1,371 results on '"Marder, Stephen"'
Search Results
2. Remote Assessment of Negative Symptoms of Schizophrenia.
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Daniel, David, Cohen, Alex, Velligan, Dawn, Harvey, Phillip, Alphs, Larry, Davidson, Michael, Potter, William, Kott, Alan, Schooler, Nina, Brodie, Christopher, Moore, Raeanne, Lindenmeyer, Pierre, and Marder, Stephen
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negative symptoms ,remote assessment ,schizophrenia - Abstract
In contrast to the validated scales for face-to-face assessment of negative symptoms, no widely accepted tools currently exist for remote monitoring of negative symptoms. Remote assessment of negative symptoms can be broadly divided into 3 categories: (1) remote administration of an existing negative-symptom scale by a clinician, in real time, using videoconference technology to communicate with the patient; (2) direct inference of negative symptoms through detection and analysis of the patients voice, appearance, or activity by way of the patients smartphone or other device; and (3) ecological momentary assessment, in which the patient self-reports their condition upon receipt of periodic prompts from a smartphone or other device during their daily routine. These modalities vary in cost, technological complexity, and applicability to the different negative-symptom domains. Each modality has unique strengths, weaknesses, and issues with validation. As a result, an optimal solution may be more likely to employ several techniques than to use a single tool. For remote assessment of negative symptoms to be adopted as primary or secondary endpoints in regulated clinical trials, appropriate psychometric standards will need to be met. Standards for substituting 1 set of measures for another, as well as what constitutes a gold reference standard, will need to be precisely defined and a process for defining them developed. Despite over 4 decades of progress toward this goal, significant work remains to be done before clinical trials addressing negative symptoms can utilize remotely assessed secondary or primary outcome measures.
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- 2023
3. Does relapse cause illness progression in first-episode psychosis? A review
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Kennedy, Kevin P., Zito, Michael F., and Marder, Stephen R.
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- 2024
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4. Effects of PDE10A inhibitor MK-8189 in people with an acute episode of schizophrenia: A randomized proof-of-concept clinical trial
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Mukai, Yuki, Lupinacci, Robert, Marder, Stephen, Snow-adami, Linda, Voss, Tiffini, Smith, Sean M., and Egan, Michael F.
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- 2024
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5. Efficacy of KarXT on negative symptoms in acute schizophrenia: A post hoc analysis of pooled data from 3 trials
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Horan, William P., Targum, Steven D., Claxton, Amy, Kaul, Inder, Yohn, Samantha E., Marder, Stephen R., Miller, Andrew C., and Brannan, Stephen K.
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- 2024
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6. Rare coding variants in ten genes confer substantial risk for schizophrenia.
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Singh, Tarjinder, Poterba, Timothy, Curtis, David, Akil, Huda, Al Eissa, Mariam, Barchas, Jack D, Bass, Nicholas, Bigdeli, Tim B, Breen, Gerome, Bromet, Evelyn J, Buckley, Peter F, Bunney, William E, Bybjerg-Grauholm, Jonas, Byerley, William F, Chapman, Sinéad B, Chen, Wei J, Churchhouse, Claire, Craddock, Nicholas, Cusick, Caroline M, DeLisi, Lynn, Dodge, Sheila, Escamilla, Michael A, Eskelinen, Saana, Fanous, Ayman H, Faraone, Stephen V, Fiorentino, Alessia, Francioli, Laurent, Gabriel, Stacey B, Gage, Diane, Gagliano Taliun, Sarah A, Ganna, Andrea, Genovese, Giulio, Glahn, David