Agomelatine in pediatric patients with moderate to severe major depressive disorder: an open-label extension study.

Major depressive disorder (MDD) in young people is a common psychiatric disorder, but treatment options are limited. Agomelatine has demonstrated short-term efficacy and safety in pediatric patients. We report here the results of a 92-week open-label extension (OLE). The international, multicenter, double-blind, study randomized 400 patients (80 children, 320 adolescents) with moderate-to-severe MDD to one of four treatment groups: agomelatine 10 mg (n = 102), agomelatine 25 mg (n = 95), placebo (n = 103), and fluoxetine 10-20 mg (n = 100). After 12 weeks, patients who could benefit from treatment continuation were offered entry into an optional OLE during which they received agomelatine 10 or 25 mg for a further 92 weeks. A total of 339 patients (271 adolescents) entered the OLE. Treatment groups considered for the OLE analysis reflected those received in the double-blind and OLE periods: agomelatine (10 or 25 mg) in both (ago/ago, n = 170); placebo then agomelatine 10-25 mg (pcb/ago, n = 85); or fluoxetine then agomelatine 10-25 mg (fluox/ago, n = 84). Mean age (± SD) at entry into the double-blind phase (Week 0) was 13.6 ± 2.7 years and 61.9% were female. Mean changes in Children's Depression Rating Scale revised (CDRS-R) raw total score from Week 12 to last post-Week 12 value in the three groups were - 16.3 ± 12.2 (ago/ago), - 18.9 ± 16.1 (pcb/ago), and - 16.1 ± 15.5 (fluox/ago), reflecting the difference in efficacy between treatments during the double-blind period, and heterogeneity at W12 between the treatment groups. Adverse events considered related to treatment occurred in 14.5% of patients: 15.3% ago/ago, 16.5% pcb/ago, and 10.7% fluox/ago. Three patients (all adolescents) experienced treatment-related severe adverse events: two treated with ago/ago and one treated with pcb/ago. Among the adolescents, one treatment-related severe adverse event in a patient in the pcb/ago group led to study withdrawal. Agomelatine was associated with continuous improvement in depressive symptoms without unexpected safety signals. These findings support the safe use of agomelatine in a pediatric population with moderate-to-severe MDD for up to 104 weeks.Trial registration No: EUDRACT No. 2015-002181-23.

Health-related quality of life after child maltreatment in institutions: Results from a representative population-based sample in Germany.

BACKGROUND: Child maltreatment (CM) is a major public health problem associated with enormous consequences, including impaired health-related quality of life (HRQOL). While the consequences of CM that occurs in the family context have been studied numerous times, studies on the consequences of institutional CM are lacking. This is of particular importance because cases of CM in churches, sport clubs and school, educational and medical settings have become increasingly apparent in Germany. OBJECTIVE: Thus, the objective of this study was to assess the association of CM in various institutions with HRQOL in adulthood. PARTICIPANTS AND SETTING: In a cross-sectional observational approach, a representative sample of the German population (N = 2516) was identified via a random-route. METHODS: Socioeconomic information, HRQOL and CM experiences in school, medical and educational institutions were obtained and statistically evaluated. RESULTS: Of the 2516 participants, 834 (33.14 %) reported CM in institutions and 1194 (47.46 %) reported impaired HRQOL. Participants who reported CM in institutions were more likely to have HRQOL impairments than participants who had been in the respective institution in childhood but had not reported having experienced CM there. In the case of CM in medical institutions, HRQOL impairments increased 2.2-3.9-fold. If CM in school was reported, HRQOL impairments increased 1.6-2.0-fold. If CM in educational institutions was reported, HRQOL impairments increased 2.1-2.7-fold. CONCLUSIONS: CM in institutions is associated with an increased likelihood of HRQOL impairments in Germany. Institutions need to be aware of the risk of CM and safeguarding measures should be implemented.

Pilot Study: Cut the Cut-A Treatment Program for Adolescent Inpatients with Nonsuicidal Self-Injury.

