Working memory moderates the relation between the brain-derived neurotropic factor (BDNF) and psychotherapy outcome for depression

Background: Insight into patient characteristics that predict response to treatment for major depressive disorder (MDD) may help to personalize treatment and improve outcomes. One mechanism that has been linked to the success of treatment for MDD is brain-derived neurotropic factor (BDNF). BDNF is implicated in learning and memory and may play a role in the effects of psychotherapy that involves changing cognitions and behaviors. In addition, only in individuals with low BDNF, low working memory capacity has been associated with increased symptoms of depression. However, the role of BDNF and working memory capacity in psychotherapy outcome is unclear. The aim of this study was to investigate the role of BDNF and its interaction with working memory capacity in psychotherapy outcomes for MDD. Method: Adult patients with MDD were randomized to weekly or twice weekly sessions of cognitive behavioral therapy or interpersonal psychotherapy. BDNF Val66Met polymorphism (rs6265) (n = 138) was defined and serum BDNF was quantified before (n = 138) and after psychotherapy (n = 82). Results: Baseline serum BDNF and the Val66Met polymorphism were not associated with outcome and associations did not differ between treatment conditions. Working memory capacity significantly moderated the relation between baseline serum BDNF and outcome: high serum BDNF at baseline was related to less depressive symptoms following psychotherapy in the presence of high working memory capacity, but not low working memory capacity. Discussion: These findings, if replicated, might indicate that while BDNF may not be related to psychotherapy outcomes in general, they may play a role in the presence of specific learning processes such as working memory capacity

The implementation and adherence to evidence-based protocols for psychotherapy for depression: the perspective of therapists in Dutch specialized mental healthcare

Abstract Background Although psychotherapy is an effective treatment for depression, a large number of patients still do not receive care according to the protocols that are used in clinical trials. Instead, patients often receive a modified version of the original intervention. It is not clear how and when treatment protocols are used or modified in the Dutch specialized mental health care and whether these changes lead to suboptimal adherence to treatment protocols. Methods In the context of an ongoing multicenter trial that investigates whether twice-weekly sessions of protocolized interpersonal psychotherapy (IPT) and cognitive behavioral therapy (CBT) for depression lead to better treatment outcomes compared to once-weekly sessions, two focus groups using semi-structured interviews were organized. Aims were to increase insight in the adherence to and modifications of CBT and IPT protocols in the Dutch specialized mental health care for depression. Participants were fifteen therapists from seven mental health locations part of five mental health organizations. Verbatim transcripts were coded and analyzed using qualitative software. Results Three themes emerged: modification as the common practice, professional and patient factors influencing the adherence to protocols and organizational boundaries and flexibility. Treatment modification appeared to happen on a frequent basis, even in the context of a trial. Definitions of treatment modifications were multiple and varied from using intuition to flexible use of the same protocol. Therapist training and supervision, the years of work experience and individual characteristics of the therapist and the patient were mentioned to influence the adherence to protocols. Modifications of the therapists depended very much on the culture within the mental health locations, who differed in terms of the flexibility offered to therapists to choose and modify treatment protocols. Conclusions Not all treatment modifications were in line with existing evidence or guidelines. Regular supervision, team meetings and a shared vision were identified as crucial factors to increase adherence to treatment protocols, whereas additional organizational factors, among which a change of mindset, may facilitate adequate implementation

Prospective Mental Imagery in Depression: Impact on Reward Processing and Reward-Motivated Behaviour

[Background] Mental imagery has long been part of cognitive behavioural therapies. More recently, a resurgence of interest has emerged for prospective mental imagery, i.e. future-directed imagery-based thought, and its relation to reward processing, motivation and behaviour in the context of depression. [Method] We conducted a selective review on the role of prospective mental imagery and its impact on reward processing and reward-motivated behaviour in depression. [Results] Based on the current literature, we propose a conceptual mechanistic model of prospective mental imagery. Prospective mental imagery of engaging in positive activities can increase reward anticipation and reward motivation, which can transfer to increased engagement in reward-motivated behaviour and more experiences of reward, thereby decreasing depressive symptoms. We suggest directions for future research using multimodal assessments to measure the impact of prospective mental imagery from its basic functioning in the lab to real-world and clinical implementation. [Conclusion] Prospective mental imagery has the potential to improve treatment for depression where the aim is to increase reward-motivated behaviours. Future research should investigate how exactly and for whom prospective mental imagery works

Measuring Patients' Acquisition of Therapy Skills in Psychotherapy for Depression:Assessing the CCTS-SR and the IPSS-SR

Objective: Valid and reliable instruments to measure therapy skills are necessary to investigate these skills as mechanisms of change in cognitive-behavioral therapy (CBT) and interpersonal psychotherapy (IPT) for depression. The authors tested two measures of the skills patients with depression acquire in CBT and IPT. Methods: Using data from 202 Dutch patients with depression, the authors conducted a psychometric evaluation of the Dutch translation of the Competencies of Cognitive Therapy Scale–Self-Report (CCTS-SR) and an initial psychometric evaluation of the newly developed Interpersonal Psychotherapy Skills Scale–Self-Report (IPSS-SR). Results: A confirmatory factor analysis (CFA) resulted in a fit outside the acceptable range for the one-factor model of the CCTS-SR. For the IPSS-SR, an exploratory factor analysis and a CFA led to a four-factor solution that provided the best fit compared with other models, although it remained outside the acceptable range. Both instruments showed excellent internal consistency. Correlations between the CCTS-SR and IPSS-SR were small to moderate. Fewer depressive symptoms and higher levels of behavioral activation were related to higher scores on the IPSS-SR and CCTS-SR, while higher levels of education and fewer dysfunctional thoughts were related to higher scores on the IPSS-SR. Conclusions: Interpreting CBT and IPT skills as unidimensional concepts should be cautioned against until future studies have investigated the factor structure of the CCTS-SR and IPSS-SR across the course of CBT and IPT for depression. Further implications for psychometric research and future directions related to increasing knowledge about the role of therapy skills in psychotherapies for depression are discussed

Mechanistic pathways of change in twice weekly versus once weekly sessions of psychotherapy for depression

BACKGROUND: Recently, we showed that twice weekly sessions of cognitive-behavioral therapy (CBT) and interpersonal psychotherapy (IPT) for depression lead to better and faster treatment outcomes compared to once weekly sessions (Bruijniks et al., 2020). The present study investigated which pathways of change may account for the effects of different session frequencies. METHOD: The sample consisted of 200 patients who were randomized to CBT weekly, CBT twice weekly, IPT weekly, or IPT twice weekly. Outcome and therapy processes were measured at baseline, two weeks and monthly up to month 6 after the start of treatment. Latent change score models investigated temporal relations between change in therapy processes and change in depression and tested whether change in the therapy processes mediated the effect of session frequency on change in depression. RESULTS: IPT skills mediated the relation between session frequency and change in depression. A decrease in depression was related to subsequent improvement in CBT skills and subsequent decrease in motivation for therapy. CONCLUSION: The development of IPT skills may explain why a twice weekly higher session frequency is more effective in reducing depression compared to a once-weekly session frequency. Future studies should disentangle the causal effects of therapy process change throughout the course of therapy

Individual differences in response to once versus twice weekly sessions of CBT and IPT for depression

OBJECTIVE: The Personalized Advantage Index (PAI) is a method to guide treatment selection by investigating which of two or more treatments is optimal for a given individual. Recently, it was shown that, on average, twice-weekly sessions of psychotherapy for depression lead to better outcomes compared to once-weekly sessions. The present study applied the PAI method to assess if subgroups of patients may have a differential response to psychotherapy frequency. METHOD: Data came from a clinical trial (n = 200) randomizing depressed patients into different session frequencies: weekly sessions versus twice-weekly sessions. Machine-learning techniques were used to select pretreatment variables and develop a multivariable prediction model that calculated each patient's PAI. Differences in observed depression post-treatment scores (Beck Depression Inventory-II [BDI-II]) were tested between patients that received their PAI-indicated versus non-indicated session frequency. Between-group effect sizes (Cohen's d) were reported. RESULTS: We identified prognostic indicators generally associated with lower post-treatment BDI-II regardless of treatment assignment. In addition, we identified specific demographic and psychometric features associated with differential response to weekly- versus twice-weekly therapy sessions. Observed post-treatment BDI-II scores were significantly different between individuals receiving the PAI-indicated versus non-indicated session frequency (d = .37). CONCLUSIONS: Although a higher session frequency is more effective on average, different session frequencies seem beneficial for different patients. Future studies should externally validate these findings before they can be generalized to other settings. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

The relation between therapy quality, therapy processes and outcomes and identifying for whom therapy quality matters in CBT and IPT for depression

Background: Research on which therapy processes are crucial for whom is necessary to optimize treatment outcomes for major depressive disorder (MDD) but may be impeded by a lack of variation in therapy quality and because of individual differences in therapy response. The present study used a dataset with large variation in therapy quality to investigate the impact of therapy quality on change in therapy processes and outcome. Machine-learning techniques were used to explore individual differences in these relationships. Method: Data come from a multicenter trial that randomized patients with MDD into weekly versus twice weekly sessions of cognitive behavioral therapy (CBT) or interpersonal psychotherapy (IPT). Correlations between quality of therapy, change in therapy processes and depressive symptoms were calculated. Using elastic net regression, a prognostic model was developed that investigated individual differences. Results: There were no significant correlations between therapy quality and change in therapy process variables or between therapy quality and therapy outcome, except between therapy quality and dysfunctional thinking and IPT skills. Improvement in therapy processes played a larger role in patients whose therapy outcome was poorly predicted by their baseline characteristics. Conclusions: In this study, in which therapy quality varied considerably, we found that therapy quality was not related to change in therapy processes or outcome. In addition, this study provides a first demonstration of proposed methods to identify individual responses to change in therapy processes. Results suggested that the importance of certain therapy processes might differ between patients. Future research into the relation between therapy quality, change in therapy processes and outcome should take into account the variation of therapy quality, focus on improved measurement of therapy quality and use a combination of machine learning techniques and experimental lab studies to determine to which extent and for whom therapy quality and change in therapy processes matter

Temporal and specific pathways of change in cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT) for depression

Background The present study investigated the specific and temporal role of putative mechanisms of change in cognitive-behavioral therapy (CBT) and interpersonal psychotherapy (IPT) for major depressive disorder (MDD). Method 200 patients were randomized to CBT weekly, CBT twice weekly, IPT weekly or IPT twice weekly. Outcome and putative mechanisms of change (i.e., dysfunctional thinking, behavioral activation, CBT skills, IPT skills, therapeutic alliance, compliance, motivation) were measured multiple times up to six months after the start of treatment. Latent change score models were used to investigate temporal relations and test mediation. Explorative analyses tested whether baseline working memory moderated the effect of mechanism change on outcome change. Results CBT skills and dysfunctional thinking mediated the relation between treatment modality and changes in depression. In both treatments, IPT skills and behavioral activation were related to subsequent change in depression while a decrease in depression led to subsequent improvement in therapeutic alliance and a decrease in autonomous motivation. Change in compliance was unrelated to change in depression. Baseline working memory was related to therapy skill improvement. Conclusion CBT skill improvement seems a specific mechanism of change leading to subsequent decrease in depression in CBT. Changes in IPT skills acted as a non-specific mechanism, subsequently reducing depression regardless of treatment modality. The specific role of cognitive change and behavioral activation remains unclear. Future studies should investigate the specificity and direction of the potential mechanisms of change throughout the course of therapy and investigate whether these mechanistic pathways differ between individuals