JustKiddo/KiddosVault huggingface dataset:
Reward learning impairment and avoidance and rumination responses at the end of Engage therapy of late-life depression.

This study examined the association between reward processing, as measured by performance on the probabilistic reversal learning (PRL) task and avoidance/rumination in depressed older adults treated with Engage, a psychotherapy that uses "reward exposure" to increase behavioral activation. Thirty older adults with major depression received 9 weeks of Engage treatment. At baseline and treatment end, the 24-item Hamilton Depression Rating Scale (HAM-D) was used to assess depression severity and the Behavioral Activation for Depression Scale (BADS) to assess behavioral activation and avoidance/rumination. Participants completed the PRL task at baseline and at treatment end. The PRL requires participants to learn stimulus-reward contingencies through trial and error, and switch strategies when the contingencies unexpectedly change. At the end of Engage treatment, the severity of depression was lower (HAM-D: t(19) = -7.67, P < .001) and behavioral activation was higher (BADS: t(19) = 2.23, P = .02) compared to baseline. Response time following all switches (r(19) = -0.63, P = .003) and error switches (r(19) = -0.57, P = .01) at baseline was negatively associated with the BADS avoidance/rumination subscale score at the end of Engage treatment. Impaired reward learning, evidenced by slower response following all switches and error switches, contributes to avoidant, ruminative behavior at the end of Engage therapy even when depression improves. Understanding reward processing abnormalities of avoidance and rumination may improve the timing and targeting of interventions for these symptoms, whose persistence compromises quality of life and increases the risk of depression relapse.
Investigating the (cost-) effectiveness of attention bias modification (ABM) for outpatients with major depressive disorder (MDD): a randomized controlled trial protocol.

Despite the range of available, evidence-based treatment options for Major Depressive Disorder (MDD), the rather low response and remission rates suggest that treatment is not optimal, yet. Computerized attention bias modification (ABM) trainings may have the potential to be provided as cost-effective intervention as adjunct to usual care (UC), by speeding up recovery and bringing more patients into remission. Research suggests, that a selective attention for negative information contributes to development and maintenance of depression and that reducing this negative bias might be of therapeutic value. Previous ABM studies in depression, however, have been limited by small sample sizes, lack of long-term follow-up measures or focus on sub-clinical samples. This study aims at evaluating the long-term (cost-) effectiveness of internet-based ABM, as add-on treatment to UC in adult outpatients with MDD, in a specialized mental health care setting. This study presents a double-blind randomized controlled trial in two parallel groups with follow-ups at 1, 6, and 12 months, combined with an economic evaluation. One hundred twenty six patients, diagnosed with MDD, who are registered for specialized outpatient services at a mental health care organization in the Netherlands, are randomized into either a positive training (towards positive and away from negative stimuli) or a sham training, as control condition (continuous attentional bias assessment). Patients complete eight training sessions (seven at home) during a period of two weeks (four weekly sessions). Primary outcome measures are change in attentional bias (pre- to post-test), mood response to stress (at post-test) and long-term effects on depressive symptoms (up to 1-year follow-up). Secondary outcome measures include rumination, resilience, positive and negative affect, and transfer to other cognitive measures (i.e., attentional bias for verbal stimuli, cognitive control, positive mental imagery), as well as quality of life and costs. This is the first study investigating the long-term effects of ABM in adult outpatients with MDD, alongside an economic evaluation. Next to exploring the mechanism underlying ABM effects, this study provides first insight into the effects of combining ABM and UC and the potential implementation of ABM in clinical practice. Trialregister.nl, NTR5285 . Registered 20 July 2015.
A digital intervention targeting cognitive control network dysfunction in middle age and older adults with major depression.

Nonpharmacological interventions targeting putative network mechanisms of major depressive disorder (MDD) may represent novel treatments. This mechanistic study investigates how a video game-like intervention, designed to improve cognitive control network (CCN) functioning by targeting multitasking, influences the CCN of middle-aged and older adults with MDD. The sample consisted of 34 adults aged 45-75 with SCID-defined diagnosis of MDD, Hamilton depression rating scale scores ≥20, and a deficit in cognitive control. Participants were instructed to play at home for 20-25min per day, at least 5 times per week, for 4 weeks. Evidence of target engagement was defined a priori as >2/3 of participants showing CCN improvement. CCN engagement was defined as a change in a Z score of ≥0.5 on functional magnetic resonance imaging (fMRI) in activation and functional connectivity of the CCN during task-based and resting-state fMRI, respectively. 74% of participants showed a change in activation of the CCN, and 72% showed an increase in resting-state functional connectivity. Sixty-eight percent demonstrated improved cognitive control function, measured as either improvement on sustained attention or working memory performance or reduced self-reported symptoms of apathy on the frontal systems behavioral scale (FrsBe). Participants also reported a significant reduction in mood symptoms measured by PHQ-9. A remotely deployed neuroscience-informed video game-like intervention improves both CCN functions and mood in middle-aged and older adults with MDD. This easily-disseminated intervention may rescue CCN dysfunction present in a substantial subset of middle-aged and older adults with MDD.
A randomised controlled trial of memory flexibility training (MemFlex) to enhance memory flexibility and reduce depressive symptomatology in individuals with major depressive disorder.

