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Psychophysiological treatment outcomes: Corticotropin-releasing factor type 1 receptor antagonist increases inhibition of fear-potentiated startle in PTSD patients
Jovanovic, Tanja; Duncan, Erica J; Kaye, Joanna; Garza, Kristie; Norrholm, Seth D; Inslicht, Sabra S; Neylan, Thomas C; Mathew, Sanjay J; Iosifescu, Dan; Rothbaum, Barbara O; Mayberg, Helen S; Dunlop, Boadie W
After exposure to a traumatic event, a subset of people develop post-traumatic stress disorder (PTSD). One of the key deficits in PTSD is regulation of fear, and impaired inhibition of fear-potentiated startle (FPS) has been identified as a potential physiological biomarker specific to PTSD. As part of a larger clinical trial, this study investigated the effects of a CRF receptor 1 antagonist, GSK561679, on inhibition of fear-potentiated startle during a conditional discrimination fear-conditioning paradigm, termed AX+/BX-. Prior research using this paradigm has demonstrated deficits in inhibition of conditioned fear in several PTSD populations. The randomized, double-blind, placebo-controlled clinical trial compared fear inhibition between female PTSD participants taking 350 mg/day GSK561679 (n = 47 pre- and 29 post-treatment) and patients taking a placebo pill (n = 52 pre- and 30 post-treatment) daily for 6 weeks. There was no significant difference between the two groups in their acquisition of fear or discrimination between threat and safety cues, and no pre-post-treatment effect on these measures. However, there was a significant effect of treatment on inhibition of FPS during the AB trials in the AX+/BX- transfer test (p < 0.05). While all PTSD participants showed typical impairments in fear inhibition prior to treatment, GSK561679 enhanced fear inhibition post-treatment, independent of clinical effects. The current study suggests that CRF receptor 1 antagonism may have specific effects within neural circuitry mediating fear inhibition responses, but not overall symptom presentation, in PTSD.
PMID: 30807663
ISSN: 1540-5958
CID: 3698372
Effects of transcranial photobiomodulation with near-infrared light on sexual dysfunction
Cassano, Paolo; Dording, Christina; Thomas, Garrett; Foster, Simmie; Yeung, Albert; Uchida, Mai; Hamblin, Michael R; Bui, Eric; Fava, Maurizio; Mischoulon, David; Iosifescu, Dan V
OBJECTIVES/OBJECTIVE:Transcranial photobiomodulation (t-PBM) consists of the delivery of near-infrared (NIR) or red light to the scalp designed to penetrate to subjacent cortical areas of the brain. NIR t-PBM has recently emerged as a potential therapy for brain disorders. This study assessed the efficacy of repeated sessions of NIR t-PBM on sexual dysfunction. METHODS:We performed a secondary analysis of a double-blind clinical trial on t-PBM for major depressive disorder (MDD). Twenty individuals received NIR t-PBM (n = 9) or sham therapy (n = 11) twice a week for 8 weeks. Sexual desire, arousal, and orgasm were assessed using the Systematic Assessment for Treatment-Emergent Effects-Specific Inquiry (SAFTEE-SI). RESULTS:The mean improvement in sexual function (decrease in SAFTEE sex total score) in subjects receiving t-PBM in NIR-mode was significantly greater than in subjects receiving sham-mode in the whole sample (NIR [n = 9] -2.55 ± 1.88 vs. sham [n = 11] -0.45 ± 1.21; z = 2.548, P = 0.011]) and in the completers (NIR [n = 5] -3.4 ± 1.95 vs. sham [n = 7] -0.14 ± 1.21; z = 2.576, P = 0.010]). CONCLUSION/CONCLUSIONS:This exploratory study with a small sample size indicates that repeated sessions of NIR t-PBM may be associated with therapeutic effects on sexual dysfunction. The latter appeared unrelated to the antidepressant effect of t-PBM in our cohort. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.
PMID: 30221776
ISSN: 1096-9101
CID: 3300182
Dysregulation of the glutamatergic system in major depressive disorder
Chapter by: Cooper, Timothy M.; Iosifescu, Dan V.
in: Major Depressive Disorder by
[S.l.] : Elsevier, 2019
pp. 161-167
ISBN: 9780323581325
CID: 4682082
Glutamate modulators in major depressive disorder
Chapter by: Cooper, Timothy M.; Iosifescu, Dan V.
in: Major Depressive Disorder by
[S.l.] : Elsevier, 2019
pp. 169-174
ISBN: 9780323581325
CID: 4682092
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
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
Correction to: Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD) (Molecular Psychiatry, (2018), 10.1038/s41380-018-0256-5) [Correction]
Fava, M; Freeman, M P; Flynn, M; Judge, H; Hoeppner, B B; Cusin, C; Ionescu, D F; Mathew, S J; Chang, L C; Iosifescu, D V; Murrough, J; Debattista, C; Schatzberg, A F; Trivedi, M H; Jha, M K; Sanacora, G; Wilkinson, S T; Papakostas, G I
Supplementary Figure 1 and Supplementary Tables 1-4 have been re-uploaded so as to reflect the versions supplied during proofs stage. The publisher apologizes for the error in versioning. The HTML version of the paper has been updated.
EMBASE:625833887
ISSN: 1359-4184
CID: 3598502
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
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
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