Publications by authors named "Elisabeth Schramm"

65 Publications

Effects of alliance ruptures and repairs on outcomes.

Psychother Res 2021 Jan 17:1-11. Epub 2021 Jan 17.

Department for Psychotherapy and Biopsychosocial Health, Danube University Krems, Krems, Austria.

Objective: This study explored whether treatment outcomes in a trial on the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) vs. Supportive Psychotherapy (SP) for patients with early-onset chronic depression differ between alliance patterns.

Method: Session-to-session ratings of the therapeutic alliance (Helping Alliance Questionnaire (HAQ)) from 254 outpatients with chronic depression (CBASP: 134; SP: 120) who took part in a multicenter randomized controlled trial of CBASP vs. SP were used to categorize patients into three alliance pattern categories for the patients' and therapists' rating separately. Based on the reliable change in the HAQ from one session to the next categories were: no rupture, unrepaired rupture, rupture-repair. Depression severity (24-item Hamilton Rating Scale for Depression) at post-treatment, at 12- and 24- months follow-up was the outcome.

Results: The alliance pattern categories for therapists and patients did not differ between CBASP and SP. Only the alliance patterns calculated for patients were associated with outcome: in the unrepaired rupture category, patients had higher HRSD-ratings across time points ( = 0.047).

Conclusions: CBASP was not associated with more or fewer ruptures or repairs as compared to SP in the treatment of chronic depression. The study highlights the need to resolve ruptures to avoid poor outcomes. ClinicalTrials.gov identifier: NCT00970437.
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http://dx.doi.org/10.1080/10503307.2021.1874070DOI Listing
January 2021

Impact of Baseline Characteristics on the Effectiveness of Disorder-Specific Cognitive Behavioral Analysis System of Psychotherapy (CBASP) and Supportive Psychotherapy in Outpatient Treatment for Persistent Depressive Disorder.

Front Psychiatry 2020 21;11:607300. Epub 2020 Dec 21.

Department of Psychiatry and Psychotherapy, Cognitive Behavioral Analysis System of Psychotherapy Center of Competence, University of Bonn, Bonn, Germany.

In the treatment of persistent depressive disorder (PDD), disorder-specific Cognitive Behavioral Analysis System of Psychotherapy (CBASP) has been shown to be superior to Supportive Psychotherapy (SP) in outpatients. It remains to clear which subgroups of patients benefit equally and differentially from both psychotherapies. To identify those patient-level baseline characteristics that predict a comparable treatment effectiveness of CBASP and SP and those that moderate the differential effectiveness of CBASP compared to SP. In this analysis of a 48-week multicenter randomized clinical trial comparing CBASP to SP in adult antidepressant-free outpatients with early-onset PDD, we evaluated baseline variables from the following domains as potential predictors and moderators of treatment effectiveness: socio-demography, clinical status, psychosocial and global functioning, life quality, interpersonal problems, childhood trauma, treatment history, preference for psychotherapy, and treatment expectancy. A 48-week treatment program with 32 sessions of either CBASP or SP. Depression severity measured by the 24-item Hamilton Rating Scale for Depression (HRSD-24) at week 48. From = 268 randomized outpatients, = 209 completed the 48-week treatment program. CBASP completers had significantly lower post-treatment HRSD-24 scores than SP completers (mean=13.96, sd= 9.56; mean= 16.69, sd= 9.87; = 0.04). A poor response to both therapies was predicted by higher baseline levels of clinician-rated depression, elevated suicidality, comorbid anxiety, lower social functioning, higher social inhibition, moderate-to-severe early emotional or sexual abuse, no preference for psychotherapy, and the history of at least one previous inpatient treatment. Moderator analyses revealed that patients with higher baseline levels of self-rated depression, comorbidity of at least one Axis-I disorder, self-reported moderate-to-severe early emotional or physical neglect, or at least one previous antidepressant treatment, had a significantly lower post-treatment depression severity with CBASP compared to SP (all < 0.05). A complex multifactorial interaction between severe symptoms of depression, suicidality, and traumatic childhood experiences characterized by abuse, social inhibition, and anxiety may represent the basis of non-response to psychotherapy in patients with early onset PDD. Specific psychotherapy with CBASP might, however, be more effective and recommendable for a variety of particularly burdened patients compared to SP.
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http://dx.doi.org/10.3389/fpsyt.2020.607300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779472PMC
December 2020

Time for a paradigm shift for psychotherapies?

Evid Based Ment Health 2021 02 5;24(1). Epub 2021 Jan 5.

Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine / School of Public Health, Kyoto, Japan

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http://dx.doi.org/10.1136/ebmental-2020-300239DOI Listing
February 2021

Review of dysthymia and persistent depressive disorder: history, correlates, and clinical implications.

