DNA methylation and gene expression of immune cell markers in adolescents with chronic cannabis use: an exploratory study.

BACKGROUND: Experimental studies indicate that phytocannabinoids have immune-modulatory properties. However, the effects of chronic cannabis use (CCU) in adolescents on their immune cells have been scarcely investigated to date, although CCU is increasingly observed in this age group. METHODS: In this study, we analyzed DNA methylation and gene expression of immune cell markers in whole-blood samples of adolescent CCU-outpatients and non-cannabis-using (NCU) controls (n = 14 vs. n = 15, mean age = 16.1 ± 1.3 years). Site-specific DNA methylation values were used to calculate A) proportion estimates of circulating white blood cell (WBC) types and B) mean DNA methylation values of common immune cell markers (CD4, CD8A, CD19, FCGR3A, CD14, FUT4, MPO), whose gene expression levels were additionally determined. RESULTS: CCU adolescents had a lower estimated proportion of B cells compared to NCU subjects. An originally observed higher proportion of granulocytes in CCU subjects, however, was attenuated when controlling for past-year tobacco use. The observed differences in mean DNA methylation and gene expression of immune cell markers were not statistically significant. CONCLUSION: The results of our explorative study indicate that CCU in adolescents is associated with altered levels of circulating WBCs. Further studies with larger cohorts are warranted to confirm our findings and to provide insights regarding their functional consequences.

Systematic review: the impact of maternal pre-and postnatal cannabis use on the behavioral and emotional regulation in early childhood.

Prenatal exposure to alcohol and tobacco has been associated with child regulatory abilities and problems, but less is known about the associations with cannabis exposure. This review seeks to address this gap primarily focusing on the effects of maternal cannabis use on the child. Thus, we investigate the association between pre- and postnatal cannabis exposure of the child and regulatory abilities and problems, as well as the underlying neurobiological mechanisms potentially mediating the associations. According to the PRISMA guidelines, a systematic literature review was performed based on a systematic literature search through Medline (PubMed), Web of Science and PsycInfo, including studies assessing children aged 0-6 years with cannabis exposure in the preconception, pre-or postnatal period (preconception, pre- and postnatal cannabis exposure [PCE]) and investigating child regulatory abilities, regulatory problems or neurobiological mechanisms. Of n = 1061 screened articles, n = 33 were finally included. Diminished regulatory abilities are more likely to be found in infants after PCE, while specific regulatory problems tend to be more frequently found after two years of age. Possible mechanisms are related to changes in methylation and expression of key genes involved in endocannabinoid, dopaminergic and opioid systems, increased cortisol reactivity and altered Secretory Immunoglobulin A levels. Furthermore, PCE has been associated with changes in brain structure and connectivity. Current findings indicate that PCE is associated with both age-dependent alterations in self-regulation and neurobiological changes in young children. However, evidence is limited due to the number of studies, small sample sizes and lack of control for maternal psychopathology. Longitudinal studies including psychometric data from mothers are needed in order to further understand the implications of PCE.Trial registration: The review is registered with PROSPERO (ID: CRD42023425115).

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.

Attenuated psychotic symptoms, substance use and self-reported PTSD in adolescence.

Background: The occurrence of attenuated psychotic symptoms (APS) is a major concern in populations with substance use disorders (SUDs). However, APS also frequently develop in the course of Post-Traumatic Stress Disorder (PTSD). This study explores how the prevalence of APS differs between adolescent patients with only SUD, SUD with a history of traumatic experiences (TEs), and with SUD and self-reported PTSD.Methods: We recruited n = 120 treatment-seeking adolescents at a German outpatient clinic for adolescents with SUD. All participants filled out questionnaires assessing APS (PQ-16, YSR schizoid scale), trauma history, PTSD symptoms (both UCLA PTSD Index), and SUD severity (DUDIT) next to an extensive substance use interview. We performed a multivariate analysis of co-variance with the four PQ-16 scales and the YSR scale as outcomes and PTSD status as predictor. Additionally, we performed five linear regressions predicting each PQ-16 score and YSR score based on tobacco, alcohol, cannabis, ecstasy, amphetamine, and methamphetamine use.Results: Participants with co-occurring SUD and self-reported PTSD showed significantly higher APS prevalence rates (PQ-16 score, p = .00002), more disturbed thought content (p = .000004), more perceptual disturbances (p = .002), more negative symptoms (p = .004) and more thought problems (p = .001) compared to adolescents with SUD and a history of trauma and adolescents with only SUD. Past-year substance use was not predictive for APS prevalence (F(75) = 0.42; p = .86; R2 = .04).Conclusion: Our data suggests that the occurrence of APS in adolescents with SUD is better explained by co-occurring self-reported PTSD than by substance use frequency or substance class. This finding might indicate that APS might be reduced through treating PTSD or focusing on TEs in SUD therapy.

