The influence of psychological traits and prior experience on treatment expectations.

BACKGROUND: Placebo and nocebo responses are modulated by the treatment expectations of participants and patients. However, interindividual differences predicting treatment expectations and placebo responses are unclear. In this large-scale pooled analysis, we aim to investigate the influence of psychological traits and prior experiences on treatment expectations. METHODS: This paper analyses data from six different placebo studies (total n = 748). In all studies, participants' sociodemographic information, treatment expectations and prior treatment experiences and traits relating to stress, somatization, depression and anxiety, the Big Five and behavioral inhibition and approach tendencies were assessed using the same established questionnaires. Correlation coefficients and structural equation models were calculated to investigate the relationship between trait variables and expectations. RESULTS: We found small positive correlations between side effect expectations and improvement expectations (r = 0.187), perceived stress (r = 0.154), somatization (r = 0.115), agitation (r = 0.108), anhedonia (r = 0.118), and dysthymia (r = 0.118). In the structural equation model previous experiences emerged as the strongest predictors of improvement (ß = 0.32, p = .005), worsening (ß = -0.24, p = .005) and side effect expectations (ß = 0.47, p = .005). Traits related to positive affect (ß = - 0.09; p = .007) and negative affect (ß = 0.04; p = .014) were associated with side effect expectations. DISCUSSION: This study is the first large analysis to investigate the relationship between traits, prior experiences and treatment expectations. Exploratory analyses indicate that experiences of symptom improvement are associated with improvement and worsening expectations, while previous negative experiences are only related to side effect expectations. Additionally, a proneness to experience negative affect may be a predictor for side effect expectation and thus mediate the occurrence of nocebo responses.

Study protocol: the pragmatic, exploratory DELTA-JU trial of the group-based multimodal DELTA intervention for abstinent adolescents with substance use disorders living in youth welfare institutions.

Background: The DELTA intervention contains 16 weekly group sessions plus additional individual sessions and educational session for parents. It aims to reduce substance use and related problems such as substance use disorders (SUD) in adolescents. Recent results indicated positive effects in psychiatric outpatients. Conducting DELTA in youth welfare settings seems feasible, however, organizational and content adjustments such as smoking cessation elements should be added in order to reduce relapse risks and to prevent negative health consequences. Methods/design: The pre-registered DELTA-JU study (German Clinical Trials Register, DRKS00027913) is separated into three stages: In the adjustment stage during months 1-4, we will revise the DELTA manual based on semi-structured interviews (n = 10) with personnel from youth welfare institutions specialized in serving adolescents with SUD in the study region, analyzed with content analysis. In the sampling stage during months 5-22, participants qualifying for a SUD and willing to regularly participate in the 16 weekly DELTA-JU group sessions will be enrolled to either one of two arms (cluster randomization: immediate intervention, waitlist with subsequent intervention 16 weeks later). Adolescents will be assessed at baseline and follow-up (16 weeks after first group session) with an additional pre-assessment (16 weeks before intervention starts) for the waitlist group. Assessment procedures include questionnaires and clinical interviews among others. At the same time, institutional personnel will receive a 1-day workshop on SUD-relevant topics based on the DELTA parental education group and on feedback from the qualitative interviews. Personnel will also be assessed twice with questionnaires. In the dissemination stage during months 23-24, final study evaluation results will be prepared and submitted for publication. Discussion: This study will create a setting-specific manual for vulnerable adolescents suffering from SUDs, and, in many cases, from co-occurring mental disorders. If shown to be effective, DELTA-JU can be disseminated within other institutions of youth welfare.

Comparing self-report and parental report of psychopathologies in adolescents with substance use disorders.

Both internalizing and externalizing psychopathologies interfere with the treatment of substance use disorders (SUD) in adolescents. Self-reports of psychopathologies are likely biased and may be validated with parental reports. We compared N = 70 standardized self-reports of adolescents entering outpatient SUD treatment (13.2-18.6 years old, 43% female) to parental reports on the same psychopathologies, and explored biases due to gender, age, SUD diagnoses and SUD severity. Bivariate bootstrapped Pearson correlation coefficients revealed several small to moderate correlations between both reporting sources (r = 0.29-0.49, all pcorrected ≤ 0.039). A repeated measures MANOVA revealed moderately stronger parental reports of adolescent psychopathologies compared to adolescent self-reports for most externalizing problems (dissocial and aggressive behaviors, p ≤ 0.016, η2part = 0.09-0.12) and social/attention problems (p ≤ 0.012, η2part = 0.10), but no differences for most internalizing problems (p ≥ 0.073, η2part = 0.02-0.05). Differences were not associated with other patient or parental characteristics including age, gender, number of co-occurring diagnoses or presence/absence of a certain SUD (all puncorrected ≥ 0.088). We concluded that treatment-seeking German adolescents with SUD present with a multitude of extensive psychopathologies. The relevant deviation between self- and parental reports indicate that the combination of both reports might help to counteract dissimulation and other reporting biases. The generalizability of results to inpatients, psychiatry patients in general, or adolescents without SUD, as well as the validity of self- and parental reports in comparison to clinical judgements remain unknown.

