Long-term neuropsychological effects of ecstasy in middle-aged ecstasy/polydrug users

RATIONALE: Studies reporting ecstasy-induced serotonin-toxicity and (neuro)psychological dysfunctions have been conducted in young adults. Little is known about ecstasy effects later in life, when serotonin levels and cognition decrease as a consequence of normal ageing. OBJECTIVE: This study aimed to assess whether harmful effects of ecstasy only add to or also interact with age-related neuropsychological decline. METHODS: Attention, verbal and visual memory, visuospatial ability, self-reported depression, sensation-seeking and impulsivity were assessed in middle-aged moderate to heavy ecstasy/polydrug users (n = 17) and compared with none or very mild ecstasy using polydrug users (matched for age, gender, intelligence and other drugs; n = 16) and a group of drug-naive controls (n = 20). RESULTS: Moderate to heavy ecstasy/polydrug users performed significantly worse on a verbal memory task than none or very mild ecstasy using polydrug users and drug naives. Moderate and heavy ecstasy/polydrug users also differed significantly from drug-naives on measures of depression, sensation-seeking and impulsivity but not from none or very mild ecstasy-using polydrug users. CONCLUSION: This study in middle-aged ecstasy/polydrug users replicated findings of studies in younger ecstasy users, showing a harmful effect of ecstasy on verbal memory. There was no clear support for an interaction between harmful effects of ecstasy use and age-related memory decline or mid-life depressio

Longitudinal hypothalamic-pituitary-adrenal axis trait and state effects in recurrent depression

SummaryBackgroundHypothalamic–pituitary–adrenal (HPA)-axis hyperactivity has been observed in (recurrent) major depressive disorder (MDD), although inconsistently and mainly cross-sectional. Longitudinal studies clarifying state-trait issues are lacking. We aimed to determine whether HPA-axis (hyper)activity in recurrent MDD is: (I) reflecting a persistent trait; (II) influenced by depressive state; (III) associated with stress or previous episodes; (IV) associated with recurrence; and (V) influenced by cognitive therapy.MethodsWe included 187 remitted highly recurrent MDD-patients (mean number of previous episodes: 6.3), participating in a randomized-controlled-trial investigating the preventive effect of additional cognitive therapy on recurrence. In an add-on two-staged patient-control and prospective-cohort design, we first cross-sectionally compared patients’ salivary morning and evening cortisol concentrations with 72 age- and sex-matched controls, and subsequently longitudinally followed-up the patients with repeated measures after three months and two years.ResultsPatients had higher cortisol concentrations than controls (p<.001), which did not change by MDD-episodes during follow-up. HPA-axis activity had no relation with daily hassles or childhood life events. Cortisol concentrations were lower in patients with more previous episodes (p=.047), but not associated with recurrence(s) during follow-up. Finally, randomly assigned cognitive therapy at study-entry enhanced cortisol declines over the day throughout the two-year follow-up (p=.052).ConclusionsOur results indicate that remitted recurrent MDD-patients have a persistent trait of increased cortisol concentrations, irrespective of stress. In combination with our finding that patients’ cortisol concentrations do not change during new MDD-episodes (and thus not represent epiphenomenal or state-effects), our results support that hypercortisolemia fulfills the state-independence criterion for an endophenotype for recurrent depression

Vulnerability for new episodes in recurrent major depressive disorder:protocol for the longitudinal DELTA-neuroimaging cohort study

