Effectiveness of Schema Therapy versus Cognitive Behavioral Therapy versus Supportive Therapy for Depression in Inpatient and Day Clinic Settings: A Randomized Clinical Trial.

INTRODUCTION: Schema therapy (ST) reduces depressive symptoms, but clinical trials have not investigated its effectiveness for patients suffering from severe forms of depression and high rates of comorbidities. There is high demand for exploring and improving treatments for this patient group. The objective of the current study was to evaluate whether ST is more effective than individual supportive therapy (IST) and noninferior compared with cognitive behavioral therapy (CBT) in treating depression. METHODS: For this clinical trial, medicated patients were recruited in inpatient and day clinic settings. The major inclusion criteria were age between 18 and 75 years and primary diagnosis of depression without psychotic symptoms. A total of 292 participants were randomized to ST, CBT, or IST and received 7 weeks of psychotherapy (up to 14 individual and 14 group sessions). The primary outcome was change in depression severity after treatment measured by Beck Depression Inventory-II. Primary test for efficacy was superiority of ST over IST. Secondary test was noninferiority of ST compared with CBT. Multilevel modeling was conducted. The results at 6-month follow-up were explored. RESULTS: Across treatment, ST was not superior to IST. Secondary outcome analyses and completer analyses showed similar results. However, ST showed clinically relevant noninferiority compared with CBT. CONCLUSION: ST for depression as part of a psychiatric care program showed clinical noninferiority compared to CBT, without being superior to IST. ST represents a potentially useful addition to the therapeutic repertoire for the treatment of depression but its efficacy, including long-term efficacy, should be evaluated further.

Worry and rumination as a transdiagnostic target in young people: a co-produced systematic review and meta-analysis.

PROTOCOL REGISTRATION: PROSPERO (CRD42023408899).

Evaluating the role of maladaptive personality traits in schema therapy and cognitive behavioural therapy for depression.

BACKGROUND: Advancements in the treatment of depression are pivotal due to high levels of non-response and relapse. This study evaluated the role of personality pathology in the treatment of depression by testing whether maladaptive personality traits (1) predict changes in depression over treatment or vice versa, (2) change themselves over treatment, (3) change differentially depending on treatment with schema therapy (ST) or cognitive behavioural therapy (CBT), and (4) moderate the effectiveness of these treatments. METHODS: We included 193 depressed inpatients (53.4% women, Mage = 42.9, SD = 13.4) participating in an assessor-blind randomized clinical trial and receiving a 7-week course of ST or CBT. The research questions were addressed using multiple indicator latent change score models as well as multigroup structural equation models implemented in EffectLiteR. RESULTS: Maladaptive traits did not predict changes in depressive symptoms at post-treatment, or vice versa. However, maladaptive trait domains decreased over treatment (standardized Δµ range: -0.38 to -0.89), irrespective of treatment with ST or CBT. Maladaptive traits at baseline did not moderate the effectiveness of these treatments. CONCLUSIONS: Self-reported maladaptive personality traits can change during treatment of depression, but may have limited prognostic or prescriptive value, at least in the context of ST or CBT. These results need to be replicated using follow-up data, larger and more diverse samples, and informant-rated measures of personality pathology.

Targeting metacognitive change mechanisms in acute inpatients with psychotic symptoms: feasibility and acceptability of a modularized group intervention.

