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).

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.

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.

Verbal learning impairment in adolescents with methamphetamine use disorder: a cross-sectional study.

BACKGROUND: Methamphetamine (MA) use has been shown to be associated with deficits in impulsivity, verbal learning, and working memory. Additionally, methamphetamine use disorder (MUD) is related to various brain changes, especially in adolescent users who might be more vulnerable to detrimental effects on brain development. However, little is known about the relationship between adolescent MA use and cognitive impairment. This cross-sectional study aims to explore how the presence of a MUD in adolescents is related to impairments of verbal memory, inhibition, and alertness. METHODS: N = 18 psychiatric outpatients with MUD were matched in terms of depressivity, age, and gender to n = 18 adolescents with other substance use disorders (SUDs), as well as n = 18 controls without SUDs. We compared these three groups on the Verbal Learning and Memory Task (VLMT), and the alertness and go/noGo subtests of the Test of Attentional Performance (TAP). Additionally, Spearman's rank order correlation coefficients were calculated to investigate whether cognitive functioning was directly associated with frequency of past year MA use. RESULTS: The three groups differed significantly in their verbal learning performance (H (2) = 11.7, p = .003, ηp2 = .19), but not in short-term memory, inhibition, cued recall, or alertness. Post hoc tests revealed significant differences in verbal learning between the MA using group and the control group without a SUD (U = 56.5, p = .001, ηp2 = .31). Frequency of past year MA use correlated negatively with short-term memory (ρ = -.25, p < .01) and verbal learning (ρ = -.41, p < .01). No other cognitive variables correlated significantly with MA use frequency. Significant p-values were considered significant after Bonferroni correction. CONCLUSIONS: Adolescent MUD outpatients with regular MA use show specific impairment in verbal learning performance, but not in other basal cognitive functions when compared to adolescents without a MUD. Verbal learning and short-term memory performance is negatively associated with the frequency of MA use. Future research should apply longitudinal designs to investigate long-term effects of methamphetamine and reversibility of these effects on cognitive functioning.

The association between prenatal alcohol consumption and preschool child stress system disturbance.

BACKGROUND: Drinking alcohol during pregnancy is considered a risk factor for child development; however, child biomarkers of prenatal alcohol exposure have been rarely studied. We examined whether a meconium alcohol metabolite (ethyl glucuronide, EtG) was associated with child cortisol concentrations at primary school age. METHODS: For 137 children, prenatal alcohol exposure was operationalized by the meconium biomarker EtG and by maternal self-reports during pregnancy. Two EtG cut-offs (EtG ≥10 ng/g and EtG ≥112 ng/g) were applied. Cortisol concentrations were measured in saliva and hair samples. RESULTS: Children with EtG ≥10 ng/g showed significantly reduced hair cortisol concentrations (HCCs) (p = .050, ηp2  = 0.042). For children with EtG ≥112 ng/g, the cortisol awakening response (CAR) was significantly decreased (p = .025, ηp2  = 0.070). These effects were also present in correlational analyses with continuous EtG data, speaking for partly dose-dependent effects. Especially, within the EtG ≥112 ng/g group, the basal (CAR: rp  = -.642, p = .120) and cumulative (HCC: rp  = -.660, p = .107) cortisol parameters were associated with child emotional symptoms at medium effect size. CONCLUSIONS: The present study showed both the biological association of intrauterine alcohol exposure with the cortisol stress system, partly dose-dependent, and the functional association with emotional and behavioral symptoms.

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.

[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.

Exploring Reference Values for Hair Cortisol: Hair Weight Versus Hair Protein.