Lancet Psychiatry 2020 09;7(9):801-812

Department of Psychiatry and Psychotherapy, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Center for Basics in Neuromodulation, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Persistent depressive disorder is a chronic mood disorder that is common and often more disabling than episodic major depression. In DSM-5, the term subsumes several chronic depressive presentations, including dysthymia with or without superimposed major depressive episodes, chronic major depression, and recurrent major depression without recovery between episodes. Dysthymia can be difficult to detect in psychiatric and primary care settings until it intensifies in the form of a superimposed major depressive episode. Although information is scarce concerning the cause of persistent depressive disorder including dysthymia, the causation is likely to be multifactorial. In this narrative Review, we discuss current knowledge about the nosology and neurobiological basis of dysthymia and persistent depressive disorder, emphasising a dimensional perspective based on course for further research. We also review new developments in psychotherapy and pharmacotherapy for persistent depressive disorder, and propose a tailored, modular approach to accommodate its multifaceted nature.
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http://dx.doi.org/10.1016/S2215-0366(20)30099-7DOI Listing
September 2020

[Anxiety and Depression in Transition - Desiderata for Improved Care and Research: Results of the Joint Task Force Transition of DGPPN and DGKJP].

Z Kinder Jugendpsychiatr Psychother 2020 Nov 3;48(6):429-433. Epub 2020 Jul 3.

Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum Freiburg.

Anxiety and Depression in Transition - Desiderata for Improved Care and Research: Results of the Joint Task Force Transition of DGPPN and DGKJP Affective disorders (e. g., anxiety, depression) frequently begin during adolescence. Yet therapeutic approaches during adolescence differ in some respects from those employed during adulthood. During the transition from adolescence to adulthood, there is a high risk of discontinuation of therapeutic treatment, which may consequently affect integration in employment. There is a need for age-specific therapeutic strategies that address the relevant issues of adolescents as well as the presently unmet needs in research and treatment for this specific population.
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http://dx.doi.org/10.1024/1422-4917/a000739DOI Listing
November 2020

Cognitive behavioural therapy for insomnia does not appear to have a substantial impact on early markers of cardiovascular disease: A preliminary randomized controlled trial.

J Sleep Res 2020 10 28;29(5):e13102. Epub 2020 Jun 28.

Department of Psychiatry and Psychotherapy, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany.

According to the World Health Organization, cardiovascular diseases are the leading cause of death in the world. Therefore, early prevention of these diseases is a public health priority. Epidemiological data suggest that insomnia may be a modifiable risk factor for cardiovascular diseases. A randomized controlled trial in a sample of insomnia patients without cardiovascular disease was conducted to investigate the effects of insomnia treatment on early markers of cardiovascular diseases assessed by 24-hr ambulatory blood pressure, heart rate and heart rate variability monitoring, and morning fasting blood samples. Forty-six patients with insomnia disorder were randomized to cognitive behavioural therapy for insomnia (CBT-I; n = 23) or a waitlist control condition (n = 23). Contrary to the hypothesis, intention-to-treat analyses did not show any significant treatment effects on early markers of cardiovascular disease (d = 0.0-0.6) despite successful insomnia treatment (d = 1.3). Potential methodological and conceptual reasons for these negative findings are discussed. Future studies might include larger sample sizes that are at risk of cardiovascular diseases and focus on other cardiovascular markers.
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http://dx.doi.org/10.1111/jsr.13102DOI Listing
October 2020

The Impact of Childhood Maltreatment on Long-Term Outcomes in Disorder-Specific vs. Nonspecific Psychotherapy for Chronic Depression.

J Affect Disord 2020 07 1;272:152-157. Epub 2020 May 1.

Department of Psychology, Clinical Psychology, and Psychotherapy, Eberhard Karls University Tübingen, Tübingen, Germany.

Background: Childhood maltreatment (CM) predicted poorer outcomes in acute depression treatment with CBT, IPT and Supportive Psychotherapy (SP). The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) fared well in patients with chronic depression and CM during acute treatment, yet there is a considerable lack of empirical evidence for long-term outcomes.

Methods: We analyzed one and two-year follow-up data of 268 patients randomized to 24 sessions (20 weeks) of acute and 8 sessions (28 weeks) of extended treatment with CBASP or SP. Primary outcome was the number of well weeks as measured by the Longitudinal Interval Follow-Up Evaluation Interview (LIFE). Secondary outcomes included self- and clinician-rated depression symptoms. We investigated this moderating effect for any CM and for specific subtypes of CM.

Results: Intent-to-treat analyses revealed that the presence of CM did not significantly moderate long-term effects of CBASP compared to SP. The analysis of trauma subtypes revealed that patients with childhood emotional abuse had statistically significant worse outcomes than patients without (main effect, p=.015) and that the advantage of CBASP over SP was larger in patients with childhood emotional abuse than in patients without (interaction effect, p=.045) after 1 year. No significant effects were found for other trauma subtypes.

Limitations: The measurement of CM was limited to retrospective self-assessment.

Conclusions: The presence of CM did not significantly moderate long-term treatment effects of CBASP compared to SP. When trauma subtypes were considered, CBASP was more effective than SP after one year in patients who retrospectively reported emotional abuse.
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http://dx.doi.org/10.1016/j.jad.2020.03.164DOI Listing
July 2020

Interpersonal Psychotherapy vs. Treatment as Usual for Major Depression Related to Work Stress: A Pilot Randomized Controlled Study.

