Pre-treatment expectations and their influence on subjective symptom change in Crohn's disease.

BACKGROUND: Treatment expectations reportedly shape treatment outcomes, but have not been studied in the context of multimodal therapy in Crohn's disease (CD). Therefore, the current study investigated the role of treatment expectations for subjective symptom changes in CD patients who have undergone an integrative multimodal therapy program. METHODS: Validated questionnaires were completed at the start of the treatment program and post intervention. Pre-treatment expectations and experienced symptom change were assessed with the Generic Rating Scale for Previous Treatment Experiences, Treatment Expectations, and Treatment Effects (GEEE); stress levels were quantified with the Perceived Stress Scale (PSS-10) and disease specific quality of life was quantified with the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ). We performed multiple linear and Bayesian regression to determine how expectations related to symptom change. RESULTS: N = 71 CD patients (66.2% female) were included. Stronger expectations regarding symptom improvement (b = 0.422, t = 3.70, p < .001) were associated with higher experienced symptom improvement. Additionally, Bayesian analysis provided strong evidence for including improvement expectations as a predictor of improvement experience (BFinclusion = 13.78). CONCLUSIONS: In line with research in other disorders, we found that positive treatment expectations were associated with experienced symptom improvement. In contrast, we found no indication that an experience of symptom worsening was associated with positive or negative baseline treatment expectations. Induction of positive expectations might be a potential avenue for improving treatment outcomes in CD therapy.

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.

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.

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.

Prenatally traumatized mice reveal hippocampal methylation and expression changes of the stress-related genes Crhr1 and Fkbp5.

In our previous study, we found that prenatal trauma exposure leads to an anxiety phenotype in mouse pups, characterized by increased corticosterone levels and increased anxiety-like behavior. In order to understand the mechanisms by which aversive in utero experience leads to these long-lasting behavioral and neuroendocrine changes, we investigated stress reactivity of prenatally traumatized (PT) mice, as well as the expression and methylation levels of several key regulatory genes of the stress axis in the dorsal hippocampus (dHPC) of the PT embryo and adult mice. We detected increased corticotropin-releasing hormone receptor 1 (Crhr1) and decreased FK506 binding protein 5 (Fkbp5) mRNA levels in the left dHPC of adult PT mice. These alterations were accompanied by a decreased methylation status of the Crhr1 promoter and an increased methylation status of the Fkbp5 promoter, respectively. Interestingly, the changes in Fkbp5 and Crhr1 mRNA levels were not detected in the embryonic dHPC of PT mice. Together, our findings provide evidence that prenatal trauma has a long-term impact on stress axis function and anxiety phenotype associated with altered Crhr1 and Fkbp5 transcripts and promoter methylation.

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.

[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.