Non-suicidal-self-injury (NSSI) in adolescents needing inpatient treatment is a serious health risk behaviour. NSSI-specific treatment programs for inpatients hardly exist. "Cut the Cut" (CTC) is a new treatment program in intervals, addressing this problem. Aim of this pilot-study was to evaluate acceptability and feasibility of CTC. 23 female inpatients (12 CTC, 11 control, aged 15-17; mean = 16.80, SD.70) engaging in NSSI were evaluated for service user satisfaction, frequency, and severity of NSSI at T1 (admission), T2 (discharge after interval 1, CTC-group) and T3 (discharge). A qualitative interview was performed at T3. Significant improvement in NSSI-frequency was given (T1-T3: CTC p = 0.010; control p = 0.038). Severity of NSSI reduced slightly (mild NSSI: CTC p = 0.022, control p = 0.087; severe NSSI: CTC p = 0.111, control p = 0.066). Satisfaction of parents (T3 mean 28.38) and adolescents (T3 mean 26.11) in CTC was rated high. CTC is a feasible treatment option for inpatients engaging in NSSI. Further studies over time are needed.Trial registration Number DRKS00016762, 05.03.2019, retrospectively registered.

Debate: Quantity of impatient beds and quality of child psychiatric and psychotherapeutic care provision - a German perspective.

Provision of care for children with mental health disorders or behavioural difficulties differs from country to country. Historically, Germany has the highest number of inpatient beds throughout Europe (64 inpatient beds per 100,000 young people). In addition, nearly 146 departments for child and adolescent psychiatry offer day-care beds as well as ambulatory care. A high number of resident child and adolescent psychiatrists/psychotherapists (more than 12,000 professionals) complement provision of care in the different regions of Germany. Yet, only 50% of children and adolescents with mental health problems receive the treatment they need. Barriers to care - for example lack of transportation, fear of stigmatization, long distances in rural regions or fear of long hospital inpatient stays - keep families from presenting their child/adolescent to the relevant institutions. Recently, a new treatment module: StäB, an intensive daily home treatment, delivered by a multiprofessional team, has been added to the portfolio of treatment options in Germany. This closes the gap between highly intensive inpatient care and low-frequency outpatient treatment, allowing a continuum of care in intensity and frequency within the treatment alternatives.

Maternal separation and contact to a stranger more than reunion affect the autonomic nervous system in the mother-child dyad: ANS measurements during Strange Situation Procedure in mother-child dyad.

BACKGROUND: The autonomic nervous system (ANS) processes underlying attachment-related mother-child interactions are not well understood. We aimed to describe and compare the responsivity of the ANS for mothers and their infants during the different phases of the Strange Situation Procedure (SSP). METHODS: Continuous measurements of the sympathetic (SNS) and parasympathetic (PNS) branches of the ANS were obtained simultaneously in 91 mothers and their infants (range 10-15 months). Heart rate (HR), respiratory sinus arrhythmia (RSA), pre-ejection period (PEP) and left ventricular ejection time (LVET), were calculated for the baseline period (e1) and seven subsequent episodes (e2-e8) of the SSP. RESULTS: The largest difference between the mother and infant was during e7, when the stranger went into the room where the infant was while the mother waited outside the room. Mothers showed reduced SNS-activity or stress reduction while the child showed PNS withdrawal or increased stress response. Additionally, LVET was found to be a marker for SNS changes in the one-year-old infant during SSP. CONCLUSION: Mothers and infants showed different stress-related ANS responses during e7. Since this study showed that simultaneous measurement of ANS responses in mother-child dyads during the SSP is feasible, future studies can assess both mother and child stress responses in different contexts. The measure of LVET may be a valid SNS-reactivity measure in the one-year-olds. Since the separation episode e7 led to the strongest ANS responses, future studies might assess stress responses in more normative circumstances, such as child care programs.

The symptom representation of posttraumatic stress disorder in a sample of unaccompanied and accompanied refugee minors in Germany: a network analysis.