Front Psychiatry 2020 18;11:193. Epub 2020 Mar 18.

Department of Psychiatry and Psychotherapy, Faculty of Medicine, University Medical Center, University of Freiburg, Freiburg, Germany.

Depressive disorders are among the leading causes of sick leave and long-term work incapacity in most modern countries. Work related stress is described by patients as the most common context of depression. It is vital to know what types of treatments are effective in improving work related problems and occupational health. However, there is only limited evidence on work-focused interventions. The aim of our study was to evaluate the feasibility and generate first data on the effectiveness of Interpersonal Psychotherapy (IPT) adapted as a group program to focus on the work context (W-IPT). In total, 28 outpatients (22 women; = 49.8 years old) with Major Depressive Disorder related to work stress were randomized to 8 weekly group sessions of W-IPT or to treatment as usual (TAU; guideline oriented treatment). Primary endpoint was the Hamilton Rating Scale for Depression (HRSD-24) score. Key secondary endpoints were, among others, Beck Depression Inventory (BDI-II), Work Ability Index (WAI), Return to Work Attitude (RTW-SE), and the Effort-Reward-Imbalance (ERI). In addition, we evaluated the participants' overall satisfaction with the W-IPT program by two items. A follow-up assessment was conducted 3 months after end of acute treatment. W-IPT was significantly more effective than TAU in reducing clinician-assessed depressive symptoms at follow-up (HRSD-24 W-IPT/TAU: = 6.6/12.0, SE: 1.46/2.17, t = -2.24, = 0.035, = 0.79) and self-assessed depression (BDI-II W-IPT/TAU post-treatment: = 8.8/18.8, SE: 1.69/2.70, t = -3.82, = 0.001, = 1.28; follow-up: = 8.8/16.1, SE: 1.62/2.26, t = -2.62, = 0.015, = 0.99). Furthermore, W-IPT was superior in improving work-ability (WAI), return-to-work attitude (RTW-SE), and the effort-reward-ratio (ERI). No dropouts were observed in both groups. The vast majority (89 percent) of participants in the W-IPT condition were "very satisfied" with the program, although wishing for a greater number of sessions (75 percent). A work-focused IPT program for the treatment of depression associated to work stress was feasible and highly acceptable. W-IPT turned out to be more effective than standard treatment in reducing depression and work-related problems. However, further evidence in a multicenter trial extending this pilot study is necessary.
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http://dx.doi.org/10.3389/fpsyt.2020.00193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093578PMC
March 2020

Sensitivity to change and minimal clinically important difference of the 7-item Generalized Anxiety Disorder Questionnaire (GAD-7).

J Affect Disord 2020 03 15;265:395-401. Epub 2020 Jan 15.

Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Background: Effective treatment requires regular follow-up and monitoring of symptoms. We investigated sensitivity to change and minimal clinically important difference of the Generalized Anxiety Disorder Scale (GAD-7).

Methods: This study included all participants from a multisite trial of chronic depression. Baseline and follow-up (12 and 48 weeks) data were used to assess treatment response. Effect sizes (ES) and standardized response means (SRM) of pre- and post-GAD-7 mean changes were calculated for subgroups of patients, who did or did not improve according to ratings in the Hamilton Rating Scale for Depression (HRSD-24).

Results: N = 261 patients were included in the analyses. In the subgroup of patients who improved according to HRSD-24, GAD-7 scores were significantly lower after 12 weeks (t = -6.31, df = 120, p < .001; ES = -0.51, SRM = -0.57), and 48 weeks of treatment (t = -12.68, df = 141, p < .001; ES = -1.0, SRM = -1.7), when compared to admission. In the group who worsened, GAD-7 scores were significantly higher after 12 weeks (t = 2.96, df = 41, p = .005; ES = 0.30, SRM = 0.46), and increased after 48 weeks (t = 1.99, df = 21, p = .059; ES = 0.37, SRM = 0.43), when compared to baseline. The unchanged group showed no significant difference between baseline and follow-up. MCID was estimated 4 points on the GAD-7 total score.

Limitations: Confirmation of these findings and further investigation of the GAD-7 in populations and trials focusing on anxiety-specific treatment is highly recommended.

Conclusions: Results show that the GAD-7 is sensitive to detect change in psychopathology over the course of treatment.
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http://dx.doi.org/10.1016/j.jad.2020.01.032DOI Listing
March 2020

Patients' interpersonal problems as moderators of depression outcomes in a randomized controlled trial comparing mindfulness-based cognitive therapy and a group version of the cognitive-behavioral analysis system of psychotherapy in chronic depression.

J Clin Psychol 2020 07 30;76(7):1241-1254. Epub 2020 Jan 30.

Department of Psychology and Psychotherapy, Witten/Herdecke University, Witten, Germany.

Objectives: Interpersonal problems were examined as moderators of depression outcomes between mindfulness-based cognitive therapy (MBCT) and cognitive behavioral analysis system of psychotherapy (CBASP) in patients with chronic depression.