Emerging evidence suggests the usefulness of psychological interventions targeting metacognitive change mechanisms in patients experiencing psychosis. Although many of these patients are treated in acute psychiatric contexts, only few studies have adapted such interventions for acute inpatient settings. The present study aimed to assess the feasibility, acceptability, and preliminary clinical outcomes of a novel modularized group intervention focusing on different aspects of metacognitive change mechanisms. In particular, the intervention aims to reduce patients' acute symptoms by enhancing cognitive insight and to relieve distress via cognitive defusion (i.e. coping). A sample of 37 participants with acute psychosis received up to nine sessions of the intervention. Baseline and post-intervention assessments were conducted for general psychopathology, psychotic symptoms, global functioning, and symptom distress. Measures of change mechanisms were assessed before and after the respective treatment module. Participants' experiences were explored in feedback questionnaires and interviews. Recruitment, retention, and attendance rate met the pre-set feasibility benchmark of 80%. The intervention was well received by participants, who emphasised the group's clear structure, positive atmosphere, and helpful contents. Response rates were high and linear mixed models revealed significant medium-to-large time effects on all clinical outcomes. As expected, increase in hypothesised change mechanisms cognitive insight and decrease in cognitive fusion was found. However, the uncontrolled design limits interpreting clinical effects. The study provides evidence that an intervention based on a metacognitive model is feasible and acceptable for acute inpatients with psychosis. Positive results on clinical outcomes and change mechanisms warrant further exploration in a randomized controlled trial.

Separating EEG correlates of stress: Cognitive effort, time pressure, and social-evaluative threat.

The prefrontal cortex is a key player in stress response regulation. Electroencephalographic (EEG) responses, such as a decrease in frontal alpha and an increase in frontal beta power, have been proposed to reflect stress-related brain activity. However, the stress response is likely composed of different parts such as cognitive effort, time pressure, and social-evaluative threat, which have not been distinguished in previous studies. This distinction, however, is crucial if we aim to establish reliable tools for early detection of stress-related conditions and monitoring of stress responses throughout treatment. This randomized cross-over study (N = 38) aimed to disentangle EEG correlates of stress. With linear mixed models accounting for missing values in some conditions, we found a decrease in frontal alpha and increase in beta power when performing the Paced Auditory Serial Addition Test (PASAT; cognitive effort; n = 32) compared to resting state (n = 33). No change in EEG power was found when the PASAT was performed under time pressure (n = 29) or when adding social-evaluative threat (video camera; n = 29). These findings suggest that frontal EEG power can discriminate stress from resting state but not more fine-grained differences of the stress response.

Psychometric Properties of the German Version of the Young Positive Schema Questionnaire (YPSQ) in the General Population and Psychiatric Patients.

Early adaptive schemas (EAS) are resilience-oriented counterparts to early maladaptive schemas (EMS), which are central in schema therapy. The Young Positive Schema Questionnaire (YPSQ) was developed as a measure of EAS but has been evaluated neither in relation to a clinical population nor in a German-speaking sample. Objectives of this study were therefore the psychometric validation of a German YPSQ in a community sample and the comparison of EAS to psychiatric patients. Participants were 1,418 individuals from a community sample and 182 psychiatric patients with a main diagnosis of major depressive disorder. A factor structure of 10 EAS, instead of the original 14, demonstrated satisfactory factorial validity and internal consistency in both samples. EAS exhibited divergent validity to EMS, childhood trauma, and psychopathology. Convergent validity was evident with resilience, self-efficacy, and satisfaction with life. Support for incremental validity beyond EMS was especially shown for resilience, self-efficacy, and satisfaction with life, and was also evident for several dimensions of psychopathology. Individuals in the community sample exhibited more pronounced EAS compared to psychiatric patients with the exception of empathic consideration. Especially for concepts associated with mental health, the YPSQ has the potential to be a highly valuable addition to current research and practice.

Psychotherapy or medication for depression? Using individual symptom meta-analyses to derive a Symptom-Oriented Therapy (SOrT) metric for a personalised psychiatry.

