{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T08:01:26Z","timestamp":1773129686514,"version":"3.50.1"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,6,6]],"date-time":"2018-06-06T00:00:00Z","timestamp":1528243200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,6,6]],"date-time":"2018-06-06T00:00:00Z","timestamp":1528243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Digital Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>There is an urgent need for more effective treatments for major depressive disorder (MDD). Digital therapeutics, such as computerized cognitive\u2013emotional training interventions, represent a promising new strategy for treating MDD. Here we report a replication of efficacy of a digital cognitive\u2013emotional training intervention designed to enhance cognitive control for emotional information-processing. In a randomized, double-blind, controlled study design, 51 participants with MDD in a current major depressive episode were randomly assigned to participate in a digital cognitive\u2013emotional training regimen (Emotional Faces Memory Task (EFMT); <jats:italic>n<\/jats:italic>\u2009=\u200928) involving 18 sessions over 6 weeks, or an active control condition (CT; <jats:italic>n<\/jats:italic>\u2009=\u200923) involving computerized working memory training. MDD symptoms were assessed weekly using a clinician-rated measure (Hamilton Depression Rating Scale; Ham-D); and neurocognition (working memory), at baseline and study outcome. Mixed-effects model for repeated measures (MMRM) analysis of all participants randomized revealed a significantly greater reduction in MDD symptom severity (Ham-D) from baseline to outcome in the EFMT group (8.65 points) compared to the CT group (4.77 points) (<jats:italic>F<\/jats:italic>(6,205)\u2009=\u20093.23, <jats:italic>p<\/jats:italic>\u2009=\u2009.005, <jats:italic>d<\/jats:italic>\u2009=\u20090.46). Ten of 28 EFMT participants achieved clinical response (\u226550% reduction in symptoms) compared to 4 of 23 in CT. Both groups exhibited similar, small improvements in working memory. This replicated the preliminary efficacy of a digital cognitive\u2013emotional training approach for the treatment of MDD. EFMT may be a feasible and effective intervention strategy for MDD, but future studies to elucidate its mechanism of action are warranted. This study is registered with Clinicaltrials.gov (NCT: 01934491).<\/jats:p>","DOI":"10.1038\/s41746-018-0025-5","type":"journal-article","created":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T09:23:40Z","timestamp":1525944220000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["A randomized, controlled pilot trial of the Emotional Faces Memory Task: a digital therapeutic for depression"],"prefix":"10.1038","volume":"1","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3662-2501","authenticated-orcid":false,"given":"Brian M.","family":"Iacoviello","sequence":"first","affiliation":[]},{"given":"James W.","family":"Murrough","sequence":"additional","affiliation":[]},{"given":"Megan M.","family":"Hoch","sequence":"additional","affiliation":[]},{"given":"Kathryn M.","family":"Huryk","sequence":"additional","affiliation":[]},{"given":"Katherine A.","family":"Collins","sequence":"additional","affiliation":[]},{"given":"Gary R.","family":"Cutter","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2512-2835","authenticated-orcid":false,"given":"Dan V.","family":"Iosifescu","sequence":"additional","affiliation":[]},{"given":"Dennis S.","family":"Charney","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2018,6,6]]},"reference":[{"key":"25_CR1","doi-asserted-by":"publisher","first-page":"3095","DOI":"10.1001\/jama.289.23.3095","volume":"289","author":"RC Kessler","year":"2003","unstructured":"Kessler, R. C. et al. The epidemiology of major depressive disorder: results from the national comorbidity survey replication (NCS-R). JAMA 289, 3095\u20133105 (2003).","journal-title":"JAMA"},{"key":"25_CR2","volume-title":"Mental health: new understanding, new hope, in World Health Report","author":"World Health Organization.","year":"2001","unstructured":"World Health Organization. Mental health: new understanding, new hope, in World Health Report. (World Health Organization, Geneva, Switzerland, 2001)."},{"key":"25_CR3","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1176\/appi.ajp.163.1.28","volume":"163","author":"MH Trivedi","year":"2006","unstructured":"Trivedi, M. H. et al. Evaluation and outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice. Am. J. Psychiatry 163, 28\u201340 (2006).","journal-title":"Am. J. Psychiatry"},{"key":"25_CR4","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1176\/ajp.2006.163.11.1905","volume":"163","author":"AJ Rush","year":"2006","unstructured":"Rush, A. J. et al. Acute and longer-term outcomes in depressed patients requiring one or several treatment steps: a STAR*D report. Am. J. Psychiatry 163, 1905\u20131917 (2006).","journal-title":"Am. J. Psychiatry"},{"key":"25_CR5","unstructured":"National Institute of Mental Health. Strategic Plan for Research https:\/\/www.nimh.nih.gov\/about\/strategic-planning-reports\/nimh_strategicplanforresearch_508compliant_corrected_final_149979.pdf (2015)."