The German research consortium for the study of bipolar disorder (BipoLife): a quality assurance protocol for MR neuroimaging data.

BACKGROUND: The German multicenter research consortium BipoLife aims to investigate the mechanisms underlying bipolar disorders. It focuses in particular on people at high risk of developing the disorder and young patients in the early stages of the disease. Functional and structural magnetic resonance imaging (MRI) data was collected in all participating centers. The collection of neuroimaging data in a longitudinal, multicenter study requires the implementation of a comprehensive quality assurance (QA) protocol. Here, we outline this protocol and illustrate its application within the BipoLife consortium. METHODS: The QA protocol consisted of (1) a training of participating research staff, (2) regular phantom measurements to evaluate the MR scanner performance and its temporal stability across the course of the study, and (3) the assessment of the quality of human MRI data by evaluating a variety of image metrics (e.g., signal-to-noise ratio, ghosting level). In this article, we will provide an overview on these QA procedures and show exemplarily the influence of its application on the results of standard neuroimaging analysis pipelines. DISCUSSION: The QA protocol helped to characterize the various MR scanners, to record their performance over the course of the study and to detect possible malfunctions at an early stage. It also assessed the quality of the human MRI data systematically to characterize its influence on various analyses. Furthermore, by setting up and publishing this protocol, we define standards that must be considered when analyzing data from the BipoLife consortium. It further promotes a systematic evaluation of data quality and a definition of subject inclusion criteria. In the long term, it will help to increase the chance of achieving clinically relevant results.

Predicting the outcome of psychotherapy for chronic depression by person-specific symptom networks.

Psychotherapies are efficacious in the treatment of depression, albeit only with a moderate effect size. It is hoped that personalization of treatment can lead to better outcomes. The network theory of psychopathology offers a novel approach suggesting that symptom interactions as displayed in person-specific symptom networks could guide treatment planning for an individual patient. In a sample of 254 patients with chronic depression treated with either disorder-specific or non-specific psychotherapy for 48 weeks, we investigated if person-specific symptom networks predicted observer-rated depression severity at the end of treatment and one and two years after treatment termination. Person-specific symptom networks were constructed based on a time-varying multilevel vector autoregressive model of patient-rated symptom data. We used statistical parameters that describe the structure of these person-specific networks to predict therapy outcome. First, we used symptom centrality measures as predictors. Second, we used a machine learning approach to select parameters that describe the strength of pairwise symptom associations. We found that information on person-specific symptom networks strongly improved the accuracy of the prediction of observer-rated depression severity at treatment termination compared to common covariates recorded at baseline. This was also shown for predicting observer-rated depression severity at one- and two-year follow-up. Pairwise symptom associations were better predictors than symptom centrality parameters for depression severity at the end of therapy and one year later. Replication and external validation of our findings, methodological developments, and work on possible ways of implementation are needed before person-specific networks can be reliably used in clinical practice. Nevertheless, our results indicate that the structure of person-specific symptom networks can provide valuable information for the personalization of treatment for chronic depression.

Childhood trauma and differential response to long-term psychoanalytic versus cognitive-behavioural therapy for chronic depression in adults.

BACKGROUND: Childhood trauma is a major risk factor for chronic depression. It has been suggested that adults with chronic depression who have experienced childhood trauma may require long-term treatment owing to a breakdown of basic trust and related difficulties in developing a productive therapeutic relationship. AIMS: As empirical studies have been preliminary and scarce, we studied the effects of psychoanalytic therapy (PAT) versus cognitive-behavioural therapy (CBT) for chronic depression in adults with a history of childhood trauma. In this subgroup, we expected a greater symptom reduction in PAT compared with CBT. METHOD: In a large trial of long-term psychotherapies for chronic depression (LAC-Study; Clinical Trial Register ISRCTN91956346), 210 adults received open-ended CBT or PAT in an out-patient setting and were examined yearly over 5 years on the Beck Depression Inventory - II (BDI-II). Based on a linear mixed model approach, we tested participant-reported childhood trauma based on the Childhood Trauma Questionnaire (CTQ) as a predictor and moderator of treatment outcome. CTQ subscales were examined exploratively. RESULTS: Depressive symptoms decreased over time (b = -4.55, s.e. = 0.90, 95% CI -6.32 to -2.81, T = -5.08; P < 0.001). A significant three-way interaction between childhood trauma, time and therapy group (b = -0.05, s.e. = 0.02, 95% CI -0.09 to -0.01, T = -2.42; P = 0.016) indicated that participants with childhood trauma profited especially well from PATs. CONCLUSIONS: Our results indicate differential benefits from PAT compared with CBT among adults with chronic depression and a history of childhood trauma. The results have important implications for differential indication and policy.

The importance of cultural understanding and practical solutions during the handover of a psychotherapy and psychotraumatology program in Northern Iraq into local hands.