C, Grove, Jakob, Hall, Mei-Hua, Hämäläinen, Eija, Heyne, Henrike O, Holi, Matti, Hougaard, David M, Howrigan, Daniel P, Huang, Hailiang, Hwu, Hai-Gwo, Kahn, René S, Kang, Hyun Min, Karczewski, Konrad J, Kirov, George, Knowles, James A, Lee, Francis S, Lehrer, Douglas S, Lescai, Francesco, Malaspina, Dolores, Marder, Stephen R, McCarroll, Steven A, McIntosh, Andrew M, Medeiros, Helena, Milani, Lili, Morley, Christopher P, Morris, Derek W, Mortensen, Preben Bo, Myers, Richard M, Nordentoft, Merete, O'Brien, Niamh L, Olivares, Ana Maria, Ongur, Dost, Ouwehand, Willem H, Palmer, Duncan S, Paunio, Tiina, Quested, Digby, Rapaport, Mark H, Rees, Elliott, Rollins, Brandi, Satterstrom, F Kyle, Schatzberg, Alan, Scolnick, Edward, Scott, Laura J, Sharp, Sally I, Sklar, Pamela, Smoller, Jordan W, Sobell, Janet L, Solomonson, Matthew, Stahl, Eli A, Stevens, Christine R, Suvisaari, Jaana, Tiao, Grace, Watson, Stanley J, Watts, Nicholas A, Blackwood, Douglas H, Børglum, Anders D, Cohen, Bruce M, Corvin, Aiden P, Esko, Tõnu, Freimer, Nelson B, Glatt, Stephen J, Hultman, Christina M, McQuillin, Andrew, Palotie, Aarno, Pato, Carlos N, Pato, Michele T, Pulver, Ann E, and St Clair, David
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Humans ,Genetic Predisposition to Disease ,Receptors ,N-Methyl-D-Aspartate ,Case-Control Studies ,Schizophrenia ,Mutation ,Exome ,Neurodevelopmental Disorders ,Human Genome ,Biotechnology ,Mental Health ,Neurosciences ,Brain Disorders ,Genetics ,Serious Mental Illness ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Neurological ,General Science & Technology - Abstract
Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P
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- 2022
7. Examining racial differences in community integration between black and white homeless veterans
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Novacek, Derek M, Wynn, Jonathan K, Gabrielian, Sonya, Glynn, Shirley M, Hellemann, Gerhard, Horan, William P, Kern, Robert S, Lee, Junghee, Marder, Stephen R, Sugar, Catherine, and Green, Michael F
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Clinical and Health Psychology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Psychology ,Behavioral and Social Science ,Homelessness ,Clinical Research ,Brain Disorders ,Mental Health ,Community Integration ,Ill-Housed Persons ,Housing ,Humans ,Race Factors ,United States ,Veterans ,Community integration ,Race/ethnicity ,Psychosis ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences ,Clinical and health psychology - Abstract
Black Americans are overrepresented in Veteran and non-Veteran homeless populations. Community integration remains a problem for many Veterans after they obtain housing, and Black Veterans may encounter additional difficulties due to systemic racism. However, no prior study has specifically examined whether there are racial differences in community integration; similarly, no study has considered racial differences in psychosocial correlates of community integration in homeless Veterans. Knowledge of these factors could inform the development of culturally congruent rehabilitative interventions for Black Veterans. Semi-structured clinical interviews were administered to Black (N = 99) and White (N = 49) homeless Veterans to examine relations among psychiatric symptoms, motivation, and community integration domains (e.g., social integration, work productivity, and independent living). There were no significant racial differences in independent living or work productivity. Black Veterans had better social integration with family compared to White Veterans. In addition, psychiatric symptoms were more strongly correlated with social integration for Black than White Veterans. The association between motivation and work productivity was also stronger for Black Veterans. Recovery-oriented interventions could harness family connections and better target psychiatric symptoms to improve community integration for Black Veterans. Work productivity may improve from interventions aimed at enhancing motivation for Black Veterans.
