Mitochondrial DNA as a marker for treatment-response in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a serious mental health condition thought to be mediated by a dysregulated stress response system. Stress, especially chronic stress, affects mitochondrial activity and their efficiency in duplicating their genomes. Human cells contain numerous mitochondria that harbor multiple copies of their own genome, which consist of a mixture of wild type and variant mtDNA - a condition known as mitochondrial heteroplasmy. Number of mitochondrial genomes in a cell and the degree of heteroplasmy may serve as an indicator of mitochondrial allostatic load. Changes in mtDNA copy number and the proportion of variant mtDNA may be related to mental disorders and symptom severity, suggesting an involvement of mitochondrial dysfunction also in PTSD. Therefore, we examined number and composition of mitochondrial DNA before and after six weeks of inpatient psychotherapy treatment in a cohort of 60 female PTSD patients. We extracted DNA from isolated monocytes before and after inpatient treatment and quantified cellular mtDNA using multiplex qPCR. We hypothesized that treatment would lead to changes in cellular mtDNA levels and that change in mtDNA level would be associated with PTSD symptom severity and treatment response. It could be shown that mtDNA copy number and the ratio of variant mtDNA decreased during therapy, however, this change did not correlate with treatment response. Our results suggest that inpatient treatment can reduce signs of mitochondrial allostatic load, which could have beneficial effects on mental health. The quantification of mtDNA and the determination of cellular heteroplasmy could represent valuable biomarkers for the molecular characterization of mental disorders in the future.

[ZSE-DUO - dual guidance structure at the centre for rare diseases]. / ZSE-DUO ­ duale Lotsenstruktur im Zentrum für Seltene Erkrankungen.

BACKGROUND: Patients with an unclear diagnosis and suspected rare disease pose special challenges to physicians, among others. AIM OF THE STUDY (RESEARCH QUESTION): The ZSE-DUO project aims to establish whether patient care under the joint supervision of a somatic expert and a mental health expert can improve diagnostic efficacy and precision, as well as shorten the time to diagnosis. MATERIAL AND METHODS: ZSE-DUO has successfully recruited more than 1000 patients at eleven national centres for rare diseases in a control and an intervention group. The findings are being analysed by three evaluating institutions. RESULTS AND DISCUSSION: The study is currently in its final phase. The results will be published in further papers.

Understanding and breaking the intergenerational cycle of abuse in families enrolled in routine mental health services: study protocol for a randomized controlled trial and two non-interventional trials investigating mechanisms of change within the UBICA II consortium.

BACKGROUND: Parents' mental illness (MI) and parental history of early life maltreatment (ELM) are known to be significant risk factors for poor parenting while poor parenting is a crucial mediator of the intergenerational continuity of child maltreatment. Hence, maltreatment prevention programs for families with an MI parent, which pay particular attention to experiences of ELM in the parent, are urgently needed. Parental mentalizing was previously found to mediate successful parenting. Interventions aimed at improving the parental mentalizing capacity reduced maltreatment risk in parents. The aim of the present study is to investigate the effectiveness of a mentalization-based parenting-counseling in acutely mentally ill parents currently treated at a psychiatric hospital. METHODS: Mentalization-based parenting-counseling (MB-PC) vs. enhanced standard clinical care (SCC+) will be administered in a cluster-randomized-controlled trial (RCT). Patients treated at psychiatric hospitals with children between 1.5 and 15 years will be included in the trial. MB-PC will be administered as a 12-h combined individual and group program enriched by social counseling (over a course of 5 weeks) as add-on to standard clinical care, while the control condition will be standard clinical care plus a 90-min psychoeducation workshop on positive parenting. Primary efficacy endpoint is self-reported parenting practices at follow-up. Embedded within the RCT will be two sub-studies investigating social cognition and dyadic synchrony as biobehavioral mechanisms of change. DISCUSSION: The main goal of the present study is to investigate ways to break the intergenerational continuity of maltreatment by assessing the benefits of a prevention program which aims at improving parenting in vulnerable mothers and fathers. MB-PC is a short, low-cost intervention which can be delivered by nurses and social workers and is applicable to MI patients with children with a broad range of diagnoses. If it is shown to be effective, it can be directly implemented into standard psychiatric hospital care thereby providing help to prevent child maltreatment. TRIAL REGISTRATION: German Clinical Trials Register DRKS00017398 . Registered on 5 July 2019.

Oxytocin and social anxiety: Interactions with sex hormones.

Oxytocin has been associated with anxiolytic and stress reducing effects in a number of studies. Less is known about the associations of endogenous oxytocin concentrations and their interaction with other hormones such as sex hormones in relation to self-reported anxiety levels. In this study, endogenous oxytocin and sex hormone levels were analyzed in 99 high (51 women) and 100 low (50 women) socially anxious individuals. Regression analyses showed that women with high oxytocin and estradiol levels reported a lower total Liebowitz Social Anxiety Score (LSAS) as well as a lower score on the subscale LSAS Fear. This association of hormonal interaction with social anxiety scores was significant in the subsample of high socially anxious women. In men there were no significant associations for endogenous hormones with LSAS scores. These findings suggest that in women the link between oxytocin and anxiety might be dependent on basal anxiety levels as well as on individual sex hormone levels.

A mechanism-based group-psychotherapy approach to aggressive behaviour in borderline personality disorder: findings from a cluster-randomised controlled trial.

BACKGROUND: Aggressive behaviour is a prevalent and harmful phenomenon in patients with borderline personality disorder (BPD). However, no short-term, low-cost programme exists that specifically focuses on aggression. AIMS: Attuning therapy modules to pathogenetic mechanisms that underlie reactive aggression in BPD, we composed a 6 week mechanism-based anti-aggression psychotherapy (MAAP) approach for the group setting, which we tested against a non-specific supportive psychotherapy (NSSP). METHOD: A cluster-randomised two-arm parallel-group phase II trial of N = 59 patients with BPD and overt aggressive behaviour was performed (German Registry for Clinical Trials, DRKS00009445). The primary outcome was the externally directed overt aggression score of the Modified Overt Aggression Scale (M-OAS) post-treatment (adjusted for pre-treatment overt aggression). Secondary outcomes were M-OAS irritability, M-OAS response rate and ecological momentary assessment of anger post-treatment and at 6 month follow-up, as well as M-OAS overt aggression score at follow-up. RESULTS: Although no significant difference in M-OAS overt aggression between treatments was found post-treatment (adjusted difference in mean 3.49 (95% CI -5.32 to 12.31, P = 0.22), the MAAP group showed a clinically relevant decrease in aggressive behaviour of 65% on average (versus 33% in the NSSP group), with particularly strong improvement among those with the highest baseline aggression. Most notably, significant differences in reduction in overt aggression between MAAP and NSSP were found at follow-up. CONCLUSIONS: Patients with BPD and aggressive behaviour benefited from a short group psychotherapy, with improvements particularly visible at 6 month follow-up. Further studies are required to show whether these effects are specific to MAAP.

[Innovative psychotherapy research: towards an evidence-based and process-based individualized and modular psychotherapy]. / Innovative Psychotherapieforschung: auf dem Weg zu einer evidenz- und prozessbasierten individualisierten und modularen Psychotherapie.

Psychotherapy has been proven to be effective; however, this statement applies in particular to the "average patient" in randomized controlled trials. As a considerable proportion of patients do not show any benefits despite the constant development of new therapy methods and the mechanisms of action are still too little understood, innovative psychotherapy research has to address both problems. In addition, the idea of personalization that originated in somatic medicine or - from our point of view more appropriately - individualization or person-centering should be taken up. After providing an overview of further developments in psychotherapy beyond disorder-specific methods, this article presents an evidence- and process-based individualized and modular psychotherapy as a visionary goal of psychotherapeutic research: Beyond syndromes and disorders, as many biopsychosocial characteristics as possible and the processes and mechanisms underlying the mental problems should be analyzed and bundled in an individual comprehensive functional analysis. Based on this functional analysis, evidence-based techniques and modules should be selected. The individual response during the course of therapy should be continuously documented, so that feedback helps to determine the further therapeutic procedure. In order to pursue this vision, studies are needed that are oriented towards the individual patient, investigate the central mechanisms of action and generate large translational datasets. These should be analyzed by ideographic analyses and reduce the gap between research and practice, thus contributing to the paradigm of a practice research network, which is now consistently moving to the centre of research.

[Impact of early life maltreatment of women on the mother-child relationship : Data from mother-child dyads from Heidelberg and Berlin]. / Einfluss früher Gewalterfahrungen von Frauen auf die Mutter-Kind-Beziehung : Daten von Heidelberger und Berliner Mutter-Kind-Dyaden.

Early life maltreatment can have severe and long-lasting consequences for the directly affected individual as well as for the next generation. Data from our research including mother-child dyads from Heidelberg and Berlin show that early life maltreatment is associated with behavioral and neural changes including personality traits and attachment style of the affected mothers that negatively affect their relationship with their child. The children of these mothers affected by early life maltreatment have an elevated risk to be maltreated and to develop mental disorders. They also show a heightened cortisol concentration and a reduced inhibition control. It seems to be of importance whether the mother has experienced early life maltreatment but is resilient, meaning that she has not developed a mental disorder (up to the time of examination) or whether in addition to the early life maltreatment she has developed a mental disorder later in life. Children of mothers with early life maltreatment and a lifetime mental disorder seem to be especially exposed to stress and show the greatest impairments and risks. Based on the existing data from our research practical and clinical implications are discussed and one possible intervention in the form of a training of mentalization competencies for parents is presented.

Gain-of-function variants in the melanocortin 4 receptor gene confer susceptibility to binge eating disorder in subjects with obesity: a systematic review and meta-analysis.

The association between coding variants in the melanocortin 4 receptor gene (MC4R) and binge eating disorder (BED) in patients with obesity is controversial. Two independent reviewers systematically searched MEDLINE, Embase, PsycINFO, BIOSIS Previews, Web of Science Core Collection and Google Scholar up to February 2018, using terms describing the MC4R gene and BED. Six of 103 identified references were included. Studies examined associations between at least one coding variant/mutation in MC4R and BED and screened for BED as per the Diagnostic and Statistical Manual of Mental Disorders. Risk of bias was assessed using a modified version of the Q-Genie tool, and overall quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation guidance. Meta-analysis was conducted via logistic regression models. A positive association between gain-of-function (GOF) variants in the MC4R and BED was observed (odds ratio [OR] = 3.05; 95% confidence interval [CI]: 1.82, 5.04; p = 1.7 × 10-5 ), while no association was detected between loss-of-function (LOF) mutations and BED (OR = 1.50; 95% CI: 0.73, 2.96; p = 0.25). Similar results were found after accounting for study quality (GOF variants: OR = 3.15; 95% CI: 1.76, 5.66; p = 1.1 × 10-4 ; LOF mutations: OR = 1.50; 95% CI: 0.73, 2.97; p = 0.25). Our systematic review and meta-analysis provides evidence that GOF variants as opposed to LOF mutations in MC4R are associated with BED in subjects with obesity.

[Borderline personality : Alterations to brain structure and function through psychotherapy]. / Borderline-Persönlichkeitsstörung : Veränderung der Hirnstruktur und -funktion durch Psychotherapie.

BACKGROUND: There are now several scientifically evaluated psychotherapeutic methods for borderline personality disorder (BPD), all of which aim to improve the ability to regulate emotions. In recent years, there have been first studies on the neuronal correlates of the mechanisms of emotion regulation and of changes caused by psychotherapeutic interventions. METHODS: This article reviews the data on functional and structural imaging studies that examine facets of disturbed emotion regulation before and after psychotherapy. RESULTS: Although the overall database is still sparse, clinical improvement in psychotherapy appears to be associated with modulation of brain structure and function. Frontolimbic regulation circuits including the amygdala, insula, anterior cingulate cortex (ACC) and other prefrontal areas appear to be involved in these changes. An important finding is the reduction of initially increased amygdala activity after successful Dialectical Behavior Therapy (DBT). CONCLUSION: The changes shown here most probably reflect an improvement in emotion regulation capacities in BPD and demonstrate the possibility of modulating disturbed emotion regulation processes. Since long-term follow-up data are still missing, the sustainability of the suggestive improvements still has to be proven in further studies.

How do patients with anorexia nervosa "process" psychotherapy between sessions? A comparison of cognitive-behavioral and psychodynamic interventions.

OBJECTIVE: Patients' processing of psychotherapy between sessions ("inter-session process" (ISP)) has been repeatedly shown to be related to outcome. The aim of this study was to compare ISP characteristics of cognitive-behavioral vs. psychodynamic psychotherapy in the treatment of anorexia nervosa (AN) and their relation to outcome. METHODS: Data of 106 patients participating in a randomized-controlled trial who received either 40 sessions of enhanced cognitive-behavioral therapy (CBT-E) or focal psychodynamic therapy (FPT) were analyzed. The ISP was measured with the Inter-session Experience Questionnaire (IEQ). Three outcome classes were distinguished: full recovery, partial recovery, and still fulfilling all AN criteria. RESULTS: Patients receiving CBT-E reported more on "applying therapy" in the initial and the final treatment phase compared to FPT patients. In terms of process-outcome relations, higher levels of "recreating the therapeutic dialogue between sessions," "recreating the therapeutic dialogue with negative emotions" as well as "applying therapy with negative emotions" in the final phase of treatment predicted negative outcome in FPT, whereas overall higher levels of negative emotions predicted negative outcome in CBT-E. CONCLUSIONS: In outpatient treatment in AN, the processing of therapy as measured by the IEQ showed surprisingly few differences between CBT-E and FPT. However, different ISP patterns were predictive of outcome, pointing to different mechanisms of change.

Oxytocin and Pain Perception: From Animal Models to Human Research.

An accumulating body of evidence suggests that the hypothalamic neuropeptide oxytocin (OT) has a modulatory effect on pain processing. Particularly strong evidence comes from animal models. Here, we review recent advances in animal research on the analgesic effects of OT and discuss possible target sites of OT within descending and ascending pain pathways in the brain. In addition to the spinal cord being a direct target of the neuropeptide, OT has also been shown to modulate the neuronal activity of limbic and cortical brain regions, which play a major role in the cognitive and emotional processing of pain. Human studies investigating the influence of OT on pain perception are less numerous and have revealed less consistent results. The human literature is therefore scanned thoroughly and different approaches to study the effects of OT on pain perception in humans are discussed. Moreover, we also address how OT might alleviate pain by influencing socio-emotional components in humans. We conclude that further investigating specific OT and OT-sensitive circuits, which modulate pain processing especially in primates, will improve our understanding of OT-analgesic effects. In human research, the increased use of neuroimaging and autonomic measures might help to bridge the gap to animal studies.

Performance of International Medical Students In psychosocial medicine.

BACKGROUND: Particularly at the beginning of their studies, international medical students face a number of language-related, social and intercultural challenges. Thus, they perform poorer than their local counterparts in written and oral examinations as well as in Objective Structured Clinical Examinations (OSCEs) in the fields of internal medicine and surgery. It is still unknown how international students perform in an OSCE in the field of psychosocial medicine compared to their local fellow students. METHODS: All students (N = 1033) taking the OSCE in the field of psychosocial medicine and an accompanying written examination in their eighth or ninth semester between 2012 and 2015 were included in the analysis. The OSCE consisted of four different stations, in which students had to perform and manage a patient encounter with simulated patients suffering from 1) post-traumatic stress disorder, 2) schizophrenia, 3) borderline personality disorder and 4) either suicidal tendency or dementia. Students were evaluated by trained lecturers using global checklists assessing specific professional domains, namely building a relationship with the patient, conversational skills, anamnesis, as well as psychopathological findings and decision-making. RESULTS: International medical students scored significantly poorer than their local peers (p < .001; η2 = .042). Within the specific professional domains assessed, they showed poorer scores, with differences in conversational skills showing the highest effect (p < .001; η2 = .053). No differences emerged within the multiple-choice examination (p = .127). CONCLUSION: International students showed poorer results in clinical-practical exams in the field of psychosocial medicine, with conversational skills yielding the poorest scores. However, regarding factual and practical knowledge examined via a multiple-choice test, no differences emerged between international and local students. These findings have decisive implications for relationship building in the doctor-patient relationship.

[Coercive measures in German hospitals for psychiatry and psychotherapy : A pilot study by the DGPPN to evaluate a uniform assessment instrument]. / Zwangsmaßnahmen in deutschen Kliniken für Psychiatrie und Psychotherapie : Eine Pilotstudie der DGPPN zur Erprobung eines einheitlichen Erfassungsinstrumentes.

STUDY OBJECTIVE: A simple instrument to record case-related coercive measures was tested as part of a pilot project of the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN). METHODS: To assess coercive measures data were collected for 3 months in 8 German hospitals for psychiatry and psychotherapy. The type of measures used, the main diagnosis and the legal basis for the coercive measures were documented. RESULTS: In the sample studied, coercive measures were applied in 8% of cases. Coercive measures were most commonly used in patients with a schizophrenic disorder. The principle of justifiable necessity according to § 34 of the German Penal Code was used particularly often as the legal basis for justifying the coercive measures. CONCLUSION: Suitable measurement instruments and reliable data that enable the learning of best practices represent the basis for a reduction of coercive measures.

Cost-effectiveness of focal psychodynamic therapy and enhanced cognitive-behavioural therapy in out-patients with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a serious illness leading to substantial morbidity and mortality. The treatment of AN very often is protracted; repeated hospitalizations and lost productivity generate substantial economic costs in the health care system. Therefore, this study aimed to determine the differential cost-effectiveness of out-patient focal psychodynamic psychotherapy (FPT), enhanced cognitive-behavioural therapy (CBT-E), and optimized treatment as usual (TAU-O) in the treatment of adult women with AN. METHOD: The analysis was conducted alongside the randomized controlled Anorexia Nervosa Treatment of OutPatients (ANTOP) study. Cost-effectiveness was determined using direct costs per recovery at 22 months post-randomization (n = 156). Unadjusted incremental cost-effectiveness ratios (ICERs) were calculated. To derive cost-effectiveness acceptability curves (CEACs) adjusted net-benefit regressions were applied assuming different values for the maximum willingness to pay (WTP) per additional recovery. Cost-utility and assumptions underlying the base case were investigated in exploratory analyses. RESULTS: Costs of in-patient treatment and the percentage of patients who required in-patient treatment were considerably lower in both intervention groups. The unadjusted ICERs indicated FPT and CBT-E to be dominant compared with TAU-O. Moreover, FPT was dominant compared with CBT-E. CEACs showed that the probability for cost-effectiveness of FTP compared with TAU-O and CBT-E was ⩾95% if the WTP per recovery was ⩾€9825 and ⩾€24 550, respectively. Comparing CBT-E with TAU-O, the probability of being cost-effective remained <90% for all WTPs. The exploratory analyses showed similar but less pronounced trends. CONCLUSIONS: Depending on the WTP, FPT proved cost-effective in the treatment of adult AN.

[Guideline-adherent inpatient psychiatric psychotherapeutic treatment of borderline personality disorder : Normative definition of personnel requirements]. / Leitliniengerechte stationäre psychiatrisch-psychotherapeutische Behandlung der Borderline-Persönlichkeitsstörung : Normative Personalbedarfsermittlung.

BACKGROUND: Borderline personality disorders (BPD) are severe mental diseases which place high pressure on the psychiatric healthcare system. Nowadays, well-tested, disorder-specific treatment concepts are available also for inpatient treatment in Germany. These show very good and long-term improvements in the psychopathology as well as posttreatment social participation; however, prerequisites for the implementation of these evidence-based inpatient psychotherapy programs are well-trained treatment teams and appropriate financing of resource expenditure. OBJECTIVE: The aim was to formulate a definition of normative needs for treatment duration and intensity for a guideline-conform, empirically proven and effective inpatient treatment of borderline personality disorder as well as the derived personnel requirements in comparison to the currently available resources within the framework of the Psychiatry Personnel Act (Psych-PV). MATERIAL AND METHODS: The resource requirements were established based on evaluated hospital ward models, the recommendations of the S2 guidelines and the criteria of specialist societies and compared with the personnel stipulations according to the Psych-PV. RESULTS: The results for a normatively established treatment program showed a pronounced deficit in the financing of the evaluated resource requirements, even when the stipulations laid down in the Psych-PV were implemented to 100 %. DISCUSSION: Disorder-specific inpatient treatment programs for borderline personality disorder have been scientifically proven to be highly effective; however, resource analyses show that the personnel requirements necessary for effective implementation of these programs are much higher than those allocated by the funding according to the Pysch-PV. The current underfunding leads to inadequate treatment outcomes with high readmission rates and as a result high direct and indirect costs of illness.

Personality disorders and obesity: a systematic review.

BACKGROUND: Studies demonstrate an association between personality traits and obesity as well as their prognostic influence on weight course. In contrast, only few studies have investigated the association between personality disorders (PDs) and obesity. OBJECTIVE: The present review summarizes through a comprehensive and critical evaluation the results of 68 studies identified by database research (PubMed and PsycINFO) covering the last 35 years that investigated the association between PDs, overweight and obesity as well as the predictive value of PDs for the development of obesity and the effectiveness of weight reduction treatments. RESULTS: Adults with any PD have a higher risk of obesity. In the female general population, there is an association between avoidant or antisocial PD and severe obesity. Further, women with paranoid or schizotypal PD have a higher risk of obesity. Clinical studies including foremost female participants showed a higher comorbidity of PDs, especially borderline PD and avoidant PD, in binge-eating disorder. Regarding both genders, patients with PD show less treatment success in conservative weight-loss treatment programmes for obesity than patients without PD. CONCLUSIONS: In prevention and conservative weight-loss treatment strategies, more care should be taken to address the special needs of patients with comorbid PDs.

[Guideline-adherent inpatient psychiatric psychotherapeutic treatment of obsessive-compulsive disorder : Normative definition of personnel requirements]. / Leitliniengerechte stationäre psychiatrisch-psychotherapeutische Behandlung der Zwangsstörung : Normative Personalbedarfsermittlung.

BACKGROUND: Guideline-oriented inpatient psychiatric and psychotherapeutic treatment of patients with obsessive-compulsive disorder (OCD) is an important part of the care available for these patients. It may not be adequately reflected in the current personnel resources available according to the German psychiatry personnel regulation (Psych-PV). OBJECTIVES: The goal of this work was to assess the personnel resources necessary for a guideline-oriented inpatient psychiatric and psychotherapeutic treatment of patients with OCD and compare the necessary resources with the resources available according to Psych-PV. METHODS: Based on the German national guidelines for OCD and a meta-analysis on treatment intensity, we formulated a normative weekly treatment plan. Based on this plan we calculated the necessary personnel resources and compared these with the resources available according to Psych-PV category A1 (standard care). RESULTS: The weekly treatment time for a guideline-oriented inpatient psychiatric and psychotherapeutic treatment of patients with OCD is 23.5 h per week. This corresponds to a weekly personnel requirement of 20.9 h. This requirement is only partly reflected in the Psych-PV (17.3 h, 82.8 %). The coverage of personnel resources by Psych-PV is even lower for psychotherapy provided by psychiatrist and psychologists (38.3 %, i. e. 183 min in the normative plan versus 70 min in Psych-PV). CONCLUSIONS: The current paper shows that the personal resources required for a guideline-oriented inpatient psychiatric and psychotherapeutic treatment of patients with OCD is not adequately reflected in the German psychiatry personnel regulation (Psych-PV). The actual shortage may be underestimated in our paper.

[Guideline-conform inpatient psychiatric psychotherapeutic treatment of chronic depression: Normative personnel requirements]. / Leitlinienentsprechende stationäre psychiatrisch-psychotherapeutische Behandlung der chronischen Depression : Normative Personalbedarfsermittlung.

BACKGROUND: Chronic depression is a frequent mental disorder representing a significant subjective and economic burden. Effective disorder-specific treatment of chronic depression presupposes sufficient funding of treatment resources. OBJECTIVE: Definition of normative needs of personnel resources for guideline-compliant and evidence-based inpatient treatment of chronic depression based on treatment duration and intensity. The personnel resources determined were compared to the resources provided on the basis of the existing reimbursement system (Psych-PV) in Germany. MATERIAL AND METHODS: Resources determined according to national treatment guidelines and empirical evidence were compared to personnel resources dictated by the German Psych-PV reimbursement algorithm. RESULTS: The current funding algorithm greatly underestimates the resources needed for a guideline-compliant and evidence-based treatment program, even if healthcare providers received 100 % reimbursement of the sum determined by the Psych-PV algorithm. DISCUSSION: The results clearly show that even in the case of a full coverage of the current German reimbursement algorithm, funding allocation for evidence-based inpatient treatment of chronic depression is insufficient. In addition, the difficulties of specific coding of chronic depression in the ICD-10 system generates a major problem in the attempt to measure the current resources needed for sufficient treatment.

European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe.

PURPOSE: Patients with chronic depression (CD) by definition respond less well to standard forms of psychotherapy and are more likely to be high utilizers of psychiatric resources. Therefore, the aim of this guidance paper is to provide a comprehensive overview of current psychotherapy for CD. The evidence of efficacy is critically reviewed and recommendations for clinical applications and research are given. METHODS: We performed a systematic literature search to identify studies on psychotherapy in CD, evaluated the retrieved documents and developed evidence tables and recommendations through a consensus process among experts and stakeholders. RESULTS: We developed 5 recommendations which may help providers to select psychotherapeutic treatment options for this patient group. The EPA considers both psychotherapy and pharmacotherapy to be effective in CD and recommends both approaches. The best effect is achieved by combined treatment with psychotherapy and pharmacotherapy, which should therefore be the treatment of choice. The EPA recommends psychotherapy with an interpersonal focus (e.g. the Cognitive Behavioural Analysis System of Psychotherapy [CBASP]) for the treatment of CD and a personalized approach based on the patient's preferences. DISCUSSION: The DSM-5 nomenclature of persistent depressive disorder (PDD), which includes CD subtypes, has been an important step towards a more differentiated treatment and understanding of these complex affective disorders. Apart from dysthymia, ICD-10 still does not provide a separate entity for a chronic course of depression. The differences between patients with acute episodic depression and those with CD need to be considered in the planning of treatment. Specific psychotherapeutic treatment options are recommended for patients with CD. CONCLUSION: Patients with chronic forms of depression should be offered tailored psychotherapeutic treatments that address their specific needs and deficits. Combination treatment with psychotherapy and pharmacotherapy is the first-line treatment recommended for CD. More research is needed to develop more effective treatments for CD, especially in the longer term, and to identify which patients benefit from which treatment algorithm.

The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications.

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.