BACKGROUND: As a marker of cumulative cortisol activity, hair cortisol has received attention in clinical and methodological research. Currently, it is a common practice to relate the hair cortisol concentration (HCC) to hair weight. This article explores the hair protein concentration (HPC) as another possible reference value for HCC. METHODS: For n = 18 hair samples cut from the posterior vertex, the HCC, HPC, and hair sample weight were determined, and the cortisol-to-weight and cortisol-to-protein ratios were calculated. Correlations were analyzed between the HCC, HPC, and hair sample weight as well as between the cortisol-to-weight and cortisol-to-protein ratios. Hair sample weight and HPC were included as independent variables in a stepwise linear regression model to predict HCC. RESULTS: The HCC and HPC did not correlate significantly (r = 0.393, P = 0.106); however, the correlation between HCC and hair sample weight was significant (r = 0.520, P = 0.027). The HPC and hair sample weight (r = 0.605, P = 0.008) as well as the cortisol-to-weight and cortisol-to-protein ratios (r = 0.858, P < 0.000) showed a high correlation. The hair sample weight was the better predictor of the HCC (ß = 0.520, P = 0.027) than HPC (ß = 0.125, P = 0.657). CONCLUSIONS: The results indicate that the hair sample weight is the more suitable reference value for the HCC. Thus, the standard cortisol-to-weight ratio should be used as the preferred expression for the cumulative cortisol activity measured in the scalp hair. However, calculating the cortisol-to-protein ratio can be considered as an alternative if the hair sample weight is not available.

Exploring Reference Values for Hair Cortisol: Hair Weight versus Hair Protein.

BACKGROUND: As a marker of cumulative cortisol activity, hair cortisol has received attention in clinical and methodological research. Currently, it is common practice to relate hair cortisol concentration (HCC) to hair weight. The present paper explores hair protein concentration (HPC) as another possible reference value for HCC. METHODS: For n = 18 hair samples cut from the posterior vertex, the HCC, HPC, and hair sample weight were determined, and the cortisol-to-weight and cortisol-to-protein ratios were calculated. Correlations were analyzed between HCC, HPC, and hair sample weight as well as between the cortisol-to-weight and cortisol-to-protein ratios. Hair sample weight and HPC were included as independent variables in a stepwise linear regression model to predict HCC. RESULTS: HCC and HPC did not correlate significantly (r = .393, p = .106); however, the correlation between HCC and hair sample weight was significant (r = .520, p = .027). HPC and hair sample weight (r = .605, p = .008) as well as the cortisol-to-weight and cortisol-to-protein ratios (r = .858, p < .000) showed a high correlation. Hair sample weight was the better predictor of HCC (ß = .520, p = .027) than HPC (ß = .125, p = .657). CONCLUSIONS: The results indicate that hair sample weight is the more suitable reference value for HCC. Thus, the standard cortisol-to-weight ratio should be used as the preferred expression for cumulative cortisol activity measured in scalp hair. However, calculating the cortisol-to-protein ratio can be considered as an alternative if the hair sample weight is not available.

Associations of prenatal depressive symptoms with DNA methylation of HPA axis-related genes and diurnal cortisol profiles in primary school-aged children.

Epigenetic DNA modifications in genes related to the hypothalamic-pituitary-adrenal (HPA) axis are discussed as a mechanism underlying the association between prenatal depression and altered child HPA activity. In a longitudinal study, DNA methylation changes related to prenatal depressive symptoms were investigated in 167 children aged 6 to 9 years. At six candidate genes, 126 cytosine-guanine dinucleotides were considered without correcting for multiple testing due to the exploratory nature of the study. Further associations with the basal child HPA activity were examined. Children exposed to prenatal depressive symptoms exhibited lower bedtime cortisol (p = .003, ηp2 = 0.07) and a steeper diurnal slope (p = .023, ηp2 = 0.06). For total cortisol release, prenatal exposure was related to lower cortisol release in boys, and higher release in girls. Furthermore, prenatal depressive symptoms were associated with altered methylation in the glucocorticoid receptor gene (NR3C1), the mineralocorticoid receptor gene (NR3C2), and the serotonin receptor gene (SLC6A4), with some sex-specific effects (p = .012-.040, ηp2 = 0.03-0.04). In boys, prenatal depressive symptoms predicted bedtime cortisol mediated by NR3C2 methylation, indirect effect = -0.07, 95% confidence interval [-0.16, -0.02]. Results indicate relations of prenatal depressive symptoms to both child basal HPA activity and DNA methylation, partially fitting a mediation model, with exposed boys and girls being affected differently.

