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Objective: Many active treatments exist for major depressive disorder (MDD), but little is known about their differential effects for various subpopulations of patients to guide precision medicine. This is the first randomized controlled trial (RCT) designed to identify differential treatment effects based on patients' attachment orientations. We tested an a priori preregistered hypothesis of the potential moderating effect of patients' attachment orientation on the outcome of supportive therapy (ST) versus supportive-expressive therapy (SET). Methods: The RCT was conducted between 2015 and 2021. Individuals with MDD were randomly assigned to 16-week ST or SET. The predefined primary outcome measure was the Hamilton Rating Scale for Depression. Hypotheses were formulated and preregistered before data collection. Results: One hundred patients with MDD were enrolled, 57% women, average age 31.2 (SD = 8.25). Data were analyzed using the intention-to-treat approach. Our hypothesis that attachment anxiety is a significant moderator of treatment outcome was supported (B = −0.09, p =.016): Patients with higher levels of attachment anxiety showed greater treatment efficacy following SET than ST. Although the hypothesis regarding a potential moderating effect of avoidant attachment was not supported, sensitivity analyses revealed that individuals with disorganized attachment orientation (higher scores on both anxious and avoidant attachment) benefited more from SET than from ST (B = −0.07, p =.04). Conclusion: The findings support the clinical utility of patients' attachment orientation in selecting the most suitable treatment for individuals and demonstrate the methodological utility of RCTs predesigned to test theoretically based models of personalized treatment. What is the public health significance of this article?: This study is the first randomized controlled trial (RCT) predesigned to test the differential effect of treatments based on the patients' pretreatment attachment orientations. The findings demonstrate the ability of attachment orientation to serve as an empirically informed tool for a personalized match between individuals and their most effective treatment. [ABSTRACT FROM AUTHOR]

Patients' attachment orientation was found to be an important predictor of the process and outcome of psychotherapy. The present study is the first to examine whether patients' attachment orientation toward significant others predicts their implicit and explicit expectations from the therapist, and whether this effect is moderated by the extent to which the therapist has become an attachment figure. In two studies (N = 308), we developed measures of implicit (lexical decision task) and explicit expectations from therapist, and tested the presence of individual differences in expectations as a function of the patients' attachment orientation, early and late in treatment. Whereas individuals higher on attachment anxiety did not report having fewer positive expectations from therapist early in treatment, they showed lower accessibility of positive expectations when measured implicitly. As treatment progressed, the extent to which the therapist has become an attachment figure may mitigate the adverse effects of pretreatment attachment anxiety. [ABSTRACT FROM AUTHOR]

Objective: Oxytocin (OT) synchrony has been suggested as a key mechanism by which bonds are formed and strengthened in various species, including those between mother and infant and between romantic partners. It is unknown whether such biological synchrony also plays a role in psychotherapy efficacy, where it may underlie the adverse effect of social impairment on the efficacy of treatment of depression. Method: Five hundred eighty OT saliva samples were collected from 37 patient–therapist dyads on a fixed schedule over a 16-session ongoing randomized controlled trial for psychotherapy for depression. Biological synchrony was operationalized as the correlation between changes occurring repeatedly over treatment in patient and therapist OT levels pre- to postsession. Results: OT synchrony between patients and therapists was found to be associated with effective treatment. The findings support the proposed mediation model: (a) poorer social functioning at baseline predicted lower levels of patient–therapist synchrony in OT changes from pre- to postsession over the course of treatment; (b) lower levels of therapist–patient OT synchrony, in turn, predicted less reduction in depressive symptoms during treatment; and (c) based on quasi-Bayesian Monte Carlo simulations, the levels of therapist–patient synchrony significantly mediated the association between social impairment and reduction in depressive symptoms. Findings were replicated using robust inferential methods. Conclusions: The findings suggest that OT synchrony between patient and therapist may be a biological mechanism by which impaired interpersonal functioning undermines treatment outcome. What is the public health significance of this article?: To our knowledge, this is the first study to focus on the biological synchrony between patients and their therapists during treatment sessions and to suggest that this synchrony is an important mechanism underlying the effects of impaired interpersonal functioning on treatment outcome. Patients with poorer social functioning at baseline were less biologically synchronized with their therapists during treatment sessions, and the poorer synchrony was associated with lower ability to benefit from treatment and to achieve symptoms reduction. [ABSTRACT FROM AUTHOR]

The therapeutic alliance is one of the most consistent predictors of therapeutic change, including symptom reduction and improvement in wellbeing and quality of life, across a variety of mental health interventions. Yet, little is known about its biological mechanisms. Oxytocin (OT) has been suggested as a biological mechanism by which bonds are formed and strengthened across species. This article is intended to demonstrate the potential of OT as a biomarker of therapeutic change in psychotherapy and counseling psychology, especially of the therapeutic alliance. We delineate three main potential paths of investigation based on the most recent research on OT in parent–child and romantic partner dyads. For each path, we provide a detailed explanation for whom, when, and how OT should be measured. Each path is illustrated using data collected in a randomized controlled trial of psychotherapy for major depressive disorder. These illustrations demonstrate the great potential of OT as a biomarker of (a) trait-like characteristics of the patients and the therapists, (b) the processes of therapeutic change, and (c) the dyadic synchrony between patients and their therapists. The potential clinical contribution of OT as a biomarker for each of these three paths is further demonstrated using a case study. Practical suggestions and directions for future research are discussed. Public Significance Statement: The article highlights the promising potential of OT as a biomarker in psychotherapy research, through the most recent research on the role of OT in parent–child and romantic relationships, as well as through data from a randomized controlled trial of psychotherapy for major depressive disorder. The article provides practical suggestions on how this potential may be realized. Interdisciplinary studies integrating the two fields of inquiry, psychotherapy and OT research, can create new important knowledge that has the potential to make a substantial contribution to clinical practice and complement existing approaches for measuring the process of therapeutic change. [ABSTRACT FROM AUTHOR]

Despite widespread clinical, theoretical, and empirical support for the importance of alliance ruptures, little is known about the underlying biological level at times of rupture. The overarching goal of the present study was to investigate dyadic patterns of in-session oxytocin (OT) change between patients and therapists (e.g., patient's OT increases more than therapist's OT) as markers of withdrawal ruptures. Hypothesis 1 construed that OT incongruence (e.g., larger patient increase in OT in comparison to their therapist OT increase) will mark the occurrence of withdrawal ruptures. Hypothesis 2 construed that this effect of OT incongruence will be more pronounced when anxious attachment orientation is low. Surface analysis was conducted on 628 saliva samples that were gathered before and after therapeutic sessions of 53 patient–therapist dyads enrolled in a randomized control trial treating major depression. Only Hypothesis 2 received empirical support, meaning it was only when anxious attachment orientation was low that there were significantly more withdrawal ruptures when the patient's OT increase was higher than their therapist's OT increase. This is consistent with the literature, suggesting that in times of withdrawal ruptures, the patient and therapist are in an incongruent state. Findings suggest that this incongruence is mirrored at the biological level only when anxious attachment orientation is low. Results shed light on what may be happening between patients and therapists on a biological level during a withdrawal rupture. Public Significance Statement: This article provides the first empirical evidence of a potential biological marker for withdrawal ruptures. Findings suggest that a dyadic pattern of incongruence in oxytocin release emerges in times of withdrawal ruptures. This dyadic pattern of incongruence manifested as a patient's increase in OT that is higher than the therapist's increase in OT. This effect of OT incongruence was found only when anxious attachment orientation was low. [ABSTRACT FROM AUTHOR]