[Inpatient Psychodynamic Therapy for Children and Adolescents with Complex ADHD: Results of a Naturalistic Clinical Trial]. / Stationäre psychodynamische Therapie bei Kindern und Jugendlichen mit komplexer ADHS: Ergebnisse einer naturalistischen klinischen Studie.

The Attention deficit/hyperactivity disorder (ADHD) is a common mental disorder in childhood and adolescence. However, it is a very heterogeneous disorder with subgroups of patients with mild symptoms and others with severe and complex impairments. Patients suffering from complex ADHD are usually characterized by multiple developmental disorders and impaired personality development. Due to the multimodal origin of the disorder, multimodal treatment approaches aimed at reducing the various deficits are usually indicated. The current study evaluated a multimodal inpatient psychodynamic treatment (PDT) for children and adolescents suffering from ADHD. 47 patients (age 9-17 years) were included in the study. Next to complex impairments (comorbid mental disorders, deficits regarding psychic structure, learning disorders and sensorimotor integration disorders), a high number of adverse childhood experiences (M = 11.71) was particularly remarkable in the sample. The PDT led to significant improvements regarding ADHD symptoms and general level of functioning. However, first symptom improvements were already evident at the end of the waiting period. For ten patients who participated in the follow-up assessment effects remained stable six months after treatment. Due to the high drop-out rate, however, the study results have to be regarded as preliminary.

[Evidence for Psychodynamic Therapy for Children and Adolescents]. / Evidenz für psychoanalytisch begründete Verfahren für Kinder und Jugendliche.

In Germany, cognitive-behavioral therapy, psychodynamic therapy, and systemic therapy are scientifically and legally approved as suitable procedures for treating mental disorders. While all methods have provided empirical evidence of their effectiveness in adults according to defined criteria of the "Scientific Advisory Board for Psychotherapy" (in German: "Wissenschaftlicher Beirat Psychotherapie"), i. e., the official board which decides upon the formal scientific approval of psychotherapeutic approaches in Germany, an evaluation is lacking for the psychodynamic methods in children and adolescents. Against this background, we evaluated the available empirical data for psychodynamic therapy in children and adolescents based on the methods paper of the "Scientific Advisory Board for Psychotherapy" (2019; version 2.9). Published reviews served as the basis for identifying relevant studies, supplemented by a systematic literature search. We identified 91 potentially relevant studies but could not consider the majority of these due to formal exclusion criteria (mainly not disorder-specific, no control group). Up to 26 of the remaining studies provide evidence of efficacy as defined by the "Scientific Advisory Board for Psychotherapy". These cover 10 of the 18 areas of application as defined by the "Scientific Advisory Board for Psychotherapy". According to our evaluation, the reviewed studies provide empirical evidence for the three most relevant areas of application (i. e., affective disorders; anxiety disorders and obsessive-compulsive disorders; hyperkinetic disorders and conduct disorders). Thus, the available evidence supports the suitability of psychodynamic therapy as a method for the treatment of children and adolescents.

The chlamydial deubiquitinase Cdu1 supports recruitment of Golgi vesicles to the inclusion.

Chlamydia trachomatis is the main cause of sexually transmitted diseases worldwide. As obligate intracellular bacteria Chlamydia replicate in a membrane bound vacuole called inclusion and acquire nutrients for growth and replication from their host cells. However, like all intracellular bacteria, Chlamydia have to prevent eradication by the host's cell autonomous system. The chlamydial deubiquitinase Cdu1 is secreted into the inclusion membrane, facing the host cell cytosol where it deubiquitinates cellular proteins. Here we show that inactivation of Cdu1 causes a growth defect of C. trachomatis in primary cells. Moreover, ubiquitin and several autophagy receptors are recruited to the inclusion membrane of Cdu1-deficient Chlamydia. Interestingly, the growth defect of cdu1 mutants is not rescued when autophagy is prevented. We find reduced recruitment of Golgi vesicles to the inclusion of Cdu1 mutants indicating that vesicular trafficking is altered in bacteria without active deubiquitinase (DUB). Our work elucidates an important role of Cdu1 in the functional preservation of the chlamydial inclusion surface.

Safe haven under constant attack-The Chlamydia-containing vacuole.

Chlamydia belong to the group of obligate intracellular bacteria that reside in a membrane bound vacuole during the entire intracellular phase of their life cycle. This vacuole called inclusion shields the bacteria from adverse influences in the cytosol of the host cell like the destructive machinery of the cell-autonomous defence system. The inclusion thereby prevents the digestion and eradication in specialised compartments of the intact and viable cell called phagolysosomes or autophagolysosomes. It is becoming more and more evident that keeping the inclusion intact also prevents the onset of cell intrinsic cell death programmes that are activated upon damage of the inclusion and direct the cell to destruct itself and the pathogen inside. Chlamydia secrete numerous proteins into the inclusion membrane to protect and stabilise their unique niche inside the host cell. We will focus in this review on the diverse attack strategies of the host aiming at the destruction of the Chlamydia-containing inclusion and will summarise the current knowledge on the protection mechanisms elaborated by the bacteria to maintain the integrity of their replication niche.

Subversion of Cell-Autonomous Host Defense by Chlamydia Infection.

Obligate intracellular bacteria entirely depend on the metabolites of their host cell for survival and generation of progeny. Due to their lifestyle inside a eukaryotic cell and the lack of any extracellular niche, they have to perfectly adapt to compartmentalized intracellular environment of the host cell and counteract the numerous defense strategies intrinsically present in all eukaryotic cells. This so-called cell-autonomous defense is present in all cell types encountering Chlamydia infection and is in addition closely linked to the cellular innate immune defense of the mammalian host. Cell type and chlamydial species-restricted mechanisms point a long-term evolutionary adaptation that builds the basis of the currently observed host and cell-type tropism among different Chlamydia species. This review will summarize the current knowledge on the strategies pathogenic Chlamydia species have developed to subvert and overcome the multiple mechanisms by which eukaryotic cells defend themselves against intracellular pathogens.

ABMA, a small molecule that inhibits intracellular toxins and pathogens by interfering with late endosomal compartments.

Intracellular pathogenic microorganisms and toxins exploit host cell mechanisms to enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat multiple pathogen infections and that should not induce drug resistance is the use of small molecules that target host components. We identified the compound 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) from a cell-based high throughput screening for its capacity to protect human cells and mice against ricin toxin without toxicity. This compound efficiently protects cells against various toxins and pathogens including viruses, intracellular bacteria and parasite. ABMA provokes Rab7-positive late endosomal compartment accumulation in mammalian cells without affecting other organelles (early endosomes, lysosomes, the Golgi apparatus, the endoplasmic reticulum or the nucleus). As the mechanism of action of ABMA is restricted to host-endosomal compartments, it reduces cell infection by pathogens that depend on this pathway to invade cells. ABMA may represent a novel class of broad-spectrum compounds with therapeutic potential against diverse severe infectious diseases.

Chlamydia trachomatis-containing vacuole serves as deubiquitination platform to stabilize Mcl-1 and to interfere with host defense.

Obligate intracellular Chlamydia trachomatis replicate in a membrane-bound vacuole called inclusion, which serves as a signaling interface with the host cell. Here, we show that the chlamydial deubiquitinating enzyme (Cdu) 1 localizes in the inclusion membrane and faces the cytosol with the active deubiquitinating enzyme domain. The structure of this domain revealed high similarity to mammalian deubiquitinases with a unique α-helix close to the substrate-binding pocket. We identified the apoptosis regulator Mcl-1 as a target that interacts with Cdu1 and is stabilized by deubiquitination at the chlamydial inclusion. A chlamydial transposon insertion mutant in the Cdu1-encoding gene exhibited increased Mcl-1 and inclusion ubiquitination and reduced Mcl-1 stabilization. Additionally, inactivation of Cdu1 led to increased sensitivity of C. trachomatis for IFNγ and impaired infection in mice. Thus, the chlamydial inclusion serves as an enriched site for a deubiquitinating activity exerting a function in selective stabilization of host proteins and protection from host defense.

Inhibitors of retrograde trafficking active against ricin and Shiga toxins also protect cells from several viruses, Leishmania and Chlamydiales.

Medical countermeasures to treat biothreat agent infections require broad-spectrum therapeutics that do not induce agent resistance. A cell-based high-throughput screen (HTS) against ricin toxin combined with hit optimization allowed selection of a family of compounds that meet these requirements. The hit compound Retro-2 and its derivatives have been demonstrated to be safe in vivo in mice even at high doses. Moreover, Retro-2 is an inhibitor of retrograde transport that affects syntaxin-5-dependent toxins and pathogens. As a consequence, it has a broad-spectrum activity that has been demonstrated both in vitro and in vivo against ricin, Shiga toxin-producing O104:H4 entero-hemorrhagic E. coli and Leishmania sp. and in vitro against Ebola, Marburg and poxviruses and Chlamydiales. An effect is anticipated on other toxins or pathogens that use retrograde trafficking and syntaxin-5. Since Retro-2 targets cell components of the host and not directly the pathogen, no selection of resistant pathogens is expected. These lead compounds need now to be developed as drugs for human use.

[Changes in OPD-CA Axis Structure During Inpatient Psychodynamic Treatment of Adolescents Suffering from Comorbid Disorders of Conduct and Emotions]. / Veränderungen der psychischen Struktur im Verlauf der stationären psychodynamischen Behandlung von jugendlichen Patienten mit einer kombinierten Störung des Sozialverhaltens und der Emotionen.

In a randomized controlled clinical trial (RCT) we evaluated an inpatient psychodynamic treatment for adolescents suffering from mixed disorders of conduct and emotions. The sample consisted of severely impaired adolescents with remarkable deficits regarding psychic structure. The current study wanted to examine if the manualized treatment did not only reduce symptoms but also enhance the structural level of the patients. The axis structure of the Operationalized Psychodynamic Diagnostics in Childhood and Adolescence (OPD-CA) was used to assess the structural level of N = 46 adolescent inpatients. To examine differences between the patients' structural level at the beginning and at the end of inpatient treatment we conducted a repeated measures ANOVA. The overall score as well as the three subscores of the axis structure improved significantly during inpatient treatment. The corresponding effect sizes were large (η(2) = .29 to .47). The inpatient psychodynamic treatment led to significant improvements regarding symptomatology as well as psychic structure. However, further studies with larger sample size and control group data should be conducted to confirm these results.

IDENTITY FORMATION DIFFICULTIES IN IMMIGRANT ADOLESCENTS: THREE CASES FROM GERMANY.

Adolescence is a period of instability caused by biological changes and restructuring of the personality. An immigration background renders the process of identity formation even more difficult or fragile, with an additional burden coming from persecution and harassment. Three case studies of mentally disturbed adolescents with different immigration backgrounds illustrate the problems in diagnosis and psychotherapy. All three cases share a common feature--the particular influence of the native country on the psychic disorder of the adolescent, be it a suitable target of narcissistic self-aggrandizement, a reactivated metaphor of the past or a deposited conflict. I point out and discuss the danger of diagnostic colonization and activation of perpetrator-victim constellations--such as the Nazi past in the present. Offering a transcultural transitional space as a container yields a therapeutic approach to the different worlds of these borderland adolescents.

Early Intervention for Borderline Personality Disorder: Psychodynamic Therapy in Adolescents.

OBJECTIVES: Borderline personality disorder (BPD) should be understood as a disorder of development (Streeck-Fischer 2008, 2013) that has its first manifestation in late childhood and adolescence. There are only few treatment studies of adolescents meeting the diagnostic criteria of borderline personality disorder, although early interventions for these patients are urgently needed (see Chanen & McCutcheon 2013). We examined the effectiveness of an inpatient psychodynamic therapy (PDT). METHODS: Twenty-eight adolescents fulfilling the DSM-IV diagnostic criteria of borderline personality disorder were treated with psychodynamic therapy. The mean duration of treatment was 29.87 weeks (SD = 15.88). Outcomes were remission rates, GAF, GSI, SDQ, IIP and BPI scores. Assessments were made at admission and after treatment. Pre-post comparisons and comparisons with normative data were conducted. RESULTS: At the end of treatment 39.29% of the patients were remitted. We found significant improvements for the GAF, GSI, SDQ, IIP (all p0.001) and the BPI (p = 0.006). CONCLUSIONS: These clinically relevant improvements demonstrate the effectiveness of psychodynamic therapy in adolescents with borderline personality disorder and stress the usefulness of an early intervention for these patients.

Academic model of trauma healing in post-war societies.

OBJECTIVE: The aim of this paper is to examine the implications for healing in a contemporary Balkan post-war context, and to provide a bridge-building model of trauma transformation, reconciliation and recovery through academic reconstruction and cross-border dialogue. Post-war societies are marked by the effects of massive, large group traumatization, and if not properly dealt with, long-term rehabilitation and social recovery cannot be expected. Unprocessed cumulative trauma that has become deeply embedded in the collective memory of the Balkan peoples over centuries, "chosen trauma", its trans-generational transmission and periodical reactivations across the Balkan have often been addressed in recent literature, in ethno-psychology, psychoanalysis, psychiatry, sociology and anthropology. In order to deepen our understanding of the roots of collective (social) trauma and the specific traumatic experiences of different groups, and to offer different perspectives and information on how trauma can be dealt with, the "Trauma Trust Memory" multinational interdisciplinary research network is being established, and a groundbreaking workshop was held in May 2013 in Tuzla, Bosnia-Herzegovina. CONCLUSION: The Tuzla Workshop showed that the active participation of affected groups in adequate coping with the past is required for post-conflict reconstruction, trauma healing and peacebuilding in the long run.

[Developmental trauma--differences between the course of inpatient treatment in adolescent patients with or without trauma history]. / Traumatisierungen in der Entwicklung--unterschiedliche Verläufe stationärer Psychotherapie bei jugendlichen Patienten mit und ohne Traumatisierung.

SUMMARY OBJECTIVE: Aim of the study was to examine differences between the course of inpatient treatment in adolescents with different extents of trauma history. METHODS: Using multilevel analysis, we investigated the differences between the course of inpatient treatment in adolescents without trauma history, with emotional trauma and complex trauma. RESULTS: Regarding the GSI of the SCL-90-R, patients with trauma history showed significantly more symptom reduction than patients without trauma history. In terms of interpersonal problems (IIP) especially adolescents with emotional trauma seemed to benefit. CONCLUSIONS: Especially patients with trauma history benefited from the examined inpatient treatment concept. However, our results also show that the complex traumatized patients required longer treatment duration since they benefited particularly in the last phase of inpatient treatment.

[Inter-rater reliability and construct validity of the OPD-CA axis structure: first study results regarding the integration of OPD-CA into clinical practice]. / Interrater-reliabilität und Konstruktvalidität der OPD-KJ-Achse Struktur--Erste Forschungsergebnisse zum Einsatz der OPD-KJ im Rahmen der klinischen Routine.

The axis structure of the Operationalized Psychodynamic Diagnostics in childhood and adolescence (OPD-CA) has proven to be a reliable and valid diagnostic tool under research conditions. However, corresponding data regarding the integration of OPD-CA axis structure into clinical practice is still lacking. Hence, this aspect was examined as part of a randomized controlled clinical trial realized at Asklepios Fachklinikum Tiefenbrunn. Here, the OPD-CA axis structure has been applied to assess the structural level of 42 adolescent patients (15-19 years). In contrast to previous studies, the assessment was not carried out by independent raters using a videotaped OPD-CA interview, but the rating was part of clinical routine procedures. Also under these conditions, inter-rater reliability was high, in particular regarding the four subscales of the OPD-CA axis structure. With respect to construct validity, the results of our study supported a two-factor solution, which is in accordance with the findings of two previous works. One factor corresponded to the dimension "self-regulation" while the other factor included both the dimension "self-perception and object perception" as well as the dimension "communication skills". Implications of the findings for research and practice are discussed.

[Containing, right hemisphere: projective identification as an interpersonal mechanism, the ability for affect regulation]. / Rechtshemisphärisch aushalten statt linkshemisphärisch deuten--Projektive Identifizierung als interpersonaler Mechanismus zur Entwicklung der Fähigkeit zur Affektregulation.

The capacity of affect regulation develops with priority in reciprocal, non-verbal communication processes between the early caregiver and the baby. In this process, the projective identification plays the role of crucial means of communication. Processes of projective identification which emerge in therapeutic and educational interactions can be understood as such an early form of communication which contributes to the afterward-ripening of the capacity of affect regulation. Before the background of recent neuro-psychological findings it becomes clear, why the reciprocal and non-verbal communication between the early caregiver and infant as well as between the therapist and the patient is of such fundamental importance for the structural (re-) maturation of the right cerebral hemisphere, as well as for the connections between the left and right hemisphere. In case the projective identification persists as a defensive strategy in dealing with other people, pathological interaction circles can develop which can be overcome only when, for example, the other person assumes the role of the "regulating other".

[Psychoanalytic-interactional psychotherapy of severely disturbed adolescents]. / Psychoanalytisch-interaktionelle Psychotherapie von Jugendlichen mit strukturellen Störungen.

Due to specific developmental conditions of adolescence like deficient self reflective capacities or reduced potential to articulate, the psychotherapy of adolescents is faced with special problems. In adolescents with severe Ego-structural disorders like Borderline (Development) Disorders these problems are increased exponentially. Patients replicate their negative and often traumatic relational experiences in everyday life as well as in therapy. The therapeutic treatment of relational entanglements often results in malignant repetitions. Here the Psychoanalytic-interactional Method (PiM) is suitable as intervention where the therapist approaches the patient as a person who influences the development positively and strives for Ego-structural advancement within the therapeutic relation. The Psychoanalytic-interactional Method allows for the adolescence-specific conditions of limited mentalization and particulary for the problem of Ego-structural disorders in adolescence. The method is demonstrated by treatment sequences of the therapy of a juvenile female patient with Borderline (Development) Disorder.