},{"key":"25_CR6","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1002\/da.22266","volume":"31","author":"BM Iacoviello","year":"2014","unstructured":"Iacoviello, B. M. et al. Cognitive\u2010emotional trianing as as intervention for major depressive disorder. Depress. Anxiety 31, 699\u2013706 (2014).","journal-title":"Depress. Anxiety"},{"key":"25_CR7","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.eurpsy.2014.09.415","volume":"30","author":"BM Iacoviello","year":"2015","unstructured":"Iacoviello, B. M. & Charney, D. S. Developing cognitive-emotional training exercises as interventions for mood and anxiety disorders. Eur. Psychiatry 30, 75\u201381 (2015).","journal-title":"Eur. Psychiatry"},{"key":"25_CR8","doi-asserted-by":"publisher","first-page":"3025","DOI":"10.1002\/hbm.22382","volume":"35","author":"D Dima","year":"2014","unstructured":"Dima, D., Jogia, J. & Frangou, S. Dynamic causal modeling of load-dependent modulation of effective connectivity within the verbal working memory network. Hum. Brain Mapp. 35, 3025\u20133035 (2014).","journal-title":"Hum. Brain Mapp."},{"key":"25_CR9","doi-asserted-by":"publisher","first-page":"14378","DOI":"10.1523\/JNEUROSCI.2400-11.2011","volume":"31","author":"D Dima","year":"2011","unstructured":"Dima, D., Stephan, K. E., Roiser, J. P., Friston, K. J. & Frangou, S. Effective connectivity during processing of facial affect: evidence for multiple parallel pathways. J. Neurosci. 31, 14378\u201314385 (2011).","journal-title":"J. Neurosci."},{"key":"25_CR10","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1016\/j.neuroimage.2011.02.051","volume":"56","author":"M Neta","year":"2011","unstructured":"Neta, M. & Whalen, P. J. Individual differences in neural activity during a facial expression vs. identity working memory task. Neuroimage 56, 1685\u20131692 (2011).","journal-title":"Neuroimage"},{"key":"25_CR11","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1111\/j.1469-7610.2010.02251.x","volume":"51","author":"Y Bar\u2010Haim","year":"2010","unstructured":"Bar\u2010Haim, Y. Research review: attention bias modification (ABM): a novel treatment for anxiety disorders. J. Child Psychol. Psychiatry 51, 859\u2013870 (2010).","journal-title":"J. Child Psychol. Psychiatry"},{"key":"25_CR12","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1016\/j.biopsych.2010.07.021","volume":"68","author":"Y Hakamata","year":"2010","unstructured":"Hakamata, Y. et al. Attention bias modification treatment: a meta-analysis toward the establishment of novel treatment for anxiety. Biol. Psychiatry 68, 982\u201399890 (2010).","journal-title":"Biol. Psychiatry"},{"key":"25_CR13","doi-asserted-by":"crossref","unstructured":"First, M. B., Spitzer, R. L., Gibbon, M., Williams, J. B. W. Structured Clinical Interview for DSM-IV Axis Disorders (SCID) (New York State Psychiatric Institute, Biometrics Research, New York, NY, 1995).","DOI":"10.1037\/t07827-000"},{"key":"25_CR14","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1136\/jnnp.23.1.56","volume":"23","author":"M Hamilton","year":"1960","unstructured":"Hamilton, M. A rating scale for depression. J. Neurol. Neurosurg. Psychiatry 23, 56\u201362 (1960).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"25_CR15","volume-title":"Wechsler Adult Intelligence Scale","author":"D Wechsler","year":"1997","unstructured":"Wechsler, D. Wechsler Adult Intelligence Scale. 3rd edn, (The Psychological Corporation, San Antonio, TX, 1997).","edition":"3rd edn"},{"key":"25_CR16","volume-title":"Manual for the Beck Depression Inventory-II","author":"AT Beck","year":"1996","unstructured":"Beck, A. T., Steer, R. A. & Brown, G. K. Manual for the Beck Depression Inventory-II. (Psychological Corporation, San Antonio, TX, 1996)."},{"key":"25_CR17","doi-asserted-by":"publisher","first-page":"6829","DOI":"10.1073\/pnas.0801268105","volume":"105","author":"S Jaeggi","year":"2008","unstructured":"Jaeggi, S., Buschkuehl, M., Jonides, J. & Perrig, W. Improving fluid intelligence with training in working memory. Proc. Natl. Acad. Sci. USA 105, 6829\u20136833 (2008).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"25_CR18","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s10608-006-9118-6","volume":"31","author":"GJ Siegle","year":"2007","unstructured":"Siegle, G. J., Ghinassi, F. & Thase, M. E. Neurobehavioral therapies in the 21st century: Summary of an emerging field and an extended example of cognitive control training for depression. Cogn. Ther. Res. 31, 235\u2013262 (2007).","journal-title":"Cogn. Ther. Res."