Evaluation of the multimodal DELTA therapy for adolescents with substance use disorders: an exploratory pilot trial.

Background: In order to address the lack of manualized treatment programs for adolescents with substance use disorders (SUDs), we developed a manualized group intervention (DELTA). DELTA focusses on substance use reduction and abstinence as well as alleviation of SUD symptoms via additional modules for co-occurring disorders. The goal of this exploratory trial was to assess if DELTA can be conducted in adolescent SUD patients and if participation is related to reductions in substance use, SUD-related problems, and further psychopathologies. Method: We recruited adolescents at a psychiatric outpatient unit, which were then allocated to either DELTA intervention group (N = 85) or to a waiting-list control group (WL, N = 61) based on parental decision to start a therapy or not. Self-report measures were used as primary outcomes (substance use via interview, use-related problems via DUDIT-Drug Use Disorder Identification Test) and secondary outcomes (psychopathologies via YSR-Youth Self Report). T-tests and Pearson correlations were used to analyze between-group differences across time. Results: On average, participants attended M = 7.7 (SD = 5.1) of the 16 sessions. Substance use and use-related problems regarding all substances but nicotine was decreased after the intervention, with small to medium not significant effects in favor of DELTA. Self-reported psychopathologies were also reduced at follow-up, with non-significant advantages for DELTA. Conclusion: DELTA showed small effects on SUD-related and depression-related variables. However, the interpretation is limited by the small sample size. Nonetheless, the DELTA intervention is viable in SUD outpatient treatment and will be further evaluated.Clinical trial registration: The study was registered at clinicaltrials.gov under NCT03444974. Registered February, 26th 2018 (https://clinicaltrials.gov/ct2/show/NCT03444974).

Are perinatal measures associated with adolescent mental health? A retrospective exploration with original data from psychiatric cohorts.

BACKGROUND: Perinatal markers of prenatal development are associated with offspring psychiatric symptoms. However, there is little research investigating the specificity of perinatal markers for the development of specific disorders. This study aimed to explore if perinatal markers are specifically associated with adolescent substance use disorder (SUDs). METHODS: Adolescent participants from two study centers, one for SUD patients (n = 196) and one for general psychopathology (n = 307), were recruited for participation. Since the SUD participants presented with a number of comorbid disorders, we performed a 1-on-1 matching procedure, based on age, gender, and specific pattern of comorbid disorders. This procedure resulted in n = 51 participants from each group. From all participants and their mothers we recorded perinatal markers (mode of birth, weeks of completed pregnancy, birth weight, Apgar score after 5 min) as well as intelligence quotient (IQ). The SUD sample additionally filled out the Youth Safe Report (YSR) as well as the PQ-16 and the DUDIT. We aimed to distinguish the two groups (SUD sample vs. general psychiatric sample) based on the perinatal variables via a logistic regression analysis. Additionally, linear regressions were performed for the total group and the subgroups to assess the relationship between perinatal variables and IQ, YSR, DUDIT and PQ-16. RESULTS: The perinatal variables were not able to predict group membership (X2 [4] = 4.77, p = .312, Cox & Snell R² = 0.053). Odds ratios indicated a small increase in probability to belonging to the general psychiatric sample instead of the SUD sample if birth was completed via C-section. After Bonferroni-correction, the linear regression models showed no relation between perinatal markers and IQ (p = .60, R² = 0.068), YSR (p = .09, R² = 0.121), DUDIT (p = .65, R² = 0.020), and PQ-16 (p = .73, R² =0.021). CONCLUSION: Perinatal markers were not able to distinguish SUD patients from patients with diverse psychopathologies. This pattern contradicts previous findings, perhaps because our chosen markers reflect general processes instead of specific mechanistic explanations. Future studies should take care to investigate specific prenatal markers and associate them with psychopathology on the symptom level.

Motives for the use of serotonergic psychedelics: A systematic review.