Introduction Major depressive disorder (MDD) is widely prevalent and severely disabling, mainly due to its recurrent nature. A better understanding of the mechanisms underlying MDD-recurrence may help to identify high-risk patients and to improve the preventive treatment they need. MDD-recurrence has been considered from various levels of perspective including symptomatology, affective neuropsychology, brain circuitry and endocrinology/metabolism. However, MDD-recurrence understanding is limited, because these perspectives have been studied mainly in isolation, cross-sectionally in depressed patients. Therefore, we aim at improving MDD-recurrence understanding by studying these four selected perspectives in combination and prospectively during remission.Methods and analysis In a cohort design, we will include 60 remitted, unipolar, unmedicated, recurrent MDD-participants (35-65years) with 2 MDD-episodes. At baseline, we will compare the MDD-participants with 40 matched controls. Subsequently, we will follow-up the MDD-participants for 2.5years while monitoring recurrences. We will invite participants with a recurrence to repeat baseline measurements, together with matched remitted MDD-participants. Measurements include questionnaires, sad mood-induction, lifestyle/diet, 3T structural (T1-weighted and diffusion tensor imaging) and blood-oxygen-level-dependent functional MRI (fMRI) and MR-spectroscopy. fMRI focusses on resting state, reward/aversive-related learning and emotion regulation. With affective neuropsychological tasks we will test emotional processing. Moreover, we will assess endocrinology (salivary hypothalamic-pituitary-adrenal-axis cortisol and dehydroepiandrosterone-sulfate) and metabolism (metabolomics including polyunsaturated fatty acids), and store blood for, for example, inflammation analyses, genomics and proteomics. Finally, we will perform repeated momentary daily assessments using experience sampling methods at baseline. We will integrate measures to test: (1) differences between MDD-participants and controls; (2) associations of baseline measures with retro/prospective recurrence-rates; and (3) repeated measures changes during follow-up recurrence. This data set will allow us to study different predictors of recurrence in combination.Ethics and dissemination The local ethics committee approved this study (AMC-METC-Nr.:11/050). We will submit results for publication in peer-reviewed journals and presentation at (inter)national scientific meetings.Trial registration number NTR3768.</p

Statistical Methodological Issues in Handling of Fatty Acid Data: Percentage or Concentration, Imputation and Indices

Basic aspects in the handling of fatty acid-data have remained largely underexposed. Of these, we aimed to address three statistical methodological issues, by quantitatively exemplifying their imminent confounding impact on analytical outcomes: (1) presenting results as relative percentages or absolute concentrations, (2) handling of missing/non-detectable values, and (3) using structural indices for data-reduction. Therefore, we reanalyzed an example dataset containing erythrocyte fatty acid-concentrations of 137 recurrently depressed patients and 73 controls. First, correlations between data presented as percentages and concentrations varied for different fatty acids, depending on their correlation with the total fatty acid-concentration. Second, multiple imputation of non-detects resulted in differences in significance compared to zero-substitution or omission of non-detects. Third, patients’ chain length-, unsaturation-, and peroxidation-indices were significantly lower compared to controls, which corresponded with patterns interpreted from individual fatty acid tests. In conclusion, results from our example dataset show that statistical methodological choices can have a significant influence on outcomes of fatty acid analysis, which emphasizes the relevance of: (1) hypothesis-based fatty acid-presentation (percentages or concentrations), (2) multiple imputation, preventing bias introduced by non-detects; and (3) the possibility of using (structural) indices, to delineate fatty acid-patterns thereby preventing multiple testing

Using the Autism-Spectrum Quotient to Discriminate Autism Spectrum Disorder from ADHD in Adult Patients With and Without Comorbid Substance Use Disorder

It is unknown whether the Autism-spectrum quotient (AQ) can discriminate between Autism Spectrum Disorder (ASD) and Attention Deficit and Hyperactivity Disorder (ADHD) with or without comorbid Substance Use Disorder (SUD). ANOVA’s were used to analyse the mean AQ (sub)scores of 129 adults with ASD or ADHD. We applied receiver operating characteristic (ROC) computations to assess discriminant power. All but one of the mean AQ (sub)scores were significantly higher for adults with ASD compared to those with ADHD. The SUD status in general was not significantly associated with AQ (sub)scores. On the Social Skills subscale patients with ASD and comorbid SUD showed less impairment than those without SUD. The cut-off score 26 yielded 73% correct classifications. The clinical use of the AQ in differentiating between ASD and ADHD is limited

Towards a New Definition of Return-to-Work Outcomes in Common Mental Disorders from a Multi-Stakeholder Perspective