Background: Given the unprecedented number of traumatized refugee minors in Europe and the increased prevalence of mental disorders such as PTSD in this vulnerable population, new methodologies that help us to better understand their symptomatology are crucial. Network analysis might help clinicians to both understand which symptoms might trigger other symptoms, and to identify relevant targets for treatment. However, to date only two studies have applied the network analysis approach to an (adult) refugee population and only three studies examined this approach in children and adolescents. Objective: The aim of this study is to explore the network structure and centrality of DSM-5 PTSD symptoms in a cross-sectional sample of severely traumatized refugee minors. Method: A total of N = 419 (M age = 16.3; 90.7% male) unaccompanied (79.9%) and accompanied (20.1%) refugee minors were recruited in five studies in southern Germany. PTSD symptoms were assessed using the Child and Adolescent Trauma Screen (CATS). The network was estimated using state-of-the-art regularized partial correlation models using the R-package qgraph. Results: The most central symptoms were nightmares, physiological and psychological reactivity, and concentration problems. The strongest connections between symptoms were established for psychological and physiological reactivity, irritability/anger and self-destructive/reckless behaviour, intrusions and nightmares, nightmares and sleep disturbance, and between concentrations problems and sleep disturbance. Conclusion: This study furnishes information relevant to research and the clinical management of PTSD in refugee minors, and also in terms of comparisons with trauma-exposed children and adolescents without a migration background. Re-experiencing symptoms seem to be central in the refugee minor PTSD profile and thus merit special consideration in the diagnostic and treatment evaluation process. Investigating the PTSD network longitudinally and complementing between-subject analyses with within-subject ones might provide further insight into the symptomatology of refugee minors and how to treat them successfully.

Antecedentes: Dado el número sin precedentes de menores traumatizados refugiados en Europa y la prevalencia aumentada de trastornos mentales tales como el TEPT en esta población vulnerable, nuevas metodologías que nos ayuden a una mejor comprensión de su sintomatologiía son cruciales. El análisis de redes podría ayudar a los clínicos, tanto para comprender qué síntomas podrían gatillar otros síntomas y para identificar blancos relevantes para el tratamiento. Sin embargo, a la fecha sólo dos estudios han aplicado la aproximación de análisis de redes a una población de refugiados (adultos) y sólo tres estudios examinaron esta aproximación en niños y adolescentes.Objetivo: El objetivo de este estudio es explorar la estructura de redes y centralidad de los síntomas de TEPT del DSM-5 en una muestra transversal de menores refugiados severamente traumatizados.Método: Fueron recrutados un total de N= 419 (edad M= 16.3; 90,7% masculino) menores refugiados en cinco estudios en el sur de Alemania, no acompañados (79,9%) y acompañados (20,1%). Los síntomas de TEPT fueron evaluados usando el Tamizaje de Trauma para niños y adolescentes (CATS por sus siglas en inglés). La red se estimó utilizando modelos de correlación parcial regularizados de última generación utilizando el gráfico de paquete R.Resultados: Los síntomas más centrales fueron las pesadillas, la reactividad fisiológica y psicológica y los problemas de concentración. Las conexiones más potentes entre síntomas estuvieron establecidas por la reactividad psicológica y fisiológica, la irritabilidad/rabia y conducta autodestructiva/impulsiva, intrusiones y pesadillas, pesadillas y alteraciones del sueño, y entre problemas de concentración y alteraciones del sueño.Conclusión: Este estudio proporciona información relevante para la investigación y el manejo clínico del TEPT en menores refugiados, y también en términos de comparaciones con niños y adolescentes expuestos a trauma sin antecedentes de migración. Los síntomas de re-experimentación parecen ser centrales en el perfil de TEPT en los menores refugiados y por lo tanto merece una consideración especial en el proceso de evaluación diagnóstica y el tratamiento. La investigación longitudinal de la red del TEPT y la complementación de los análisis entre sujetos con los de otro sujeto podrían proporcionar una mayor comprensión de la sintomatología de los menores refugiados y cómo tratarlos en forma exitosa.

[Post-traumatic stress disorders (PTSD) and trauma sequel disorders in adolescence]. / Posttraumatische Belastungsstörungen (PTBS) und Traumafolgestörungen in der Adoleszenz.

This text examines post-traumatic stress disorders and trauma sequel disorders in adolescence, focusing in particular on the problem of transition. On the one hand, on the diagnostic level traumatizations are often not PTSD-specific, but rather self-help and self-medication measures as well as alcohol and drug addiction and dissociality, which are often not sufficiently questioned in the adult psychiatric system. On the other hand, it is about the further development and implementation of trauma pedagogical approaches, especially for young people who grow up in critical high-risk constellations or who are already in institutions of youth welfare or integration assistance. Here, not only a blatant lack of initial, further and continuing training for the occupational groups involved is noted, but also a lack of empirical therapy studies.

