A randomized-controlled trial of cognitive-behavioral therapy for depression with integrated techniques from emotion-focused and exposure therapies.

BACKGROUND: Emotional processing (EP) is hypothesized to be a key mechanism of change in psychotherapy that may enhance its long-term efficacy. To study the effects of fostering EP in psychotherapy for depression, this randomized-controlled clinical trial compares the efficacy and pattern of change of a cognitive-behavioral therapy that integrates emotion-focused techniques within an exposure framework (Exposure-Based Cognitive Therapy for depression; EBCT-R) to a standard cognitive-behavioral therapy (CBT). METHODS: One hundred and forty-nine depressed outpatients were randomized to a maximum of 22 sessions of manualized EBCT-R (N = 77) or CBT (N = 72). Primary outcomes were self-reported and clinician-rated depressive symptoms at posttreatment and 12-month follow-up. Secondary outcomes were self-esteem, interpersonal problems, and avoidance thoughts and behaviors. RESULTS: Depressive symptoms improved significantly over therapy in both treatments, with large within-group effect sizes for CBT (d = -1.95) and EBCT-R (d = -1.77). The pattern of depression change during treatment did not differ between treatments. Symptom relief lasted over 12 months and did not differ between EBCT-R and CBT. CONCLUSIONS: Results suggest that both treatments produced significant short- and long-term improvement in depression symptoms, but the integration of emotion-focused techniques within an exposure framework did not have added benefit. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01012856 Clinical or methodological significance of this article: This trial compares cognitive-behavioral therapy (CBT) with a similarly structured CBT that was designed to foster emotional processing by integrating emotion-focused techniques within an exposure framework. Results indicate that this form of assimilative integration did not improve outcomes at 12-month follow-up.

Resting state brain network function in major depression - Depression symptomatology, antidepressant treatment effects, future research.

The alterations of functional connectivity brain networks in major depressive disorder (MDD) have been subject of a large number of studies. Using different methodologies and focusing on diverse aspects of the disease, research shows heterogeneous results lacking integration. Disrupted network connectivity has been found in core MDD networks like the default mode network (DMN), the central executive network (CEN), and the salience network, but also in cerebellar and thalamic circuitries. Here we review literature published on resting state brain network function in MDD focusing on methodology, and clinical characteristics including symptomatology and antidepressant treatment related findings. There are relatively few investigations concerning the qualitative aspects of symptomatology of MDD, whereas most studies associate quantitative aspects with distinct resting state functional connectivity alterations. Such depression severity associated alterations are found in the DMN, frontal, cerebellar and thalamic brain regions as well as the insula and the subgenual anterior cingulate cortex. Similarly, different therapeutical options in MDD and their effects on brain function showed patchy results. Herein, pharmaceutical treatments reveal functional connectivity alterations throughout multiple brain regions notably the DMN, fronto-limbic, and parieto-temporal regions. Psychotherapeutical interventions show significant functional connectivity alterations in fronto-limbic networks, whereas electroconvulsive therapy and repetitive transcranial magnetic stimulation result in alterations of the subgenual anterior cingulate cortex, the DMN, the CEN and the dorsal lateral prefrontal cortex. While it appears clear that functional connectivity alterations are associated with the pathophysiology and treatment of MDD, future research should also generate a common strategy for data acquisition and analysis, as a least common denominator, to set the basis for comparability across studies and implementation of functional connectivity as a scientifically and clinically useful biomarker.

Self-reported interpersonal problems and impact messages as perceived by significant others are differentially associated with the process and outcome of depression therapy.

Interpersonal factors play a major role in causing and maintaining depression. This study sought to investigate how patients' self-perceived interpersonal problems and impact messages as perceived by significant others are interrelated, change over therapy, and differentially predict process and outcome in psychotherapy of depression. For the present study, we used data from 144 outpatients suffering from major depression that were treated within a psychotherapy study. Interpersonal variables were assessed pre- and posttherapy with the self-report Inventory of Interpersonal Problems-Circumplex Scale (IIP-32; Thomas, Brähler, & Strauss, 2011) and with the informant-based Impact Message Inventory (Caspar, Berger, Fingerle, & Werner, 2016). Patients' levels on the dimensions of Agency and Communion were calculated from both measures; their levels on Interpersonal Distress were measured with the IIP. Depressive and general symptomatology was assessed at pre-, post-, and at 3-month follow-up; patient-reported process measures were assessed during therapy. The Agency scores of IIP and IMI correlated moderately, but the Communion scores did not. IIP Communion was positively associated with the quality of the early therapeutic alliance and with the average level of cognitive-emotional processing during therapy. Whereas IIP Communion and IMI Agency increased over therapy, IIP Distress decreased. A pre-post-decrease in IIP Distress was positively associated with pre-postsymptomatic change over and above the other interpersonal variables, but pre-post-increase in IMI Agency was positively associated with symptomatic improvement from post- to 3-month follow-up. These findings suggest that significant others seem to provide important additional information about the patients' interpersonal style. (PsycINFO Database Record

Functional lateralization of the anterior insula during feedback processing.

Effective adaptive behavior rests on an appropriate understanding of how much responsibility we have over outcomes in the environment. This attribution of agency to ourselves or to an external event influences our behavioral and affective response to the outcomes. Despite its special importance to understanding human motivation and affect, the neural mechanisms involved in self-attributed rewards and punishments remain unclear. Previous evidence implicates the anterior insula (AI) in evaluating the consequences of our own actions. However, it is unclear if the AI has a general role in feedback evaluation (positive and negative) or plays a specific role during error processing. Using functional magnetic resonance imaging and a motion prediction task, we investigate neural responses to self- and externally attributed monetary gains and losses. We found that attribution effects vary according to the valence of feedback: significant valence × attribution interactions in the right AI, the anterior cingulate cortex (ACC), the midbrain, and the right ventral putamen. Self-attributed losses were associated with increased activity in the midbrain, the ACC and the right AI, and negative BOLD response in the ventral putamen. However, higher BOLD activity to self-attributed feedback (losses and gains) was observed in the left AI, the thalamus, and the cerebellar vermis. These results suggest a functional lateralization of the AI. The right AI, together with the midbrain and the ACC, is mainly involved in processing the salience of the outcome, whereas the left is part of a cerebello-thalamic-cortical pathway involved in cognitive control processes important for subsequent behavioral adaptations.

Assessment of serotonin release capacity in the human brain using dexfenfluramine challenge and [18F]altanserin positron emission tomography.

Although alterations of serotonin (5-HT) system functioning have been proposed for a variety of psychiatric disorders, a direct method quantitatively assessing 5-HT release capacity in the living human brain is still lacking. Therefore, we evaluated a novel method to assess 5-HT release capacity in vivo using dexfenfluramine challenge and [(18)F]altanserin positron emission tomography (PET). Thirteen healthy male subjects received placebo and single oral doses of 40 mg (n = 6) or 60 mg (n = 7) of the potent 5-HT releaser dexfenfluramine separated by an interval of 14 days. Three further subjects received placebo on both days. Two hours after placebo/drug administration, 250 MBq of the 5-HT(2A) receptor selective PET-radiotracer [(18)F]altanserin was administered intravenously as a 30s bolus. Dynamic PET data were subsequently acquired over 90 min. Moreover, arterial blood samples were drawn for measurement of total activity and metabolite correction of the input function. Dexfenfluramine as well as cortisol and prolactin plasma concentration-time profiles was quantitatively determined. Tracer distribution volumes for five volumes-of-interest (prefrontal and occipital cortex, insula, thalamus, caudatum) were calculated by the Logan plot and a 2-tissue compartment model. Dexfenfluramine dose-dependently decreased the total distribution volume of [(18)F]altanserin in cortical regions independent of the PET modeling approach. Cortisol and prolactin plasma concentrations were dose-dependently increased by dexfenfluramine. The decrease in cortical [(18)F]altanserin receptor binding under dexfenfluramine was correlated with the increase of plasma prolactin. These data suggest that the combination of a dexfenfluramine-induced 5-HT release and subsequent assessment of 5-HT(2A) receptor availability with [(18)F]altanserin PET is suitable to measure cortical 5-HT release capacity in the human brain.