Methods: Patients received treatment-as-usual and, in addition, were randomized to 8-weeks of MBCT (n = 34) or 8-weeks of CBASP (n = 34). MBCT and CBASP were given in a group format. The Hamilton depression rating scale (HAM-D) was the primary and the Beck Depression Inventory (BDI-II) the secondary outcome. The subscales of the Inventory of interpersonal problems (IIP-32) were moderators. Multilevel models were performed.

Results: Higher scores on the "vindictive/self-centered" subscale were associated with a better outcome in MBCT than in CBASP (HAM-D: p < .01; BDI-II: p < .01). Higher scores on the "nonassertive" subscale were associated with a better outcome in CBASP than in MBCT (HAM-D: p < .01; BDI-II: p < .01).

Conclusions: If these results can be replicated in larger trials, MBCT should be preferred to CBASP in chronically depressed patients being vindictive/self-centered, whereas CBASP should be preferred to MBCT in chronically depressed patients being nonassertive.
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http://dx.doi.org/10.1002/jclp.22931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318258PMC
July 2020

Cognitive behavioural therapy for the treatment of late life depression: study protocol of a multicentre, randomized, observer-blinded, controlled trial (CBTlate).

BMC Psychiatry 2019 12 27;19(1):423. Epub 2019 Dec 27.

Department of Psychiatry and Psychotherapy, University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Straße 62, 50931, Cologne, Germany.

Background: Late-life depression (LLD) is one of the most prevalent mental disorders in old age. It is associated with various adverse outcomes and frequent use of health care services thereby remaining a serious public health concern. Compared with depression in early adulthood, most treatment options of LLD are less effective. Psychotherapy may be particularly beneficial for LLD due to specific psychological conditions in old age and a low risk of side effects. Although cognitive behavioural therapy (CBT) is highly established and effective in depression in young and mid-life there is only a limited number of small studies on CBT in LLD. An LLD-specific CBT has not yet been compared to an active, but unspecific supportive psychological intervention in a multicentre trial.

Methods: Here we present the design of the CBTlate trial, which is a multicentre, randomized, observer-blinded, active-controlled, parallel group trial. CBTlate aims at including 248 patients with LLD of both genders at 7 sites in Germany. The purpose of the study is to test the hypothesis that a 15-session individually-delivered CBT specific for LLD is of superior efficacy in reducing symptoms of depression in comparison with a supportive unspecific intervention (SUI) of the same quantity. The intervention includes 8 weeks of individual treatment sessions twice per week and a follow-up period of 6 months after randomization. The primary end point is the severity of depression at the end of treatment measured by the self-rated 30-item Geriatric Depression Scale (GDS). Secondary endpoints include depressive symptoms at week 5 and at follow-up (6 months after randomization). Additional secondary endpoints include the change of depressive symptoms assessed with a clinician-rating-scale and a patient reported outcome instrument for major depressive disorder, anxiety symptoms, sleep, cognition, quality of life, and overall health status from baseline to end-of treatment and to end of follow-up. Add-on protocols include MRI and the collection of blood samples.

Discussion: This study is the first multicentre trial of a specific CBT intervention for LLD compared to an unspecific supportive psychological intervention administered in a specialist setting. It has important implications for developing and implementing efficient psychotherapeutic strategies for LLD and may be a significant step to broaden treatment options for people suffering from LLD.

Trial Registration: ClinicalTrials.gov (NCT03735576, registered on 24 October 2018); DRKS (DRKS00013769, registered on 28 June 2018).
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http://dx.doi.org/10.1186/s12888-019-2412-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935201PMC
December 2019

Combining baseline characteristics to disentangle response differences to disorder-specific versus supportive psychotherapy in patients with persistent depressive disorder.

Behav Res Ther 2020 01 4;124:103512. Epub 2019 Nov 4.

Department of Psychiatry and Psychotherapy, CBASP Center of Competence, University of Bonn, Sigmund-Freud-Strasse 25, D-53127, Bonn, Germany; Department of Psychiatry and Psychotherapy, Vitos Weil-Lahn, Mönchberg 8, D-65589, Hadamar, Germany.

Does the pre-treatment profile of individuals with persistent depressive disorder (PDD) moderate their benefit from disorder-specific Cognitive Behavioral System of Psychotherapy (CBASP) versus supportive psychotherapy (SP)? We investigated this question by analyzing data from a multi-center randomized clinical trial comparing the effectiveness of 48 weeks of CBASP to SP in n  =  237 patients with early-onset PDD who were not taking antidepressant medication. We statistically developed an optimal composite moderator as a weighted combination of 13 preselected baseline variables and used it for identifying and characterizing subgroups for which CABSP may be preferable to SP or vice versa. We identified two distinct subgroups: 58.65% of the patients had a better treatment outcome with CBASP, while the remaining 41.35% had a better outcome with SP. At baseline, patients responding more favorably to CBASP were more severely depressed and more likely affected by moderate-to-severe childhood trauma including early emotional, physical, or sexual abuse, as well as emotional or physical neglect. In contrast, patients responding more favorably to SP had a higher pre-treatment global and social functioning level, a higher life quality and more often a recurrent illness pattern without complete remission between the episodes. These findings emphasize the relevance of considering pre-treatment characteristics when selecting between disorder-specific CBASP and SP for treating PDD. The practical implementation of this approach would advance personalized medicine for PDD by supporting mental health practitioners in their selection of the most effective psychotherapy for an individual patient.
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http://dx.doi.org/10.1016/j.brat.2019.103512DOI Listing
January 2020

Adverse events during a disorder-specific psychotherapy compared to a nonspecific psychotherapy in patients with chronic depression.

