previously seen > new words effect for P540 in Study 2. Conclusions: This study is the first examination of ERPs in the RAVLT in healthy control participants, as well as substance-using individuals, and represents an important advance in methodology. The results indicate alterations in recognition memory processing, which even if not manifesting in overt behavioral impairment, underline the potential for brain dysfunction with early exposure to alcohol and cannabis.

Online computer-aided vicarious exposure for OCD symptoms: A pilot study.

BACKGROUND AND OBJECTIVES: Computer-aided vicarious exposure (CAVE) for obsessive-compulsive disorder (OCD) is an intervention in which participants learn and rehearse exposure with response prevention (ERP) by directing a character around a virtual world. This study aimed to pilot an online CAVE program for OCD in a community sample with high OCD symptomatology. METHODS: Participants (n = 78) were allocated to an intervention group (three 45-min weekly CAVE sessions) or to a waitlist control group. The treatment group were asked to complete three 45-min sessions over a four week period. RESULTS: Those who completed at least one CAVE session showed greater improvement on measures of OCD symptomatology at one-month post-treatment (d = 0.49-0.81) compared to waitlist (d = 0.01-0.1). Older age, past treatment and higher symptom severity were associated with non-adherence. LIMITATIONS: These findings should be considered preliminary due to sample size limitations and an absence of an active control group. However, the findings suggest that further development and evaluation of the program is warranted. CONCLUSIONS: Preliminary findings suggest that online CAVE programs have potential to bridge treatment gaps among those reluctant to attend treatment or engage with in vivo exposure exercises. These programs may also have potential applications as an adjunct to face-to-face or online cognitive behavioural therapy.

Habituation of self-reported anxiety and cortical hyper-vigilance during image-based exposure to spiders.

BACKGROUND AND OBJECTIVES: The aim of the study was to examine habituation of subjective anxiety and electrophysiological correlates of cortical hyper-vigilance during exposure to spider images among high (n = 12) and low (n = 11) spider fear groups. METHODS: Participants viewed a six-stage hierarchy of spider images. The images used at stage 1 and stage 6 were the same. Subjective anxiety was rated at four intervals during each three-minute exposure stage (0, 60, 120, and 180 s) and event-related potentials (ERPs) were averaged across these epochs (0-60, 60-120, 120-180). RESULTS: High spider fearfuls demonstrated greater habituation of self-reported anxiety within and between exposure stages compared to low fearfuls. Consistent with attentional hyper-vigilance, the high-fear group also demonstrated greater P1 amplitude in response to spider images. In both groups, habituation of P1 amplitude was found at later relative to earlier stages, but increased at stage six when the stage 1 image was re-presented, despite low subjective anxiety. LIMITATIONS: While the passive viewing paradigm mirrored image-based exposure, it was not possible to determine whether participants engaged in avoidance strategies. In addition, further research is needed to assess the relevance of habituation and reinstatement of P1 amplitude to therapeutic outcome. CONCLUSIONS: Habituation of subjective anxiety during image-based exposure is not necessarily accompanied by a reduction in measures of cortical hyper-vigilance. The reinstatement of the P1 response may indicate either re-activation of previous associations, less avoidance, or a more generalised dishabituation mechanism.

Is khat use disorder a valid diagnostic entity?

AIMS: This study aimed to validate the presence of a khat use disorder syndrome using DSM-5 criteria and to examine its relationship with increased experience of harms. DESIGN: Cross-sectional, purposive sample of current khat-chewers, recruited from khat markets and cafes. SETTING: Participants were recruited from the general community and from Adama Science and Technology University in Ethiopia. PARTICIPANTS: A total of 400 current khat consumers aged 16 and above were recruited between September 2014 and January 2015 MEASURES: Survey comprising current clinical symptoms (using a modified Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV), and validated measures of health, psychological distress, quality of life and academic functioning. FINDINGS: A third [35.5% 95% confidence interval (CI) = 31.0-40.3] of respondents reported daily khat use and a quarter (25.4% 95% CI = 21.4-30.0) using three times or more per week. Using DSM-5 criteria, 10.5% (95% CI = 7.9-13.9) were categorized as experiencing mild, 8.8% (95% CI = 6.4-12.0) moderate and 54.5% (95% CI = 49.6-59.3) severe khat use disorder. Confirmatory factor analysis demonstrated a good fit of symptoms to a single underlying construct, consistent with other substance use disorders. Individuals categorized as experiencing khat use disorder demonstrated significantly greater frequency [odds ratio (OR) = 45.29; 95% CI = 10.97-19.01) and quantity of khat use (OR = 2.35; 95% CI = 1.29-4.29). They also demonstrated increased financial problems associated with use, greater problems with academic functioning and higher rates of self-reported mental health problems, higher psychological distress and poorer quality of life. Treatment access was poor, with only one-third (32.9%) of individuals with khat use disorder reporting life-time access, near-exclusively related to help-seeking from friends and relatives. CONCLUSION: The construct of a substance use disorder syndrome for khat using DSM-5 criteria appears valid and performs in a manner consistent with other substances of dependence. Individuals with khat use disorder experience substantial problems in association with khat use. Despite this, there are low levels of help-seeking for these problems.