Successful navigation within the autobiographical memory store is integral to daily cognition. Impairment in the flexibility of memory retrieval can thereby have a detrimental impact on mental health. This randomised controlled phase II exploratory trial (N = 60) evaluated the potential of a novel intervention drawn from basic science - an autobiographical Memory Flexibility (MemFlex) training programme - which sought to ameliorate memory difficulties and improve symptoms of Major Depressive Disorder. MemFlex was compared to Psychoeducation (an evidence-based low-intensity intervention) to determine the likely range of effects on a primary cognitive target of memory flexibility at post-intervention, and co-primary clinical targets of self-reported depressive symptoms and diagnostic status at three-month follow-up. These effect sizes could subsequently be used to estimate sample size for a fully-powered trial. Results demonstrated small-moderate, though as expected statistically non-significant, effect sizes in favour of MemFlex for memory flexibility (d = 0.34, p = .20), and loss of diagnosis (OR = 0.65, p = .48), along with the secondary outcome of depression-free days (d = 0.36, p = .18). A smaller effect size was observed for between-group difference in self-reported depressive symptoms (d = 0.24, p = .35). Effect sizes in favour of MemFlex in this early-stage trial suggest that fully-powered evaluation of MemFlex may be warranted as an avenue to improving low-intensity treatment of depression. ClinicalTrials.gov, Identifier NCT02371291.
Cognitive remediation for depressed inpatients: Results of a pilot randomized controlled trial.

Neurocognitive deficits that persist despite antidepressive treatment and affect social and vocational functioning are well documented in major depressive disorder. Cognitive training approaches have proven successful in ameliorating these deficits in other psychiatric groups, but very few studies have been conducted in unipolar depressive patients by now. In contrast to previous studies solely including outpatients, effects of a cognitive remediation intervention on neurocognitive functioning of depressed inpatients were assessed by the present study. A randomized controlled trial was carried out with 46 depressed inpatients of a psychiatric hospital. Patients were randomly assigned to either a control group that received standard drug and non-drug (cognitive behavioural, occupational, sports, relaxation and music therapy) antidepressive treatment or a remediation group that additionally received 12 sessions of cognitive training for a total of 4 weeks (three sessions per week). An intent to treat analysis and a last observation carried forward method was used for data analyses. Patients of the remediation group demonstrated greater improvements in neurocognitive measures of verbal and nonverbal memory, working memory and executive function (Cohen's d effect sizes between .52 and .98). These results provide preliminary evidence that cognitive remediation interventions can be successfully applied also in psychiatric inpatients experiencing an acute depressive episode.
Attentional bias modification treatment for depression: Study protocol for a randomized controlled trial.

Theoretical models and empirical research point to negatively biased attention as a maintaining factor in depression. Although preliminary studies suggest experimentally modifying attentional biases (i.e., attentional bias modification; ABM) reduces depression symptoms and depression risk, relatively few rigorous studies with clinical samples have been completed. This clinical trial examines the impact of ABM on a sample of adults (N = 123) with elevated depression severity who also exhibit at least modest levels of negatively biased attention prior to treatment. Participants will be randomly assigned to either active ABM, placebo ABM, or an assessment-only control condition. Individuals assigned to ABM will complete 5 trainings per week (2 in-clinic, 3 brief trainings at-home) during a four-week period. Throughout this four-week period, participants will complete weekly assessments of symptom severity and putative treatment mediators measured across different levels of analysis (e.g., eye tracking, behavioral measures, and functional Magnetic Resonance Imaging). This article details the rationale and design of the clinical trial, including methodological issues that required more extensive consideration. Our findings may not only point to an easily-accessible, efficacious treatment for depression but may also provide a meaningful test of whether a theoretically important construct, negatively biased attention, maintains depression.
Testing the efficacy of INtegral Cognitive REMediation (INCREM) in major depressive disorder: study protocol for a randomized clinical trial.