ISSUES: Serotonergic psychedelics (SP) are psychoactive substances that produce unique sets of subjective effects, such as hallucinatory experiences. This systematic review is the first to summarise which motives for SP use have been assessed in medical, psychological, sociological and ethnological research across different types of SPs and across cultural backgrounds. Findings on use motives can be especially important in the context of harm reduction. APPROACH: We searched academic databases (Medline, Web of Science and Embase) and included publications if they were peer-reviewed and written in English, German, Spanish or Dutch. We analysed which type of motives were reported, comparing motives from quantitative and qualitative reports, and investigating associations between motives and year of publication, specific SPs and specific participant populations. KEY FINDINGS: Our search in November 2020 resulted in 30,257 unique articles of which 37 were included in the analysis. Across all studies, the most common motive for SP use was the desire to expand awareness (78% of included studies), followed by coping (67%) and enhancement (57%) motives. There were no statistically significant associations between reported motive and type of report (quantitative vs. qualitative), year of publication (range: 1967-2020), type of SP and participant population. IMPLICATIONS: If SP-related harms are to be reduced, harm-reduction services could focus on providing non-pharmacological ways of fulfilling an expansion motive. Additionally, future studies should aim to assess specific motives for specific SPs. CONCLUSIONS: SPs are most commonly used to expand (self-)knowledge, promote spiritual development or for curiosity, notably across different SP user populations including patients.

Neuropsychological Functioning in Users of Serotonergic Psychedelics - A Systematic Review and Meta-Analysis.

Background: Serotonergic psychedelics (SPs) like LSD, psilocybin, DMT, and mescaline are a heterogeneous group of substances that share agonism at 5-HT2a receptors. Besides the ability of these substances to facilitate profoundly altered states of consciousness, persisting psychological effects have been reported after single administrations, which outlast the acute psychedelic effects. In this review and meta-analysis, we investigated if repeated SP use associates with a characteristic neuropsychological profile indicating persisting effects on neuropsychological function. Methods: We conducted a systematic review of studies investigating the neuropsychological performance in SP users, searching studies in Medline, Web of Science, embase, ClinicalTrials.gov, and EudraCT. Studies were included if they reported at least one neuropsychological measurement in users of SPs. Studies comparing SP users and non-users that reported mean scores and standard deviations were included in an exploratory meta-analysis. Results: 13 studies (N = 539) published between 1969 and 2020 were included in this systematic review. Overall, we found that only three SPs were specifically investigated: ayahuasca (6 studies, n = 343), LSD (5 studies, n = 135), and peyote (1 study, n = 61). However, heterogeneity of the methodological quality was high across studies, with matching problems representing the most important limitation. Across all SPs, no uniform pattern of neuropsychological impairment was identified. Rather, the individual SPs seemed to be associated with distinct neuropsychological profiles. For instance, one study (n = 42) found LSD users to perform worse in trials A and B of the Trail-Making task, whereas meta-analytic assessment (5 studies, n = 352) of eleven individual neuropsychological measures indicated a better performance of ayahuasca users in the Stroop incongruent task (p = 0.03) and no differences in the others (all p > 0.05). Conclusion: The majority of the included studies were not completely successful in controlling for confounders such as differences in non-psychedelic substance use between SP-users and non-users. Our analysis suggests that LSD, ayahuasca and peyote may have different neuropsychological consequences associated with their use. While LSD users showed reduced executive functioning and peyote users showed no differences across domains, there is some evidence that ayahuasca use is associated with increased executive functioning.

Diagnostic Accuracy of the Drug Use Disorder Identification Test and Its Short Form, the DUDIT-C, in German Adolescent Psychiatric Patients.

BACKGROUND: A common screening instrument for substance use disorders (SUDs) is the Drug Use Disorders Identification Test (DUDIT) which includes a short form regarding only drug consumption (DUDIT-C). We aim to assess if a German version of the DUDIT, adapted for adolescents, is a suitable screening instrument in a sample of adolescent psychiatric patients. METHODS: N = 124 (54 female) German adolescent (M = 15.6 + 1.5 years) psychiatric patients completed the DUDIT and received a diagnostic interview (MINI-KID) assessing DSM-5 SUD criteria. A confirmatory factor analysis (CFA), receiver operating characteristic (ROC) curves, the area under the curve (AUC), and Youden's Index were calculated. RESULTS: A two-factor model of the DUDIT shows the best model fit (CFI = 0.995, SRMR = 0.055, RMSEA = 0.059, WRMR = 0.603). The DUDIT as well as the DUDIT-C show high diagnostic accuracy, with AUC = 0.95 and AUC = 0.88, respectively. For the DUDIT a cut-off value of 8.5 was optimal (sensitivity = 0.93, specificity = 0.91, J = 0.84), while for the DUDIT-C the optimal cut-off value was at 1.5 (sensitivity = 0.86, specificity = 0.84, J = 0.70). CONCLUSION: This is the first psychometric evaluation of the DUDIT in German, adolescent psychiatric outpatients, using the DSM-5 diagnostic criteria. The DUDIT as well as the DUDIT-C are well suited for use in this population. Since in our sample only few patients presented with a mild or moderate SUD, our results need to be replicated in a sample of adolescents with mild SUD.

Beyond the tip of the iceberg: A narrative review to identify research gaps on comorbid psychiatric disorders in adolescents with methamphetamine use disorder or chronic methamphetamine use.