In post war regions, especially in low-income countries, the health care systems often require immediate support. For example, after the terror of the so-called Islamic State of Iraq and Syria (ISIS) in 2014, many internally displaced persons took refuge in the Kurdistan Region of Iraq (KRI). Those displaced by war have had to face the reality that psychotherapy did not exist as a service in the Kurdish health system. Many projects and Non-Government-Organizations (NGOs) that work in post-conflict regions focus on short term and quick response and/or basic psychological services. The implementation of the "Institute for Psychotherapy and Psychotraumatology" (IPP) at the University of Dohuk, follows a long-term approach. The 3-year-program teaches students to become professional psychotherapists, with respect to evidence-based and culturally adapted methods of psychotherapy. To achieve sustainability, the project is working towards handing over the teaching and organizational responsibilities into local hands. This article highlights the chances and challenges during this transition, as well as the importance of cultural understanding and realistic, practical solutions. An honest reflection on existing cultural challenges, e.g. inflexible hierarchical structures or an "old-fashioned" religious view of homosexuality, can then lead to practical solutions. These include winning over local authorities by including them in the process, culturally adapting to customs with the help of educated locals, demonstrating non-authoritarian forms of leadership, and explicitly promoting newly graduated young lecturers into positions of authority.

Childhood Trauma Questionnaire-based child maltreatment profiles to predict efficacy of the Cognitive Behavioral Analysis System of Psychotherapy versus non-specific psychotherapy in adults with early-onset chronic depression: cluster analysis of data from a randomised controlled trial.

BACKGROUND: Child maltreatment is a broadly confirmed risk factor for mental and physical illness. Some psychological treatments specifically target mental health conditions associated with child maltreatment. For example, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) focuses on maladaptive interpersonal behaviours in chronic depression. However, how the assessment of child maltreatment could inform personalised treatment is unclear. We used data from a previously published clinical trial to investigate whether a pre-established child maltreatment clustering approach predicts differential outcomes after CBASP versus non-specific supportive psychotherapy in patients with early-onset chronic depression. METHODS: We did a cluster analysis of data from a previous randomised controlled trial of unmedicated adult outpatients with early-onset chronic depression who were treated at eight university clinics and psychological institutes in Germany with 32 sessions of CBASP or non-specific supportive psychotherapy. Participants were eligible for the original trial if they were aged 18-65 years; had major depressive disorder (MDD) with an early onset and duration of at least 2 years, current MDD superimposed on a pre-existing dysthymic disorder, or recurrent MDD with incomplete remission between episodes as defined by DSM-IV; and had a score of at least 20 points on the 24-item Hamilton Rating Scale for Depression (HRSD-24). Participants were included in the current study if they had completed the short form of the Childhood Trauma Questionnaire (CTQ) at trial baseline. We used an agglomerative hierarchical clustering approach to derive child maltreatment clusters from individual patterns across the five domains of the CTQ. We used linear mixed models to investigate whether clustering could predict differential clinical outcomes (change in symptom severity on the HRSD-24) up to 2 years after treatment onset. People with lived experience were involved in the current study. FINDINGS: 253 patients (129 [51%] treated with CBASP and 124 [49%] with supportive psychotherapy) had complete CTQ records and were included in the analysis. 169 (67%) participants were women, 84 (33%) were men, and the mean age was 45·9 years (SD 11·7). We identified seven child maltreatment clusters and found significant differences in treatment effects of CBASP and supportive psychotherapy between the clusters (F(6,948·76)=2·47; p=0·023); differences were maintained over the 2-year follow-up. CBASP was superior in distinct clusters of co-occurring child maltreatment: predominant emotional neglect (change in ß -6·02 [95% CI -11·9 to -0·13]; Cohen's d=-0·98 [95% CI -1·94 to -0·02]; p=0·045), predominant emotional neglect and abuse (-6·39 [-10·22 to -2·56]; -1·04 [-1·67 to -0·42]; p=0·0011), and emotional neglect and emotional and physical abuse (-9·41 [-15·91 to -2·91]; -1·54 [-2·6 to -0·47]; p=0·0046). INTERPRETATION: CTQ-based cluster analysis can facilitate identification of patients with early-onset chronic depression who would specifically benefit from CBASP. Child maltreatment clusters could be implemented in clinical assessments and serve to develop and personalise trauma-informed care in mental health. FUNDING: The German Research Foundation and the German Federal Ministry of Education and Research.

[Relapse prevention of bipolar disorders: an explorative cluster analytical approach in a randomized controlled psychotherapy study]. / Rückfallprävention bipolarer Störungen: ein explorativer, clusteranalytischer Ansatz bei einer randomisierten, kontrollierten Psychotherapiestudie.

The aim of this study was to differentiate between types of bipolar disorders and the associated features using explorative analysis. The focus was particularly on the role of bipolar 1 and bipolar 2 disorders as well as the influence of prophylactic interventions for relapse in a randomized, controlled treatment study. A total of 274 of the 305 originally included persons could be investigated in the study. Patients participated in either cognitive behavioral group therapy (SEKT) or supportive, patient-centered group therapy (FEST). Treatment took place over 4 days separated by a 1-month interval (equivalent to 16 double hours). Depressive and manic symptoms were assessed using the longitudinal interval follow-up evaluation (LIFE). The symptoms were retrospectively assessed for the previous 6 months, with respect to each week before and after the intervention phase and for 6­month and 12-month follow-ups. The results show that the effects of both group therapies were comparable; however, there were statistically significant differences in a multivariate proportional hazards model for the factors bipolar 1 and 2 as well as the interaction of therapy with bipolar 1 and 2. In particular, bipolar 2 patients benefited significantly less from the SEKT intervention than from the FEST intervention. There were three clusters identified that separated bipolar 1 (SEKT, no comorbidity, predominantly no recurrences, younger patients), from bipolar 2 (FEST, no comorbidity, at least 1 often 2 recurrences, older patients) and from a heterogeneous group (SEKT and FEST, comorbidity). The distinction between bipolar 1 and bipolar 2 disorder is important and has so far not received sufficient attention. Bipolar 2 disorders generally have a worse course and respond particularly poorly to cognitive behavioral therapy (SEKT). An open, unstructured, supportive, patient-centered psychotherapy (FEST) is generally effective.