Given the limitation of pharmacological treatments to treat cognitive symptoms in patients with Major Depressive Disorder (MDD), cognitive remediation programs has been proposed as a possible procognitive intervention but findings are not conclusive. This study investigates the efficacy of an INtegral Cognitive REMediation (INCREM) that includes a combination of a Functional Remediation (FR) strategy plus a Computerized Cognitive Training (CCT) in order to improve not only cognitive performance but also the psychosocial functioning and the quality of life. A single blind randomized controlled clinical trial in 81 patients with a diagnosis of MDD in clinical remission or in partial remission. Participants will be randomized to one of three conditions: INCREM (FR+CCT), Psychoeducation plus online games and Treatment As Usual (TAU). Intervention will consist in 12 group sessions, of approximately 110min once a week. The primary outcome measure will be % of change in psychosocial functioning after treatment measured by the Functional Assessment Short Test (FAST); additionally, number of sick leaves and daily activities will also be recorded as pragmatic outcomes. To our knowledge, this is the first randomized controlled clinical trial using a combination of two different approaches (FR+CCT) to treat the present cognitive deficits and to promote their improvements into a better psychosocial functioning. Clinical Trials NCT03624621 . Date registered 10th of August 2018 and last updated 24th August 2018.
Computerised memory specificity training (c-MeST) for the treatment of major depression: a study protocol for a randomised controlled trial.

Major depression is a prevalent and debilitating disorder, but many sufferers do not receive support or respond to current treatments. The development of easily accessible and low-intensity treatments that have clear cognitive mechanisms of change is indicated. Memory specificity training (MeST) is an intervention for depression that targets deficits in recalling detailed memories of past experiences through repeated practice of autobiographical memory retrieval. This randomised controlled trial will assess the efficacy of an online, computerised version of MeST (c-MeST). Adults aged 18 and over with a current major depressive episode (MDE) will be recruited and randomised to have access to the seven session, online c-MeST programme for 2weeks, or to a wait-list control group. The primary outcomes will be diagnostic status of MDE and self-reported depressive symptoms at postintervention. One-month and three-month follow-ups will be collected. Increases in autobiographical memory specificity will be assessed as a mediator of change, as well as other variables thought to contribute to reduced memory specificity, such as rumination and cognitive avoidance. Ethics approval has been granted by the Deakin University Human Research Ethics Committee to conduct the study (ID: 2017_168). The findings will be disseminated through scholarly publications and workshops and will inform future trials, such as with an active comparator or as an adjunct treatment. ACTRN12618000257268; Pre-results.
Positivity-approach training for depressive symptoms: A randomized controlled trial.

Depression is highly comorbid and depressive symptoms are very common. Symptom severity adversely affects treatment outcome and later health status. Established interventions for depression leave ample room for improvement. Short interventions that target specific vulnerabilities emerge as plausible augmentation strategies. In this study, we tested the efficacy of a computerized general positivity-approach training and its effect on depressive symptoms. Patients (N = 240) with various diagnoses of mental disorders who received treatment-as-usual in an inpatient setting were randomly assigned to also receive either 4 sessions of a positivity-approach training or 4 sessions of sham training. Depression severity was assessed at baseline and post-treatment. Training data were analyzed for a subset of 111 patients. Depressive symptoms were reduced more after positivity-approach training than after sham training. Initial depression symptom severity moderated the intervention effects, such that approach tendencies and depression symptoms were only affected positively among patients with higher levels of initial depression symptom severity. The findings provide preliminary support for positivity-approach training as an add-on treatment option for depressive symptoms.
Can increased cognitive load help people with subthreshold depression to forget negative information?

Given that major depression is a global public health problem, and that sub-threshold depression (SD) has been shown to be a significant risk indicator of major depression disorder, the awareness of SD interventions has increased. The current study explored the effect of increasing cognitive load on the forgetting of unwanted and negative memories of sub-threshold depression individuals (SDs) (Study 1) and proposed a cognitive load intervention (CLI) (study 2). 53 SDs and 52 normal participants were recruited to explore the effect of cognitive load on the directed forgetting of negative items (Study 1). The treatment effect of CLI on 62 SDs was investigated. SDs completed up to 8 CLI/control sessions over an 8-week period while regularly recording their depression symptoms (Study 2). The results showed that it is more difficult for SDs to forget negative 'to-be-forgotten' items than normal controls (F (1, 99) = 27.98, p < 0.001, η2 = 0.22). In study 1, increasing cognitive load promoted directed forgetting for negative items in SDs. Study 2 showed that there were significant reductions in depression symptoms of SDs over the 8-week CLI (e.g. BDI-Ⅱ scores: F (1, 60) = 99.93, p < 0.001, η2 = 0.63). Small sample size and lack of verification by neuroimaging may limit the generalizability of these results. The study revealed that increasing cognitive load can promote SDs to forget negative information, while the CLI project effectively reduced the depression level of SDs, thus providing encouraging initial support for its use in the treatment of SD.
Cognitive remediation therapy for partially remitted unipolar depression: A single-blind randomized controlled trial.