},{"key":"25_CR19","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1111\/psyp.12010","volume":"50","author":"M Owens","year":"2013","unstructured":"Owens, M., Koster, E. H. & Derakshan, N. Improving attention control in dysphoria through cognitive training: transfer effects on working memory capacity and filtering efficiency. Psychophysiology 50, 297\u2013307 (2013).","journal-title":"Psychophysiology"},{"key":"25_CR20","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.jad.2015.09.022","volume":"189","author":"JN Motter","year":"2016","unstructured":"Motter, J. N. et al. Computerized cognitive training and functional recovery in major depressive disorder: a meta-analysis. J. Affect. Disord. 189, 184\u2013191 (2016).","journal-title":"J. Affect. Disord."},{"key":"25_CR21","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1177\/1529100616661983","volume":"17","author":"DJ Simons","year":"2016","unstructured":"Simons, D. J. et al. Do brain-training programs work? Psychological science in the public interest. Psychol Sci Public Interest 17, 103\u2013186 (2016).","journal-title":"Psychol Sci Public Interest"}],"container-title":["npj Digital Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41746-018-0025-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41746-018-0025-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41746-018-0025-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T12:38:40Z","timestamp":1671626320000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41746-018-0025-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,6]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["25"],"URL":"https:\/\/doi.org\/10.1038\/s41746-018-0025-5","relation":{},"ISSN":["2398-6352"],"issn-type":[{"value":"2398-6352","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,6]]},"assertion":[{"value":"5 September 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2018","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 March 2018","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2018","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Dr. Brian Iacoviello (the Principal Investigator) is an adjunct faculty member of the ISMMS and is employed full time as the Director of Scientific Affairs of Click Therapeutics. Prior to joining Click Therapeutics, Dr. Iacoviello (in his role as a full time faculty member at ISMMS) and Dr. Dennis Charney (Dean of the ISMMS) co-developed EFMT as a computer-based brain training exercise for the treatment of depression. Drs. Iacoviello and Charney are named co-inventors on a patent filed by ISMMS to develop this therapeutic approach as a mobile\/remote program (app). There is a licensing agreement between Mount Sinai and Click Therapeutics to develop this technology; if a commercial product is developed, Mount Sinai, Dr. Iacoviello, and Dr. Charney would benefit financially. A management plan was enacted proactively by the Financial Conflicts of Interest in Research (FCOIR) board at Mount Sinai for this study to mitigate conflicts of interest. According to this management plan, an independent statistical analyst (Dr. Gary Cutter) was secured to conduct all data analyses independently of the study investigators. Dr. Cutter conducted the analyses and provided the write-up and interpretations of the results to be included in the manuscript, to remove any potential bias of conflicted investigators conducting analyses or interpreting results. Dr. Cutter oversees the drafting of all manuscripts including these results and interpretations and approves any manuscript prior to submission. Dr. Iacoviello has served as a consultant to Fortress Biotech, Inc., and reports grant funding from the National Institutes of Health and the Brain and Behavior Research Foundation. In the past 3 years, Dr. Murrough has served as a consultant to Fortress Biotech, Inc., Novartis, Janssen Research and Development and Genentech and has received research support from Avanir Pharmaceuticals, Inc.; he is named on a patent pending for neuropeptide Y as a treatment for mood and anxiety disorders and on a patent pending for the combination of ketamine and lithium for suicidal ideation and for relapse prevention following ketamine in patients with depression. He is an employee of the ISMMS and has received external funding from the National Institutes of Health, the Brain and Behavioral Research Foundation, the Doris Duke Charitable Foundation, and the American Foundation for Suicide Prevention. Dr. Collins performs clinical trial assessments for ProPhase, LLC as an independent contractor. In the past five years, Dr. Iosifescu has consulted for Avanir, Axome, CNS Response, INSYS Therapeutics, Lundbeck, Otsuka, Servier, and Sunovion and he has received grant\/research support through the ISMMS from Alkermes, Astra Zeneca, Brainsway, Euthymics, Litecure, Neosync, Roche, Shire. Dr. Cutter, Ms. Hoch and Ms. Huryk declares no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21"}}