The effects of childhood maltreatment on epigenetic regulation of stress-response associated genes: an intergenerational approach.

While biological alterations associated with childhood maltreatment (CM) have been found in affected individuals, it remains unknown to what degree these alterations are biologically transmitted to the next generation. We investigated intergenerational effects of maternal CM on DNA methylation and gene expression in N = 113 mother-infant dyads shortly after parturition, additionally accounting for the role of the FKBP5 rs1360780 genotype. Using mass array spectrometry, we assessed the DNA methylation of selected stress-response-associated genes (FK506 binding protein 51 [FKBP5], glucocorticoid receptor [NR3C1], corticotropin-releasing hormone receptor 1 [CRHR1]) in isolated immune cells from maternal blood and neonatal umbilical cord blood. In mothers, CM was associated with decreased levels of DNA methylation of FKBP5 and CRHR1 and increased NR3C1 methylation, but not with changes in gene expression profiles. Rs1360780 moderated the FKBP5 epigenetic CM-associated regulation profiles in a gene × environment interaction. In newborns, we found no evidence for any intergenerational transmission of CM-related methylation profiles for any of the investigated epigenetic sites. These findings support the hypothesis of a long-lasting impact of CM on the biological epigenetic regulation of stress-response mediators and suggest for the first time that these specific epigenetic patterns might not be directly transmitted to the next generation.

Trauma-focused group intervention for unaccompanied young refugees: "Mein Weg"-predictors of treatment outcomes and sustainability of treatment effects.

BACKGROUND: Current research on treatment predictors and long-term effects of trauma-focused interventions for (unaccompanied) refugee minors is limited. This secondary analysis of a recent randomised controlled trial (RCT), evaluating the trauma-focused group intervention "Mein Weg" (English "My Way") compared to usual care, investigated several refugee-specific factors such as treatment predictors and sustainability of treatment gains. METHODS: In total N = 50 participants (M age = 17.00, 94% male) were included in this analysis. Evaluation of 3-month follow-up data included: posttraumatic stress symptoms [(PTSS) CATS-Self, CATS-Care], depression (PHQ-8), and dysfunctional posttraumatic cognitions (CPTCI-S). Baseline symptom severity of the above-mentioned measures, trauma load and socio-demographic factors were investigated as the treatment predictors. RESULTS: Intention-to-treat-analyses (ITT) revealed the sustainability of treatment effects in self-reported PTSS (pre to post change: 6.48 ± 1.60, d = 0.62, p < 0.001; post to 3-month follow-up change: 1.41 ± 1.96, d = 0.11, p = 0.47) and depression (pre to post change: 7.82 ± 2.09, d = 0.64, p < 0.001; post to 3-month follow-up change: 1.35 ± 2.17, d = 0.05, p = 0.54). Country of origin alone was a significant predictor of the change in PTSS (b = - 8.22 ± 3.53, t(30) = - 2.33, p = 0.027), and baseline levels of depression were a significant predictor of the change in depression (b = 0.83 ± 0.19, t(33) = 4.46, p < 0.001). CONCLUSION: This group intervention can serve as a valuable component in a stepped care approach with promising long-term effects for young refugees.Trial registration DRKS, #DRKS00010915. Registered 15 September 2016, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00010915.

Associations of adverse childhood experiences and bullying on physical pain in the general population of Germany.

BACKGROUND: Chronic pain is a frequent burden in the general population. Child maltreatment and bullying are risk factors for the development of chronic pain. Aim of this cross-sectional study was to investigate the association of child maltreatment and bullying and pain experiences in a representative sample of the general population. MATERIALS AND METHODS: A total of N=2,491 people from the general population of Germany participated in the study (Mage=48.3 years [SD=18.2], 53.2 % female). Child maltreatment was assessed with the Childhood Trauma Questionnaire (CTQ), pain was rated with the Polytrauma Outcome (POLO)-physical state domain, depression scores were assessed with the Patient Health Questionnaire, and anxiety scores via the General Anxiety Disorder Questionnaire. Regression analyses were calculated to investigate the effect of bullying and child maltreatment, as well as depression, anxiety, and gender on pain experiences. RESULTS: A significant correlation between increasing pain levels and number of adverse childhood experiences was found. With regard to specific types of maltreatment, largest effect sizes were found for emotional abuse. Bullying was significantly, but overall rather moderately, related to pain suffering. In women, all forms of maltreatment were associated with pain, while in men only sexual and physical abuse revealed significant effects. Although depression and anxiety scores were significantly associated with the experience of current pain, they did not change the effect of child maltreatment on pain significantly. CONCLUSION: In this sample of the general population, adverse childhood experiences were significantly associated with pain and showed cumulative effects, over and above depressive and anxiety symptoms.

