The prognostic role of emotion regulation dynamics in the treatment of major depressive disorder.

OBJECTIVE: The potential prognostic role of emotion regulation in the treatment of major depressive disorder (MDD) has been highlighted by transtheoretical literature and supported by promising empirical findings. The majority of the literature is based on self-report observations at a single snapshot, thus little is known about the prognostic value of moment-to-moment dynamic evolvement of emotion. The present study is the first to examine the prognostic value of both intra- and interpersonal, moment-to-moment emotion regulation dynamics, and the potential moderating effect of the type of treatment. METHOD: To assess the prognostic value of emotion regulation dynamics, we focused on the first session, using 6,780 talk-turns within 52 patient-therapist dyads. Emotion regulation dynamics were measured using fundamental frequencies of the voice and were calculated using empirical Bayes residuals of the actor-partner interdependence model. Symptomatic change was measured using the Hamilton Rating Scale for Depression across 16 weeks of supportive treatment (ST) or supportive-expressive treatment (SET). RESULTS: Findings suggest that patients who show less regulated intrapersonal dynamics during the first session show less reduction of symptoms throughout treatment (ß = .26, p = .019). Findings further suggest that this association is mitigated when these patients receive SET, as opposed to ST (ß = .72, p = .020). CONCLUSIONS: The findings demonstrate the ability of first-session emotion regulation dynamics to serve as a prognostic variable. The findings further suggest that the adverse effect of emotion regulation dynamics on the patient's prognosis can be mitigated by explicit work on changing maladaptive emotional patterns. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The development of a comprehensive coding system for evaluating insight based on a clinical interview: The SUIP-I coding system.

Gaining insight is considered a cornerstone of psychodynamic psychotherapy. Existing tools used to measure insight mainly include patients' self-report questionnaires and external coding of therapy sessions. To expand on the available tools, the present study developed a comprehensive coding system for the Self-Understanding of Interpersonal Patterns Scales-Interview (SUIP-I; Gibbons & Crits-Christoph, 2017). A total of 55 patients enrolled in a randomized controlled trial received psychodynamic psychotherapy for depression and were interviewed using the SUIP-I at baseline. A comprehensive coding system was developed for rating the interviews, based on a Likert scale for each of the six levels of insight. The content validity, psychometric properties, and the reliability and validity of the coding system were examined. The new SUIP-I coding system demonstrated interrater reliability in the "excellent" range, ICC (1, 1) = .91-.97, for all the six levels, and adequate internal consistency (Cronbach's α = .81). Support for convergent validity was gained, as manifested in a significant positive association of the SUIP-I with alliance expectation and affiliation, and a significant negative association with avoidance attachment. Support for discriminant validity was also gained, as manifested in a weak, nonsignificant association between the SUIP-I and self-esteem. The proposed comprehensive coding system shows good initial reliability and validity. Research is needed to further establish the psychometric properties of the new SUIP-I coding system. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

p53 is a central regulator driving neurodegeneration caused by C9orf72 poly(PR).

The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a GGGGCC repeat expansion in the C9orf72 gene. We developed a platform to interrogate the chromatin accessibility landscape and transcriptional program within neurons during degeneration. We provide evidence that neurons expressing the dipeptide repeat protein poly(proline-arginine), translated from the C9orf72 repeat expansion, activate a highly specific transcriptional program, exemplified by a single transcription factor, p53. Ablating p53 in mice completely rescued neurons from degeneration and markedly increased survival in a C9orf72 mouse model. p53 reduction also rescued axonal degeneration caused by poly(glycine-arginine), increased survival of C9orf72 ALS/FTD-patient-induced pluripotent stem cell (iPSC)-derived motor neurons, and mitigated neurodegeneration in a C9orf72 fly model. We show that p53 activates a downstream transcriptional program, including Puma, which drives neurodegeneration. These data demonstrate a neurodegenerative mechanism dynamically regulated through transcription-factor-binding events and provide a framework to apply chromatin accessibility and transcription program profiles to neurodegeneration.

What do these sounds tell us about the therapeutic alliance: Acoustic markers as predictors of alliance.