Adjuvant Psychotherapies to Prevent Relapse in Bipolar Disorder: A Randomized Clinical Trial.

Importance: Several psychotherapy protocols have been evaluated as adjuncts to pharmacotherapy for patients with bipolar disorder (BD). Little is known about their comparative effectiveness. Objective: To compare the effectiveness of 2 types of group psychotherapy, skill-oriented, material-based cognitive behavioral therapy (SEKT) and supportive, patient-centered, emotion-focused therapy (FEST), to prevent relapse in patients with euthymic BD. Design, Setting, and Participants: This was a large, observer-blind, randomized clinical trial conducted over 18 months (posttreatment after 6 months; follow-up at 12 and 18 months). In addition to psychiatric care as usual (including mood-stabilizing medication), each participant at 9 clinical outpatient units in Germany received 24 hours of group psychotherapy over 4, full-day sessions spread over 5 months. Patients with euthymic BD type 1 (BD 1) or BD type 2 (BD 2) between the ages of 18 and 50 years were randomly assigned to 1 of 2 forms of psychotherapy, SEKT or FEST. Independent clinicians blinded to patient grouping performed assessments using structured interviews (Structured Clinical Interview for DSM Disorders and Longitudinal Interval Follow-Up Evaluation) and self-rating and clinician rating for inclusion criteria and outcome. Kaplan-Meier survival curves were calculated for time to relapse. Cox proportional hazards statistics and propensity score matching were calculated for the multivariate analysis. Study data were analyzed from March 2020 to September 2022. Interventions: SEKT intervention is a structured cognitive behavioral therapy integrating elements of interpersonal social rhythm therapy, and of mindfulness-based cognitive therapy. FEST psychotherapy has its roots in emotion-focused, supportive, and nondirective therapy. Main Outcomes and Measures: Recurrence of a new affective episode assessed by blinded interviewer with the LIFE interview. In addition, self-rating and clinician rating of depressive and mania symptoms as well as level of social functioning were assessed. Results: Of 348 screened referrals, 305 patients (median [IQR] age, 34 [18-50] years; 162 male [53%]) with euthymic BD 1 or BD 2 were included in the study. A total of 207 patients (68%) had BD 1, 98 (32%) had BD 2, and 278 (91%) received psychiatric care. Both therapies were equally effective in preventing recurrence of a new episode. Outcome (higher rate of new episodes) was not predicted by kind of treatment (SEKT: 69 [49%] relapse; FEST: 63 [46%] relapse) but was predicted by BD 2, comorbidity, attending all sessions, and the interaction of type of treatment by BD 1 or 2. Patients with BD 2 had the highest rate of relapse (60 [61%] relapse), in particular, when treated by SEKT (39 [70%] relapse). Conclusions and Relevance: Results of this randomized clinical trial revealed that a structured, skill-oriented, material-based cognitive behavioral therapy (SEKT) and a supportive, patient-centered, emotion-focused therapy (FEST) were equally effective in preventing relapse of affective episodes when delivered in a new, intensive group format. Additionally, there were baseline factors, in particular BD 2, that influenced outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02506322.

Differential Psychological Treatment Effects in Patients With Late-Life Depression and a History of Childhood Maltreatment.

OBJECTIVE: This is the first interventional study to assess the impact of childhood maltreatment (CM) on psychological treatment outcomes in patients with late-life depression (LLD). METHODS: This is a secondary analysis of a multicenter, randomized controlled trial with 251 participants aged ≥60 years with moderate to severe depression. Participants were randomly assigned to cognitive behavioral therapy for late life depression (LLD-CBT) or to a supportive intervention (SUI). Treatment outcomes were measured by changes in the Geriatric Depression Scale (GDS). RESULTS: In the intention-to-treat sample (n = 229), both LLD-CBT (n = 115) and SUI (n = 114) significantly reduced depressive symptoms in patients with CM, with large effects at post-treatment (d = 0.95 [95% CI: 0.65 to 1.25] in LLD-CBT; d = 0.82 [95% CI: 0.52 to 1.12] in SUI). A significant treatment group*CM interaction (F(1,201.31) = 4.71; p = .031) indicated greater depressive symptom reduction in LLD-CBT compared to SUI at week 5 and post-treatment for patients without CM, but not at 6-month follow-up. Across both treatments, higher severity of the CM subtype 'physical neglect' was associated with a smaller depressive symptom reduction (F(1,207.16) = 5.37; p = .021). CONCLUSIONS: Specific and non-specific psychotherapy effectively reduced depressive symptoms in older individuals with depression and early trauma. For patients without early trauma, LLD-CBT may be preferable over SUI. Considering early trauma subtypes may contribute to develop personalized treatment approaches.