Adolescents with co-occurring substance use disorders and PTSD show increased rates of Attenuated Psychotic Symptoms (APS).A history of traumatic experiences and PTSD are stronger predictors for APS than substance use.APS in adolescents with substance use disorders may be an indication of undiagnosed and/or untreated co-occurring PTSD.

[Non-smoker protection and tobacco cessation]. / Nichtraucherschutz und Tabakentwöhnung.

Non-smoker protection and tobacco cessation Abstract. Objective: Whereas, on the one hand, employees in child and adolescent psychiatric institutions (CAP) have to enforce smoking bans among patients, on the other hand, they have a high likelihood of being smokers themselves. Little data are available on the enforcement of smoking regulations and what cessation support is offered by CAP institutions. Method: In an online survey, n = 78 senior staff members or directors of German CAP institutions (41.9 % of all addressed CAP institutions) responded to questions on smoking regulations, exceptions, and cessation support for employees. Results: The enforcement of comprehensive smoking bans is rarely reported (<20 % of CAP institutions). Employees are exempted or allowed to smoke mostly outside of the building (e. g., in designated smoking areas: 69-78 % depending on ward type). Cessation support was offered by less than half of the CAP institutions (47%). Conclusions: The data presented point toward future areas for tobacco control in CAP care, including transparent regulations, staff training, and dissemination of support for occupational smoking cessation.

Coping motives mediate the relationship between PTSD and MDMA use in adolescents with substance use disorders.

BACKGROUND: Post-traumatic stress disorder (PTSD) and substance use disorders (SUDs) often co-occur in adolescent patients. Previous research has shown that these patients differ from SUD patients without PTSD in terms of their substance use patterns. In this study, we aimed to test whether substance use in this population is related to an attempt to self-medicate PTSD-related symptoms. METHODS: German adolescent patients (aged 13-18 years) at an outpatient clinic for SUD treatment, n = 111 (43% female), completed a self-designed questionnaire on use motives, a measure of PTSD-related experiences, and underwent a standardized psychiatric interview including structured substance use questions. Participants were subsequently classified as 'no traumatic experiences ('noTEs' but SUD), 'traumatic experiences but no current PTSD diagnosis' ('TEs' with SUD), and 'PTSD' with SUD. After establishing a self-designed motive measurement through exploratory and confirmatory factor analyses, we calculated non-parametric group differences and a mediation analysis in a linear regression framework. RESULTS: The past-year frequency of MDMA use was highest in the PTSD group and lowest in the noTE group (H (2) = 7.2, p = .027, η2 = .058), but no differences were found for frequencies of tobacco, alcohol, cannabis, or stimulant use (all H ≤ 4.9, p ≥ .085, η2 ≤ .033). While controlling for sex, the three groups showed a similar pattern (highest in the PTSD group and lowest in the noTE group) for coping scores (F (103) = 5.77, p = .004, η2 = .101). Finally, mediation analyses revealed an indirect effect of coping score (b = 0.61, 95% CI [0.29, 1.58], p = .145) on the association between group membership and MDMA use frequency. CONCLUSIONS: In adolescent SUD patients, we found an association of current PTSD and lifetime traumatic experiences with higher MDMA use that could be partially explained by substance use being motivated by an attempt to cope with mental health symptoms. This indicates a coping process involved specifically in MDMA use compared to the use of other psychoactive substances, possibly due to unique psychoactive effects of MDMA.

[Implementation of Tobacco Control Strategies in Psychiatric Institutions for Children and Adolescents: an Online Survey of Leading Staff Members]. / Umsetzung von Tabakkontrollmaßnahmen in Einrichtungen der Kinder- und Jugendpsychiatrie: Eine Online-Befragung von leitenden Mitarbeitenden.