J Clin Psychol 2020 01 1;76(1):7-19. Epub 2019 Oct 1.

Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Objectives: A recent trial comparing Cognitive Behavioral Analysis System of Psychotherapy (CBASP) and supportive psychotherapy in chronic depression found CBASP to be more effective in treating depressive symptoms. We aimed to evaluate adverse events that occurred during this trial.

Materials And Method: A randomized trial of chronically depressed outpatients was performed. The treatment included 32 sessions of CBASP or supportive psychotherapy. Therapists asked patients about adverse events and their intensity in each session using a standardized checklist. We analyzed the mean number of (severe) adverse events per patient up to Session 32 with gamma frailty recurrent event models.

Results: Two hundred and sixty patients were included in the analyses (66% female, mean age 45 years). Patients in the supportive psychotherapy group reported less severe adverse events in general, and less severe adverse events related to personal life and to occupational life than patients in the CBASP group. Less adverse events related to suicidal thoughts were reported in the CBASP compared with the supportive psychotherapy group.

Conclusions: Differences in the adverse events profile may be explained by the treatment elements. Adverse events related to personal and occupational life for example might be considered a necessary and expected yet temporary adverse treatment outcome of an effective CBASP treatment.
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http://dx.doi.org/10.1002/jclp.22869DOI Listing
January 2020

Two-Year Follow-Up after Treatment with the Cognitive Behavioral Analysis System of Psychotherapy versus Supportive Psychotherapy for Early-Onset Chronic Depression.

Psychother Psychosom 2019 23;88(3):154-164. Epub 2019 May 23.

Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg-Eppendorf, Germany.

Background: Evidence on the long-term efficacy of psychotherapeutic approaches for chronic depression is scarce.

Objective: To evaluate the effects of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) compared to Supportive Psychotherapy (SP) 1 year and 2 years after treatment termination.

Methods: In this study, we present 1- and 2-year follow-up assessments of a prospective, multicenter, evaluator-blinded, randomized clinical trial of outpatients with early-onset chronic major depression (n = 268). The initial treatment included 32 sessions of CBASP or SP over 48 weeks. The primary outcome was the rate of "well weeks" (Longitudinal Interval Follow-Up Evaluation; no/minimal symptoms) after 1 year and 2 years. The secondary outcomes were, among others, clinician- and self-rated depressive symptoms, response/remission rates, and quality of life.

Results: Of the 268 randomized patients, 207 (77%) participated in the follow-up. In the intention-to-treat analysis, there was no statistically significant difference between CBASP and SP patients in experiencing well weeks (CBASP: mean [SD] of 48.6 [36.9] weeks; SP: 39.0 [34.8]; rate ratio 1.26, 95% CI 0.99-1.59, p = 0.057, d = 0.18) and in remission rates (CBASP: 1 year 40%, 2 years 40.2%; SP: 1 year 28.9%, 2 years 33%) in the 2 years after treatment. Statistically significant effects were found in favor of CBASP 1 year after treatment termination regarding the rate of well weeks, self-rated depressive symptoms, and depression-related quality of life.

Conclusions: CBASP lost its superiority over SP at some point between the first and the second year. This suggests the necessity of maintenance treatment for early-onset chronically depressed patients remitted with CBASP during the acute therapy phase, as well as the sequential integration of other treatment strategies, including medication for those who did not reach remission.
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http://dx.doi.org/10.1159/000500189DOI Listing
February 2020

Interactive impact of childhood maltreatment, depression, and age on cortical brain structure: mega-analytic findings from a large multi-site cohort.

Psychol Med 2020 04 14;50(6):1020-1031. Epub 2019 May 14.

Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany.

Background: Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.

Methods: Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.

Results: CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.

Conclusions: Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
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http://dx.doi.org/10.1017/S003329171900093XDOI Listing
April 2020

Do interpersonal fears mediate the association between childhood maltreatment and interpersonal skills deficits? A matched cross-sectional analysis.

Psychother Res 2020 02 11;30(2):267-278. Epub 2018 Oct 11.

Department of Psychiatry and Psychotherapy, Lübeck University, Lübeck, Germany.

Childhood maltreatment, interpersonal fear and a specific kind of interpersonal skills deficit (preoperational thinking) have all been associated with persistent depressive disorder (PDD). We hypothesize that interpersonal fears mediate the association between childhood maltreatment and preoperational thinking. A total of 108 matched participants have been examined cross-sectionally (31 healthy controls, 30 patients with episodic depression and 47 patients with PDD) with the following instruments: the Childhood Trauma Questionnaire (CTQ-SF), a measure of interpersonal fear (CBASP Interpersonal Questionnaire) and the Lübeck Questionnaire of Preoperational Thinking. Patients with PDD reported significantly more childhood maltreatment than patients with episodic depression ( = 0.65) and healthy controls ( = 1.29). They also had more interpersonal fears ( = 0.71 and  = 2.11 respectively) and higher levels of preoperational thinking ( = 0.90 and  = 2.78 respectively). The association between childhood maltreatment and preoperational thinking was mediated through interpersonal fears. Our findings might have important implications for psychotherapy of PDD because they demonstrate how specific problems in social interactions can be associated with interpersonal fears that arise secondary to childhood maltreatment.
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http://dx.doi.org/10.1080/10503307.2018.1532125DOI Listing
February 2020

Moderating effect of comorbid anxiety disorders on treatment outcome in a randomized controlled psychotherapy trial in early-onset persistently depressed outpatients.

Depress Anxiety 2018 10 10;35(10):1001-1008. Epub 2018 Sep 10.

Department of Psychiatry and Psychotherapy, Lübeck University, Lübeck, Germany.

Background: Persistent depressive disorder (PDD) is associated with high rates of comorbid psychiatric disorders, mostly anxiety disorders (ADs). Comorbid AD was found to be associated with poorer treatment outcome in PDD patients. The effect of comorbid AD on disorder-specific treatment for PDD (Cognitive Behavioral Analysis System of Psychotherapy [CBASP]) has not been studied yet.

Methods: We analyzed whether the presence of a comorbid AD was moderating the effectiveness of disorder-specific (CBASP) versus nonspecific psychotherapy (supportive therapy [SP]) on depressive symptoms (24-item Hamilton Rating Scale for Depression [HRSD-24]) in a sample of unmedicated early-onset PDD outpatients (N = 268). Secondary outcomes were response and remission of depressive symptoms and the extent of interpersonal problems (Inventory of Interpersonal Problems [IIP-64]).

Results: The superiority of CBASP over SP was significantly stronger in PDD patients with comorbid AD compared to patients without AD (in HRSD-24 and IIP-64). There was no significant moderation for remission or response of depressive symptoms.

Discussion: Our hypothesis of a moderating effect of comorbid AD was confirmed. The main limitation might be the exclusion criteria of our sample limiting the generalizability. The major strength is the systematic analysis of the effect of AD in treating early-onset PDD with high quality of psychotherapy in both arms of this trial.

Conclusion: Patients suffering from PDD comorbid with AD might experience greater benefit when they are treated with specific as opposed to unspecific therapy. Analyzing subgroups of patients with PDD seems worthwhile to improve treatment effectiveness even within disorder-specific treatment programms.
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http://dx.doi.org/10.1002/da.22839DOI Listing
October 2018

Cognitive-Behavioral Analysis System of Psychotherapy, Drug, or Their Combination for Persistent Depressive Disorder: Personalizing the Treatment Choice Using Individual Participant Data Network Metaregression.

Psychother Psychosom 2018 30;87(3):140-153. Epub 2018 May 30.

Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany.

Background: Persistent depressive disorder is prevalent, disabling, and often difficult to treat. The cognitive-behavioral analysis system of psychotherapy (CBASP) is the only psychotherapy specifically developed for its treatment. However, we do not know which of CBASP, antidepressant pharmacotherapy, or their combination is the most efficacious and for which types of patients. This study aims to present personalized prediction models to facilitate shared decision-making in treatment choices to match patients' characteristics and preferences based on individual participant data network metaregression.

Methods: We conducted a comprehensive search for randomized controlled trials comparing any two of CBASP, pharmacotherapy, or their combination and sought individual participant data from identified trials. The primary outcomes were reduction in depressive symptom severity for efficacy and dropouts due to any reason for treatment acceptability.

Results: All 3 identified studies (1,036 participants) were included in the present analyses. On average, the combination therapy showed significant superiority over both monotherapies in terms of efficacy and acceptability, while the latter 2 treatments showed essentially similar results. Baseline depression, anxiety, prior pharmacotherapy, age, and depression subtypes moderated their relative efficacy, which indicated that for certain subgroups of patients either drug therapy or CBASP alone was a recommendable treatment option that is less costly, may have fewer adverse effects and match an individual patient's preferences. An interactive web app (https://kokoro.med.kyoto-u.ac.jp/CBASP/prediction/) shows the predicted disease course for all possible combinations of patient characteristics.

Conclusions: Individual participant data network metaregression enables treatment recommendations based on individual patient characteristics.
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http://dx.doi.org/10.1159/000489227DOI Listing
October 2018

The German version of the helping alliance questionnaire: psychometric properties in patients with persistent depressive disorder.

BMC Psychiatry 2018 04 23;18(1):107. Epub 2018 Apr 23.

Central Institute of Mental Health, Department of Clinical Psychology, Medical Faculty Mannheim/Heidelberg University, J5, 68159 Mannheim, Heidelberg, Germany.

Background: The Helping Alliance Questionnaire (HAQ) is a frequently used and highly relevant instrument to assess the therapeutic alliance. The questionnaire was translated into German by Bassler and colleagues (1995) and is available for patients (HAQ-P) and therapists (HAQ-T). Whereas the HAQ-P has been tested regarding psychometrics, the HAQ-T has not. This study aimed at further investigating the psychometric properties of both the HAQ-P and HAQ-T. We hypothesized that the instrument is reliable and shows factorial as well as convergent validity.

Methods: Within the framework of a multisite, randomized-controlled clinical trial, comparing the efficacy of Cognitive Behavioral Analyses System of Psychotherapy (CBASP) and supportive psychotherapy (SP) in the treatment of early onset persistently depressed outpatients, the HAQ was filled out by patients (n = 255) and therapists (n = 81). 66.0% of patients were female; average age at randomization was 44.9 years (SD = 11.8). Several confirmatory factor analyses were conducted to test different structures for the HAQ. In addition, correlations between the HAQ and the Inventory of Interpersonal Problems (IIP) were calculated to test for convergent validity.

Results: Goodness of fit indices for both a model with two different but strongly related factors named 'relation to the patient/ therapist ' and 'satisfaction with therapeutic outcome' and a second model with only one global helping alliance factor were comparable: Chi-Square-based indices rejected the models; RMSEA closely approached the threshold of good model fit, and CFI/ TLI and SRMR suggested that both models sufficiently fit the data. The internal consistency (Cronbach's α) calculated for the different scales of the HAQ ranges between questionable to good. Finally, the HAQ scores were significantly related to some of the IIP scores.

Conclusions: The German versions of the HAQ offer sufficient reliable instruments for the quick assessment of different facets of the therapeutic alliance. The HAQ global scores can be used as indicators for the global impression of the patients and therapists perception of the quality of the therapeutic alliance. However, the small correlations found between the IIP and the HAQ puts the question of external validity into perspective.

Trial Registration: This study analysed data from a RCT which was registered on ClinicalTrials.com ( NCT00970437 ). First submitted on September 1, 2009.
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http://dx.doi.org/10.1186/s12888-018-1697-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914037PMC
April 2018

Association of comorbid personality disorders with clinical characteristics and outcome in a randomized controlled trial comparing two psychotherapies for early-onset persistent depressive disorder.

J Affect Disord 2018 03 4;229:262-268. Epub 2018 Jan 4.

Department of Psychiatry and Psychotherapy, Lübeck University, Lübeck, Germany.

Background: Persistent depressive disorder (PDD) is associated with high rates of comorbid personality disorders (PD). The association of comorbid PD and clinical characteristics has not been systematically studied in PDD. Results regarding effects on treatment outcome are heterogeneous.

Methods: We analyzed the association of comorbid personality disorders with clinical characteristics and outcome in a randomized controlled trial comparing the disorder-specific Cognitive Behavioral Analysis System of Psychotherapy (CBASP) with nonspecific supportive psychotherapy (SP) in patients with early-onset PDD. The main outcome measure was the Hamilton Rating Scale for Depression (HRSD-24). Further baseline measures were comorbid axis-I diagnoses (SCID-I), quality of life (QLDS), global functioning (GAF), interpersonal problems (IIP-64) and childhood maltreatment (CTQ).

Results: Out of the 268 patients, 103 (38.4%) met criteria for at least one PD. PD was associated with higher rates of axis I comorbidities (mainly anxiety disorders) and interpersonal problems (patients with PD were more vindictive, more self-sacrificing, less assertive and more inhibited socially than patients without PD). There was no significant main effect of PD on treatment outcome and no significant interaction between PD and treatment group.

Limitations: The main limitation was the exclusion of patients with certain personality disorders (antisocial, schizotypal, and borderline personality disorders). Furthermore, the study was underpowered to find interaction effects of small size.

Conclusion: Persistently depressed patients with and without comorbid PD primarily seemed to differ in the rate of axis I comorbidity and the severity of interpersonal problems. Treatment outcomes appear to be not significantly affected by the presence of PD.
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http://dx.doi.org/10.1016/j.jad.2017.12.091DOI Listing
March 2018

The impact of childhood maltreatment on the differential efficacy of CBASP versus escitalopram in patients with chronic depression: A secondary analysis.

Clin Psychol Psychother 2017 Sep 21;24(5):1155-1162. Epub 2017 Mar 21.

Department of Psychiatry, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Childhood maltreatment (CM) has been indicated as a predictor of a differential response to antidepressant treatment with psychotherapy compared to medication. In this secondary analysis, we investigated whether the presence of CM results in a differential indication for the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) or escitalopram plus clinical management (ESC). Sixty patients with chronic depression were randomized to either 22 sessions of CBASP or ESC over the course of 8 weeks of acute and 20 weeks of extended treatment at 2 German treatment sites. CM was assessed using the Childhood Trauma Questionnaire and the clinician rated Early Trauma Inventory. Intention-to-treat analyses were used to examine the impact of CM on depression, global functioning, and quality of life. The presence of CM did not result in significant differences in treatment response to CBASP or ESC on any outcome measure after 28 weeks of treatment independent of the type of CM assessment. After 8 weeks, a significant CM × treatment interaction was found for scores on the Montgomery-Asberg Depression Rating Scale. Patients with a history of CM receiving CBASP had a significantly lower response rate compared to patients without CM and to those receiving ESC after 8 weeks. Conclusively, CBASP and ESC are equally effective treatment options for the difficult to treat subgroup of patients with chronic depression and a history of CM. CM may be a predictor of a longer latency of treatment response in the case of psychotherapy.

Key Practitioner Message: CBASP and escitalopram are equally effective treatment options for chronic depression. Both treatments are also equally effective for the difficult to treat subgroup of patients with chronic depression and a history of childhood maltreatment. Childhood maltreatment may result in a longer latency of treatment response in the case of psychotherapy.
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http://dx.doi.org/10.1002/cpp.2081DOI Listing
September 2017

Identification of Childhood Abuse in Patients with Late-Life Depression May Help to Optimize Treatment.

Am J Geriatr Psychiatry 2017 06 24;25(6):644-645. Epub 2017 Feb 24.

Amsterdam Public Health Research Institute, Department of Research and Innovation, GGZ inGeest, VU University Medical Center, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1016/j.jagp.2017.02.016DOI Listing
June 2017

Effect of Disorder-Specific vs Nonspecific Psychotherapy for Chronic Depression: A Randomized Clinical Trial.

JAMA Psychiatry 2017 Mar;74(3):233-242

Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg-Eppendorf, Germany.

Importance: Chronic depression is a highly prevalent and disabling disorder. There is a recognized need to assess the value of long-term disorder-specific psychotherapy.

Objective: To evaluate the efficacy of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) compared with that of nonspecific supportive psychotherapy (SP).

Design, Setting, And Participants: A prospective, multicenter, evaluator-blinded, randomized clinical trial was conducted among adult outpatients with early-onset chronic depression who were not taking antidepressant medication. Patients were recruited between March 5, 2010, and October 16, 2012; the last patient finished treatment on October 14, 2013. Data analysis was conducted from March 5, 2014, to October 27, 2016.

Interventions: The treatment included 24 sessions of CBASP or SP for 20 weeks in the acute phase, followed by 8 continuation sessions during the next 28 weeks.

Main Outcomes And Measures: The primary outcome was symptom severity after 20 weeks (blinded observer ratings) as assessed by the 24-item Hamilton Rating Scale for Depression (HRSD-24). Secondary outcomes were rates of response (reduction in HRSD-24 score of ≥50% from baseline) and remission (HRSD-24 score ≤8), as well as self-assessed ratings of depression, global functioning, and quality of life.

Results: Among 622 patients assessed for eligibility, 268 were randomized: 137 to CBASP (96 women [70.1%] and 41 men [29.9%]; mean [SD] age, 44.7 [12.1] years) and 131 to SP (81 women [61.8%] and 50 men [38.2%]; mean [SD] age, 45.2 [11.6] years). The mean (SD) baseline HRSD-24 scores of 27.15 (5.49) in the CBASP group and 27.05 (5.74) in the SP group improved to 17.19 (10.01) and 20.39 (9.65), respectively, after 20 weeks, with a significant adjusted mean difference of -2.51 (95% CI, -4.16 to -0.86; P = .003) and a Cohen d of 0.31 in favor of CBASP. After 48 weeks, the HRSD-24 mean (SD) scores were 14.00 (9.72) for CBASP and 16.49 (9.96) for SP, with an adjusted difference of -3.13 (95% CI, -5.01 to -1.25; P = .001) and a Cohen d of 0.39. Patients undergoing CBASP were more likely to reach response (48 of 124 [38.7%] vs 27 of 111 [24.3%]; adjusted odds ratio, 2.02; 95% CI, 1.09 to 3.73; P = .03) or remission (27 of 124 [21.8%] vs 14 of 111 [12.6%]; adjusted odds ratio, 3.55; 95% CI, 1.61 to 7.85; P = .002) after 20 weeks. Patients undergoing CBASP showed significant advantages in most other secondary outcomes.

Conclusions And Relevance: Highly structured specific psychotherapy was moderately more effective than nonspecific therapy in outpatients with early-onset chronic depression who were not taking antidepressant medication. Adding an extended phase to acute psychotherapy seems promising in this population.

Trial Registration: clinicaltrials.gov Identifier: NCT00970437.
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http://dx.doi.org/10.1001/jamapsychiatry.2016.3880DOI Listing
March 2017

Childhood adversity impacts on brain subcortical structures relevant to depression.

J Psychiatr Res 2017 03 19;86:58-65. Epub 2016 Nov 19.

Center for Integrative Psychiatry, University of Lübeck, Lübeck, Germany.

Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression.
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http://dx.doi.org/10.1016/j.jpsychires.2016.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564511PMC
March 2017
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