Larger putamen in individuals at risk and with manifest bipolar disorder.

BACKGROUND: Individuals at risk for bipolar disorder (BD) have a wide range of genetic and non-genetic risk factors, like a positive family history of BD or (sub)threshold affective symptoms. Yet, it is unclear whether these individuals at risk and those diagnosed with BD share similar gray matter brain alterations. METHODS: In 410 male and female participants aged 17-35 years, we compared gray matter volume (3T MRI) between individuals at risk for BD (as assessed using the EPIbipolar scale; n = 208), patients with a DSM-IV-TR diagnosis of BD (n = 87), and healthy controls (n = 115) using voxel-based morphometry in SPM12/CAT12. We applied conjunction analyses to identify similarities in gray matter volume alterations in individuals at risk and BD patients, relative to healthy controls. We also performed exploratory whole-brain analyses to identify differences in gray matter volume among groups. ComBat was used to harmonize imaging data from seven sites. RESULTS: Both individuals at risk and BD patients showed larger volumes in the right putamen than healthy controls. Furthermore, individuals at risk had smaller volumes in the right inferior occipital gyrus, and BD patients had larger volumes in the left precuneus, compared to healthy controls. These findings were independent of course of illness (number of lifetime manic and depressive episodes, number of hospitalizations), comorbid diagnoses (major depressive disorder, attention-deficit hyperactivity disorder, anxiety disorder, eating disorder), familial risk, current disease severity (global functioning, remission status), and current medication intake. CONCLUSIONS: Our findings indicate that alterations in the right putamen might constitute a vulnerability marker for BD.

Algorithm-based modular psychotherapy vs. cognitive-behavioral therapy for patients with depression, psychiatric comorbidities and early trauma: a proof-of-concept randomized controlled trial.

Effect sizes of psychotherapies currently stagnate at a low-to-moderate level. Personalizing psychotherapy by algorithm-based modular procedures promises improved outcomes, greater flexibility, and a better fit between research and practice. However, evidence for the feasibility and efficacy of modular-based psychotherapy, using a personalized treatment algorithm, is lacking. This proof-of-concept randomized controlled trial was conducted in 70 adult outpatients with a primary DSM-5 diagnosis of major depressive disorder, a score higher than 18 on the 24-item Hamilton Rating Scale for Depression (HRSD-24), at least one comorbid psychiatric diagnosis according to the Structured Clinical Interview for DSM-5 (SCID-5), a history of at least "moderate to severe" childhood maltreatment on at least one domain of the Childhood Trauma Questionnaire (CTQ), and exceeding the cut-off value on at least one of three measures of early trauma-related transdiagnostic mechanisms: the Rejection Sensitivity Questionnaire (RSQ), the Interpersonal Reactivity Index (IRI), and the Difficulties in Emotion Regulation Scale-16 (DERS-16). Patients were randomized to 20 sessions of either standard cognitive-behavioral therapy alone (CBT) or CBT plus transdiagnostic modules according to a mechanism-based treatment algorithm (MoBa), over 16 weeks. We aimed to assess the feasibility of MoBa, and to compare MoBa vs. CBT with respect to participants' and therapists' overall satisfaction and ratings of therapeutic alliance (using the Working Alliance Inventory - Short Revised, WAI-SR), efficacy, impact on early trauma-related transdiagnostic mechanisms, and safety. The primary outcome for efficacy was the HRSD-24 score at post-treatment. Secondary outcomes included, among others, the rate of response (defined as a reduction of the HRSD-24 score by at least 50% from baseline and a score <16 at post-treatment), the rate of remission (defined as a HRSD-24 score ≤8 at post-treatment), and improvements in early trauma-related mechanisms of social threat response, hyperarousal, and social processes/empathy. We found no difficulties in the selection of the transdiagnostic modules in the individual patients, applying the above-mentioned cut-offs, and in the implementation of MoBa. Both participants and therapists reported higher overall satisfaction and had higher WAI-SR ratings with MoBa than CBT. Both approaches led to major reductions of depressive symptoms at post-treatment, with a non-significant superiority of MoBa over CBT. Patients randomized to MoBa were nearly three times as likely to experience remission at the end of therapy (29.4% vs. 11.4%; odds ratio, OR = 3.2, 95% CI: 0.9-11.6). Among mechanism-based outcomes, MoBa patients showed a significantly higher post-treatment effect on social processes/empathy (p<0.05) compared to CBT patients, who presented an exacerbation on this domain at post-treatment. Substantially less adverse events were reported for MoBa compared to CBT. These results suggest the feasibility and acceptability of an algorithm-based modular psychotherapy complementing CBT in depressed patients with psychiatric comorbidities and early trauma. While initial evidence of efficacy was observed, potential clinical advantages and interindividual heterogeneity in treatment outcomes will have to be investigated in fully powered confirmation trials.

Perceived Physical Health and Cognitive Behavioral Therapy vs Supportive Psychotherapy Outcomes in Adults With Late-Life Depression: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Physical diseases co-occur with late-life depression (LLD). The influence of physical diseases and the subjective perception of physical health (PPH) on treatment outcome in LLD, however, is not well understood. Objective: To assess the association of physical diseases and PPH with the outcomes of 2 different types of psychotherapy in LLD. Design, Setting, and Participants: This post hoc secondary analysis of a multicenter, observer-blinded, controlled, parallel-group randomized clinical trial assessed participants 60 years or older with moderate to severe depression recruited at 7 psychiatric-psychotherapeutic outpatient trial sites in Germany from October 1, 2018, to November 11, 2020. Data analysis was performed from April 1 to October 31, 2023. Interventions: Patients received LLD-specific cognitive behavioral therapy (LLD-CBT) or supportive unspecific intervention (SUI). Main Outcomes and Measures: Depression severity, response, and remission were measured during treatment and at 6-month follow-up by the change in the 30-item Geriatric Depression Scale (GDS) score. Physical health and PPH were assessed by the number of physical diseases, Charlson Comorbidity Index (CCI), and the World Health Organization Quality of Life Brief Version physical health subscale. Results: A total of 251 patients were randomized to LLD-CBT (n = 126) or SUI (n = 125), of whom 229 (mean [SD] age, 70.2 [7.1] years; 151 [66%] female) were included in the intention-to-treat analysis. Patients with low and moderate PPH at baseline had significantly less reduction in the GDS score across both treatment groups than patients with high PPH (estimated marginal mean difference [EMMD], 2.67; 95% CI, 0.37-4.97; P = .02 for low PPH and EMMD, 1.82; 95% CI, 0.22-3.42; P = .03 for moderate vs high PPH). Higher PPH at baseline was associated with higher likelihood of response (odds ratio [OR], 1.04; 95% CI, 1.00-1.06; P = .009) and remission at the end of treatment (OR, 1.04; 95% CI, 1.02-1.08; P = .002) and response (OR, 1.05; 95% CI, 1.02-1.08; P < .001) and remission at follow-up (OR, 1.06; 95% CI, 1.03-1.10; P < .001) across both treatment groups. However, a significant interaction of PPH with treatment group was observed with low PPH at baseline being associated with significantly larger reduction in GDS scores in SUI compared with LLD-CBT at the end of treatment (EMMD, -6.48; 95% CI, -11.31 to -1.64; P = .009) and follow-up (EMMD, -6.49; 95% CI, -11.51 to -1.47; P = .01). In contrast, patients with high PPH at baseline had a significantly greater reduction in GDS scores in LLD-CBT compared with SUI at all time points (week 5: EMMD, -4.08; 95% CI, -6.49 to -1.67; P = .001; end-of-treatment: EMMD, -3.67; 95% CI, -6.72 to -0.61; P = .02; and follow-up: EMMD, -3.57; 95% CI, -6.63 to -0.51; P = .02). The number of physical diseases or CCI at baseline did not have an effect on the change in GDS score, response, or remission, neither across both groups nor within either group. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, subjective PPH was associated with treatment outcome, response, and remission in psychotherapy of LLD. Patients with LLD responded differently to LLD-CBT and SUI, depending on their baseline PPH score. Treatment approaches for patients with LLD should address PPH in personalized interventions. Trial Registration: ClinicalTrials.gov Identifier: NCT03735576; Deutsches Register Klinischer Studien Identifier: DRKS00013769.

A transdiagnostic group exercise intervention for mental health outpatients in Germany (ImPuls): results of a pragmatic, multisite, block-randomised, phase 3 controlled trial.

BACKGROUND: Globally, mental health conditions pose a substantial burden of disease. Despite the availability of evidence-based pharmacological and psychological treatments, the symptoms of a substantial subgroup of patients do not respond to these interventions, and only a minority of patients have access to them. This study aimed to assess the efficacy of ImPuls, a 6-month transdiagnostic group exercise intervention, plus treatment-as-usual, compared with treatment-as-usual alone in outpatients with various mental disorders. METHODS: In this pragmatic, two-arm, multisite, randomised controlled trial in Germany, ten outpatient rehabilitative and medical care facilities were involved as study sites. Participants were outpatients diagnosed according to ICD-10 with one or more of the following disorders based on structured clinical interviews: moderate or severe depression, primary insomnia, post-traumatic stress disorder (PTSD), panic disorder, or agoraphobia. Participants were required to be aged between 18 years and 65 years, insured by the health insurers Allgemeine Ortskrankenkasse Baden-Württemberg or Techniker Krankenkasse, fluent in German, and without medical contraindications for exercise. Blocks of six participants were randomly allocated to ImPuls plus treatment-as-usual or treatment-as-usual alone (allocation ratio: 1:1), stratified by study site. The randomisation sequence was generated by an external data manager. The team responsible for data collection and management was masked to the randomisation sequence. The ImPuls intervention comprised evidence-based outdoor exercises lasting 30 min, and aimed at achieving at least moderate intensity. It also incorporated behavioural change techniques targeting motivational and volitional determinants of exercise behaviour. Treatment-as-usual was representative of typical outpatient health care in Germany, allowing patients access to any standard treatments. The primary outcome was global symptom severity at 6 months after randomisation, measured using self-report on the Brief Symptom Inventory (BSI-18) and analysed in the intention-to-treat sample. No individuals with lived experience of mental illness were involved in conducting the study or writing the final publication. Safety was assessed in all participants. The trial was registered with the German Clinical Trials Register (DRKS00024152) with a completion date of June 30, 2024. FINDINGS: 600 patients provided informed consent, were recruited to the study, and underwent a diagnostic interview between Jan 1, 2021, and May 31, 2022. Following this, 199 were excluded on the basis of inclusion and exclusion criteria and one withdrew consent during the baseline assessment. Of the 400 eligible participants, 284 (71%) self-identified as female, 106 (27%) self-identified as male, and nine (2%) self-identified as other. The mean age was 42·20 years (SD 13·23; range 19-65). Ethnicity data were not assessed. 287 (72%) participants met the criteria for moderate or severe depression, 81 (20%) for primary insomnia, 37 (9%) for agoraphobia, 46 (12%) for panic disorder, and 72 (18%) for PTSD. 199 participants were allocated to the intervention group of ImPuls plus treatment-as-usual and 201 to the control group of treatment-as-usual alone. 38 (19%) participants did not receive the minimum ImPuls intervention dose. ImPuls plus treatment-as-usual demonstrated superior efficacy to treatment-as-usual alone in reducing global symptom severity, with an adjusted difference on BSI-18 of 4·11 (95% CI 1·74-6·48; d=0·35 [95% CI 0·14-0·56]; p=0·0007) at 6 months. There were no significant differences in the total number of adverse events or serious adverse events between the two groups. There was one serious adverse event (male, torn ligament) related to the intervention. INTERPRETATION: ImPuls is an efficacious transdiagnostic adjunctive treatment in outpatient mental health care. Our findings suggest that exercise therapy should be implemented in outpatient mental health care as an adjunctive transdiagnostic treatment for mental disorders such as depression, insomnia, panic disorder, agoraphobia, and PTSD. Transdiagnostic group exercise interventions might ameliorate the existing disparity in care provision between the many individuals in need of evidence-based treatment and the few who are receiving it. FUNDING: The German Innovation Fund of the Federal Joint Committee of Germany.

Social support in older adults: Validation and norm values of a brief form of the Perceived Social Support Questionnaire (F-SozU K-6).

BACKGROUND: Social relations are crucial for maintaining physical and mental health across the life span. As social roles, networks and needs change with age a valid assessment of social support in older adults and age-specific norms are necessary. The present work aims to [1) assess the level of social support in individuals > 60 years of the general German population, [2) evaluate the brief six-item form of the Perceived Social Support Questionnaire (F-SozU K-6) in this age group and to [3) provide age-specific norm values. METHODS: We analyze data of N = 706 people representative for the German population collected in 2021. To assess social support, we used the F-SozU K-6. We tested for selectivity, item difficulty, internal consistency, construct and factor validity, as well as factorial invariance. Additionally, we assessed correlations and associations with depression, loneliness, and sociodemographic factors. Furthermore, we reported norm values for respondents > 60 years. RESULTS: Participants > 60 years reported a mean level of 23.97 (SD = 4.82) of social support. Results of the CFA confirmed a very good model fit. Measurement invariance across sex and age was shown. Associations with ADS and LS-S supported construct validity. Multiple regression analysis showed that female sex, increasing age, having a partner, and a higher equivalized household income were associated with higher levels of social support. CONCLUSION: The F-SozU K-6 is a reliable and economical tool to assess perceived social support in older adults. Norm values for individual > 60 years are provided.

Longitudinal Clusters of Long-Term Trajectories in Patients with Early-Onset Chronic Depression: 2 Years of Naturalistic Follow-Up after Extensive Psychological Treatment.

INTRODUCTION: In clinical trials, mostly group-level treatment effects of repeated cross-sectional measures are analyzed. However, substantial heterogeneity regarding individual symptom profiles and the variability of treatment effects are often neglected, especially over the long-term course. To provide effective personalized treatments, investigations of these characteristics are urgently needed. METHODS: Depression severity ratings over 104 weeks of follow-up after year-long treatment with the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) or Supportive Psychotherapy (SP) were analyzed. Longitudinal cluster analysis and multinomial logistic regression analysis were conducted to investigate intraindividual trajectories from one of the largest psychotherapy trials in early-onset chronic depression. RESULTS: Two-year post-study-treatment trajectories of N = 188 patients with early-onset chronic depression were grouped into four prototypical clusters. Overall, 16.0% of patients remitted (cluster 1) and most of them did not receive any treatment during the 2-year follow-up. However, 84.0% of patients continued to experience subthreshold (37.2% cluster 2) or major depressive symptoms (46.8% clusters 3-4) and spent on average more than half of the follow-up in pharmacological and psychological treatment. Hierarchical regression analysis indicated that previous study treatment with CBASP or SP did not significantly predict cluster allocation, while baseline variables accounted for a large proportion of explained variance (R2 N = 0.64). CONCLUSION: While some patients experienced stable remission over 2 years of follow-up, the majority of patients experienced subthreshold or major depressive symptoms regardless of former study treatment with CBASP or SP. This calls for a long-term perspective implementing staging and innovative treatment approaches such as the sequential model or modular psychotherapy.

Long-term efficacy of exercise across diagnostically heterogenous mental disorders and the mediating role of affect regulation skills.

BACKGROUND: Exercise interventions are efficacious in reducing disorder-specific symptoms in various mental disorders. However, little is known about long-term transdiagnostic efficacy of exercise across heterogenous mental disorders and the potential mechanisms underlying treatment effects. METHODS: Physically inactive outpatients, with depressive disorders, anxiety disorders, insomnia or attention deficit hyperactivity disorder were randomized to a standardized 12-week exercise intervention, combining moderate exercise with behavior change techniques (BCTs) (n = 38), or a passive control group (n = 36). Primary outcome was global symptom severity (Symptom Checklist-90, SCL-90-R) and secondary outcomes were self-reported exercise (Physical Activity, Exercise, and Sport Questionnaire), exercise-specific affect regulation (Physical Activity-related Health Competence Questionnaire) and depression (SCL-90-R) assessed at baseline (T1), post-treatment (T2) and one year after post-treatment (T3). Intention-to-treat analyses were conducted using linear mixed models and structural equations modeling. RESULTS: From T1 to T3, the intervention group significantly improved on global symptom severity (d = -0.43, p = .031), depression among a depressed subsample (d = -0.62, p = .014), exercise (d = 0.45, p = .011) and exercise-specific affect regulation (d = 0.44, p = .028) relative to the control group. The intervention group was more likely to reveal clinically significant changes from T1 to T3 (p = .033). Increases in exercise-specific affect regulation mediated intervention effects on global symptom severity (ß = -0.28, p = .037) and clinically significant changes (ß = -0.24, p = .042). CONCLUSIONS: The exercise intervention showed long-term efficacy among a diagnostically heterogeneous outpatient sample and led to long-lasting exercise behavior change. Long-term increases in exercise-specific affect regulation within exercise interventions seem to be essential for long-lasting symptom reduction.

Implications of the Network Theory for the Treatment of Mental Disorders: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Conceptualizing mental disorders as latent entities has been challenged by the network theory of mental disorders, which states that psychological problems are constituted by a network of mutually interacting symptoms. While the implications of the network approach for planning and evaluating treatments have been intensively discussed, empirical support for the claims of the network theory regarding treatment effects is lacking. Objective: To assess the extent to which specific hypotheses derived from the network theory regarding the (interindividual) changeability of symptom dynamics in response to treatment align with empirical data. Design, Setting, and Participants: This secondary analysis entails data from a multisite randomized clinical trial, in which 254 patients with chronic depression reported on their depressive symptoms at every treatment session. Data collection was conducted between March 5, 2010, and October 14, 2013, and this analysis was conducted between November 1, 2021, and May 31, 2022. Intervention: Thirty-two sessions of either disorder-specific or nonspecific psychotherapy for chronic depression. Main Outcomes and Measures: Longitudinal associations of depressive symptoms with each other and change of these associations through treatment estimated by a time-varying longitudinal network model. Results: In a sample of 254 participants (166 [65.4%] women; mean [SD] age, 44.9 [11.9] years), symptom interactions changed through treatment, and this change varied across treatments and individuals. The mean absolute (ie, valence-ignorant) strength of symptom interactions (logarithmic odds ratio scale) increased from 0.40 (95% CI, 0.36-0.44) to 0.60 (95% CI, 0.52-0.70) during nonspecific psychotherapy and to 0.56 (95% CI, 0.48-0.64) during disorder-specific psychotherapy. In contrast, the mean raw (ie, valence-sensitive) strength of symptom interactions decreased from 0.32 (95% CI, 0.28-0.36) to 0.26 (95% CI, 0.20-0.32) and to 0.09 (95% CI, 0.02-0.16), respectively. Changing symptom severity could be explained to a large extent by symptom interactions. Conclusions and Relevance: These findings suggest that specific treatment-related hypotheses of the network theory align well with empirical data. Conceptualizing mental disorders as symptom networks and treatments as measures that aim to change these networks is expected to give further insights into the working mechanisms of mental health treatments, leading to the improvement of current and the development of new treatments. Trial Registration: ClinicalTrials.gov Identifier: NCT00970437.

Concept and study protocol of the process evaluation of a pragmatic randomized controlled trial to promote physical activity in outpatients with heterogeneous mental disorders-the ImPuls study.

BACKGROUND: Evidence suggests that patients suffering from different mental disorders benefit from exercise programs combined with behavior change techniques. Based on this evidence, we have developed an exercise program (ImPuls) specifically designed to provide an additional treatment option in the outpatient mental health care system. The implementation of such complex programs into the outpatient context requires research that goes beyond the evaluation of effectiveness, and includes process evaluation. So far, process evaluation related to exercise interventions has rarely been conducted. As part of a current pragmatic randomized controlled trial evaluating ImPuls treatment effects, we are therefore carrying out comprehensive process evaluation according to the Medical Research Council (MRC) framework. The central aim of our process evaluation is to support the findings of the ongoing randomized controlled trial. METHODS: The process evaluation follows a mixed-methods approach. We collect quantitative data via online-questionnaires from patients, exercise therapists, referring healthcare professionals and managers of outpatient rehabilitative and medical care facilities before, during, and after the intervention. In addition, documentation data as well as data from the ImPuls smartphone application are collected. Quantitative data is complemented by qualitative interviews with exercise therapists as well as a focus-group interview with managers. Treatment fidelity will be assessed through the rating of video-recorded sessions. Quantitative data analysis includes descriptive as well as mediation and moderation analyses. Qualitative data will be analyzed via qualitative content analysis. DISCUSSION: The results of our process evaluation will complement the evaluation of effectiveness and cost-effectiveness and will, for example, provide important information about mechanisms of impact, structural prerequisites, or provider qualification that may support the decision-making process of health policy stakeholders. It might contribute to paving the way for exercise programs like ImPuls to be made successively available for patients with heterogeneous mental disorders in the German outpatient mental health care system. TRIAL REGISTRATION: The parent clinical study was registered in the German Clinical Trials Register (ID: DRKS00024152, registered 05/02/2021, https://drks.de/search/en/trial/DRKS00024152 ).