OBJECTIVE: Tobacco control measures are relevant also in child and adolescent psychiatric institutions and their implementation in Germany will be assessed in this study. METHODS: In an online survey, n=78 leading staff members responded to standardized questions assessing how smoking in patients was dealt in such institutions. RESULTS: The majority of institutions (70-87%) had smoking bans in the psychiatric clinic buildings and premises. Depending on the type of psychiatric ward, exceptions were in place in the form of a designated smoking area (38%), smoking pavilion (19%), or when patients suffered from certain mental disorders (28%). Documentation of violations of the ban varied with the type of ward (30-79%), while in most cases violations led to consequences (84-93%) including confiscation of smoking utilities (42-63%) or a curfew (25-38%). Smoking cessation aids were reported by 78% of the institutions, most often as consultations (64%). Pharmacological treatments for smoking were provided in inpatient wards (71-83%). One in two institutions documented the result of cessation attempts (54%). Smoking-related working groups (14%) or the use of standardized diagnostic instruments (0-4%) were much less frequently reported. DISCUSSION: We provide a first look at tobacco control policy measures in child and adolescent psychiatric institutions on a national scale. This allows us to derive future areas for tobacco control.

[Substance Use, Resulting Disorders, and Collateral Mental Disorders Among Adolescents in a Special Outpatient Institutions for Addictions]. / Substanzkonsum, Störungen durch Substanzkonsum und begleitende psychische Störungen bei Jugendlichen.

Substance Use, Resulting Disorders, and Collateral Mental Disorders Among Adolescents in a Special Outpatient Institutions for Addictions Abstract. Objective: Only few clinics offer the outpatient treatment of substance use disorders (SUDs) among adolescents. Therefore, only limited data describe substance use patterns, SUDs, and co-occurring psychiatric disorders characteristic of adolescents who present in such outpatient clinics specialized in the treatment of SUDs. Method: Via interview we collected data from n = 201 patients between 12 and 19 years concerning their substance use, SUDs, and current co-occurring psychiatric disorders. We created descriptive presentation of data regarding use patterns, SUDs, and co-occurring disorders divided by sex and current age. Results: Tobacco (88 %) and cannabis (86 %) were the most frequently used substances. 67 % of all patients presented with more than one SUD, cannabis use disorder being the most prevalent one (84 %). 72 % presented with at least one co-occurring disorder, with conduct disorders (40 %), attention deficit (hyperactivity) disorders (21 %), and depressive disorders (18 %) being the most frequent ones. Conclusions: Adolescent SUD patients often present with co-occurring psychiatric disorders. Institutions for adolescent SUD treatment should also focus on treating co-occurring conduct disorders, depression, and attention deficit disorders.

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.

Alcohol Use Disorders Identification Test (AUDIT) and mortality risk: a systematic review and meta-analysis.

BACKGROUND: We summarise the evidence for an association between screening scores from the Alcohol Use Disorders Identification Test (AUDIT) and all-cause mortality. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, prospective cohort studies reporting all-cause mortality risk by AUDIT scores (complete AUDIT-10 or AUDIT-C) were identified through MEDLINE, Embase, PubMed and Web of Science up to September 2016. Risk estimates were pooled using random effects meta-analyses. RESULTS: Seven observational studies with 18 920 observed deaths among 309 991 participants were identified. At-risk drinking (ie, hazardous/harmful consumption, AUDIT-10 ≥8 and AUDIT-C ≥4) was associated with elevated mortality risk after 2-10 years of follow-up (pooled relative risk (RR)=1.24, 95% CI 1.12 to 1.37) compared with moderate drinking (AUDIT-10=1-7, AUDIT-C=1-3). Compared to past year abstainers (AUDIT=0), moderate drinkers had a lower mortality risk (RR=0.75, 95% CI 0.71 to 0.79) in US Veterans and a similar mortality risk (RR=0.99, 95% CI 0.72 to 1.38) in population-based studies. Most data came from studies among Veterans using the short AUDIT-C in men and showed a dose-response relationship (RR=1.04, 95% CI 1.04 to 1.05 for each AUDIT-C score among drinkers). Data for women and young adults were scarce. CONCLUSION: AUDIT screening scores were associated with mortality risk. The association was differential depending on the population examined, which may be related to prevalence of former drinkers among current abstainers. Due to heterogeneity between studies and the small number of populations examined, generalisability may be limited.