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- 2022
8. Assessment of Negative Symptoms in Clinical Trials of Acute Schizophrenia: Test of a Novel Enrichment Strategy.
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Hopkins, Seth, Tomioka, Sasagu, Ogirala, Ajay, Loebel, Antony, Koblan, Kenneth, and Marder, Stephen
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antipsychotic agents ,lurasidone ,trace amine-associated receptor 1 (TAAR1) ,ulotaront - Abstract
Drug trials for negative symptoms in schizophrenia select patients based on the severity and stability of negative symptoms, using criteria that are not suitable for trials of acute exacerbation of schizophrenia. Here we present a method to prognostically enrich subjects having a predefined factor structure in PANSS and apply it to the measurement of negative symptoms specifically in trials of acute schizophrenia. A vector of 1335 elements based on between- and within-item variances, covariances, and differences of PANSS items was created to calculate an index of heterogeneity and to enrich for a predetermined symptom construct in PANSS. Using prerandomization PANSS scores across N = 4876 subjects in 13 trials of acute schizophrenia, we demonstrate an ability to select for a subpopulation having the greatest amount of variance explained across the 7-items of the Marder PANSS negative symptom (MPNS) construct. Network analyses on subjects enriched for MPNS construct confirm that negative symptoms were most influential in overall psychopathology, distinct from subjects without the MPNS construct. As expected for D2 antagonists, drug-placebo differences on negative symptoms with lurasidone were not specific to the subpopulation having the MPNS construct. In contrast, the novel TAAR1 agonist ulotaront demonstrated specific improvements in negative symptoms which were greatest in the MPNS subpopulation. These results demonstrate the utility of a novel prognostic enrichment strategy that can address heterogeneity in clinical trials, where patients can be selected on the basis of a greater likelihood of having the measured symptom construct (negative symptoms) related to the disorder (schizophrenia). ClinicalTrials.gov Identifiers: NCT0296938, NCT00088634, NCT00549718, NCT00615433, NCT00790192.
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- 2022
9. Schizophrenia Spectrum and Other Psychotic Disorders
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Burns, Alaina V., Marder, Stephen, and IsHak, Waguih William, editor
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- 2023
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10. Relapse in clinically stable adult patients with schizophrenia or schizoaffective disorder: evidence-based criteria derived by equipercentile linking and diagnostic test accuracy meta-analysis
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Siafis, Spyridon, Brandt, Lasse, McCutcheon, Robert A, Gutwinski, Stefan, Schneider-Thoma, Johannes, Bighelli, Irene, Kane, John M, Arango, Celso, Kahn, René S, Fleischhacker, W Wolfgang, McGorry, Patrick, Carpenter, William T, Falkai, Peter, Hasan, Alkomiet, Marder, Stephen R, Schooler, Nina, Engel, Rolf R, Honer, William G, Buchanan, Robert W, Davidson, Michael, Weiser, Mark, Priller, Josef, Davis, John M, Howes, Oliver D, Correll, Christoph U, and Leucht, Stefan
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- 2024
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11. Changing the Face of Schizophrenia
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Marder, Stephen R
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Clinical and Health Psychology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Psychology ,Humans ,Psychotic Disorders ,Schizophrenia ,Schizophrenic Psychology ,Schizoaffective Disorder see Schizophrenia Spectrum and Other Psychotic Disorders ,Sociopolitical Issues ,Stigma / Discrimination ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences ,Clinical and health psychology - Published
- 2021
12. Onset and Resolution of Key Adverse Events in Valbenazine-Treated Patients with Tardive Dyskinesia: Pooled Analyses from Two Long-Term Clinical Trials
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Marder, Stephen R, Lindenmayer, Jean-Pierre, Shah, Chirag, Carmack, Tara, Angelov, Angel S, and Lundt, Leslie
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Biological Psychology ,Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Psychology ,Clinical Trials and Supportive Activities ,Patient Safety ,Brain Disorders ,Mental Health ,Clinical Research ,Neurosciences ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Humans ,Parkinsonian Disorders ,Dizziness ,Akathisia ,Drug-Induced ,Tetrabenazine ,Valine ,Incidence ,Vesicular Monoamine Transport Proteins ,Suicidal Ideation ,Tardive Dyskinesia ,Clinical Sciences ,Psychiatry ,Clinical sciences ,Biological psychology - Abstract
ObjectiveTardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Long-term safety of the approved TD medication, valbenazine, was demonstrated in 2 clinical trials (KINECT 3 [NCT02274558], KINECT 4 [NCT02405091]). Data from these trials were analyzed post hoc to evaluate the onset and resolution of adverse events (AEs).MethodsParticipants in KINECT 3 and KINECT 4 received up to 48 weeks of once-daily valbenazine (40 or 80 mg). Data from these studies were pooled and analyzed to assess the incidence, time to first occurrence, and resolution for the following AEs of potential clinical interest: akathisia, balance disorder, dizziness, parkinsonism, somnolence/sedation, suicidal behavior/ideation, and tremor.ResultsIn the pooled population (N=314), all AEs of potential clinical interest occurred in 85% (somnolence/sedation, dizziness); >70% (akathisia, balance disorder, tremor).ConclusionsIn long-term clinical trials, the incidence of AEs of potential clinical interest was low (70-100%). All patients taking valbenazine should be routinely monitored for AEs, particularly those that may exacerbate the motor symptoms associated with TD.FundingNeurocrine Biosciences, Inc.