The impact of child maltreatment on non-suicidal self-injury: data from a representative sample of the general population.

BACKGROUND: Child maltreatment is an identified risk factor for Non-Suicidal Self-Injury (NSSI). The aim of the current study was to investigate effects of different types of maltreatment, and mediating effects of depression and anxiety on NSSI in the general population. METHODS: A representative sample of the German population, comprising N = 2498 participants (mean age = 48.4 years (SD = 18.2), 53.3% female) participated in this study. Child maltreatment was assessed using the Childhood Trauma Questionnaire (CTQ),NSSI was assessed with a question on lifetime engagement in NSSI, depressive symptoms were assessed by the Patient Health Questionnaire (PHQ-2) and anxiety symptoms by the General Anxiety Disorder questionnaire (GAD-2). RESULTS: Lifetime prevalence of NSSI in this sample was 3.3, and 30.8% reported at least one type of child maltreatment. Participants in the NSSI group reported significantly more experiences of child maltreatment. Emotional abuse was endorsed by 72% of all participants with NSSI. A path analytic model demonstrated an unmediated direct effect of emotional neglect, a partially mediated effect of emotional abuse, and a fully mediated effect of sexual abuse and physical neglect by depression and anxiety on NSSI. CONCLUSIONS: Especially emotional neglect and abuse seem to play a role in the etiology of NSSI above and beyond depression and anxiety, while sexual and physical abuse seem to have a rather indirect effect.

Knowledge transfer: a worldwide challenge in child mental health: a recommendation to the readership of CAPMH concerning the revised version of the IACAPAP Textbook of Child and Adolescent Mental Health.

BACKGROUND: Transfer of knowledge is an important issue throughout all scientific disciplines, especially in the medical and psycho-social field. The issue of worldwide knowledge transfer in child mental health is one of the aims and goals of the journal Child and Adolescent Psychiatry and Mental Health (CAPMH). The demand for mental health training is high worldwide, and especially in low- to lower-middle income countries, where inadequate access to knowledge resources in the field of child and adolescent mental health (CAMH) is prevalent. At the same time, many of these countries are showing an increased risk for mental health issues in children and adolescents. The International Association for Child and Adolescent Psychiatry and Allied Professions (IACAPAP) Textbook of Child and Adolescent Mental Health counters this problem. It is an open-access e-textbook aiming to provide an overview of current and established treatment and practical approaches for child and adolescent psychiatrists, psychotherapists and allied (mental health) professionals worldwide. First published in 2012, the updated and revised version was launched in 2015. The aim of this commentary is to review and disseminate the usefulness and practicability of content and further material included in the new version of the textbook. REVIEW: Overall, the textbook contains ten sections divided into 59 chapters, with a total of 1435 pages. The original version of the textbook was written in English. The revised version contains translations of 49 chapters into different languages (to date French, Spanish, Hebrew, Arabic, Portuguese, Russian, Norwegian and/or Japanese), with additional material for knowledge dissemination and self-directed learning (e.g. videos and quizzes) for several chapters. The textbook and the add-on materials for dissemination are of high quality and convey a great introduction to important topics concerning mental health. Apart from knowledge transfer, there is a pragmatic focus on clinical practice and on regional and cultural differences. CONCLUSION: The textbook is a new and unique opportunity for professionals all over the world to improve their knowledge, skills and expertise in CAMH. High-quality, up-to-date and freely accessible materials in the field of CAMH are combined with the opportunity to share insights with colleagues.

A German e-learning-training in the context of early preventive intervention and child protection: preliminary findings of a pre-post evaluation.

