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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]

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]

Background: Major depressive disorder (MDD) is the leading cause of disability worldwide and one of the most heterogeneous mental health disorders. Although there are effective treatments for MDD, about 50% of patients do not respond to treatment. One of the greatest challenges in improving current treatments is identifying the mechanisms responsible for therapeutic change in MDD. The proposed study aims to identify patient-specific mechanisms of change in two treatments for MDD by investigating whether subpopulations of patients differ in the mechanisms of change that operate when receiving a given treatment. Based on theories of targeting weakness and building on strength, we will examine whether the mechanism of change operating when a treatment is provided depends on whether the treatment targets the patient's strength or weakness. Method: To test our hypothesis that two treatments, supportive-expressive treatment (SET) and emotion-focused treatment (EFT), differ in their mechanisms of change and to explore whether focusing on the patient's strength or weakness will result in better treatment outcome, we conduct a mechanistic randomized controlled trial. One hundred and twenty-four individuals diagnosed with MDD are randomized to 16 sessions of either SET or EFT. The two treatments are theorized to differ in their main mechanism of change: SET places emphasis on insight as its main mechanism of change, and EFT places emphasis on emotional processing. Both can serve as strength- or weakness-focused treatments, based on the patient's baseline levels of insight and emotional processing. The primary outcome is the Hamilton Rating Scale for Depression. Additional measures include self-report measures and clinical interviews, hormonal, motion, acoustic, physiological, and neuroimaging assessments, performance on cognitive tasks, and narrative material (collected from the sessions and interviews). Discussion: The RCT will expand our understanding of mechanisms of change in psychotherapy, from one-size-fits-all to patient-specific mechanisms of change. By informing therapists about which of the two approaches is most effective with patients based on their baseline characteristics, the RCT will contribute to progress toward personalized treatment. Trial registration: clinicaltrials.gov Identifier: NCT04576182 submitted on October 1st 2020. Funding: The Israel Science Foundation. Trial status: Recruitment is ongoing. [ABSTRACT FROM AUTHOR]