Objectives: To examine the perspectives of key stakeholders involved in the return-to-work (RTW) process regarding the definition of successful RTW outcome after sickness absence related to common mental disorders (CMD's). Methods: A mixed-method design was used: First, we used qualitative methods (focus groups, interviews) to identify a broad range of criteria important for the definition of successful RTW (N = 57). Criteria were grouped into content-related clusters. Second, we used a quantitative approach (online questionnaire) to identify, among a larger stakeholder sample (N = 178), the clusters and criteria most important for successful RTW. Results: A total of 11 clusters, consisting of 52 unique criteria, were identified. In defining successful RTW, supervisors and occupational physicians regarded "Sustainability'' and "At-work functioning" most important, while employees regarded "Sustainability," "Job satisfaction," "Work-home balance,'' and " Mental Functioning" most important. Despite agreement on the importance of certain criteria, considerable differences among stakeholders were observed. Conclusions: Key stakeholders vary in the aspects and criteria they regard as important when defining successful RTW after CMD-related sickness absence. Current definitions of RTW outcomes used in scientific research may not accurately reflect these key stakeholder perspectives. Future studies should be more aware of the perspective from which they aim to evaluate the effectiveness of a RTW intervention, and define their RTW outcomes accordingly

Evaluating real-time internet therapy and online self-help for problematic alcohol consumers: a three-arm RCT protocol

<p>Abstract</p> <p>Background</p> <p>Only a minority of all alcohol- and drug abusers is receiving professional care. In an attempt to narrow this treatment gap, treatment facilities experiment with online healthcare. Therefore, it is important to test the (cost-)effectiveness of online health interventions in a randomized clinical trial.</p> <p>Methods</p> <p>This paper presents the protocol of a three-arm randomized clinical trial to test the (cost-) effectiveness of online treatment for problem drinkers. Self-help online, therapy online and a waiting list are tested against each other. Primary outcome is change in alcohol consumption. Secondary outcome measures include quality of life and working ability. Incremental cost-effectiveness ratios for self-help online alcohol and therapy online alcohol will be calculated. The predictive validity of participant characteristics on treatment adherence and outcome will be explored.</p> <p>Discussion</p> <p>To our best knowledge, this randomized clinical trial will be the first to test the effectiveness of therapy online against both self-help online and a waiting-list. It will provide evidence on (cost-) effectiveness of online treatment for problem drinkers and investigate outcome predictors.</p> <p>Trial registration</p> <p>This trial is registered in the Dutch Trialregister (Cochrane Collaboration) and traceable as NTR-TC1155.</p

Decision making as a predictor of first ecstasy use: a prospective study

Ecstasy (+/- 3,4-methylenedioxymethamphetamine) is a widely used recreational drug that may damage the serotonin system and may entail neuropsychological dysfunctions. Few studies investigated predictors for ecstasy use. Self-reported impulsivity does not predict the initiation of ecstasy use; the question is if neuropsychological indicators of impulsivity can predict first ecstasy use. This study tested the hypothesis that a neuropsychological indicator of impulsivity predicts initiation of ecstasy use. Decision-making strategy and decision-making reaction times were examined with the Iowa Gambling Task in 149 ecstasy-naive subjects. The performance of 59 subjects who initiated ecstasy use during a mean follow-up period of 18 months (range, 11-26) was compared with the performance of 90 subjects that remained ecstasy-naive. Significant differences in decision-making strategy between female future ecstasy users and female persistent ecstasy-naive subjects were found. In addition, the gap between decision-making reaction time after advantageous choices and reaction time after disadvantageous choices was smaller in future ecstasy users than in persistent ecstasy-naives. Decision-making strategy on a gambling task was predictive for future use of ecstasy in female subjects. Differences in decision-making time between future ecstasy users and persistent ecstasy-naives may point to lower punishment sensitivity or higher impulsivity in future ecstasy users. Because differences were small, the clinical relevance is questionabl

Persistence and Subtype Stability of ADHD Among Substance Use Disorder Treatment Seekers

OBJECTIVE: To examine ADHD symptom persistence and subtype stability among substance use disorder (SUD) treatment seekers. METHOD: In all, 1,276 adult SUD treatment seekers were assessed for childhood and adult ADHD using Conners' Adult ADHD Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; CAADID). A total of 290 (22.7%) participants met CAADID criteria for childhood ADHD and comprise the current study sample. RESULTS: Childhood ADHD persisted into adulthood in 72.8% (n = 211) of cases. ADHD persistence was significantly associated with a family history of ADHD, and the presence of conduct disorder and antisocial personality disorder. The combined subtype was the most stable into adulthood (78.6%) and this stability was significantly associated with conduct disorder and past treatment of ADHD. CONCLUSION: ADHD is highly prevalent and persistent among SUD treatment seekers and is associated with the more severe phenotype that is also less likely to remit. Routine screening and follow-up assessment for ADHD is indicated to enhance treatment management and outcomes