BACKGROUND: Methamphetamine use disorder (MUD) frequently begins in adolescence, often accompanied by other psychiatric or mental disorders. Up to now, no comprehensive review about MUD and comorbid disorders in adolescents is available. We thus aimed to review the literature on comorbid mental disorders and MUD in adolescents in order to identify future research topics. Method: A PubMed search was conducted in July 2019. Relevant comorbidities were defined as attention-deficit disorder with/without hyperactivity, anxiety disorders, depression, eating disorders, post-traumatic stress disorder, psychosis, borderline personality disorder, conduct disorder and antisocial personality disorder, as well as other substance use disorders. For each comorbidity, we summarized prevalence rates, findings on comorbidity mechanisms, and recommended treatment options, if applicable. Results: Few articles focused on MUD in adolescents. Prevalence rates differed largely between comorbid disorders, with tobacco use disorder, conduct disorder, post-traumatic stress disorder, anxiety disorders, and attention-deficit disorders being the most prevalent comorbidities while eating disorders were rare. Examined onset patterns and comorbidity mechanisms indicated three groups of comorbidities: preexisting disorders self-medicated with methamphetamine, disorders induced by chronic methamphetamine use, and disorders arising due to risk factors shared with MUD. Reviewed comorbidities were frequently associated with worse treatment outcomes. Conclusions: The limited evidence is in stark contrast to the presumably high prevalence and relevance of comorbid mental disorders in adolescents with MUD. Suggestions for future research topics, informed by adult findings, include genetic vulnerabilities, biological changes, and consequences of different use patterns. Surprisingly few MUD treatment programs explicitly integrate comorbid mental disorder modules.

Attenuated Psychotic Symptoms in Adolescents With Chronic Cannabis and MDMA Use.

OBJECTIVES: Both substance use, on the one hand, and the first signs of psychosis, on the other, commonly begin in adolescence. Adolescents with substance use disorder (SUD) frequently show recreational use of cannabis and 3,4-methylenedioxymethamphetamine (MDMA). When attenuated psychotic symptoms (APS) occur during the course of SUD, they are commonly attributed to the cannabis use, neglecting the role of other substances abused, such as MDMA in the risk of psychosis. METHODS: We analyzed retrospective self-reports on APS (Prodromal Questionnaire, PQ-16) and amount of cannabis and MDMA use in n = 46 adolescent psychiatry outpatients with SUD. N = 17 (35%) individuals reported MDMA consume additional to cannabis. Furthermore, we examined the associations of APS with cannabis and MDMA use in stepwise hierarchical regressions while controlling for trauma history, birth complications and gender. RESULTS: APS were not related to cannabis (B = 0.04, p = 0.842), but to MDMA use (B = 4.88, p = 0.001) and trauma history (B = 0.72, p = 0.001). Gender (B = -0.22, p = 0.767) and birth complications (B = -0.68, p = 0.178) were not associated with APS. DISCUSSION: Our results indicate that MDMA use additional to cannabis use is associated with APS among adolescent SUD patients. Contrary to our expectations, we did not see an association of cannabis use and APS. We speculate that cannabis increases the risk for psychosis after a longer period of use and in combination with other risk factors, such as trauma history. Clinicians should screen for APS among SUD patients using MDMA and cannabis in order to adapt treatment plans of SUDs. Future research should validate these findings in longitudinal studies including polysubstance use and trauma history.

Traumatic Events and Substance Use Disorders in Adolescents.

OBJECTIVES: Adolescents with substance use disorders (SUD) frequently report traumatic events (TEs) and symptoms of post-traumatic stress disorder (PTSD). This study aimed to assess whether lifetime prevalence rates of TEs and PTSD are related to SUD severity in adolescent psychiatric patients. METHODS: We analyzed N = 114 self-reports of treatment-seeking German adolescents aged 12 to 18 years, who visited a specialized SUD outpatient unit. Standardized questionnaires were applied to assess SUD severity, the number of TEs and DSM-IV PTSD criteria. RESULTS: Patients fulfilling PTSD criteria (28% of the total sample) had a higher Drug Use Disorders Identification Test (DUDIT) score compared to non-PTSD patients with TEs (p <.001), and compared to adolescents without TEs or PTSD (p = .003). Additionally, SUD severity was positively associated with the number of TEs and the number of intrusion, hyperarousal, and avoidance symptoms (all r = .33 to.48, all p <.01). DISCUSSION: Adolescent patients with SUD reported 3-times higher rates of TEs, and a 5-time higher prevalence of PTSD following TEs, than the general adolescent population. Adolescent SUD patients with PTSD reported more severe substance use problems than patients without PTSD-regardless of previous TEs. Longitudinal studies are needed in order to investigate the temporal relationship between TEs, PTSD and SUD.