[Epigenetic modifications in children associated with maternal emotional stress during pregnancy]. / Affektive Belastungen der Mutter in der Schwangerschaft und assoziierte epigenetische Veränderungen beim Kind: Eine Übersicht.

Besides typical physical and hormonal changes during pregnancy, this life period is often associated with an increased emotional and mental stress for women. For the child, the time in utero is regarded as a critical developmental period since adverse stimuli during pregnancy can have lasting consequences for the fetal and postnatal health and development. Thus, prenatal depression, anxiety and stress are considered as risk factors for developmental delay, emotional and behavioral problems. Epigenetic modifications, especially modifications in DNA methylation, are discussed as a possible biological mechanism that could explain the association between prenatal emotional stress and altered developmental and health outcomes of the child. This review summarizes evidence for DNA methylation changes related to prenatal emotional stress from studies with a candidate-gene approach as well as epigenome-wide association studies. Problematic issues are discussed and recommendations for future research are presented.

Activation of GABAA receptors in the medial prefrontal cortex produces an anxiolytic-like response.

OBJECTIVES: There has been increasing evidence that the γ-aminobutyric acid (GABA)ergic system is involved in the neurobiology of anxiety. The present study aimed to investigate the role of GABAergic systems in the modulation of anxiety in the medial prefrontal cortex (mPFC) of rats using the elevated plus maze test. METHODS: Rats were anaesthetised with a mixture of ketamine and xylazine, and then special cannulae were inserted stereotaxically into the mPFC. After 5-7 days of recovery, the effects of intra-mPFC administration of GABAergic agents were studied. RESULTS: Bilateral injection of the GABAA receptor agonist muscimol (0.25, 0.5 and 1 µg/rat) produces an anxiolytic-like effect, shown by significant increases in the percentage of open-arm time (%OAT) and percentage of open-arm entries (%OAE). Intra-mPFC administration of the GABAA receptor antagonist bicuculline (0.25, 0.5 and 1 µg/rat) produces significant anxiogenic-like behaviour. However, intra-mPFC injection of the GABAB receptor agonist baclofen (0.05, 0.1 and 0.2 µg/rat) and the GABAB receptor antagonist CGP35348 (5, 10 and 15 µg/rat) did not alter %OAT and %OAE significantly. CONCLUSION: The results of the present study demonstrate that the GABAergic system of the mPFC modulates anxiety-related behaviours of rats through GABAA receptors.

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.

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).

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.

DNA methylation changes associated with cannabis use and verbal learning performance in adolescents: an exploratory whole genome methylation study.

The association between extent of chronic cannabis use (CCU-extent) and cognitive impairment among adolescents has been the subject of controversial debate. Linking DNA methylation to CCU-extent could help to understand cannabis associated changes in cognitive performance. We analyzed cognitive task performances, CpG methylation in peripheral whole-blood samples and self-reported past-year CCU-extent of n = 18 adolescents (n = 9 psychiatric outpatients with chronic cannabis use (CCU), n = 9 without) who were matched for age, gender and psychiatric disorders. Patients with CCU were at least 24 h abstinent when cognitive tasks were performed. A Principal Component Analysis (PCA) was carried out to identify group differences in whole genome DNA methylation. Mediation analyses were performed between CCU-extent associated CpG sites and CCU-extent associated variables of cognitive tasks. PCA results indicated large differences in whole genome DNA methylation levels between the groups that did not reach statistical significance. Six CpG sites revealed reduced methylation associated with CCU-extent. Furthermore, CCU-extent was associated with lower scores in verbal learning. All six CpG sites mediated the effects between CCU-extent and verbal learning free recall. Our results indicate that CCU is associated with certain patterns in the methylome. Furthermore, CCU-extent associated impairments in memory function are mediated via differential methylation of the six CCU-associated CpG sits. Six identified CpG are located in genes previously described in the context of neurodegeneration, hippocampus-dependent learning and neurogenesis. However, these results have to be carefully interpreted due to a small sample size. Replication studies are warranted.