There is an urgent need for the development and evaluation of targeted interventions for cognitive impairment (CI) in patients with (partially) remitted major depressive disorder (MDD). The aim of our study was therefore to evaluate the effect of cognitive remediation therapy (CRT) on cognitive and psychosocial functioning in a sample of patients with MDD, taking into account comorbidity, psychopathology, remission status and CI profile. Furthermore, we compared a generalized training (GT) with an individualized training (IT) approach regarding their effects on cognition. Sixty-two MDD patients in partial remission with CI were randomly assigned to a control group (CG), IT or GT. Participants of GT trained six cognitive subdomains (divided attention, selective attention, alertness, working memory, planning and response inhibition), whereas participants of IT trained their three most deficient cognitive subdomains as identified at baseline. Participants of both intervention groups trained three times per week over a five-week period. Both training groups received additional 30-minute compensatory-transfer sessions once per week. Attention appeared to be the most frequently impaired cognitive domain as well as the domain which was significantly improved by CRT, with medium to large effect sizes. No difference in improvement was found between IT and GT. The analyses also revealed greater improvement in self-assessed psychosocial functioning in training participants (GT and IT combined) compared to the CG. Due to the small sample size, the present results are preliminary in nature. CRT was well accepted, and patients transferred the attentional improvement to real life, as measured by self-assessed psychosocial functioning. IT yielded no additional advantages over GT. We propose CRT as an integral part of the treatment plan for patients with depression suffering from CI.
Deep learning for the prediction of treatment response in depression.

Mood disorders are characterized by heterogeneity in severity, symptoms and treatment response. The possibility of selecting the correct therapy on the basis of patient-specific biomarker may be a considerable step towards personalized psychiatry. Machine learning methods are gaining increasing popularity in the medical field. Once trained, the possibility to consider single patients in the analyses instead of whole groups makes them particularly appealing to investigate treatment response. Deep learning, a branch of machine learning, lately gained attention, due to its effectiveness in dealing with large neuroimaging data and to integrate them with clinical, molecular or -omics biomarkers. In this mini-review, we summarize studies that use deep learning methods to predict response to treatment in depression. We performed a bibliographic search on PUBMED, Google Scholar and Web of Science using the terms "psychiatry", "mood disorder", "depression", "treatment", "deep learning", "neural networks". Only studies considering patients' datasets are considered. Eight studies met the inclusion criteria. Accuracies in prediction of response to therapy were considerably high in all studies, but results may be not easy to interpret. The major limitation for the current studies is the small sample size, which constitutes an issue for machine learning methods. Deep learning shows promising results in terms of prediction of treatment response, often outperforming regression methods and reaching accuracies of around 80%. This could be of great help towards personalized medicine. However, more efforts are needed in terms of increasing datasets size and improved interpretability of results.
Neurofeedback Treatment on Depressive Symptoms and Functional Recovery in Treatment-Resistant Patients with Major Depressive Disorder: an Open-Label Pilot Study.

We evaluated the effects of neurofeedback as an augmentation treatment on depressive symptoms and functional recovery in patients with treatment-resistant depression (TRD). We included 24 adult patients with TRD and 12 healthy adults. 24 TRD patients were assigned to the neurofeedback augmentation group (n = 12) and the medication-only (treatment as usual [TAU]) group (n = 12). The neurofeedback augmentation group underwent combined therapy comprising medication and 12-24 sessions of neurofeedback training for 12 weeks. To assess the serum levels of brain-derived neurotrophic factor (BDNF) in both groups, pre- and post-treatment blood samples were obtained. Patients were evaluated using the Hamilton Depression Rating Scale (HAM-D), Beck Depression Inventory (BDI), Clinical Global Impression-Severity (CGI-S), 5-level version of European Quality of Life Questionnaire 5-Dimensional Classification (EQ-5D-5L), and Sheehan Disability Scale (SDS) at baseline, and at the 1-, 4-, and 12-week. From baseline to week 12, neurofeedback training reduced mean scores on HAM-D, BDI-II, CGI-S, and SDS, and increased mean EQ-5D-5L tariff score. In the neurofeedback augmentation group, the response and remission rates were 58.3% and 50.0%, respectively, at week 12. Changes in HAM-D, EQ-5D-5L tariff score, and SDS were significantly larger in the neurofeedback group than in the medication-only (TAU) group. No significant difference in BDNF level was found pre- vs. post-treatment in any of the groups. Despite the small sample size, these results suggest that neurofeedback treatment may be effective as an augmentation treatment, not only for depressive symptoms, but also for functional recovery, in patients with TRD. Clinical Research Information Service Identifier: KCT0004183 ClinicalTrials.gov Identifier: NCT04078438.