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- 2021
13. Guía internacional para una dosificación más segura de la clozapina en adultos mediante el uso de 6 titulaciones personalizadas de dosis basados en la etnicidad, la proteína C reactiva y los niveles de clozapina
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de Leon, Jose, Schoretsanitis, Georgios, Smith, Robert L., Molden, Espen, Solismaa, Anssi, Seppälä, Niko, Kopeček, Miloslav, Švancer, Patrik, Olmos, Ismael, Ricciardi, Carina, Iglesias-Garcia, Celso, Iglesias-Alonso, Ana, Spina, Edoardo, Ruan, Can-Jun, Wang, Chuan-Yue, Wang, Gang, Tang, Yi-Lang, Lin, Shih-Ku, Lane, Hsien-Yuan, Kim, Yong Sik, Kim, Se Hyun, Rajkumar, Anto P., González-Esquivel, Dinora F., Jung-Cook, Helgi, Baptista, Trino, Rohde, Christopher, Nielsen, Jimmi, Verdoux, Hélène, Quiles, Clelia, Sanz, Emilio J., De las Cuevas, Carlos, Cohen, Dan, Schulte, Peter F.J., Ertuğrul, Aygün, Anıl Yağcıoğlu, A. Elif, Chopra, Nitin, McCollum, Betsy, Shelton, Charles, Cotes, Robert O., Kaithi, Arun R., Kane, John M., Farooq, Saeed, Ng, Chee H., Bilbily, John, Hiemke, Christoph, López-Jaramillo, Carlos, McGrane, Ian, Lana, Fernando, Eap, Chin B., Arrojo-Romero, Manuel, Rădulescu, Flavian Ştefan, Seifritz, Erich, Every-Palmer, Susanna, Bousman, Chad A., Bebawi, Emmanuel, Bhattacharya, Rahul, Kelly, Deanna L., Otsuka, Yuji, Lazary, Judit, Torres, Rafael, Yecora, Agustin, Motuca, Mariano, Chan, Sherry Kit Wa, Zolezzi, Monica, Ouanes, Sami, De Berardis, Domenico, Grover, Sandeep, Procyshyn, Ric M., Adebayo, Richard A., Kirilochev, Oleg O., Soloviev, Andrey, Fountoulakis, Konstantinos N., Wilkowska, Alina, Cubała, Wiesław Jerzy, Ayub, Muhammad, Silva, Alzira, Bonelli, Raphael M., Villagrán-Moreno, José María, Crespo-Facorro, Benedicto, Temmingh, Henk, Decloedt, Eric, Pedro, Maria Rosel, Takeuchi, Hiroyoshi, Tsukahara, Masaru, Gründer, Gerhard, Sagud, Marina, Celofiga, Andreja, Ignjatovic Ristic, Dragana, Ortiz, Bruno Bertolucci, Elkis, Helio, Pacheco Palha, António José, Llerena, Adrián, Fernandez-Egea, Emilio, Siskind, Dan, Weizman, Abraham, Masmoudi, Rim, Mohd Saffian, Shamin, Leung, Jonathan G., Buckley, Peter F., Marder, Stephen R., Citrome, Leslie, Freudenreich, Oliver, Correll, Christoph U., and Müller, Daniel J.
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- 2023
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14. Psychosis among individuals with methamphetamine use disorder is associated with elevated rates of hospitalizations and emergency department visits across an academic health care system
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Zito, Michael F., Fei, Zhe, Zhu, Yuhui, Clingan, Sarah E., Marder, Stephen R., and Mooney, Larissa J.