Cognitive Behavioral Therapy for Late-Life Depression (CBTlate): Results of a Multicenter, Randomized, Observer-Blinded, Controlled Trial.

INTRODUCTION: Different psychotherapeutic interventions for late-life depression (LLD) have been proposed, but their evaluation in large, multicenter trials is rare. OBJECTIVE: The present study evaluated the efficacy of a specific cognitive behavioral therapy (CBT) for LLD (LLD-CBT) in comparison with a supportive unspecific intervention (SUI), both administered in a specialist psychiatric outpatient setting. METHODS: In this randomized, controlled, parallel group trial, we recruited participants (≥60 years) with moderate to severe depression at 7 trial sites in Germany. Participants were randomly assigned to the LLD-CBT or SUI group. The primary outcome was depression severity at the end of treatment measured by change on the Geriatric Depression Scale (GDS). Secondary outcomes included change in observer-rated depression, anxiety, sleep ratings, and quality of life throughout the treatment phase and at 6-month follow-up. RESULTS: Between October 1, 2018, and November 11, 2020, we randomly assigned 251 patients to either LLD-CBT (n = 126) or SUI (n = 125), of whom 229 provided primary-outcome data. There was no significant between-group difference in the change in GDS scores at the end of treatment (estimated marginal mean difference: -1.01 [95% CI: -2.88 to 0.86]; p = 0.287). Secondary analyses showed significant improvements in several outcomes after 8 weeks and at follow-up in both treatment arms. CONCLUSIONS: Our data suggest that LLD-specific CBT and a supportive unspecific treatment both provide clinical benefit in patients with moderate to severe LLD without evidence for superiority of LLD-CBT.

Daring to Feel: Emotion-Focused Psychotherapy Increases Amygdala Activation and Connectivity in Euthymic Bipolar Disorder-A Randomized Controlled Trial.

BACKGROUND: In bipolar disorder (BD), the alternation of extreme mood states indicates deficits in emotion processing, accompanied by aberrant neural function of the emotion network. The present study investigated the effects of an emotion-centered psychotherapeutic intervention on amygdala responsivity and connectivity during emotional face processing in BD. METHODS: In a randomized controlled trial within the multicentric BipoLife project, euthymic patients with BD received one of two interventions over 6 months: an unstructured, emotion-focused intervention (FEST), where patients were guided to adequately perceive and label their emotions (n = 28), or a specific, structured, cognitive behavioral intervention (SEKT) (n = 31). Before and after interventions, functional magnetic resonance imaging was conducted while patients completed an emotional face-matching paradigm (final functional magnetic resonance imaging sample of patients completing both measurements: SEKT, n = 17; FEST, n = 17). Healthy control subjects (n = 32) were scanned twice after the same interval without receiving any intervention. Given the focus of FEST on emotion processing, we expected FEST to strengthen amygdala activation and connectivity. RESULTS: Clinically, both interventions stabilized patients' euthymic states in terms of affective symptoms. At the neural level, FEST versus SEKT increased amygdala activation and amygdala-insula connectivity at postintervention relative to preintervention time point. In FEST, the increase in amygdala activation was associated with fewer depressive symptoms (r = 0.72) 6 months after intervention. CONCLUSIONS: Enhanced activation and functional connectivity of the amygdala after FEST versus SEKT may represent a neural marker of improved emotion processing, supporting the FEST intervention as an effective tool in relapse prevention in patients with BD.

Comprehensive Prevention: An Evaluation of Peripheral Outcomes of a School-based Prevention Program.

By age 18, 22-27% of adolescents have experienced depressive symptoms increasing their risk of peripheral mental health and social issues. Despite the development of effective depression prevention programs, issues related to dissemination persist. This study aims to identify ways of increasing the likelihood of dissemination by a) investigating how prevention effects differ based on the professional background of the prevention program group leader and b) evaluating adolescent depression prevention in terms of comprehensive prevention - prevention with the breadth to reduce peripheral mental health and social issues. This cluster-randomized trial included 646 eighth-grade students recruited from German secondary schools. Adolescents were randomized into three conditions: teacher-led prevention, psychologist-led prevention, or school-as-usual. Results from hierarchical linear models reveal differences in effects based on implementation type and adolescent gender and provide preliminary evidence for a wider reach of depression prevention such that, regardless of implementation type or gender, the tested program was effective in reducing hyperactivity over time. Taken together, our findings warrant further research and suggest that depression prevention programs may have an effect on some peripheral outcomes, but not others, and that these effects may differ based on the profession of the group leader and adolescent gender. With continued empirical research investigating the efficaciousness of comprehensive prevention, this type of prevention has the potential to impact a larger proportion of the population and improve the cost-benefit ratio of prevention, thus increasing the likelihood of dissemination.