Searched for: in-biosketch:true
person:iosifd01
Initial Evidence for Brain Plasticity Following a Digital Therapeutic Intervention for Depression
Hoch, Megan M; Doucet, Gaelle E; Moser, Dominik A; Hee Lee, Won; Collins, Katherine A; Huryk, Kathryn M; DeWilde, Kaitlin E; Fleysher, Lazar; Iosifescu, Dan V; Murrough, James W; Charney, Dennis S; Frangou, Sophia; Iacoviello, Brian M
Background/UNASSIGNED:Digital therapeutics such as cognitive-emotional training have begun to show promise for the treatment of major depressive disorder. Available clinical trial data suggest that monotherapy with cognitive-emotional training using the Emotional Faces Memory Task is beneficial in reducing depressive symptoms in patients with major depressive disorder. The aim of this study was to investigate whether Emotional Faces Memory Task training for major depressive disorder is associated with changes in brain connectivity and whether changes in connectivity parameters are related to symptomatic improvement. Methods/UNASSIGNED:Fourteen major depressive disorder patients received Emotional Faces Memory Task training as monotherapy over a six-week period. Patients were scanned at baseline and posttreatment to identify changes in resting-state functional connectivity and effective connectivity during emotional working memory processing. Results/UNASSIGNED:Compared to baseline, patients showed posttreatment reduced connectivity within resting-state networks involved in self-referential and salience processing and greater integration across the functional connectome at rest. Moreover, we observed a posttreatment increase in the Emotional Faces Memory Task-induced modulation of connectivity between cortical control and limbic brain regions, which was associated with clinical improvement. Discussion/UNASSIGNED:These findings provide initial evidence that cognitive-emotional training may be associated with changes in short-term plasticity of brain networks implicated in major depressive disorder. Conclusion/UNASSIGNED:Our findings pave the way for the principled design of large clinical and neuroimaging studies.
PMCID:7219906
PMID: 32440602
ISSN: 2470-5470
CID: 4447062
Transcranial Photobiomodulation For The Management Of Depression: Current Perspectives
Askalsky, Paula; Iosifescu, Dan V
Major depressive disorder (MDD) is a prevalent condition associated with high rates of disability, as well as suicidal ideation and behavior. Current treatments for MDD have significant limitations in efficacy and side effect burden. FDA-approved devices for MDD are burdensome (due to repeated in-office procedures) and are most suitable for severely ill subjects. There is a critical need for device-based treatments in MDD that are efficacious, well-tolerated, and easy to use. In this paper, we review a novel neuromodulation strategy, transcranial photobiomodulation (t-PBM) with near-infrared light (NIR). The scope of our review includes the known biological mechanisms of t-PBM, as well as its efficacy in animal models of depression and in patients with MDD. Theoretically, t-PBM penetrates into the cerebral cortex, stimulating the mitochondrial respiratory chain, and also significantly increases cerebral blood flow. Animal and human studies, using a variety of t-PBM settings and experimental models, suggest that t-PBM may have significant efficacy and good tolerability in MDD. In aggregate, these data support the need for large confirmatory studies for t-PBM as a novel, likely safe, and easy-to-administer antidepressant treatment.
PMCID:6878920
PMID: 31819453
ISSN: 1176-6328
CID: 4228402
Reported Side Effects, Weight and Blood Pressure, After Repeated Sessions of Transcranial Photobiomodulation
Cassano, Paolo; Caldieraro, Marco Antonio; Norton, Richard; Mischoulon, David; Trinh, Nhi-Ha; Nyer, Maren; Dording, Christina; Hamblin, Michael R; Campbell, Benjamin; Iosifescu, Dan V
PMID: 31647774
ISSN: 2578-5478
CID: 4147642
Neural Predictors of the Antidepressant Placebo Response
Rette, Danielle; McDonald, Erin; Iosifescu, Dan V; Collins, Katherine A
The antidepressant placebo response remains a barrier to the development of novel therapies for depression, despite decades of efforts to identify and methodologically address its clinical correlates. This manuscript reviews recent neuroimaging studies that aim to identify the neural signature of antidepressant placebo response. Data captured in clinical trials have primarily focused on antidepressant efficacy or predicting antidepressant response and have reliably implicated the rostral anterior cingulate cortex (rACC) in antidepressant placebo response, but also in medication response. Imaging and electroencephalography (EEG) experiments specifically interrogating the mechanism of antidepressant placebo response, while few, suggest the reward network, including opiate neurotransmission, is also involved. Therefore, while the rACC is likely involved in the antidepressant placebo response, its observation in isolation is unlikely to prospectively distinguish antidepressant placebo from medication responders. Instead, future studies of antidepressant placebo response should probe the reward network as a whole and incorporate sophisticated computational analytical approaches.
PMID: 31635043
ISSN: 1424-8247
CID: 4147052
Time to relapse after a single administration of intravenous ketamine augmentation in unipolar treatment-resistant depression
Salloum, Naji C; Fava, Maurizio; Hock, Rebecca S; Freeman, Marlene P; Flynn, Martina; Hoeppner, Bettina; Cusin, Cristina; Iosifescu, Dan V; Trivedi, Madhukar H; Sanacora, Gerard; Mathew, Sanjay J; Debattista, Charles; Ionescu, Dawn F; Papakostas, George I
OBJECTIVE:To examine the rate and time to relapse for remitters and responders to ketamine in treatment-resistant depression (TRD). METHODS:Subjects with TRD were randomized to a single infusion of one of several doses of intravenous ketamine, or midazolam. Using Kaplan-Meier survival function, the current report examines the rate and time to relapse, defined as MADRS ≥ 22, over a period of 30 days, in subjects who achieved remission (MADRS ≤ 10) or response (≥ 50% reduction in MADRS) on day three post-infusion of intravenous ketamine 0.1, 0.5, or 1.0 mg/kg. RESULTS:Of the 60 randomized participants who received a single ketamine (0.1, 0.5, or 1.0 mg/kg) infusion, 19 (34%) met criteria for remission and 27 (48%) for response, on day 3 post-infusion. A numerical dose-response relationship was observed, with remitters/responders on ketamine 1.0 mg/kg having the lowest relapse rate, followed by ketamine 0.5 mg/kg and 0.1 mg/kg, respectively (% of remitters who relapsed by day 14: 38% with 1.0 mg/kg, 50% with 0.5 mg/kg, 100% with 0.1 mg/kg;% of responders who relapsed by day 14: 30% with 1.0 mg/kg, 50% with 0.5 mg/kg, 80% with 0.1 mg/kg). LIMITATIONS/CONCLUSIONS:The sample size was small. No MADRS measurements at day one post-infusion. The study was not powered to assess differences in relapse prevention between different doses of ketamine. CONCLUSION/CONCLUSIONS:Time to relapse after successful treatment with a single infusion of ketamine appears to follow a dose-response relationship, where higher dosage leads to increased time to relapse.
PMID: 31494365
ISSN: 1573-2517
CID: 4085792
Protein Biomarkers in Major Depressive Disorder: An Update
Woods, Alisa G; Wormwood, Kelly L; Iosifescu, Dan V; Murrough, James; Darie, Costel C
Major depressive disorder (MDD) is common. Despite numerous available treatments, many individuals fail to improve clinically. Diagnosis of MDD continues to be commonly accomplished via behavioral rather than biological methods. Biomarkers may provide objective diagnosis of MDD, and could include measurements of genes, proteins, and patterns of brain activity. Proteomic analysis and validation of biomarkers is less explored than other areas of biomarker research in MDD. Mass spectrometry (MS) is a comprehensive, unbiased means of proteomic analysis, which can be complemented by directed protein measurements, such as Western Blotting. Prior studies have focused on MS analysis of several human biomaterials in MDD, including human post-mortem brain, cerebrospinal fluid (CSF), blood components, and urine. Further studies utilizing MS and proteomic analysis in MDD may help solidify and establish biomarkers for use in diagnosis, identification of new treatment targets, and understanding of the disorder. A biomarker or a biomarker signature that facilitates a convenient and inexpensive predictive test for depression treatment response is highly desirable.
PMID: 31347073
ISSN: 0065-2598
CID: 3988272
Results of the NIMH FAST-MAS Phase IIa Proof of Mechanism Study of the Effects of the Selective kappa Opioid Antagonist JNJ-67953964 on fMRI Ventral Striatal Activity in Anhedonic Patients [Meeting Abstract]
Krystal, Andrew; Pizzagalli, Diego; Smoski, Moria; Mathew, Sanjay; Nurnberger, John; Lisanby, Sarah; Iosifescu, Dan; Murrough, James; Weiner, Richard; Calabrese, Joseph; Sanacora, Gerard; Keefe, Richard; Song, Allen; Goodman, Wayne; Szabo, Steven; Whitten, Alexis; Gao, Keming; Potter, William
ISI:000472661000117
ISSN: 0006-3223
CID: 3974182
Reported Side-Effects, Weight and Blood Pressure After Repeated Sessions of Transcranial Photobiomodulation [Meeting Abstract]
Norton, Richard; Caldieraro, Marco; Mischoulon, David; Nhi-Ha Trinh; Nyer, Maren; Dording, Christina; Hamblin, Michael R.; Campbell, Benjamin; Iosifescu, Dan V.; Cassano, Paolo
ISI:000472661000598
ISSN: 0006-3223
CID: 3974042
Effects of Transcranial Photobiomodulation With Near-Infrared Light on Sexual Dysfunction [Meeting Abstract]
Thomas, Garrett; Dording, Christina; Foster, Simmie; Yeung, Albert; Uchida, Mai; Hamblin, Michael R.; Bui, Eric; Fava, Maurizio; Mischoulon, David; Iosifescu, Dan V.; Cassano, Paolo
ISI:000472661000915
ISSN: 0006-3223
CID: 3974242
Correlation between white blood cell count and mood-stabilising treatment response in two bipolar disorder trials
Köhler-Forsberg, Ole; Sylvia, Louisa G; Bowden, Charles L; Calabrese, Joseph R; Thase, Michael E; Shelton, Richard C; McInnis, Melvin; Tohen, Mauricio; Kocsis, James H; Ketter, Terence A; Friedman, Edward S; Deckersbach, Thilo; Ostacher, Michael J; Iosifescu, Dan V; McElroy, Susan; Nierenberg, Andrew A
BACKGROUND:Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear. METHODS:Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response. RESULTS:Compared to participants with WBC counts of 4.5-10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses. CONCLUSIONS:An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.
PMID: 31169098
ISSN: 1601-5215
CID: 3918002