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- 2023
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15. Negative symptoms in schizophrenia: Newly emerging measurements, pathways, and treatments
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Marder, Stephen R. and Umbricht, Daniel
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- 2023
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16. Effects of Brexpiprazole Across Symptom Domains in Patients With Schizophrenia: Post Hoc Analysis of Short- and Long-Term Studies
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Marder, Stephen R, Meehan, Stine R, Weiss, Catherine, Chen, Dalei, Hobart, Mary, and Hefting, Nanco
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Schizophrenia ,Clinical Research ,Mental Health ,Clinical Trials and Supportive Activities ,Brain Disorders ,Neurosciences ,Depression ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Mental health ,Marder factors ,Positive and Negative Syndrome Scale ,antipsychotic ,clinical trial ,Clinical sciences - Abstract
The successful treatment of schizophrenia entails improvement across a spectrum of symptoms. The aim of this post hoc analysis was to characterize the short- and long-term effects of brexpiprazole on Positive and Negative Syndrome Scale (PANSS) 'Marder factors.' Data were included from three 6-week, randomized, double-blind, placebo-controlled studies; a 52-week, randomized, double-blind, placebo-controlled maintenance treatment study; and two 52-week open-label extension (OLEx) studies-all in schizophrenia (DSM-IV-TR criteria). Patients receiving oral brexpiprazole were dosed at 2-4 mg/day (short-term studies) or 1-4 mg/day (long-term studies). At Week 6, least squares mean differences (LSMDs, with 95% confidence limits [CLs]) for brexpiprazole (n = 868) vs placebo (n = 517) were: Positive symptoms: -1.55 (-2.30, -0.80), P < .0001, Cohen's d effect size (ES) = 0.27; Negative symptoms: -1.12 (-1.63, -0.61), P < .0001, ES = 0.29; Disorganized thought: -1.26 (-1.78, -0.74), P < .0001, ES = 0.32; Uncontrolled hostility/excitement: -0.76 (-1.15, -0.37), P = .0002, ES = 0.26; Anxiety/ depression: -0.56 (-0.91, -0.22), P = .0014, ES = 0.22. At last visit of the maintenance study, LSMDs (95% CLs) for brexpiprazole (n = 96) vs placebo (n = 104) were: Positive symptoms: -3.44 (-4.99, -1.89), P < .0001, ES = 0.62; Negative symptoms: -1.23 (-2.52, 0.07), P = .063, ES = 0.27; Disorganized thought: -1.69 (-2.81, -0.56), P = .0035, ES = 0.42; Uncontrolled hostility/excitement: -1.26 (-2.12, -0.39), P = .0046, ES = 0.41; Anxiety/depression: -0.72 (-1.47, 0.03), P = .061, ES = 0.27. In the OLEx studies, improvements were maintained over 58 (6 + 52) weeks of brexpiprazole treatment. In conclusion, these data suggest that brexpiprazole treats the continuum of schizophrenia symptoms, in the short- and long-term. Trial Registration: Data used in this post hoc analysis came from ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380, NCT01668797, NCT01397786, NCT01810783.
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- 2021
17. PANSS Individual Item and Marder Dimension Analyses From a Pivotal Trial of RBP-7000 (Monthly Extended-Release Risperidone) in Schizophrenia Patients.
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Le Moigne, Anne, Csernansky, John, Leadbetter, Robert A, Andorn, Anne C, Graham, James A, Heath, Amy T, Walling, David P, Newcomer, John W, and Marder, Stephen R
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Clinical Trials and Supportive Activities ,Brain Disorders ,Mental Health ,Clinical Research ,Schizophrenia ,Cancer ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Mental health ,Adult ,Antipsychotic Agents ,Delayed-Action Preparations ,Dose-Response Relationship ,Drug ,Female ,Humans ,Male ,Psychiatric Status Rating Scales ,Risperidone ,Treatment Outcome ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences - Abstract
Background: Positive and Negative Syndrome Scale (PANSS) data from a pivotal phase 3 study in participants with schizophrenia of RBP-7000, a recently marketed long-acting subcutaneous injectable risperidone formulation, were examined to determine if dose-response relationships existed for different items of the PANSS. Methods: Changes in the 30 PANSS items were analyzed individually and using the 5 factor-analysis-derived dimensions defined by Marder and colleagues. Subgroups of patients who could benefit from the RBP-7000 120 mg dose were investigated. Results: 337 participants were randomized and received study medication (RBP-7000 90 mg n = 111, RBP-7000 120 mg n = 114, placebo n = 112). Dose-dependent responses were observed in items from the study-specified PANSS positive and general psychopathology exploratory subscales. Dose-dependent responses were observed across all 5 Marder dimensions, with the largest effect sizes observed with the 120 mg dose in the uncontrolled hostility/excitement (UHE) and anxiety/depression dimensions. Participants with baseline UHE dimension scores ≥ 9 demonstrated greater improvement in PANSS total score at the 120 mg dose compared to the 90 mg dose. Conclusions: RBP-7000 demonstrated efficacy across both the primary and exploratory PANSS study endpoints and the post hoc Marder dimensions. Schizophrenia patients with higher baseline Marder UHE scores may benefit from initiation of treatment at the 120 mg dose. Trial Registration: ClinicalTrials.gov identifier: NCT02109562.
