Improving Mild to Moderate Depression With an App-Based Self-Guided Intervention: Protocol for a Randomized Controlled Trial.

BACKGROUND: Depression is one of the most prevalent mental disorders and frequently co-occurs with other mental disorders. Despite the high direct and indirect costs to both individuals and society, more than 80% of those diagnosed with depression remain with their primary care physician and do not receive specialized treatment. Self-guided digital interventions have been shown to improve depression and, due to their scalability, have a large potential public health impact. Current digital interventions often focus on specific disorders, while recent research suggests that transdiagnostic approaches are more suitable. OBJECTIVE: This paper presents the protocol for a study that aims to assess the efficacy of a self-guided transdiagnostic app-based self-management intervention in patients with mild or moderate depression with and without comorbid mental disorders. Specifically, we are investigating the impact of the intervention on symptoms of depression, quality of life, anxiety symptoms, and mental health-related patient empowerment and self-management skills. METHODS: The intervention under investigation, MindDoc with Prescription, is a self-guided digital intervention aimed at supporting individuals with mild to moderate mental disorders from the internalizing spectrum, including depression. The app can be used as a low-threshold psychosocial intervention. Up to 570 adult patients will be randomized to either receive the intervention in addition to care as usual or only care as usual. We are including adults with a permanent residency in Germany and mild or moderate depression according to International Classification of Diseases, 10th Revision, criteria (F32.0, F32.1, F33.0, and F33.1). Clinical interviews will be conducted to confirm the diagnosis. Data will be collected at baseline as well as 8 weeks and 6 months after randomization. The primary outcome will be depression symptom severity after 8 weeks. Secondary outcomes will be quality of life, anxiety symptom severity, and patient empowerment and self-management behaviors. Data will be analyzed using multiple imputations, using the intention-to-treat principle, while sensitivity analyses will be based on additional imputation strategies and a per-protocol analysis. RESULTS: Recruitment for the trial started on February 7, 2023, and the first participant was randomized on February 14, 2023. As of September 5, 2023, 275 participants have been included in the trial and 176 have provided the primary outcome. The rate of missing values in the primary outcome is approximately 20%. CONCLUSIONS: Data from this efficacy trial will be used to establish whether access to the intervention is associated with an improvement in depression symptoms in individuals diagnosed with mild or moderate depression. The study will contribute to expanding the evidence base on transdiagnostic digital interventions. TRIAL REGISTRATION: German Registry of Clinical Trials DRKS00030852; https://drks.de/search/de/trial/DRKS00030852. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46651.

CERAD-NAB and flexible battery based neuropsychological differentiation of Alzheimer's dementia and depression using machine learning approaches.

Depression (DEP) and dementia of the Alzheimer's type (DAT) represent the most common neuropsychiatric disorders in elderly patients. Accurate differential diagnosis is indispensable to ensure appropriate treatment. However, DEP can yet mimic cognitive symptoms of DAT and patients with DAT often also present with depressive symptoms, impeding correct diagnosis. Machine learning (ML) approaches could eventually improve this discrimination using neuropsychological test data, but evidence is still missing. We therefore employed Support Vector Machine (SVM), Naïve Bayes (NB), Random Forest (RF) and conventional Logistic Regression (LR) to retrospectively predict the diagnoses of 189 elderly patients (68 DEP and 121 DAT) based on either the well-established Consortium to Establish a Registry for Alzheimer's Disease neuropsychological assessment battery (CERAD-NAB) or a flexible battery approach (FLEXBAT). The best performing combination consisted of FLEXBAT and NB, correctly classifying 87.0% of patients as either DAT or DEP. However, all accuracies were similar across algorithms and test batteries (83.0% - 87.0%). Accordingly, our study is the first to show that common ML algorithms with their default parameters can accurately differentiate between patients clinically diagnosed with DAT or DEP using neuropsychological test data, but do not necessarily outperform conventional LR.

Flexible and specific contributions of thalamic subdivisions to human cognition.

The thalamus participates in multiple functional brain networks supporting different cognitive abilities. How thalamo-cortical connections map onto the architecture of human cognition remains an outstanding question. The aim of this meta-analysis is to map co-activation between thalamic and extra-thalamic brain regions onto separate cognitive domains and to assess thalamic subdivision specificity within each of the cognitive domains considered. We parsed 93 fMRI studies into twelve cognitive domains. Signed Differential Mapping served to obtain co-activation maps. We then projected the contribution of thalamic subdivisions onto a thalamic atlas to assess cognitive domain specificity. A set of brain regions was flexibly involved with thalamus in several cognitive domains. Thalamic subdivisions showed ample cognitive heterogeneity. Our proposed model represents thalamic involvement in cognition as an "ensemble" of functional subdivisions with common cell properties embedded in separate cortical circuits rather than a homogeneous functional unit.

Action inhibition in individuals with high obsessive-compulsive trait of incompleteness: An ERP study.

BACKGROUND: Missing action completion signals are assumed to trigger repetitive behavior and feelings of the action "not being right". This proposal is based mostly on individual's self-reports. Here, we investigated the influence of experimentally manipulated action completion experience and the obsessive-compulsive (OC) trait of incompleteness on behavioral and neurophysiological measures of action inhibition. METHODS: Action completion was manipulated in an adapted Go/NoGo task, and OC trait incompleteness was assessed in healthy participants. More commission errors and faster responses were expected after missing action completion, especially for individuals with high OC trait incompleteness. The inhibition-related event-related potentials (ERPs) N200 and P300 were also measured. RESULTS: High OC trait incompleteness led to more errors following omitted- and faster responses during commission errors following incongruent outcomes. Furthermore, lower N200 was associated with worse response inhibition, and high OC trait incompleteness was associated with reduced N200, but not reduced P300 amplitude. These findings provide evidence that trait-like feelings of incompleteness may underlie maladaptive action repetition and impaired inhibitory control as observed in OCD.

Multi-outcome meta-analysis (MOMA) of cognitive remediation in schizophrenia: Revisiting the relevance of human coaching and elucidating interplay between multiple outcomes.

Cognitive remediation (CR) is nowadays mainly administered in a computerized fashion, yet frequently supplemented by human guidance. The effects of CR on cognitive, functional and clinical outcomes are consistently reported, yet the response is heterogeneous. In order to resolve this heterogeneity, we employed a multi-outcome meta-analytic approach, examined effects of CR on each outcome category separately and estimated directed effects between three outcome categories. We extracted treatment effects from 67 studies that trained patients with schizophrenia (total n = 4067) using either 1) computerized CR modality alone or 2) in combination with supplementary human guidance (SHG). All three outcome domains were significantly improved by CR with small to moderate effect sizes when assessing outcomes across all studies. The comparison between CR administered with SHG revealed largest effects on the cognitive subdomains of working and verbal memory. Structural equation modeling in the single-study data suggests that cognitive gains trigger restoration of psychosocial functioning which in turn facilitates improvement in clinical symptoms.