STAT3 restrains RANK- and TLR4-mediated signalling by suppressing expression of the E2 ubiquitin-conjugating enzyme Ubc13.

The transcriptional regulator STAT3 curbs pro-inflammatory cytokine production mediated by NF-κB signalling in innate immune cells, yet the mechanism by which this occurs has been unclear. Here we identify STAT3 as a pivotal negative regulator of Ubc13, an E2 ubiquitin-conjugating enzyme that facilitates TRAF6 K63-linked ubiquitination and NF-κB activation. Ubc13 accumulates intracellularly in the absence of STAT3. Depletion of Ubc13 in Stat3-deficient macrophages subdues excessive RANKL- or LPS-dependent gene expression, indicating that Ubc13 overexpression mediates enhanced transcriptional responses in the absence of STAT3. In RANKL-activated macrophages, STAT3 is stimulated by autocrine IL-6 and inhibits accrual of Ets-1, Set1 methyltransferase and trimethylation of histone H3 lysine 4 (H3K4me3) at the Ube2n (Ubc13) promoter. These results delineate a mechanism by which STAT3 operates as a transcriptional repressor on Ube2n, thus modulating NF-κB activity by regulation of Ubc13 abundance. Our data suggest that this pathway plays important roles in bone homeostasis and restraint of inflammation.

Emerging psychoactive substance use among regular ecstasy users in Australia.

BACKGROUND: The past decade has seen the development of an array of emerging psychoactive substances (EPS), however, there is minimal information on the extent of their use outside Europe. This study aimed to determine the extent of use of EPS from stimulant (such as mephedrone) and psychedelic classes (such as 5-methoxy-dimethyltryptamine [5-MeO-DMT]) among an Australian sample of regular ecstasy users (REU). Further, to determine if consumers of these drugs represent a distinct subgroup of REU. METHODS: Australian national cross-sectional surveys of 693 regular (at least monthly) ecstasy users conducted during 2010. RESULTS: More than one quarter (28%) of REU had used an EPS in the past six months, most commonly from the stimulant class (20%, typically mephedrone, 17%) rather than the psychedelic class (13%). Demographics and risk behaviours of REU that used stimulant EPS were largely no different from non-EPS consuming REU. Those using psychedelic EPS were distinct, initiating ecstasy use earlier, more frequently using multiple substances (cannabis, inhalants, GHB, ketamine) and more commonly experiencing legal, psychological and social problems. CONCLUSIONS: Psychedelic EPS use appears largely restricted to a distinct subset of REU with high-level non-injecting polydrug use, but use appears generally limited. The demographic similarity of stimulant EPS consumers with 'mainstream' REU, in conjunction with positive responses to the psychoactive effects of these drugs and declining ecstasy purity, suggests strong potential for stimulant EPS to expand further into ecstasy markets. Such drugs may have a greater public health impact than ecstasy, and merit careful monitoring into the future.

Can the severity of dependence scale be usefully applied to 'ecstasy'?

BACKGROUND/AIMS: Although use of 'ecstasy' (drugs sold as containing 3,4-methylenedioxymethamphetamine) is prevalent, it is typically infrequent, and treatment presentations involving ecstasy as a principal problem drug are relatively rare. Human case reports and animal literature suggest dependence potential, although there may be some unique aspects to this syndrome for ecstasy in comparison to other substances. The Severity of Dependence Scale (SDS) was examined to determine whether this could usefully identify 'dependent' ecstasy consumers. METHODS: We conducted a cross-sectional survey of 1,658 frequent (at least monthly) ecstasy consumers across Australia, assessing drug use, associated harms and risk behaviours. Dependence was evaluated with the SDS, using a cut-off of > or =4 to identify potential 'dependence'. RESULTS: One fifth of the participants were screened as potentially dependent. These individuals used ecstasy more frequently, in greater amounts, engaged more extensively in risk behaviours and reported greater role interference than other participants. These findings were independent of methamphetamine use or dependence. The underlying structure of the ecstasy SDS was bifactorial. CONCLUSIONS: The SDS has demonstrated construct validity as a screening tool to identify ecstasy users at elevated risk of experiencing adverse consequences, including features of dependence. The underlying structure of dependence symptoms differs for ecstasy compared to other drug classes, and some dependent consumers use the drug infrequently. The unique neurotoxic potential and entactogenic effects of ecstasy may require a distinct nosological classification for the experience of dependence associated with the drug.