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- 2021
18. Proof of mechanism and target engagement of glutamatergic drugs for the treatment of schizophrenia: RCTs of pomaglumetad and TS-134 on ketamine-induced psychotic symptoms and pharmacoBOLD in healthy volunteers
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Kantrowitz, Joshua T, Grinband, Jack, Goff, Donald C, Lahti, Adrienne C, Marder, Stephen R, Kegeles, Lawrence S, Girgis, Ragy R, Sobeih, Tarek, Wall, Melanie M, Choo, Tse-Hwei, Green, Michael F, Yang, Yvonne S, Lee, Junghee, Horga, Guillermo, Krystal, John H, Potter, William Z, Javitt, Daniel C, and Lieberman, Jeffrey A
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Brain Disorders ,Serious Mental Illness ,Clinical Research ,Neurosciences ,Clinical Trials and Supportive Activities ,Mental Health ,Schizophrenia ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Mental health ,Antipsychotic Agents ,Double-Blind Method ,Healthy Volunteers ,Humans ,Ketamine ,Pharmaceutical Preparations ,Single-Blind Method ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
Glutamate neurotransmission is a prioritized target for antipsychotic drug development. Two metabotropic glutamate receptor 2/3 (mGluR2/3) agonists (pomaglumetad [POMA] and TS-134) were assessed in two Phase Ib proof of mechanism studies of comparable designs and using identical clinical assessments and pharmacoBOLD methodology. POMA was examined in a randomized controlled trial under double-blind conditions for 10-days at doses of 80 or 320 mg/d POMA versus placebo (1:1:1 ratio). The TS-134 trial was a randomized, single-blind, 6-day study of 20 or 60 mg/d TS-134 versus placebo (5:5:2 ratio). Primary outcomes were ketamine-induced changes in pharmacoBOLD in the dorsal anterior cingulate cortex (dACC) and symptoms reflected on the Brief Psychiatric Rating Scale (BPRS). Both trials were conducted contemporaneously. 95 healthy volunteers were randomized to POMA and 63 to TS-134. High-dose POMA significantly reduced ketamine-induced BPRS total symptoms within and between-groups (p
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- 2020
19. Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry
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Bigdeli, Tim B, Genovese, Giulio, Georgakopoulos, Penelope, Meyers, Jacquelyn L, Peterson, Roseann E, Iyegbe, Conrad O, Medeiros, Helena, Valderrama, Jorge, Achtyes, Eric D, Kotov, Roman, Stahl, Eli A, Abbott, Colony, Azevedo, Maria Helena, Belliveau, Richard A, Bevilacqua, Elizabeth, Bromet, Evelyn J, Byerley, William, Carvalho, Celia Barreto, Chapman, Sinéad B, DeLisi, Lynn E, Dumont, Ashley L, O’Dushlaine, Colm, Evgrafov, Oleg V, Fochtmann, Laura J, Gage, Diane, Kennedy, James L, Kinkead, Becky, Macedo, Antonio, Moran, Jennifer L, Morley, Christopher P, Dewan, Mantosh J, Nemesh, James, Perkins, Diana O, Purcell, Shaun M, Rakofsky, Jeffrey J, Scolnick, Edward M, Sklar, Brooke M, Sklar, Pamela, Smoller, Jordan W, Sullivan, Patrick F, Macciardi, Fabio, Marder, Stephen R, Gur, Ruben C, Gur, Raquel E, Braff, David L, Nicolini, Humberto, Escamilla, Michael A, Vawter, Marquis P, Sobell, Janet L, Malaspina, Dolores, Lehrer, Douglas S, Buckley, Peter F, Rapaport, Mark H, Knowles, James A, Fanous, Ayman H, Pato, Michele T, McCarroll, Steven A, and Pato, Carlos N
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Human Genome ,Serious Mental Illness ,Clinical Research ,Schizophrenia ,Brain Disorders ,Genetics ,Mental Health ,Aetiology ,2.1 Biological and endogenous factors ,Black People ,Female ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Hispanic or Latino ,Humans ,Male ,Polymorphism ,Single Nucleotide ,Consortium on the Genetics of Schizophrenia (COGS) Investigators ,Genomic Psychiatry Cohort (GPC) Consortium ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke's R2 = 0.032; liability R2 = 0.017; P
