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2. Disturbed sex hormone milieu in males and females with major depressive disorder and low-grade inflammation

Author

Lombardo, Giulia, Mondelli, Valeria, Worrell, Courtney, Sforzini, Luca, Mariani, Nicole, Nikkheslat, Naghmeh, Nettis, Maria A., Kose, Melisa, Zajkowska, Zuzanna, Cattaneo, Annamaria, Pointon, Linda, Turner, Lorinda, Cowen, Philip J., Drevets, Wayne C., Cavanagh, Jonathan, Harrison, Neil A., Bullmore, Edward T., Dazzan, Paola, and Pariante, Carmine M.

Published
2024
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6. The effects of inhibition of fatty acid amide hydrolase (FAAH) by JNJ-42165279 in social anxiety disorder: a double-blind, randomized, placebo-controlled proof-of-concept study

Author

Schmidt, Mark E, Liebowitz, Michael R, Stein, Murray B, Grunfeld, Jennifer, Van Hove, Ilse, Simmons, W Kyle, Van Der Ark, Peter, Palmer, James A, Saad, Ziad S, Pemberton, Darrel J, Van Nueten, Luc, and Drevets, Wayne C

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Clinical Trials and Supportive Activities, Mental Health, Behavioral and Social Science, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Amidohydrolases, Dose-Response Relationship, Drug, Double-Blind Method, Humans, Phobia, Social, Piperazines, Treatment Outcome, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Neurosciences, Biological psychology
Abstract

JNJ-42165279 is a selective inhibitor of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of fatty acid amides (FAA) including anandamide (AEA), palmitoylethanolamide (PEA), and N-oleoylethanolamide (OEA). We assessed the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of treatment with JNJ-42165279 in subjects with social anxiety disorder (SAD). This was a multicenter, double-blind, placebo-controlled study randomizing subjects to 12 weeks of treatment with either JNJ-42165279 (25 mg daily) or placebo (PBO). The primary endpoint was the change in the Liebowitz Social Anxiety Scale (LSAS) total score from baseline to end of study. Secondary endpoints included the Hamilton Anxiety Scale (HAM-A), Hamilton Depression Rating Scale (HDRS17), and the Clinical Global Impression-Improvement (CGI-I). Samples were collected for plasma concentration of AEA, PEA, OEA, and JNJ-42165279. A total of 149 subjects were enrolled with a mean baseline LSAS total score of 102.6 (SD 16.84). The mean change from baseline (SD) in LSAS total score at week 12 was numerically greater for JNJ-42165279: -29.4 (27.47) compared to PBO: -22.4 (23.57) but not significant. The percentage of subjects with ≥30% improvement from baseline in the LSAS total score was significantly higher for JNJ-42165279 (42.4%) compared to PBO (23.6%) (p value = 0.04). The percentage of subjects with a CGI-I score of much or very much improved was also significantly higher for JNJ-42165279 (44.1%) than for PBO (23.6%) (p value = 0.02). The drug was well tolerated. JNJ-42165279 appears to elicit an anxiolytic effect in subjects with SAD although trough concentrations with 25 mg once daily appeared to be insufficient to completely inhibit FAAH activity which may have led to suboptimal efficacy. ClinicalTrials.gov Identifier: NCT02432703.

Published
2021

11. Comparison of Long-Term Efficacy and Safety of Esketamine Nasal Spray Plus Oral Antidepressant in Younger Versus Older Patients With Treatment-Resistant Depression: Post-Hoc Analysis of SUSTAIN-2, a Long-Term Open-Label Phase 3 Safety and Efficacy Study

Author

Ochs-Ross, Rachel, Wajs, Ewa, Daly, Ella J., Zhang, Yun, Lane, Rosanne, Lim, Pilar, Drevets, Wayne C., Steffens, David C., Sanacora, Gerard, Jamieson, Carol, Hough, David, Manji, Husseini, and Singh, Jaskaran B.

Published
2022
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15. Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder: Association with sleep disturbance

Author

Suzuki, Hideo, Savitz, Jonathan, Teague, T Kent, Gandhapudi, Siva K, Tan, Chibing, Misaki, Masaya, McKinney, Brett A, Irwin, Michael R, Drevets, Wayne C, and Bodurka, Jerzy

Subjects
Mental Health, Major Depressive Disorder, Depression, 2.1 Biological and endogenous factors, Aetiology, Adult, Depressive Disorder, Major, Female, Flow Cytometry, Humans, Killer Cells, Natural, Male, Sleep Wake Disorders, T-Lymphocytes, Cytotoxic, T-Lymphocytes, Regulatory, Flow cytometry, Sleep, Regulatory T cells, CD8(+) cells, Natural killer cells, Immunology, Neurosciences, Psychology, Neurology & Neurosurgery
Abstract

A subset of individuals with major depressive disorder (MDD) have impaired adaptive immunity characterized by a greater vulnerability to viral infection and a deficient response to vaccination along with a decrease in the number and/or activity of T cells and natural killer cells (NKC). Nevertheless, it remains unclear which specific subsets of lymphocytes are altered in MDD, a shortcoming we address here by utilizing an advanced fluorescence-activated cell sorting (FACS) method that allows for the differentiation of important functionally-distinct lymphocyte sub-populations. Furthermore, despite evidence that sleep disturbance, which is a core symptom of MDD, is itself associated with alterations in lymphocyte distributions, there is a paucity of studies examining the contribution of sleep disturbance on lymphocyte populations in MDD populations. Here, we measured differences in the percentages of 13 different lymphocytes and 6 different leukocytes in 54 unmedicated MDD patients (partially remitted to moderate) and 56 age and sex-matched healthy controls (HC). The relationship between self-reported sleep disturbance and cell counts was evaluated in the MDD group using the Pittsburgh Sleep Quality Index (PSQI). The MDD group showed a significantly increased percentage of CD127low/CCR4+ Treg cells, and memory Treg cells, as well as a reduction in CD56+CD16- (putative immunoregulatory) NKC counts, the latter, prior to correction for body mass index. There also was a trend for higher effector memory CD8+ cell counts in the MDD group versus the HC group. Further, within the MDD group, self-reported sleep disturbance was associated with an increased percentage of effector memory CD8+ cells but with a lower percentage of CD56+CD16- NKC. These results provide important new insights into the immune pathways involved in MDD, and provide novel evidence that MDD and associated sleep disturbance increase effector memory CD8+ and Treg pathways. Targeting sleep disturbance may have implications as a therapeutic strategy to normalize NKC and memory CD8+ cells in MDD.

Published
2017

16. Sleep disturbance and kynurenine metabolism in depression

Author

Cho, Hyong Jin, Savitz, Jonathan, Dantzer, Robert, Teague, T Kent, Drevets, Wayne C, and Irwin, Michael R

Subjects
Depression, Brain Disorders, Clinical Research, Mental Health, Behavioral and Social Science, Sleep Research, Adult, Female, Humans, Kynurenic Acid, Kynurenine, Male, Quinolinic Acid, Sleep Wake Disorders, Sleep disturbance, Inflammation, Kynurenine pathway, Kynurenic acid, Quinolinic acid, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

ObjectiveAlthough the interrelationships between sleep disturbance, inflammation, and depression have been found, molecular mechanisms that link these conditions are largely unknown. Kynurenine metabolism is hypothesized to be a key mechanism that links inflammation and depression. Inflammation activates the kynurenine pathway, leading to increases in 3-hydroxykynurenine (3HK) and quinolinic acid (QA), potentially neurotoxic metabolites, and decreases in kynurenic acid (KynA), a potentially neuroprotective compound. This relative neurotoxic shift in the balance of kynurenine metabolites has been associated with depression, but never been examined regarding sleep disturbance. We tested the association between sleep disturbance and this relative neurotoxic shift in 68 currently depressed, 26 previously depressed, and 66 never depressed subjects.MethodsSleep disturbance was assessed using the Pittsburgh Sleep Quality Index. Serum concentrations of kynurenine metabolites were measured using high performance liquid chromatography. Putative neuroprotective indices reflecting the relative activity of neuroprotective and neurotoxic kynurenine metabolites were calculated as KynA/QA and KynA/3HK (primary outcomes).ResultsSleep disturbance was associated with reduced KynA/QA in the currently depressed group only (unadjusted beta -0.43, p

Published
2017

18. Meaningful Change in Depression Symptoms Assessed with the Patient Health Questionnaire (PHQ-9) and Montgomery-Åsberg Depression Rating Scale (MADRS) Among Patients with Treatment Resistant Depression in Two, Randomized, Double-blind, Active-controlled Trials of Esketamine Nasal Spray Combined With a New Oral Antidepressant

Author

Hudgens, Stacie, Floden, Lysbeth, Blackowicz, Michael, Jamieson, Carol, Popova, Vanina, Fedgchin, Maggie, Drevets, Wayne C., Cooper, Kimberly, Lane, Rosanne, and Singh, Jaskaran

Published
2021
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25. Prefrontal control of the amygdala during real-time fMRI neurofeedback training of emotion regulation

Author

Zotev, Vadim, Phillips, Raquel, Young, Kymberly D., Drevets, Wayne C., and Bodurka, Jerzy

Subjects
Physics - Medical Physics
Abstract

We observed in a previous study (PLoS ONE 6:e24522) that the self-regulation of amygdala activity via real-time fMRI neurofeedback (rtfMRI-nf) with positive emotion induction was associated, in healthy participants, with an enhancement in the functional connectivity between the left amygdala (LA) and six regions of the prefrontal cortex. These regions included the left rostral anterior cingulate cortex (rACC), bilateral dorsomedial prefrontal cortex (DMPFC), bilateral superior frontal gyrus (SFG), and right medial frontopolar cortex (MFPC). Together with the LA, these six prefrontal regions thus formed the functional neuroanatomical network engaged during the rtfMRI-nf procedure. Here we perform a structural vector autoregression (SVAR) analysis of the effective connectivity for this network. The SVAR analysis demonstrates that the left rACC plays an important role during the rtfMRI-nf training, modulating the LA and the other network regions. According to the analysis, the rtfMRI-nf training leads to a significant enhancement in the time-lagged effect of the left rACC on the LA. The training is also accompanied by significant increases in the instantaneous (contemporaneous) effects of the left rACC on four other regions - the bilateral DMPFC, the right MFPC, and the left SFG. The instantaneous effects of the LA on the bilateral DMPFC are also significantly enhanced. Our results are consistent with a broad literature supporting the role of the rACC in emotion processing and regulation. Our analysis provides, for the first time, insights into the causal relationships within the network of regions engaged during the rtfMRI-nf procedure targeting the amygdala. It suggests that the rACC may constitute a promising target for rtfMRI-nf training along with the amygdala in patients with affective disorders, particularly posttraumatic stress disorder (PTSD)., Comment: 17 pages, 7 figures, submitted

Published
2013
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26. Inflammatory biomarkers in Alzheimer's disease plasma

Author

Bullmore, Edward T., Bhatti, Junaid, Chamberlain, Samuel J., Correia, Marta M., Crofts, Anna L., Dickinson, Amber, Foster, Andrew C., Kitzbichler, Manfred G., Knight, Clare, Lynall, Mary-Ellen, Maurice, Christina, O'Donnell, Ciara, Pointon, Linda J., St George Hyslop, Peter, Turner, Lorinda, Vertes, Petra, Widmer, Barry, Williams, Guy B., Morgan, B. Paul, Leckey, Claire A., Morgan, Angharad R., O'Hagan, Caroline, Touchard, Samuel, Cavanagh, Jonathan, Deith, Catherine, Farmer, Scott, McClean, John, McColl, Alison, McPherson, Andrew, Scouller, Paul, Sutherland, Murray, Boddeke, H.W.G.M., Richardson, Jill C., Khan, Shahid, Murphy, Phil, Parker, Christine A., Patel, Jai, Jones, Declan, de Boer, Peter, Kemp, John, Drevets, Wayne C., Nye, Jeffrey S., Wittenberg, Gayle, Isaac, John, Bhattacharya, Anindya, Carruthers, Nick, Kolb, Hartmuth, Pariante, Carmine M., Turkheimer, Federico, Barker, Gareth J., Byrom, Heidi, Cash, Diana, Cattaneo, Annamaria, Gee, Antony, Hastings, Caitlin, Mariani, Nicole, McLaughlin, Anna, Mondelli, Valeria, Nettis, Maria, Nikkheslat, Naghmeh, Randall, Karen, Sheridan, Hannah, Simmons, Camilla, Singh, Nisha, Van Loo, Victoria, Vicente-Rodriguez, Marta, Wood, Tobias C., Worrell, Courtney, Zajkowska, Zuzanna, Plath, Niels, Egebjerg, Jan, Eriksson, Hans, Gastambide, Francois, Adams, Karen Husted, Jeggo, Ross, Thomsen, Christian, Pederson, Jan Torleif, Campbell, Brian, Möller, Thomas, Nelson, Bob, Zorn, Stevin, O'Connor, Jason, Attenburrow, Mary Jane, Baird, Alison, Benjamin, Jithen, Clare, Stuart, Cowen, Philip, Huang, I-Shu (Dante), Hurley, Samuel, Jones, Helen, Lovestone, Simon, Mada, Francisca, Nevado-Holgado, Alejo, Oladejo, Akintayo, Ribe, Elena, Smith, Katy, Vyas, Anviti, Hughes, Zoe, Balice-Gordon, Rita, Duerr, James, Piro, Justin R., Sporn, Jonathan, Perry, V. Hugh, Cleal, Madeleine, Fryatt, Gemma, Gomez-Nicola, Diego, Mancuso, Renzo, Reynolds, Richard, Harrison, Neil A., Cercignani, Mara, Clarke, Charlotte L., Hoskins, Elizabeth, Kohn, Charmaine, Murray, Rosemary, Wilcock, Lauren, Wlazly, Dominika, Mount, Howard, Leckey, Claire, Nevado-Holgado, Alejo J., Barkhof, Frederik, Bertram, Lars, Blin, Olivier, Bos, Isabelle, Dobricic, Valerija, Engelborghs, Sebastiaan, Frisoni, Giovanni, Frölich, Lutz, Gabel, Silvey, Johannsen, Peter, Kettunen, Petronella, Kłoszewska, Iwona, Legido-Quigley, Cristina, Lleó, Alberto, Martinez-Lage, Pablo, Mecocci, Patrizia, Meersmans, Karen, Molinuevo, José Luis, Peyratout, Gwendoline, Popp, Julius, Richardson, Jill, Sala, Isabel, Scheltens, Philip, Streffer, Johannes, Soininen, Hikka, Tainta-Cuezva, Mikel, Teunissen, Charlotte, Tsolaki, Magda, Vandenberghe, Rik, Visser, Pieter Jelle, Vos, Stephanie, Wahlund, Lars-Olof, Wallin, Anders, Westwood, Sarah, and Zetterberg, Henrik

Published
2019
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27. Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Depressive Symptoms in Adolescents With MDD at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Psychoactive-Controlled Study

Author

DelBello, Melissa P., primary, Kosik-Gonzalez, Colette, additional, Fu, Dong-Jing, additional, Chen, Li (Nancy), additional, Lane, Rosanne, additional, Drevets, Wayne C., additional, Moreno, Carmen, additional, and Canuso, Carla M., additional

Published
2023
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35. Genetic variants for head size share genes and pathways with cancer

Author

Amouyel, Philippe, Arfanakis, Konstantinos, Aribisala, Benjamin S., Bastin, Mark E., Chauhan, Ganesh, Chen, Christopher, Cheng, Ching-Yu, de Jager, Philip L., Deary, Ian J., Fleischman, Debra A., Gottesman, Rebecca F., Gudnason, Vilmundur, Hilal, Saima, Hofer, Edith, Janowitz, Deborah, Jukema, J. Wouter, Liewald, David C.M., Lopez, Lorna M., Lopez, Oscar, Luciano, Michelle, Martinez, Oliver, Niessen, Wiro J., Nyquist, Paul, Rotter, Jerome I., Rundek, Tatjana, Sacco, Ralph L., Schmidt, Helena, Tiemeier, Henning, Trompet, Stella, van der Grond, Jeroen, Völzke, Henry, Wardlaw, Joanna M., Yanek, Lisa, Yang, Jingyun, Agartz, Ingrid, Alhusaini, Saud, Almasy, Laura, Ames, David, Amunts, Katrin, Andreassen, Ole A., Armstrong, Nicola, Bernard, Manon, Blangero, John, Blanken, Laura M.E., Boks, Marco P., Boomsma, Dorret I., Brickman, Adam M., Brodaty, Henry, Buckner, Randy L., Buitelaar, Jan K., Cannon, Dara M., Carr, Vaughan J., Catts, Stanley V., Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R.K., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Davies, Gareth E., de Geus, Eco J.C., de Zubicaray, Greig I., den Braber, Anouk, Desrivières, Sylvane, Dillman, Allissa, Djurovic, Srdjan, Drevets, Wayne C., Duggirala, Ravi, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernández, Guillén, Fisher, Simon E., Foroud, Tatiana M., Ge, Tian, Giddaluru, Sudheer, Glahn, David C., Goldman, Aaron L., Green, Robert C., Greven, Corina U., Grimm, Oliver, Hansell, Narelle K., Hartman, Catharina A., Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans, Hibar, Derrek P., Ho, Beng-Choon, Hoekstra, Pieter J., Holmes, Avram J., Hoogman, Martine, Hottenga, Jouke-Jan, Hulshoff Pol, Hilleke E., Jablensky, Assen, Jenkinson, Mark, Jia, Tianye, Jöckel, Karl-Heinz, Jönsson, Erik G., Kim, Sungeun, Klein, Marieke, Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Le Hellard, Stephanie, Lemaître, Hervé, Loughland, Carmel, Marquand, Andre F., Martin, Nicholas G., Martinot, Jean-Luc, Matarin, Mar, Mathalon, Daniel H., Mather, Karen A., Mattay, Venkata S., McDonald, Colm, McMahon, Francis J., McMahon, Katie L., E, Rebekah, McWhirter, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Michie, Patricia T., Milaneschi, Yuri, Morris, Derek W., Mowry, Bryan, Nho, Kwangsik, Nichols, Thomas E., Nöthen, Markus N., Olvera, Rene L., Oosterlaan, Jaap, Ophoff, Roel A., Pandolfo, Massimo, Pantelis, Christos, Pappa, Irene, Penninx, Brenda, Pike, G. Bruce, Rasser, Paul E., Rentería, Miguel E., Reppermund, Simone, Rietschel, Marcella, Risacher, Shannon L., Romanczuk-Seiferth, Nina, Rose, Emma Jane, Sachdev, Perminder S., Sämann, Philipp G., Saykin, Andrew J., Schall, Ulrich, Schofield, Peter R., Schramm, Sara, Schumann, Gunter, Scott, Rodney, Shen, Li, Sisodiya, Sanjay M., Soininen, Hilkka, Sprooten, Emma, Srikanth, Velandai, Steen, Vidar M., Strike, Lachlan T., Thalamuthu, Anbupalam, Toga, Arthur W., Tooney, Paul, Tordesillas-Gutiérrez, Diana, Turner, Jessica A., Valdés Hernández, Maria del C., van der Meer, Dennis, Van der Wee, Nic J.A., Van Haren, Neeltje E.M., van 't Ent, Dennis, Veltman, Dick J., Walter, Henrik, Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westlye, Lars T., Westman, Eric, Winkler, Anderson M., Woldehawariat, Girma, Wright, Margaret J., Wu, Jingqin, Knol, Maria J., Poot, Raymond A., Evans, Tavia E., Satizabal, Claudia L., Mishra, Aniket, Sargurupremraj, Muralidharan, van der Auwera, Sandra, Duperron, Marie-Gabrielle, Jian, Xueqiu, Hostettler, Isabel C., van Dam-Nolen, Dianne H.K., Lamballais, Sander, Pawlak, Mikolaj A., Lewis, Cora E., Carrion-Castillo, Amaia, van Erp, Theo G.M., Reinbold, Céline S., Shin, Jean, Scholz, Markus, Håberg, Asta K., Kämpe, Anders, Li, Gloria H.Y., Avinun, Reut, Atkins, Joshua R., Hsu, Fang-Chi, Amod, Alyssa R., Lam, Max, Tsuchida, Ami, Teunissen, Mariël W.A., Aygün, Nil, Patel, Yash, Liang, Dan, Beiser, Alexa S., Beyer, Frauke, Bis, Joshua C., Bos, Daniel, Bryan, R. Nick, Bülow, Robin, Caspers, Svenja, Catheline, Gwenaëlle, Cecil, Charlotte A.M., Dalvie, Shareefa, Dartigues, Jean-François, DeCarli, Charles, Enlund-Cerullo, Maria, Ford, Judith M., Franke, Barbara, Freedman, Barry I., Friedrich, Nele, Green, Melissa J., Haworth, Simon, Helmer, Catherine, Hoffmann, Per, Homuth, Georg, Ikram, M. Kamran, Jack, Clifford R., Jr., Jahanshad, Neda, Jockwitz, Christiane, Kamatani, Yoichiro, Knodt, Annchen R., Li, Shuo, Lim, Keane, Longstreth, W.T., Macciardi, Fabio, Mäkitie, Outi, Mazoyer, Bernard, Medland, Sarah E., Miyamoto, Susumu, Moebus, Susanne, Mosley, Thomas H., Muetzel, Ryan, Mühleisen, Thomas W., Nagata, Manabu, Nakahara, Soichiro, Palmer, Nicholette D., Pausova, Zdenka, Preda, Adrian, Quidé, Yann, Reay, William R., Roshchupkin, Gennady V., Schmidt, Reinhold, Schreiner, Pamela J., Setoh, Kazuya, Shapland, Chin Yang, Sidney, Stephen, St Pourcain, Beate, Stein, Jason L., Tabara, Yasuharu, Teumer, Alexander, Uhlmann, Anne, van der Lugt, Aad, Vernooij, Meike W., Werring, David J., Windham, B. Gwen, Witte, A. Veronica, Wittfeld, Katharina, Yang, Qiong, Yoshida, Kazumichi, Brunner, Han G., Le Grand, Quentin, Sim, Kang, Stein, Dan J., Bowden, Donald W., Cairns, Murray J., Hariri, Ahmad R., Cheung, Ching-Lung, Andersson, Sture, Villringer, Arno, Paus, Tomas, Cichon, Sven, Calhoun, Vince D., Crivello, Fabrice, Launer, Lenore J., White, Tonya, Koudstaal, Peter J., Houlden, Henry, Fornage, Myriam, Matsuda, Fumihiko, Grabe, Hans J., Ikram, M. Arfan, Debette, Stéphanie, Thompson, Paul M., Seshadri, Sudha, and Adams, Hieab H.H.

Published
2024
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41. Translational evaluation of novel selective orexin-1 receptor antagonist JNJ-61393215 in an experimental model for panic in rodents and humans

Author

Salvadore, Giacomo, Bonaventure, Pascal, Shekhar, Anantha, Johnson, Philip L., Lord, Brian, Shireman, Brock T., Lebold, Terry P., Nepomuceno, Diane, Dugovic, Christine, Brooks, Sander, Zuiker, Rob, Bleys, Cathy, Tatikola, Kanaka, Remmerie, Bart, Jacobs, Gabriel E., Schruers, Koen, Moyer, John, Nash, Abigail, Van Nueten, Luc G. M., and Drevets, Wayne C.

Published
2020
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44. A Meta-Analysis of the Antidepressant Responses in Pivotal Trials on Esketamine Nasal Spray and Atypical Antipsychotics.

Author

Wang, Lien, Chen, Xiaowei, Gu, Xiaojing, De Smedt, Heidi, Popova, Vanina, Fu, Dong-Jing, Canuso, Carla M, Drevets, Wayne C, and Chen, Guang

Subjects
INTRANASAL medication, ANTIPSYCHOTIC agents, ANTIDEPRESSANTS, DEPRESSED persons, MENTAL depression
Abstract

Purpose: This meta-analysis assessed whether atypical antipsychotics (AAPs) and esketamine nasal spray (ESK-NS), which are mechanistically distinct, differ in antidepressant outcomes.Patients and Methods: Data were extracted from 12 trials of ESK-NS or AAPs in depressed patients (4276) with inadequate response or resistance to conventional antidepressants. Montgomery-Åsberg Depression Rating Scale (MADRS) score reductions from baseline and response rates (≥ 50% reduction) were analyzed.Results: At endpoint, the estimated MADRS score reduction of pooled ESK-NS arms was greater than pooled AAP arms (+9.16 points, p < 0.0001). The reduction also was greater in the pooled control arms of the ESK-NS trials than the pooled control arms of the AAP trials (+7.57 points, p < 0.0001). The mean difference in the reductions between pooled ESK-NS and control arms was 1.87 points greater than that between pooled AAP and control arms, but this difference was not significant (95% CI: − 4.49, 0.74, p = 0.16). Relative to their respective control arms, the mean difference in response rates was 25% for the pooled ESK-NS and 9% for the pooled AAP arms; the mean response rate was 16% greater in the pooled ESK-NS studies than the pooled AAP studies (p = 0.0004). Comparisons against specific AAPs showed mean differences in the MADRS score reductions at 1 week between the experimental and control arms that were numerically larger in the ESK-NS trials than in the aripiprazole trials (mean difference of 1.71 points, p = 0.06) and the brexpiprazole trials (mean difference of 2.05 points, p = 0.02).Conclusion: The ESK-NS arms showed numerically larger MADRS score reductions at week-1 and endpoint, and a significantly larger response rate compared with AAP arms. Prospective studies involving direct comparisons are warranted to compare the relative efficacy between these treatment regimens. [ABSTRACT FROM AUTHOR]

Published
2023
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46. Higher immune-related gene expression in major depression is independent of CRP levels: results from the BIODEP study

Author

Sforzini, Luca, Cattaneo, Annamaria, Ferrari, Clarissa, Turner, Lorinda, Mariani, Nicole, Enache, Daniela, Hastings, Caitlin, Lombardo, Giulia, Nettis, Maria A, Nikkheslat, Naghmeh, Worrell, Courtney, Zajkowska, Zuzanna, Kose, Melisa, Cattane, Nadia, Lopizzo, Nicola, Mazzelli, Monica, Pointon, Linda, Cowen, Philip J, Cavanagh, Jonathan, Harrison, Neil A, Jones, Declan, Drevets, Wayne C, Mondelli, Valeria, Bullmore, Edward T, Pariante, Carmine M, Sforzini, Luca [0000-0001-6795-0391], Cattaneo, Annamaria [0000-0002-9963-848X], Mariani, Nicole [0000-0001-7918-3492], Enache, Daniela [0000-0003-4684-9352], Nettis, Maria A [0000-0002-5401-8391], Worrell, Courtney [0000-0003-0539-2376], Zajkowska, Zuzanna [0000-0002-5214-305X], Pointon, Linda [0000-0003-2738-8589], Cowen, Philip J [0000-0001-5518-6138], Cavanagh, Jonathan [0000-0003-0640-8050], Harrison, Neil A [0000-0002-9584-3769], Mondelli, Valeria [0000-0001-8690-6839], Pariante, Carmine M [0000-0002-9132-5091], and Apollo - University of Cambridge Repository

Abstract

Compelling evidence demonstrates that some individuals suffering from major depressive disorder (MDD) exhibit increased levels of inflammation. Most studies focus on inflammation-related proteins, such as serum or plasma C-reactive protein (CRP). However, the immune-related modifications associated with MDD may be not entirely captured by CRP alone. Analysing mRNA gene expression levels, we aimed to identify broader molecular immune-related phenotypes of MDD. We examined 168 individuals from the non-interventional, case–control, BIODEP study, 128 with a diagnosis of MDD and 40 healthy controls. Individuals with MDD were further divided according to serum high-sensitivity (hs)CRP levels (n = 59 with CRP n = 33 with CRP 1–3 and n = 36 with CRP >3 mg/L). We isolated RNA from whole blood and performed gene expression analyses using RT-qPCR. We measured the expression of 16 immune-related candidate genes: A2M, AQP4, CCL2, CXCL12, CRP, FKBP5, IL-1-beta, IL-6, ISG15, MIF, GR, P2RX7, SGK1, STAT1, TNF-alpha and USP18. Nine of the 16 candidate genes were differentially expressed in MDD cases vs. controls, with no differences between CRP-based groups. Only CRP mRNA was clearly associated with serum CRP. In contrast, plasma (proteins) IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-16, IL-17A, IFN-gamma and TNF-alpha, and neutrophils counts, were all differentially regulated between CRP-based groups (higher in CRP >3 vs. CRP

Published
2023

49. Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study

Author

Zaki, Naim, primary, Chen, Li, additional, Lane, Rosanne, additional, Doherty, Teodora, additional, Drevets, Wayne C., additional, Morrison, Randall L., additional, Sanacora, Gerard, additional, Wilkinson, Samuel T., additional, Popova, Vanina, additional, and Fu, Dong-Jing, additional

Published
2023
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