BACKGROUND: Antidepressant medication (ADM) and psychotherapy are effective treatments for major depressive disorder (MDD). It is unclear, however, if treatments differ in their effectiveness at the symptom level and whether symptom information can be utilised to inform treatment allocation. The present study synthesises comparative effectiveness information from randomised controlled trials (RCTs) of ADM versus psychotherapy for MDD at the symptom level and develops and tests the Symptom-Oriented Therapy (SOrT) metric for precision treatment allocation. METHODS: First, we conducted systematic review and meta-analyses of RCTs comparing ADM and psychotherapy at the individual symptom level. We searched PubMed Medline, PsycINFO, and the Cochrane Central Register of Controlled Trials databases, a database specific for psychotherapy RCTs, and looked for unpublished RCTs. Random-effects meta-analyses were applied on sum-scores and for individual symptoms for the Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI) measures. Second, we computed the SOrT metric, which combines meta-analytic effect sizes with patients' symptom profiles. The SOrT metric was evaluated using data from the Munich Antidepressant Response Signature (MARS) study (n = 407) and the Emory Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study (n = 234). RESULTS: The systematic review identified 38 RCTs for qualitative inclusion, 27 and 19 for quantitative inclusion at the sum-score level, and 9 and 4 for quantitative inclusion on individual symptom level for the HAM-D and BDI, respectively. Neither meta-analytic strategy revealed significant differences in the effectiveness of ADM and psychotherapy across the two depression measures. The SOrT metric did not show meaningful associations with other clinical variables in the MARS sample, and there was no indication of utility of the metric for better treatment allocation from PReDICT data. CONCLUSIONS: This registered report showed no differences of ADM and psychotherapy for the treatment of MDD at sum-score and symptom levels. Symptom-based metrics such as the proposed SOrT metric do not inform allocation to these treatments, but predictive value of symptom information requires further testing for other treatment comparisons.

Schema therapy versus cognitive behavioral therapy versus individual supportive therapy for depression in an inpatient and day clinic setting: study protocol of the OPTIMA-RCT.

BACKGROUND: Major depressive disorder represents (MDD) a major cause of disability and disease burden. Beside antidepressant medication, psychotherapy is a key approach of treatment. Schema therapy has been shown to be effective in the treatment of psychiatric disorders, especially personality disorders, in a variety of settings and patient groups. Nevertheless, there is no evidence on its effectiveness for MDD in an inpatient nor day clinic setting and little is known about the factors that drive treatment response in such a target group. METHODS: In the current protocol, we outline OPTIMA (OPtimized Treatment Identification at the MAx Planck Institute): a single-center randomized controlled trial of schema therapy as a treatment approach for MDD in an inpatient and day clinic setting. Over the course of 7 weeks, we compare schema therapy with cognitive behavioral therapy and individual supportive therapy, conducted in individual and group sessions and with no restrictions regarding concurrent antidepressant medication, thus approximating real-life treatment conditions. N = 300 depressed patients are included. All study therapists undergo a specific training and supervision and therapy adherence is assessed. Primary outcome is depressive symptom severity as self-assessment (Beck Depression Inventory-II) and secondary outcomes are clinical ratings of MDD (Montgomery-Asberg Depression Rating Scale), recovery rates after 7 weeks according to the Munich-Composite International Diagnostic Interview, general psychopathology (Brief Symptom Inventory), global functioning (World Health Organization Disability Assessment Schedule), and clinical parameters such as dropout rates. Further parameters on a behavioral, cognitive, psychophysiological, and biological level are measured before, during and after treatment and in 2 follow-up assessments after 6 and 24 months after end of treatment. DISCUSSION: To our knowledge, the OPTIMA-Trial is the first to investigate the effectiveness of schema therapy as a treatment approach of MDD, to investigate mechanisms of change, and explore predictors of treatment response in an inpatient and day clinic setting by using such a wide range of parameters. Insights from OPTIMA will allow more integrative approaches of psychotherapy of MDD. Especially, the identification of intervention-specific markers of treatment response can improve evidence-based clinical decision for individualizing treatment. TRIAL REGISTRATION: Identifier on clinicaltrials.gov : NCT03287362 ; September, 12, 2017.

Can an intervention designed to reduce repetitive negative thinking alter the response to a psychosocial stressor? A randomized controlled study.