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- 2020
20. The characteristics of cognitive neuroscience tests in a schizophrenia cognition clinical trial: Psychometric properties and correlations with standard measures
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Kraus, Michael S, Gold, James M, Barch, Deanna M, Walker, Trina M, Chun, Charlotte A, Buchanan, Robert W, Csernansky, John G, Goff, Donald C, Green, Michael F, Jarskog, L Fredrik, Javitt, Daniel C, Kimhy, David, Lieberman, Jeffrey A, McEvoy, Joseph P, Mesholam-Gately, Raquelle I, Seidman, Larry J, Ball, M Patricia, Kern, Robert S, McMahon, Robert P, Robinson, James, Marder, Stephen R, and Keefe, Richard SE
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Applied and Developmental Psychology ,Biological Psychology ,Clinical and Health Psychology ,Cognitive and Computational Psychology ,Psychology ,Clinical Research ,Behavioral and Social Science ,Schizophrenia ,Basic Behavioral and Social Science ,Neurosciences ,Brain Disorders ,Mind and Body ,Mental Health ,Mental health ,Cognitive Sciences ,Biological psychology ,Cognitive and computational psychology - Abstract
In comparison to batteries of standard neuropsychological tests, cognitive neuroscience tests may offer a more specific assessment of discrete neurobiological processes that may be aberrant in schizophrenia. However, more information regarding psychometric properties and correlations with standard neuropsychological tests and functional measures is warranted to establish their validity as treatment outcome measures. The N-back and AX-Continuous Performance Task (AX-CPT) are two promising cognitive neuroscience tests designed to measure specific components of working memory and contextual processing respectively. In the current study, we report the psychometric properties of multiple outcome measures from these two tests as well as their correlations with standard neuropsychological measures and functional capacity measures. The results suggest that while the AX-CPT and N-back display favorable psychometric properties, they do not exhibit greater sensitivity or specificity with functional measures than standard neurocognitive tests.
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- 2020
21. The neurobiology of treatment-resistant schizophrenia: paths to antipsychotic resistance and a roadmap for future research.
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Potkin, Steven G, Kane, John M, Correll, Christoph U, Lindenmayer, Jean-Pierre, Agid, Ofer, Marder, Stephen R, Olfson, Mark, and Howes, Oliver D
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Treatment-resistant schizophrenia (TRS), the persistence of positive symptoms despite ≥2 trials of adequate dose and duration of antipsychotic medication with documented adherence, is a serious clinical problem with heterogeneous presentations. TRS can vary in its onset (at the first episode of psychosis or upon relapse), in its severity, and in the response to subsequent therapeutic interventions (i.e., clozapine, electroconvulsive therapy). The heterogeneity of TRS indicates that the underlying neurobiology of TRS may differ not only from treatment-responsive schizophrenia but also among patients with TRS. Several hypotheses have been proposed for the neurobiological mechanisms underlying TRS, including dopamine supersensitivity, hyperdopaminergic and normodopaminergic subtypes, glutamate dysregulation, inflammation and oxidative stress, and serotonin dysregulation. Research supporting these hypotheses is limited in part by variations in the criteria used to define TRS, as well as by the biological and clinical heterogeneity of TRS. Clinical trial designs for new treatments should be informed by this heterogeneity, and further clinical research is needed to more clearly understand the underlying neurobiology of TRS and to optimize treatment for patients with TRS.