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.

Self-reported PTSD is associated with increased use of MDMA in adolescents with substance use disorders.

Background: Adolescent patients with a substance use disorder (SUD) often fulfil the criteria for a co-occurring post-traumatic stress disorder (PTSD). However, it is not clear if these dual-diagnosed adolescents present with unique levels of substance use and how their substance use relates to PTSD symptom clusters. Objective: To investigate substance use in adolescents with co-occurring PTSD and SUD. Additionally, we explored how the use of specific substances is related to specific PTSD symptom clusters. Method: We recruited n = 121 German adolescent SUD patients, in three groups: no history of traumatic events (TEs) (n = 35), TEs but not PTSD (n = 48), probable PTSD (n = 38). All groups were administered a trauma questionnaire and were asked to report their past-month substance use. Results: Adolescents with probable PTSD and SUD report a higher frequency of MDMA use than adolescents with no PTSD and no TE (PTSD vs. noTE: U = 510.5, p = .016; PTSD vs. TE: U = 710.0, p = .010). The use of MDMA was more frequent in adolescents with avoidance symptoms (X2 (1) = 6.0, p = .014). Participants report using substances at a younger age (PTSD vs. noTE: U = 372.0, p = .001; PTSD vs. TE: U = 653.5, p = .022) and PTSD symptom onset was on average 2.2 years earlier than first MDMA use (t (26) = -2.89, p = .008). Conclusions: Adolescent SUD patients with probable PTSD are more likely to use MDMA than SUD patients without PTSD. The use of MDMA was associated with reported avoidance symptoms. The first age of MDMA use is initiated after PTSD onset. It is unclear whether the association of MDMA use with avoidance symptoms is due to efforts to reduce these symptoms or a result of regular MDMA use.

Antecedentes: Los pacientes adolescentes con un trastorno por uso de sustancias (TUS) a menudo cumplen los criterios para un trastorno de estrés postraumático concurrente (TEPT). Sin embargo, no está claro si estos adolescentes con diagnóstico dual presentan niveles únicos de consumo de sustancias y cómo su consumo de sustancias se relaciona con los conglomerados de síntomas del TEPT.Objetivo: Investigar el uso de sustancias en adolescentes con concurrencia de TEPT y TUS. Además, exploramos cómo el uso de sustancias específicas se relaciona con grupos específicos de síntomas de TEPT.Método: Reclutamos un n=121 pacientes adolescentes alemanes con TUS, en tres grupos: sin antecedentes de eventos traumáticos (no ETs) (n=35), ETs pero no TEPT (n=48), probable TEPT (n=38). A todos los grupos se les administró un cuestionario sobre traumas y se les pidió que informaran sobre su consumo de sustancias durante el mes anterior.Resultados: Los adolescentes con probable TEPT y TUS informan una mayor frecuencia de uso de MDMA que los adolescentes sin TEPT y sin ETs (TEPT versus no ETs: U= 510.5, p= .016; TEPT versus ETs: U= 710.0, p=.010). El uso de MDMA fue más frecuente en adolescentes con síntomas de evitación (X² (1) = 6.0, p = .014). Los participantes informan que consumen sustancias a una edad más temprana (TEPT versus no ETs: U= 372.0, p= .001; TEPT frente a TE: U= 653.5, p= .022) y el inicio de los síntomas del TEPT fue en promedio 2.2 años antes del primer uso de MDMA (t (26) = −2.89, p = .008).Conclusiones: Los pacientes adolescentes con TUS con probable TEPT son más propensos a usar MDMA que los pacientes con TUS sin TEPT. El uso de MDMA se asoció con el reporte de síntomas de evitación. La primera edad de uso de MDMA se inicia después del inicio del TEPT. No está claro si la asociación del uso de MDMA con los síntomas de evitación se debe a los esfuerzos por reducir estos síntomas o al resultado del uso regular de MDMA.

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.