Prior research suggests that repetitive negative thinking (RNT) negatively impacts mental health by intensifying and prolonging emotional reactivity to stress. This study investigated whether an intervention designed to reduce RNT alters emotional reactivity. Young adults with high trait RNT (N = 79) were randomly allocated to an RNT-focused intervention (smartphone app-based, 10 days) or a waiting list before exposure to a standardized stressor. The pre-registered analysis did not reveal a significant condition * time interaction for negative affect. However, exploratory analyses showed that whilst initial increases in negative affect in response to the stressor did not differ between conditions, participants in the intervention condition reported less negative affect throughout the following recovery phase. Additionally, participants in the intervention condition appraised their ability to cope with the stressor as higher and reported less RNT in the recovery phase. In contrast, the intervention did not affect biological stress responses. The findings indicate that RNT-focused interventions might have positive effects on mental health by breaking the self-reinforcing cycle of RNT, negative affect and maladaptive appraisals in response to stress. However, as findings are partly based on exploratory analyses, further research is needed to confirm whether reduced subjective stress reactivity mediates the effects of RNT-focused interventions on psychopathological symptoms.

Does an app designed to reduce repetitive negative thinking decrease depression and anxiety in young people? (RETHINK): a randomized controlled prevention trial.

BACKGROUND: The first onset of common mental health disorders, such as mood and anxiety disorders, mostly lies in adolescence or young adulthood. Hence, effective and scalable prevention programs for this age group are urgently needed. Interventions focusing on repetitive negative thinking (RNT) appear especially promising as RNT is an important transdiagnostic process involved in the development of depression and anxiety disorders. First clinical trials indeed show positive effects of preventative interventions targeting RNT on adult as well as adolescent mental health. Self-help interventions that can be delivered via a mobile phone app may have the advantage of being highly scalable, thus facilitating prevention on a large scale. This trial aims to investigate whether an app-based RNT-focused intervention can reduce depressive and anxiety symptoms in young people at risk for mental health disorders. METHODS: The trial will be conducted in a sample (planned N = 351) of individuals aged 16-22 years with elevated levels of RNT but no current depression or anxiety disorder. In a randomized controlled between-subjects design, two versions of the app-based self-help intervention will be compared to a waiting list control condition. The full RNT-focused intervention encompasses a variety of RNT-reducing strategies, whereas the concreteness training intervention focuses on only one of these strategies, i.e., concrete thinking. The primary outcome (depressive symptoms) and secondary outcomes (anxiety symptoms and RNT) will be measured at pre-intervention, post-intervention (6 weeks after pre-intervention), and follow-up (18 weeks after pre-intervention). DISCUSSION: This trial aims to find out whether targeting RNT via an app is an effective and feasible way of preventing depression and anxiety disorders in adolescents. Since app-based interventions are highly scalable, this trial might contribute to tackling challenges related to the increasing rates of mental health disorders among young people. TRIAL REGISTRATION: https://www.drks.de , DRKS00027384. Registered on 21 February 2022-prospectively registered.

Developing a mechanism-based therapy for acute psychiatric inpatients with psychotic symptoms: an Intervention Mapping approach.

Background: Treatment guidelines for psychosis recommend offering psychotherapy already in the acute illness phase. However, there is a lack of available interventions adapted to the specific needs and key change mechanisms of inpatients experiencing severe symptoms and crisis. In this article we outline the scientific development process of a needs-oriented and mechanism-based group intervention for acute psychiatric inpatients with psychosis (MEBASp). Methods: To guide our intervention design, we used Intervention Mapping (IM), a six-step framework for developing evidence-based health interventions that consisted of an extensive literature review, an in-depth problem definition and needs analysis, the modeling of change mechanisms and outcomes and the production of an intervention prototype. Results: Our low-threshold modularized group intervention consists of nine stand-alone sessions (two per week) within three modules and targets different aspects of metacognitive and social change mechanisms. Module I and II aim to reduce acute symptoms by fostering cognitive insight, Module III focuses on reducing distress via cognitive defusion. Therapy contents are adapted from existing metacognitive treatments such as the Metacognitive Training and presented in a destigmatizing, simply understandable and experience-oriented way. Conclusion: MEBASp is currently evaluated in a single-arm feasibility trial. Using a systematic and rigorous development methodology and providing a detailed description of the development steps demonstrated to be invaluable in improving the intervention's scientific foundation, validity, and replicability for similar research.

Transdiagnostic evaluation of epigenetic age acceleration and burden of psychiatric disorders.

Different psychiatric disorders as well as exposure to adverse life events have individually been associated with multiple age-related diseases and mortality. Age acceleration in different epigenetic clocks can serve as biomarker for such risk and could help to disentangle the interplay of psychiatric comorbidity and early adversity on age-related diseases and mortality. We evaluated five epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge and DunedinPoAm) in a transdiagnostic psychiatric sample using epigenome-wide DNA methylation data from peripheral blood of 429 subjects from two studies at the Max Planck Institute of Psychiatry. Burden of psychiatric disease, represented by a weighted score, was significantly associated with biological age acceleration as measured by GrimAge and DunedinPoAm (R2-adj. 0.22 and 0.33 for GrimAge and DunedinPoAm, respectively), but not the other investigated clocks. The relation of burden of psychiatric disease appeared independent of differences in socioeconomic status and medication. Our findings indicate that increased burden of psychiatric disease may associate with accelerated biological aging. This highlights the importance of medical management of patients with multiple psychiatric comorbidities and the potential usefulness of specific epigenetic clocks for early detection of risk and targeted intervention to reduce mortality in psychiatric patients.

Adapting the randomised controlled trial (RCT) for precision medicine: introducing the nested-precision RCT (npRCT).

Adaptations to the gold standard randomised controlled trial (RCT) have been introduced to decrease trial costs and avoid high sample sizes. To facilitate development of precision medicine algorithms that aim to optimise treatment allocation for individual patients, we propose a new RCT adaptation termed the nested-precision RCT (npRCT). The npRCT combines a traditional RCT (intervention A versus B) with a precision RCT (stratified versus randomised allocation to A or B). This combination allows online development of a precision algorithm, thus providing an integrated platform for algorithm development and its testing. Moreover, as both the traditional and the precision RCT include participants randomised to interventions of interest, data from these participants can be jointly analysed to determine the comparative effectiveness of intervention A versus B, thus increasing statistical power. We quantify savings of the npRCT compared to two independent RCTs by highlighting sample size requirements for different target effect sizes and by introducing an open-source power calculation app. We describe important practical considerations such as blinding issues and potential biases that need to be considered when designing an npRCT. We also highlight limitations and research contexts that are less suited for an npRCT. In conclusion, we introduce the npRCT as a novel precision medicine trial design strategy which may provide one opportunity to efficiently combine traditional and precision RCTs.

Imagery of negative interpersonal experiences influence the neural mechanisms of social interaction.

Negative interpersonal experiences are a key contributor to psychiatric disorders. While previous research has shown that negative interpersonal experiences influence social cognition, less is known about the effects on participation in social interactions and the underlying neurobiology. To address this, we developed a new naturalistic version of a gaze-contingent paradigm using real video sequences of gaze behaviour that respond to the participants' gaze in real-time in order to create a believable and continuous interactive social situation. Additionally, participants listened to two autobiographical audio-scripts that guided them to imagine a recent stressful and a relaxing situation and performed the gaze-based social interaction task before and after the presentation of either the stressful or the relaxing audio-script. Our results demonstrate that the social interaction task robustly recruits brain areas with known involvement in social cognition, namely the medial prefrontal cortex, bilateral temporoparietal junction, superior temporal sulcus as well as the precuneus. Imagery of negative interpersonal experiences compared to relaxing imagery led to a prolonged change in affective state and to increased brain responses during the subsequent social interaction paradigm in the temporoparietal junction, medial prefrontal cortex, anterior cingulate cortex, precuneus and inferior frontal gyrus. Taken together this study presents a new naturalistic social interaction paradigm suitable to study the neural mechanisms of social interaction and the results demonstrate that the imagery of negative interpersonal experiences affects social interaction on neural levels.