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- 2020
22. Motivational and Cognitive Correlates of Community Integration in Homeless Veterans Entering a Permanent Supported Housing Program
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Horan, William P, Wynn, Jonathan K, Gabrielian, Sonya, Glynn, Shirley M, Hellemann, Gerhard S, Kern, Robert S, Lee, Junghee, Marder, Stephen R, Sugar, Catherine A, and Green, Michael F
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Brain Disorders ,Mental Health ,Homelessness ,Clinical Research ,Mind and Body ,Serious Mental Illness ,Behavioral and Social Science ,Schizophrenia ,Basic Behavioral and Social Science ,Aetiology ,2.3 Psychological ,social and economic factors ,Mental health ,Good Health and Well Being ,Adult ,Community Integration ,Female ,Ill-Housed Persons ,Humans ,Male ,Mentally Ill Persons ,Middle Aged ,Motivation ,Psychotic Disorders ,Public Housing ,United States ,Veterans ,homelessness ,motivation ,community integration ,neurocognition ,social cognition ,Psychology ,Developmental & Child Psychology - Abstract
Homelessness is a major public health problem, and serious mental illness (SMI) is highly prevalent in the homeless population. Although supported housing services-which provide permanent housing in the community along with case management-improve housing outcomes, community integration typically remains poor, and little is known about the underlying determinants of poor community integration postresidential placement. The general SMI literature has indicated that motivational and cognitive ability factors are key determinants of successful community integration, which provides a foundation for examining this issue. This study evaluated whether interview- and performance-based assessments of motivation, nonsocial and social-cognitive ability, and psychiatric symptoms were associated with community integration indices in 2 samples of homeless veterans either with (N = 96) or without (N = 80) a psychotic disorder who had recently been admitted to a supported housing program but who had not yet attained housing. Motivation indices, including experiential negative symptoms and defeatist performance attitudes, stood out as the most robust correlates (rs = -.30 to -.69) of community integration across both samples, particularly for social role participation. Demographics, general psychiatric symptoms, and nonsocial cognition showed generally weak relations with community integration, though social cognition showed a few relations. The consistent findings across samples point to the importance of motivational factors for understanding the determinants of poor community integration in this complex population. Further, interventions that target motivational challenges may have widespread usefulness for enhancing community integration outcomes beyond obtaining housing. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
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- 2020
23. Evaluating visual neuroplasticity with EEG in schizophrenia outpatients
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Wynn, Jonathan K, Roach, Brian J, McCleery, Amanda, Marder, Stephen R, Mathalon, Daniel H, and Green, Michael F
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Biomedical and Clinical Sciences ,Clinical Sciences ,Eye Disease and Disorders of Vision ,Schizophrenia ,Clinical Research ,Mental Health ,Brain Disorders ,Adult ,Electroencephalography ,Evoked Potentials ,Visual ,Female ,Humans ,Long-Term Potentiation ,Male ,Middle Aged ,Neuronal Plasticity ,Occipital Lobe ,Parietal Lobe ,Photic Stimulation ,Synapses ,Visual Pathways ,Young Adult ,Visual neuroplasticity ,EEG ,VEP ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences - Abstract
Deficient neuroplasticity has been implicated in schizophrenia and can be examined with non-invasive methods in humans. High frequency visual stimulation (HFS) induces neuroplastic changes in visual evoked potential (VEP) components, similar to the tetanizing electrical stimulation that induces synaptic long-term potentiation (LTP). While visual HFS paradigms have been used in schizophrenia, the use of a single visual stimulus has precluded demonstration of whether the plasticity effects are specific to the stimulus presented during HFS (i.e., input specific). Additionally, test-retest reliability of VEP plasticity effects, an important consideration for applications of HFS paradigms in schizophrenia clinical trials, remains unknown. Accordingly, we administered a visual HFS paradigm to 38 schizophrenia patients and 27 healthy controls at baseline and two-weeks later. VEPs were elicited by horizontal and vertical line gratings before and after HFS; only one orientation was tetanized with HFS. Using a mass univariate permutation approach, we identified an input-specific cluster across groups that was broadly distributed over parietal-occipital areas between 108 and 183 ms. However, the groups did not differ in terms of the strength of plasticity effect. The test-retest reliability of the input-specific plasticity effect was modest over two weeks, suggesting that this HFS paradigm requires further development before it could be used to track plasticity change in clinical trials. Moreover, while the current HFS paradigm induced significant input-specific neuroplasticity, it did not replicate prior studies showing deficient neuroplasticity in schizophrenia. Accordingly, demonstration of deficient visual LTP-like neuroplasticity in schizophrenia may depend on paradigm parameters that remain to be fully elucidated.
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- 2019
24. