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4. Cognitive function based on theta-gamma coupling vs. clinical diagnosis in older adults with mild cognitive impairment with or without major depressive disorder

Author

Brooks, Heather, Wang, Wei, Zomorrodi, Reza, Blumberger, Daniel M., Bowie, Christopher R., Daskalakis, Zafiris J., Fischer, Corinne E., Flint, Alastair J., Herrmann, Nathan, Kumar, Sanjeev, Lanctôt, Krista L., Mah, Linda, Mulsant, Benoit H., Pollock, Bruce G., Voineskos, Aristotle N., and Rajji, Tarek K.

Published
2024
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6. Neurophysiological and other features of working memory in older adults at risk for dementia

Author

Patterson, Rachel A., Brooks, Heather, Mirjalili, Mina, Rashidi-Ranjbar, Neda, Zomorrodi, Reza, Blumberger, Daniel M., Fischer, Corinne E., Flint, Alastair J., Graff-Guerrero, Ariel, Herrmann, Nathan, Kennedy, James L., Kumar, Sanjeev, Lanctôt, Krista L., Mah, Linda, Mulsant, Benoit H., Pollock, Bruce G., Voineskos, Aristotle N., Wang, Wei, and Rajji, Tarek K.

Published
2024
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7. Towards Outcome-Driven Patient Subgroups: A Machine Learning Analysis Across Six Depression Treatment Studies

Author

Benrimoh, David, Kleinerman, Akiva, Furukawa, Toshi A., Reynolds III, Charles F., Lenze, Eric, Karp, Jordan, Mulsant, Benoit, Armstrong, Caitrin, Mehltretter, Joseph, Fratila, Robert, Perlman, Kelly, Israel, Sonia, Tanguay-Sela, Myriam, Popescu, Christina, Golden, Grace, Qassim, Sabrina, Anacleto, Alexandra, Kapelner, Adam, Rosenfeld, Ariel, and Turecki, Gustavo

Subjects
Computer Science - Machine Learning, Computer Science - Artificial Intelligence
Abstract

Major depressive disorder (MDD) is a heterogeneous condition; multiple underlying neurobiological substrates could be associated with treatment response variability. Understanding the sources of this variability and predicting outcomes has been elusive. Machine learning has shown promise in predicting treatment response in MDD, but one limitation has been the lack of clinical interpretability of machine learning models. We analyzed data from six clinical trials of pharmacological treatment for depression (total n = 5438) using the Differential Prototypes Neural Network (DPNN), a neural network model that derives patient prototypes which can be used to derive treatment-relevant patient clusters while learning to generate probabilities for differential treatment response. A model classifying remission and outputting individual remission probabilities for five first-line monotherapies and three combination treatments was trained using clinical and demographic data. Model validity and clinical utility were measured based on area under the curve (AUC) and expected improvement in sample remission rate with model-guided treatment, respectively. Post-hoc analyses yielded clusters (subgroups) based on patient prototypes learned during training. Prototypes were evaluated for interpretability by assessing differences in feature distributions and treatment-specific outcomes. A 3-prototype model achieved an AUC of 0.66 and an expected absolute improvement in population remission rate compared to the sample remission rate. We identified three treatment-relevant patient clusters which were clinically interpretable. It is possible to produce novel treatment-relevant patient profiles using machine learning models; doing so may improve precision medicine for depression. Note: This model is not currently the subject of any active clinical trials and is not intended for clinical use.

Published
2023

8. Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression.

Author

Lenze, Eric, Mulsant, Benoit, Roose, Steven, Lavretsky, Helen, Reynolds, Charles, Blumberger, Daniel, Brown, Patrick, Cristancho, Pilar, Flint, Alastair, Gebara, Marie, Gettinger, Torie, Lenard, Emily, Miller, J, Nicol, Ginger, Pham, Vy, Rollman, Bruce, Yang, Lei, Karp, Jordan, and Oughli, Hanadi

Subjects
Aged, Humans, Antidepressive Agents, Aripiprazole, Bupropion, Depression, Drug Therapy, Combination, Nortriptyline, Treatment Switching, Lithium Compounds
Abstract

BACKGROUND: The benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied. METHODS: We conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to nortriptyline. Each step lasted approximately 10 weeks. The primary outcome was the change from baseline in psychological well-being, assessed with the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales (population mean, 50; higher scores indicate greater well-being). A secondary outcome was remission of depression. RESULTS: In step 1, a total of 619 patients were enrolled; 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. Well-being scores improved by 4.83 points, 4.33 points, and 2.04 points, respectively. The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P = 0.014, with a prespecified threshold P value of 0.017); the between-group differences were not significant for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion. Remission occurred in 28.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. The rate of falls was highest with bupropion augmentation. In step 2, a total of 248 patients were enrolled; 127 were assigned to lithium augmentation and 121 to a switch to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively (difference, 0.99; 95% CI, -1.92 to 3.91). Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group; rates of falling were similar in the two groups. CONCLUSIONS: In older adults with treatment-resistant depression, augmentation of existing antidepressants with aripiprazole improved well-being significantly more over 10 weeks than a switch to bupropion and was associated with a numerically higher incidence of remission. Among patients in whom augmentation or a switch to bupropion failed, changes in well-being and the occurrence of remission with lithium augmentation or a switch to nortriptyline were similar. (Funded by the Patient-Centered Outcomes Research Institute; OPTIMUM ClinicalTrials.gov number, NCT02960763.).

Published
2023

9. Intravenous Ketamine for Late-Life Treatment-Resistant Depression: A Pilot Study of Tolerability, Safety, Clinical Benefits, and Effect on Cognition.

Author

Gebara, Marie, Ciarleglio, Adam, Lavretsky, Helen, Brown, Patrick, Flint, Alastair, Farber, Nuri, Karp, Jordan, Mulsant, Benoit, Reynolds, Charles, Roose, Steven, Yang, Lei, Butters, Meryl, Lenze, Eric, and Oughli, Hanadi

Subjects
Treatment-resistant depression, cognition, geriatric, intravenous ketamine, Aged, Humans, Cognition, Depression, Infusions, Intravenous, Ketamine, Pilot Projects
Abstract

OBJECTIVE: Evidence-based treatment options for late-life treatment-resistant depression (TRD) are limited. Ketamine is a promising treatment for TRD; however, there is a paucity of data on its safety and efficacy in older adults. METHODS: In this pilot clinical trial, 25 adults aged ≥60 years with TRD received IV ketamine openly twice a week for 4 weeks; partial responders at the end of this acute phase were eligible to receive weekly infusions for 4 more weeks in a continuation phase. Acceptability, tolerability, and safety, including adverse and serious adverse events (AEs and SAEs), blood pressure changes, dissociation, craving, in addition to rates of depression response and remission were evaluated. The NIH Toolbox Cognitive Battery was used to assess specific measures of executive function (EF) and overall fluid cognition. RESULTS: Completion rates were 88% for the acute phase and 100% for the continuation phase. No AEs resulted in participant discontinuation, and there were no SAEs. Treatment-emergent elevation of blood pressure, dissociation, and craving were transient and did not result in any participant discontinuation. Depressive symptoms improved significantly and 48% of participants responded. During the acute phase, the EF measures and the fluid cognition composite score improved (Cohens d = 0.61), and these improvements were sustained in the continuation phase. CONCLUSION: This pilot study suggests that repeated IV ketamine infusions are well-tolerated and are associated with improvement in depression and EF in older adults with TRD. These promising findings need to be confirmed and extended in a larger randomized controlled trial.

Published
2023

10. Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies

Author

Adams, Mark J., Streit, Fabian, Meng, Xiangrui, Awasthi, Swapnil, Adey, Brett N., Choi, Karmel W., Chundru, V. Kartik, Coleman, Jonathan R.I., Ferwerda, Bart, Foo, Jerome C., Gerring, Zachary F., Giannakopoulou, Olga, Gupta, Priya, Hall, Alisha S.M., Harder, Arvid, Howard, David M., Hübel, Christopher, Kwong, Alex S.F., Levey, Daniel F., Mitchell, Brittany L., Ni, Guiyan, Ota, Vanessa K., Pain, Oliver, Pathak, Gita A., Schulte, Eva C., Shen, Xueyi, Thorp, Jackson G., Walker, Alicia, Yao, Shuyang, Zeng, Jian, Zvrskovec, Johan, Aarsland, Dag, Actkins, Ky'Era V., Adli, Mazda, Agerbo, Esben, Aichholzer, Mareike, Aiello, Allison, Air, Tracy M., Als, Thomas D., Andersson, Evelyn, Andlauer, Till F.M., Arolt, Volker, Ask, Helga, Bäckman, Julia, Badola, Sunita, Ballard, Clive, Banasik, Karina, Bass, Nicholas J., Beekman, Aartjan T.F., Belangero, Sintia, Bigdeli, Tim B., Binder, Elisabeth B., Bjerkeset, Ottar, Bjornsdottir, Gyda, Børte, Sigrid, Bränn, Emma, Braun, Alice, Brodersen, Thorsten, Brückl, Tanja M., Brunak, Søren, Bruun, Mie T., Burmeister, Margit, Buspavanich, Pichit, Bybjerg-Grauholm, Jonas, Byrne, Enda M., Cai, Jianwen, Campbell, Archie, Campbell, Megan L., Campos, Adrian I., Castelao, Enrique, Cervilla, Jorge, Chaumette, Boris, Chen, Chia-Yen, Chen, Hsi-Chung, Chen, Zhengming, Cichon, Sven, Colodro-Conde, Lucía, Corbett, Anne, Corfield, Elizabeth C., Couvy-Duchesne, Baptiste, Craddock, Nick, Dannlowski, Udo, Davies, Gail, de Geus, E.J.C., Deary, Ian J., Degenhardt, Franziska, Dehghan, Abbas, DePaulo, J. Raymond, Deuschle, Michael, Didriksen, Maria, Dinh, Khoa Manh, Direk, Nese, Djurovic, Srdjan, Docherty, Anna R., Domschke, Katharina, Dowsett, Joseph, Drange, Ole Kristian, Dunn, Erin C., Eaton, William, Einarsson, Gudmundur, Eley, Thalia C., Elsheikh, Samar S.M., Engelmann, Jan, Benros, Michael E., Erikstrup, Christian, Escott-Price, Valentina, Fabbri, Chiara, Fang, Yu, Finer, Sarah, Frank, Josef, Free, Robert C., Gallo, Linda, Gao, He, Gill, Michael, Gilles, Maria, Goes, Fernando S., Gordon, Scott Douglas, Grove, Jakob, Gudbjartsson, Daniel F., Gutierrez, Blanca, Hahn, Tim, Hall, Lynsey S., Hansen, Thomas F., Haraldsson, Magnus, Hartman, Catharina A., Havdahl, Alexandra, Hayward, Caroline, Heilmann-Heimbach, Stefanie, Herms, Stefan, Hickie, Ian B., Hjalgrim, Henrik, Hjerling-Leffler, Jens, Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M., Hovatta, Iiris, Huang, Qin Qin, Hucks, Donald, Huider, Floris, Hunt, Karen A., Ialongo, Nicholas S., Ising, Marcus, Isometsä, Erkki, Jansen, Rick, Jiang, Yunxuan, Jones, Ian, Jones, Lisa A., Jonsson, Lina, Kanai, Masahiro, Karlsson, Robert, Kasper, Siegfried, Kendler, Kenneth S., Kessler, Ronald C., Kloiber, Stefan, Knowles, James A., Koen, Nastassja, Kraft, Julia, Kranzler, Henry R., Krebs, Kristi, Kallak, Theodora Kunovac, Kutalik, Zoltán, Lahtela, Elisa, Lake, Marilyn, Larsen, Margit Hørup, Lenze, Eric J., Lewins, Melissa, Lewis, Glyn, Li, Liming, Lin, Bochao Danae, Lin, Kuang, Lind, Penelope A., Liu, Yu-Li, MacIntyre, Donald J., MacKinnon, Dean F., Maher, Brion S., Maier, Wolfgang, Marshe, Victoria S., Martinez-Levy, Gabriela A., Matsuda, Koichi, Mbarek, Hamdi, McGuffin, Peter, Medland, Sarah E., Meinert, Susanne, Mikkelsen, Christina, Mikkelsen, Susan, Milaneschi, Yuri, Millwood, Iona Y., Molina, Esther, Mondimore, Francis M., Mortensen, Preben Bo, Mulsant, Benoit H., Naamanka, Joonas, Najman, Jake M., Nauck, Matthias, Nenadić, Igor, Nielsen, Kasper R., Nolt, Ilja M., Nordentoft, Merete, Nöthen, Markus M., Nyegaard, Mette, O'Donovan, Michael C., Oddsson, Asmundur, Oliveira, Adrielle M., Olsen, Catherine M., Oskarsson, Hogni, Ostrowski, Sisse Rye, Owen, Michael J., Packer, Richard, Palviainen, Teemu, Pan, Pedro M., Pato, Carlos N., Pato, Michele T., Pedersen, Nancy L., Pedersen, Ole Birger, Peyrot, Wouter J., Potash, James B., Preisig, Martin, Preuss, Michael H., Quiroz, Jorge A., Renteria, Miguel E., Reynolds III, Charles F., Rice, John P., Sakaue, Saori, Santoro, Marcos L., Schoevers, Robert A., Schork, Andrew, Schulze, Thomas G., Send, Tabea S., Shi, Jianxin, Sigurdsson, Engilbert, Singh, Kritika, Sinnamon, Grant C.B., Sirignano, Lea, Smeland, Olav B., Smith, Daniel J., Sofer, Tamar, Sørensen, Erik, Srinivasan, Sundararajan, Stefansson, Hreinn, Stefansson, Kari, Straub, Peter, Su, Mei-Hsin, Tadic, André, Teismann, Henning, Teumer, Alexander, Thapar, Anita, Thomson, Pippa A., Thørner, Lise Wegner, Topaloudi, Apostolia, Tsai, Shih-Jen, Tzoulaki, Ioanna, Uhl, George, Uitterlinden, André G., Ullum, Henrik, Umbricht, Daniel, Ursano, Robert J., Van der Auwera, Sandra, van Hemert, Albert M., Veluchamy, Abirami, Viktorin, Alexander, Völzke, Henry, Walters, G. Bragi, Wang, Xiaotong, Wani, Agaz, Weissman, Myrna M., Wellmann, Jürgen, Whiteman, David C., Wildman, Derek, Willemsen, Gonneke, Williams, Alexander T., Winsvold, Bendik S., Witt, Stephanie H., Xiong, Ying, Zillich, Lea, Zwart, John-Anker, Twenty-Three and Me Research Team, China Kadoorie Biobank Collaborative Group, Estonian Biobank Research Team, Genes & Health Research Team, HUNT All-In Psychiatry, The BioBank Japan Project, VA Million Veteran Program, Andreassen, Ole A., Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Børglum, Anders D., Breen, Gerome, Cai, Na, Coon, Hilary, Copeland, William E., Creese, Byron, Cruz-Fuentes, Carlos S., Czamara, Darina, Davis, Lea K., Derks, Eske M., Domenici, Enrico, Elliott, Paul, Forstner, Andreas J., Gawlik, Micha, Gelernter, Joel, Grabe, Hans J., Hamilton, Steven P., Hveem, Kristian, John, Catherine, Kaprio, Jaakko, Kircher, Tilo, Krebs, Marie-Odile, Kuo, Po-Hsiu, Landén, Mikael, Lehto, Kelli, Levinson, Douglas F., Li, Qingqin S., Lieb, Klaus, Loos, Ruth J.F., Lu, Yi, Lucae, Susanne, Luykx, Jurjen J., Maes, Hermine H.M., Magnusson, Patrik K., Martin, Hilary C., Martin, Nicholas G., McQuillin, Andrew, Middeldorp, Christel M., Milani, Lili, Mors, Ole, Müller, Daniel J., Müller-Myhsok, Bertram, Okada, Yukinori, Oldehinkel, Albertine J., Paciga, Sara A., Palmer, Colin N.A., Paschou, Peristera, Penninx, Brenda W.J.H., Perlis, Roy H., Peterson, Roseann E., Pistis, Giorgio, Polimanti, Renato, Porteous, David J., Posthuma, Danielle, Rabinowitz, Jill A., Reichborn-Kjennerud, Ted, Reif, Andreas, Rice, Frances, Ricken, Roland, Rietschel, Marcella, Rivera, Margarita, Rück, Christian, Salum, Giovanni A., Schaefer, Catherine, Sen, Srijan, Serretti, Alessandro, Skalkidou, Alkistis, Smoller, Jordan W., Stein, Dan J., Stein, Frederike, Stein, Murray B., Sullivan, Patrick F., Tesli, Martin, Thorgeirsson, Thorgeir E., Tiemeier, Henning, Timpson, Nicholas J., Uddin, Monica, Uher, Rudolf, van Heel, David A., Verweij, Karin J.H., Walters, Robin G., Wassertheil-Smoller, Sylvia, Wendland, Jens R., Werge, Thomas, Zwinderman, Aeilko H., Kuchenbaecker, Karoline, Wray, Naomi R., Ripke, Stephan, Lewis, Cathryn M., and McIntosh, Andrew M.

Published
2025
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12. Bipolar I and bipolar II subtypes in older age: Results from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE‐BD) project

Author

Beunders, Alexandra JM, Klaus, Federica, Kok, Almar AL, Schouws, Sigfried NTM, Kupka, Ralph W, Blumberg, Hilary P, Briggs, Farren, Eyler, Lisa T, Forester, Brent P, Forlenza, Orestes V, Gildengers, Ariel, Jimenez, Esther, Mulsant, Benoit H, Patrick, Regan E, Rej, Soham, Sajatovic, Martha, Sarna, Kaylee, Sutherland, Ashley, Yala, Joy, Vieta, Eduard, Villa, Luca M, Korten, Nicole CM, and Dols, Annemieke

Subjects
Bipolar Disorder, Serious Mental Illness, Depression, Clinical Research, Mental Health, Aging, Brain Disorders, 2.4 Surveillance and distribution, Aetiology, Mental health, Humans, Aged, Cross-Sectional Studies, Cognition, Cognitive Dysfunction, bipolar disorder, cognition, comorbidities, diagnostic subtypes, elderly, functioning, geriatrics, impairment, older-age bipolar disorder, psychiatry, Clinical Sciences, Neurosciences, Psychiatry
Abstract

ObjectivesThe distinction between bipolar I disorder (BD-I) and bipolar II disorder (BD-II) has been a topic of long-lasting debate. This study examined differences between BD-I and BD-II in a large, global sample of OABD, focusing on general functioning, cognition and somatic burden as these domains are often affected in OABD.MethodsCross-sectional analyses were conducted with data from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) database. The sample included 963 participants aged ≥50 years (714 BD-I, 249 BD-II). Sociodemographic and clinical factors were compared between BD subtypes including adjustment for study cohort. Multivariable analyses were conducted with generalized linear mixed models (GLMMs) and estimated associations between BD subtype and (1) general functioning (GAF), (2) cognitive performance (g-score) and (3) somatic burden, with study cohort as random intercept.ResultsAfter adjustment for study cohort, BD-II patients more often had a late onset ≥50 years (p = 0.008) and more current severe depression (p = 0.041). BD-I patients were more likely to have a history of psychiatric hospitalization (p

Published
2023

17. Demographic and clinical characteristics of lithium-treated older adults with bipolar disorder.

Author

Forlenza, Orestes, Hajek, Tomas, Almeida, Osvaldo, Beunders, Alexandra, Blumberg, Hilary, Briggs, Farren, De-Paula, Vanessa, Dols, Annemiek, Forester, Brent, Gildengers, Ariel, Jimenez, Esther, Korten, Nicole, Lafer, Beny, McWhinney, Sean, Mulsant, Benoit, Rej, Soham, Sarna, Kaylee, Schouws, Sigfried, Sutherland, Ashley, Tsai, Shangying, Vieta, Eduard, Yala, Joy, Sajatovic, Martha, and Eyler, Lisa

Subjects
bipolar disorder, lithium, older adults, pharmacology, Aged, Antipsychotic Agents, Bipolar Disorder, Demography, Female, Humans, Lithium, Lithium Compounds, Male, Middle Aged
Abstract

OBJECTIVES: There is limited information on the characteristics of older adults with bipolar disorder (OABD) treated with lithium, along with safety concerns about its use by older adults. The aim of the present study is to describe the demographic and clinical characteristics of OABD receiving lithium therapy, using data from the Global Ageing & Geriatric Experiments in Bipolar Disorder (GAGE-BD). EXPERIMENTAL PROCEDURES: Cross-sectional analysis of the GAGE-BD dataset to determine differences and similarities between lithium users and non-users. We analysed data from 986 participants aged 50 years or older (mean age 63.5 years; 57.5% females) from 12 study sites. Two subgroups (Lithium; Non-lithium) were defined according to the current prescription of lithium. We compared several outcomes between these groups, controlling for age, gender, and study site. RESULTS: OABD treated with lithium had lower scores on depression rating scales and were less likely to be categorised as with moderate or severe depression. There was a lower proportion of lithium users than non-users among those with evidence of rapid cycling and non-bipolar psychiatric diagnoses. Assessment of global cognitive state and functionality indicated better performance among lithium users. The current use of antipsychotics was less frequent among lithium users, who also reported fewer cardiovascular comorbidities than non-users. CONCLUSION: We found several potentially relevant differences in the clinical profile of OABD treated with lithium compared with those treated with other mood stabilisers. However, the interpretation of the present results must take into account the methodological limitations inherent to the cross-sectional approach and data harmonisation.

Published
2022

18. Symptom Severity Mixity in Older-Age Bipolar Disorder: Analyses From the Global Aging and Geriatric Experiments in Bipolar Disorder Database (GAGE-BD).

Author

Briggs, Farren, Dols, Annemiek, Rej, Soham, Almeida, Osvaldo, Beunders, Alexandra, Blumberg, Hilary, Forester, Brent, Patrick, Regan, Forlenza, Orestes, Gildengers, Ariel, Jimenez, Esther, Vieta, Eduard, Mulsant, Benoit, Schouws, Sigfried, Paans, Nadine, Strejilevich, Sergio, Sutherland, Ashley, Tsai, Shangying, Sajatovic, Martha, and Eyler, Lisa

Subjects
Bipolar disorder, depression, elderly, geriatric, mania, Aged, Aging, Bipolar Disorder, Cohort Studies, Cross-Sectional Studies, Humans, Mania
Abstract

OBJECTIVE: Some individuals with bipolar disorder (BD) experience manic and depressive symptoms concurrently, but data are limited on symptom mixity in older age bipolar disorder (OABD). Using the Global Aging & Geriatric Experiments in Bipolar Disorder Database, we characterized mixity in OABD and associations with everyday function. METHODS: The sample (n = 805), from 12 international studies, included cases with both mania and depression severity ratings at a single timepoint. Four mixity groups were created: asymptomatic (A), mixed (Mix), depressed only (Dep), and manic only (Man). Generalized linear mixed models used mixity group as the predictor variable; cohort was included as a random intercept. Everyday function was assessed with the Global Assessment of Functioning score. RESULTS: Group proportions were Mix (69.6%; n = 560), followed by Dep (18.4%; n = 148), then A (7.8%; n = 63), then Man (4.2%; n= 34); levels of depression and mania were similar in Mix compared to Dep and Man, respectively. Everyday function was lowest in Mix, highest in A, and intermediate in Man and Dep. Within Mix, severity of depression was the main driver of worse functioning. Groups differed in years of education, with A higher than all others, but did not differ by age, gender, employment status, BD subtype, or age of onset. CONCLUSIONS: Mixed features predominate in a cross-sectional, global OABD sample and are associated with worse everyday function. Among those with mixed symptoms, functional status relates strongly to current depression severity. Future studies should include cognitive and other biological variables as well as longitudinal designs to allow for evaluation of causal effects.

Published
2022

20. Relationship between Patient Health Questionnaire (PHQ-9) and Montgomery-Asberg Depression Rating Scale (MADRS) total scores in older adults with major depressive disorder: An analysis of the OPTIMUM clinical trial

Author

Kim, Helena K., Lenze, Eric J., Ainsworth, Nicholas J., Blumberger, Daniel M., Brown, Patrick J., Flint, Alastair J., Karp, Jordan F., Lavretsky, Helen, Lenard, Emily, Miller, J. Philip, Reynolds, Charles F., 3rd, Roose, Steven P., and Mulsant, Benoit H.

Published
2024
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23. Cognition in older age bipolar disorder: An analysis of archival data across the globe

Author

Klaus, Federica, Ng, Hui Xin, Barbosa, Izabela G., Beunders, Alexandra, Briggs, Farren, Burdick, Katherine E., Dols, Annemieke, Forlenza, Orestes, Gildengers, Ariel, Millett, Caitlin, Mulsant, Benoit H., Orhan, Melis, Rajji, Tarek K., Rej, Soham, Sajatovic, Martha, Sarna, Kaylee, Schouws, Sigfried, Sutherland, Ashley, Teixeira, Antonio L., Yala, Joy A., and Eyler, Lisa T.

Published
2024
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25. Demographic and Clinical Characteristics of Antipsychotic Drug-Treated Older Adults with Bipolar Disorder from the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD).

Author

Chen, Peijun, Eyler, Lisa T, Gildengers, Ariel, Beunders, Alexandra Jm, Blumberg, Hilary P, Briggs, Farren Bs, Dols, Annemiek, Rej, Soham, Forlenza, Orestes V, Jimenez, Esther, Mulsant, Benoit, Schouws, Sigfried, Orhan, Melis, Sarna, Kaylee, Sutherland, Ashley N, Vieta, Eduard, Tsai, Shangying, Yala, Joy, Villa, Luca M, and Sajatovic, Martha

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Mental Health, Bipolar Disorder, Aging, Serious Mental Illness, Clinical Research, Brain Disorders, Aetiology, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 2.4 Surveillance and distribution, Mental health, Adult, Aged, Antipsychotic Agents, Cross-Sectional Studies, Demography, Female, Humans, Male, Middle Aged, aging, antipsychotic medication, bipolar disorder, geriatric, manic-depressive disorder, Psychiatry
Abstract

ObjectivesAntipsychotic drugs (APS) are widely used to treat patients with bipolar disorder (BD), but there is limited information in older-age bipolar disorder (OABD). This analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated characteristics of OABD patients prescribed APS vs. those not prescribed APS.Experimental designThe observational analysis used baseline, cross-sectional data from 16 international studies for adults aged ≥ 50 years with BD comprising 1,007 individuals with mean age 63.2 years (SD = 9.0), 57.4% women, and mean age of onset 31.6 years (SD = 15.0). The dependent variable was current APS treatment status. The independent variables included demographic and clinical variables, and a random effect for study, that were included in generalized mixed models.Principal observations46.6% of individuals (n = 469) were using APS. The multivariate model results suggest that those treated with APS were younger (p = 0.01), less likely to be employed (p < 0.001), had more psychiatric hospitalizations (p = 0.009) and were less likely to be on lithium (p < 0.001). Of individuals on APS, only 6.6% of those (n = 27) were on first-generation antipsychotics (FGAs) and experienced a greater burden of psychiatric hospitalizations (p = 0.012).ConclusionsAPS are widely prescribed in OABD, observed in nearly half of this sample with great variation across sites. Individuals with OABD on APS have more severe illness, more frequent hospitalizations and are more often unemployed vs. those not on APS. Future studies need to examine longitudinal outcomes in OABD prescribed APS to characterize underlying causal relationships.

Published
2022

26. Effect of high frequency versus theta-burst repetitive transcranial magnetic stimulation on suicidality in patients with treatment-resistant depression.

Author

Mehta, Shobha, Downar, Jonathan, Mulsant, Benoit, Voineskos, Daphne, Daskalakis, Zafiris, Weissman, Cory, Vila-Rodriguez, Fidel, and Blumberger, Daniel

Subjects
brain stimulation, repetitive transcranial magnetic stimulation, suicidality, treatment-resistant depression, Depression, Depressive Disorder, Treatment-Resistant, Humans, Prefrontal Cortex, Suicide, Transcranial Magnetic Stimulation, Treatment Outcome
Abstract

OBJECTIVE: To investigate the effect of 10 Hz repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) on suicidality in patients with treatment-resistant depression (TRD). METHODS: We used data from a three-site randomized clinical trial comparing 10 Hz rTMS and iTBS applied to the left dorsolateral prefrontal cortex (DLPFC) in patients with TRD. We compared the effect of 10Hz rTMS and iTBS on suicidality as measured by the suicide item of the Hamilton Depression Rating Scale 17-item (HDRS-17). RESULTS: Suicidality remitted in 71 (43.7%) participants randomized to 10Hz stimulation and 91 (49.1%) participants randomized to iTBS, without a significant difference between the proportions in the two groups (Χ2  = 0.674, df = 1, p = 0.4117). There was a significant correlation between change in suicidality and change in depression severity for both modalities (10 Hz, Pearsons r = 0.564; iTBS, Pearsons r = 0.502), with a significantly larger decrease in depression severity for those in whom suicidality remitted compared to those in whom it did not (t = 10.912, df = 276.8, p

Published
2022

27. Bipolar symptoms, somatic burden, and functioning in older‐age bipolar disorder: Analyses from the Global Aging & Geriatric Experiments in Bipolar Disorder Database project

Author

Sajatovic, Martha, Dols, Annemiek, Rej, Soham, Almeida, Osvaldo P, Beunders, Alexandra JM, Blumberg, Hilary P, Briggs, Farren BS, Forester, Brent P, Patrick, Regan E, Forlenza, Orestes V, Gildengers, Ariel, Jimenez, Esther, Vieta, Eduard, Mulsant, Benoit, Schouws, Sigfried, Paans, Nadine, Strejilevich, Sergio, Sutherland, Ashley, Tsai, Shangying, Wilson, Betsy, and Eyler, Lisa T

Subjects
Serious Mental Illness, Aging, Depression, Bipolar Disorder, Brain Disorders, Mental Health, Mental health, Aged, Cross-Sectional Studies, Female, Humans, Male, Medically Unexplained Symptoms, Middle Aged, Psychiatric Status Rating Scales, aging, bipolar disorder, depression, functioning, mania, medical burden, Clinical Sciences, Neurosciences, Psychiatry
Abstract

ObjectiveLiterature on older-age bipolar disorder (OABD) is limited. This first-ever analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated associations among age, BD symptoms, comorbidity, and functioning.MethodsThis analysis used harmonized, baseline, cross-sectional data from 19 international studies (N = 1377). Standardized measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Global Assessment of Functioning (GAF).ResultsMean sample age was 60.8 years (standard deviation [SD] 12.2 years), 55% female, 72% BD I. Mood symptom severity was low: mean total YMRS score of 4.3 (SD 5.4) and moderate-to-severe depression in only 22%. Controlled for sample effects, both manic and depressive symptom severity appeared lower among older individuals (p's

Published
2022

30. Sex Differences Among Older Adults With Bipolar Disorder: Results From the Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) Project

Author

Blanken, Machteld A.J.T., Oudega, Mardien L., Almeida, Osvaldo P., Schouws, Sigfried N.T.M., Orhan, Melis, Beunders, Alexandra J.M., Klumpers, Ursula M.H., Sonnenberg, Caroline, Blumberg, Hilary P., Eyler, Lisa T., Forester, Brent P., Forlenza, Orestes V., Gildengers, Ariel, Mulsant, Benoit H., Rajji, Tarek, Rej, Soham, Sarna, Kaylee, Sutherland, Ashley, Yala, Joy, Vieta, Eduard, Tsai, Shangying, Briggs, Farren B.S., Sajatovic, Martha, and Dols, Annemiek

Published
2024
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31. Towards Outcome-Driven Patient Subgroups: A Machine Learning Analysis Across Six Depression Treatment Studies

Author

Benrimoh, David, Kleinerman, Akiva, Furukawa, Toshi A., III, Charles F. Reynolds, Lenze, Eric J., Karp, Jordan, Mulsant, Benoit, Armstrong, Caitrin, Mehltretter, Joseph, Fratila, Robert, Perlman, Kelly, Israel, Sonia, Popescu, Christina, Golden, Grace, Qassim, Sabrina, Anacleto, Alexandra, Tanguay-Sela, Myriam, Kapelner, Adam, Rosenfeld, Ariel, and Turecki, Gustavo

Published
2024
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34. Protocol for an economic evaluation of scalable strategies to improve mental health among perinatal women: non-specialist care delivered via telemedicine vs. specialist care delivered in-person

Author

Singla, Daisy R., de Oliveira, Claire, Murphy, Sean M., Patel, Vikram, Charlebois, Jaime, Davis, Wendy N., Dennis, Cindy-Lee, Kim, J. Jo, Kurdyak, Paul, Lawson, Andrea, Meltzer-Brody, Samantha, Mulsant, Benoit H., Schoueri-Mychasiw, Nour, Silver, Richard K., Tschritter, Dana, Vigod, Simone N., and Byford, Sarah

Published
2023
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43. Predictors of change in suicidal ideation across treatment phases of major depressive disorder: analysis of the STAR*D data

Author

Weissman, Cory R, Hadas, Itay, Yu, Dengdeng, Jones, Brett, Kong, Dehan, Mulsant, Benoit H, Blumberger, Daniel M, and Daskalakis, Zafiris J

Subjects
Prevention, Major Depressive Disorder, Suicide Prevention, Depression, Serious Mental Illness, Behavioral and Social Science, Suicide, Brain Disorders, Mental Health, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Mental health, Good Health and Well Being, Antidepressive Agents, Bupropion, Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant, Humans, Suicidal Ideation, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

The effects of common antidepressants on suicidal ideation (SI) is unclear. In the landmark STAR*D trial antidepressants were effective for Major Depressive Disorder (MDD) in early treatment phases, but less effective in later phases. The effects of antidepressants on SI across the entire sample of the STAR*D trial has never been investigated. We performed a secondary analysis of the STAR*D data with the primary outcome of change in score on the suicide item (item three) of the Hamilton Rating Scale for Depression (HRSD17) across all four study levels. We used descriptive statistics and logistic regression analyses. Pearson correlation was used for change in SI versus change in depression (HRSD16). Reduction in mean (SD) SI was greater in levels one: 0.29 (±0.78) (p

Published
2021

44. Brain-Cognition Associations in Older Patients With Remitted Major Depressive Disorder or Mild Cognitive Impairment: A Multivariate Analysis of Gray and White Matter Integrity

Author

Mulsant, Benoit H., Rajji, Tarek K., Herrmann, Nathan, Pollock, Bruce G., Lourenco, Lillian, Blumberger, Daniel M., Bowie, Christopher R., Butters, Meryl A., Fischer, Corinne, Flint, Alastair, Gallagher, Damien, Golas, Angela, Graff, Ariel, Kennedy, James L., Lanctôt, Krista, Kumar, Sanjeev, Mah, Linda, Ovaysikia, Shima, Rapoport, Mark, Thorpe, Kevin E., Verhoeff, Nicolaas P.L.G., Voineskos, Aristotle N., Marawi, Tulip, Zhukovsky, Peter, Rashidi-Ranjbar, Neda, Brooks, Heather, Fischer, Corinne E., Flint, Alastair J., and Tartaglia, Maria Carmela

Published
2023
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49. Enhancing Cognition in Older Persons with Depression or Anxiety with a Combination of Mindfulness-Based Stress Reduction (MBSR) and Transcranial Direct Current Stimulation (tDCS): Results of a Pilot Randomized Clinical Trial.

Author

Brooks, Heather, Oughli, Hanadi, Kamel, Lojine, Subramanian, Subha, Morgan, Gwen, Blumberger, Daniel, Kloeckner, Jeanne, Kumar, Sanjeev, Mulsant, Benoit, Lenze, Eric, and Rajji, Tarek

Subjects
Cognitive function, Late-life anxiety, Late-life depression, MBSR, Mindfulness, Subjective cognitive complaints, tDCS
Abstract

OBJECTIVES: Individuals with subjective memory complaints and symptoms of depression and/or anxiety are at high risk for further cognitive decline, and possible progression to dementia. Low-burden interventions to help slow or prevent cognitive decline in this high-risk group are needed. The objective of this study is to assess the feasibility of combining Mindfulness-Based Stress Reduction (MBSR) with transcranial direct current stimulation (tDCS) to increase putative benefits of MBSR for cognitive function and everyday mindfulness in depressed or anxious older adults with subjective cognitive decline. METHODS: We conducted a two-site pilot double-blind randomized sham-controlled trial, combining active MBSR with either active or sham tDCS. The intervention included weekly in-class group sessions at the local university hospital and daily at-home practice. Anodal tDCS was applied for 30 min during MBSR meditative practice, both in-class and at-home. RESULTS: Twenty-six individuals with subjective cognitive complaints and symptoms of depression and/or anxiety were randomized to active (n = 12) or sham tDCS (n = 14). The combination of MBSR and tDCS was safe and well tolerated, though at-home adherence and in-class attendance were variable. While they were not statistically significant, the largest effect sizes for active vs. sham tDCS were for everyday mindfulness (d = 0.6) and social functioning (d = 0.9) (F (1,21) = 3.68, p = 0.07 and F (1,21) = 3.9, p = 0.06, respectively). CONCLUSIONS: Our findings suggest that it is feasible and safe to combine tDCS with MBSR in older depressed and anxious adults, including during remote, at-home use. Furthermore, tDCS may enhance MBSR via transferring its meditative learning and practice into increases in everyday mindfulness. Future studies need to improve adherence to MBSR with tDCS. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03653351 and NCT03680664). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12671-021-01764-9.

Published
2021

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