The Impact of Intravenous Ketamine on Attentional Bias: Probing Mechanisms of Rapid-Acting Antidepressant Effects Across Two Clinical Studies.

Background: Ketamine is known for its rapid antidepressant effect, but its impact on affective information processing (including attentional bias, a putative cognitive mechanism of depression), remains largely unexplored. We leveraged a novel measurement of attentional bias and sought to: (1) establish adequate test-retest reliability and validity among depressed participants prior to ketamine treatment; and (2) harness a single dose of ketamine to assess mechanistic shifts in attentional bias and their relation to antidepressant efficacy.

Methods: A novel dual probe video task was used to index attentional bias toward sad film clips.

Improved implicit self-esteem is associated with extended antidepressant effects following a novel synergistic intervention.

Introduction: In a previously published randomized controlled trial, automated self-association training (ASAT), a novel digital intervention, was found to extend the rapid antidepressant effect of a single infusion of ketamine for at least 30 days. In this secondary analysis, we aimed to understand the potential role of implicit self-esteem in the combined antidepressant effect of ketamine and ASAT training, by investigating the novel synergistic treatment's effects on implicit self-associations and their relation to symptom improvement.

Methods: A total of 154 adults (ages 18-60) with treatment-resistant unipolar depression and lower-than-normative explicit self-esteem were randomized in a double-blind, parallel-arm design to receive one of three treatment allocations: an active/active treatment combination consisting of one infusion of ketamine (0.

Neural connectivity moderators and mechanisms of ketamine treatment among treatment-resistant depressed patients: a randomized controlled trial.

Background: Intravenous (IV) ketamine has emerged as a rapid and effective treatment for TRD. However, the specific neural mechanisms of ketamine's effects in humans remains unclear. Although neuroplasticity is implicated as a mechanism of action in animal models, relatively few randomized controlled trials (RCTs) in TRD patients have examined ketamine's impact on functional connectivity, a posited functional marker of neuroplasticity-particularly in the context of a mood-induction paradigm (termed miFC).

Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression.

Intravenous ketamine is posited to rapidly reverse depression by rapidly enhancing neuroplasticity. In human patients, we quantified gray matter microstructural changes on a rapid (24-h) timescale within key regions where neuroplasticity enhancements post-ketamine have been implicated in animal models. In this study, 98 unipolar depressed adults who failed at least one antidepressant medication were randomized 2:1 to a single infusion of intravenous ketamine (0.

A Novel, Brief, Fully Automated Intervention to Extend the Antidepressant Effect of a Single Ketamine Infusion: A Randomized Clinical Trial.

Objective: Intravenous ketamine, which displays rapid antidepressant properties, is posited to reverse depression by rapidly enhancing neuroplasticity. The authors tested whether an automated, computer-based approach could efficiently leverage enhanced neuroplasticity to extend the durability of rapid clinical response.

Methods: A total of 154 adults (ages 18-60) with treatment-resistant unipolar depression were randomized in a double-blind, parallel-arm design to receive an active/active treatment combination (ketamine plus active "automated self-association training" [ASAT]; N=53) or one of two control arms that lacked either the active drug component (saline plus active ASAT; N=51) or the active behavioral component (ketamine plus sham ASAT; N=50).

Cytokine and Reward Circuitry Relationships in Treatment-Resistant Depression.

Background: Depressive disorders are linked to dysfunction in reward-related behaviors and corticostriatal reward circuitry. Low-grade dysregulation of the immune system, e.g.

Resting state functional connectivity subtypes predict discrete patterns of cognitive-affective functioning across levels of analysis among patients with treatment-resistant depression.

Resting state functional connectivity (RSFC) in ventral affective (VAN), default mode (DMN) and cognitive control (CCN) networks may partially underlie heterogeneity in depression. The current study used data-driven parsing of RSFC to identify subgroups of patients with treatment-resistant depression (TRD; n = 70) and determine if subgroups generalized to transdiagnostic measures of cognitive-affective functioning relevant to depression (indexed across self-report, behavioral, and molecular levels of analysis). RSFC paths within key networks were characterized using Subgroup-Group Iterative Multiple Model Estimation.

Biobehavioral correlates of an fMRI index of striatal tissue iron in depressed patients.

Dopaminergic function is a critical transdiagnostic neurophysiological dimension with broad relevance in psychiatry. Normalized T2*-weighted (nT2*w) imaging has been previously investigated as a method to quantify biological properties of tissue in the striatum (e.g.

Repeated measurement of implicit self-associations in clinical depression: Psychometric, neural, and computational properties.

Implicit self-associations are theorized to be rigidly and excessively negative in affective disorders like depression. Such information processing patterns may be useful as an approach to parsing heterogeneous etiologies, substrates, and treatment outcomes within the broad syndrome of depression. However, there is a lack of sufficient data on the psychometric, neural, and computational substrates of Implicit Association Test (IAT) performance in patient populations.