Predicting the trajectories of alliance formation that the patient is likely to establish with the therapist during treatment, even before their first meeting, can help prevent the potentially harmful consequences of deterioration in alliance, such as poor outcome and premature dropout. The present study aimed to examine the ability of four pretreatment acoustic markers to predict the alliance that is likely to be formed in the course of treatment: F0 span, speech rate, pause proportion and jitter. Data from 560 observations of 38 patients were collected as part of an ongoing randomized clinical trial of short-term psychotherapy for major depressive disorder. The acoustic markers were measured using high-quality recordings at baseline, before the patient and therapist ever met or had any type of communication. A multilevel model was used to examine the ability of the four acoustic markers to predict the slopes of alliance formation in the course of treatment, all markers being introduced in the same model. The clinical utility of the acoustic markers was explored in two case studies. The model explained 22% of the variance in alliance formation. Higher levels of both jitter and pause proportion at baseline predicted less strengthening of the alliance in the course of treatment. The findings, which should be replicated in larger samples, suggest that much of the therapeutic alliance can be predicted based on the acoustic characteristics of the patient's voice in the first 3 min of their intake, before they even meet their therapist.

"Take a sad song and make it better": What makes an interpretation growth facilitating for the patient?

Interpretations are considered to be an important active ingredient in psychodynamic treatment. Research shows mixed results regarding the empirical utility of interpretations, and continuing efforts are needed to investigate what makes interpretations helpful and effective. Our aim was to examine what allows an interpretation to facilitate growth, promoting the flourishing of the patient. We developed a coding system for evaluating the growth-facilitating elements of interpretation (GFI). The GFI is based on 3 scales: the optimal context for implementing the interpretation, the extent to which the interpretation includes positive regard and collaboration, and instills hope, and the immediate results of the interpretation. The GFI was used in a case study of a patient receiving supportive-expressive psychotherapy for depression. Analyses examined between-sessions and within-session processes. The integration of findings from the between-sessions and within-session analyses suggests that growth-facilitating techniques, manifest in growing positive regard, collaboration, and instilling hope, resulted in better outcomes, as reflected in the patient's new associations, mood, and self-esteem, as well as in alliance, attachment to the therapist, and reduction of depressive symptoms. The present study demonstrates the benefits of integrating the psychodynamic perspective with that of positive psychology, for building interpretations that facilitate hope, growth, and flourishing. The GFI shows promise both for psychotherapy research and clinical practice and helps bridge the gap between the two. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

"We can work it out": Working through termination ruptures.

Supportive-expressive (SE) psychodynamic treatment is based on the identification of and working through the patient's signature core conflictual relationship theme. According to the SE framework, when termination is anticipated, separation conflict arises, and the actualization of the patient's interpersonal wish in the relationship with the therapist is no longer possible. The disactualization of the patient's wish in the relationship with the therapist may cause patients to regress to their maladaptive prototype responses (Nof, Leibovich, & Zilcha-Mano, 2017), which may manifest as a rupture in the therapeutic alliance. The present work integrates constructs based on the SE framework, specifically the disactualization of the patient's wish at the end of treatment, with the framework of alliance ruptures and their resolution (Safran & Muran, 2000). We propose a conceptual clinical model to guide therapists in the successful resolution of alliance ruptures, which are the result of the disactualization of the patient's interpersonal wish. We propose a two-stage process to achieve successful resolution of termination ruptures: (a) identification of termination ruptures and (b) addressing and resolving termination ruptures. For each stage, we propose practice-based guidelines and steps to follow. We demonstrate the proposed guidelines based on the case study of a patient with major depressive disorder. We used three sources of information from the case study: verbal transcripts of the therapy sessions, questionnaires, and semistructured posttreatment interviews. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

If you believe that breaking is possible, believe also that fixing is possible: a framework for ruptures and repairs in child psychotherapy.

Safran and Muran's classic theoretical framework of alliance rupture and repair suggests effective techniques for repairing alliance ruptures. Accumulating empirical evidence suggests that successful processes of rupture and repair result in better therapeutic outcome and reduced dropout rates. Although ruptures in the alliance in child psychotherapy are frequent, little is known about how to repair them. The present paper proposes a model for identifying and repairing ruptures in child psychotherapy based on Safran and Muran. It consists of four phases: i) identifying the rupture and understanding its underlying communication message, ii) indicating the presence of the rupture, iii) accepting responsibility over the therapists' part in the rupture and emphasizing the children's active role as communicators of their distress, and iv) resolving the rupture using change strategies and meta-communication by constructing a narrative story. The theoretical rationale of each phase is explained in detail, and practical clinical guidelines are provided. Empirical studies are needed to examine the effectiveness of the proposed framework.