BACKGROUND: In recent years, a number of government-sponsored initiatives have been implemented in Germany that are focused on early preventive intervention in child protection. In response to the need for interdisciplinary training in this area, the internet-based e-learning program "Early Preventive Intervention and Child Protection" was developed for professionals in the child welfare and health care systems working with families with infants and toddlers. The program is currently undergoing evaluation for effectiveness and user satisfaction. METHODS: In a pre-post design, users are requested to complete questionnaires that assess three measures of expertise: theoretical knowledge of relevant fields, the ability to correctly identify subtle signals of infant communication, and the ability to assess maternal sensitivity. This article presents the contents of the program and the pre-training results (N = 1.294 participants). Descriptive analyses as well as Pearson correlations and Bonferroni corrections of error were conducted using the statistical program SPSS v. 21.0. RESULTS: The findings show that a wide range of professionals are making use of the program, and that their existing theoretical knowledge about early preventive intervention, as well as their ability to identify subtle signals of infant communication, is relatively good. However, their ability to assess maternal sensitivity, which is considered a crucial indicator for the risk of child abuse, was low. CONCLUSIONS: The outcome of the pre-training results indicates that professionals working in the area of child protection need to develop more capability in recognizing maternal sensitivity, in order to ensure early detection of families who are at risk and thus in need of support. Finally, the number of years of professional experience did not correlate with the scores on any of the three measures, which emphasizes the importance of providing interdisciplinary training in this area for all those working in child and family services, regardless of background.

[Home treatment - especially effective among boys with externalizing disorders? Age- and sex-specific effectiveness of home treatment for internalizing and externalizing disorders]. / Home treatment - insbesondere für expansive Jungen? Alters- und geschlechtsspezifische Wirksamkeit von Home treatment bei internalisierenden vs. externalisierenden Störungen.

OBJECTIVE: Indications for home treatment for specific diagnoses in child and adolescent psychiatry have not yet been evaluated. METHOD: In a recent intervention study (primary outcome: length of stay), 92 patients aged 5 to 17 years were randomized into an intervention group (early discharge followed by home treatment in combination with inpatient treatment, where needed) and a control group (regular length inpatient treatment). The aim of this explorative analysis was to retrieve additional information on "what works for whom." Outcome parameters were as follows: Children's Global Assessment Scale (CGAS), Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA), Strengths and Difficulties Questionnaire (SDQ) and Columbia Impairment Scale (CIS) at T1 (within 14 days after intake), T2 (end of treatment) and T3 (∅ 8.4-month follow-up). Multiple regression was used to investigate the association between diagnoses, treatment setting, age, sex, and improvement in both groups. RESULTS: In children externalizing disorders were predominant, whereas in adolescents internalizing disorders were prominent. Patients improved equally under both types of treatment. Home treatment, however, was rated by the patients to be significantly more effective in adolescents (SDQ p = .017), boys (CIS p = .009, SDQ p < .001), and with externalizing disorders (SDQ p = .005). CONCLUSIONS: Home treatment may be considered an alternative to inpatient treatment, especially in boys with externalizing disorders.

Pilot study of a program delivered within the regular service system in Germany: effect of a short-term attachment-based intervention on maternal sensitivity in mothers at risk for child abuse and neglect.

This pilot study examined the effectiveness of a short-term attachment-based intervention, the Ulm Model, in a German population at risk for child abuse and neglect. The intervention used home visits and video feedback to promote maternal sensitivity, and was implemented by trained staff within the health care and youth welfare systems. Mothers in the control group (n=33) received standard services only, while those in the intervention group (n=63) additionally the Ulm Model intervention. The outcomes measured were maternal sensitivity, as assessed by the CARE-Index at pre-intervention, after the last session, and at about 6 and 12 months of age; and infant socio-emotional development, as assessed by the ET6-6 development test at about 6 and 12 months of age. The moderating effects on treatment outcomes of two variables were examined: risk for child abuse (moderate vs. high) and type of maternal attachment representation (secure vs. insecure). Among participants at moderate risk for child abuse, no differences were found between the intervention group and control group in either maternal sensitivity or infant development. Among those considered high risk, mothers in the intervention group showed a significant increase in maternal sensitivity from pre- to post-intervention; however, no group differences were seen at follow-up. There were some indications that infants of mothers in the intervention group showed better emotional development. The variable of maternal attachment representation was not a significant moderator for the intervention effect, but post hoc analysis indicated that the mean sensitivity of secure mothers was significant higher at the 6-month follow-up.