A practical clinical suggestion for strengthening the alliance based on a supportive-expressive framework.

Supportive-expressive psychodynamic psychotherapy builds on the core conflictual relationship theme (CCRT) as a framework for case formulation and interpretations. Much has been written on how interpretive techniques should be implemented in the treatment sessions to bring about therapeutic change, but less is known about implementing supportive techniques for strengthening the alliance using this framework. The present article uses CCRT formulations to articulate clear and concrete supportive techniques that clinicians can use in clinical practice. To this end, we offered 4 main steps and used clinical case examples to illustrate them. We described how the CCRT formulation may be used to rise above relational enactments in a supportive way and how it can provide a corrective emotional experience to enhance the emotional bond between the patient and the therapist. Clinical cases from the pilot phase of a randomized clinical trial, together with theoretical conceptualizations and empirical findings, are intertwined to demonstrate the potential of the techniques presented. (PsycINFO Database Record

Supportive-expressive interventions in working through treatment termination.

Supportive-expressive (SE) psychodynamic treatment has been receiving much empirical support. It is based on conceptualizing and working through the patients' Core Conflictual Relationship Theme, which includes their main wish (W) in the context of an interpersonal relationship, an actual or anticipated subjective response from the other (RO) in relation to the W, and the subsequent emotional and behavioral response from the self (RS) to the RO. Studies suggest that the RO and RS components show the greatest change as a result of effective SE treatment. Clinical experience, however, suggests that in the last phase of treatment, when termination is anticipated, at least some patients regress to their original RS. This process is part of a separation conflict, which includes unconsciously renouncing their RS gains. In the present article we make recommendations regarding the timing and manner of initiating the termination discussion (the "clock-like reminder" and the "symbolic listening to termination cues"), integrating both supportive and expressive techniques. The article contains practice-based guidelines on how to work through the potential RS regression. We pay specific attention to what to do and not to do in the very last session and use examples from the pilot phase of a randomized controlled trial to demonstrate each recommended technique. Lastly, we suggest paths for future research to examine the proposed framework for working through termination. (PsycINFO Database Record

Axonal Degeneration Is Regulated by a Transcriptional Program that Coordinates Expression of Pro- and Anti-degenerative Factors.

Developmental neuronal cell death and axonal elimination are controlled by transcriptional programs, of which their nature and the function of their components remain elusive. Here, we identified the dual specificity phosphatase Dusp16 as part of trophic deprivation-induced transcriptome in sensory neurons. Ablation of Dusp16 enhanced axonal degeneration in response to trophic withdrawal, suggesting that it has a protective function. Moreover, axonal skin innervation was severely reduced while neuronal elimination was increased in the Dusp16 knockout. Mechanistically, Dusp16 negatively regulates the transcription factor p53 and antagonizes the expression of the pro-degenerative factor, Puma (p53 upregulated modulator of apoptosis). Co-ablation of Puma with Dusp16 protected axons from rapid degeneration and specifically reversed axonal innervation loss early in development with no effect on neuronal deficits. Overall, these results reveal that physiological axonal elimination is regulated by a transcriptional program that integrates regressive and progressive elements and identify Dusp16 as a new axonal preserving factor.

Axonal pruning is actively regulated by the microtubule-destabilizing protein kinesin superfamily protein 2A.

Extensive axonal pruning and neuronal cell death are critical events for the development of the nervous system. Like neuronal cell death, axonal elimination occurs in discrete steps; however, the regulators of these processes remain mostly elusive. Here, we identify the kinesin superfamily protein 2A (KIF2A) as a key executor of microtubule disassembly and axonal breakdown during axonal pruning. Knockdown of Kif2a, but not other microtubule depolymerization or severing proteins, protects axonal microtubules from disassembly upon trophic deprivation. We further confirmed and extended this result to demonstrate that the entire degeneration process is delayed in neurons from the Kif2a knockout mice. Finally, we show that the Kif2a-null mice exhibit normal sensory axon patterning early during development, but abnormal target hyperinnervation later on, as they compete for limited skin-derived trophic support. Overall, these findings reveal a central regulatory mechanism of axonal pruning during development.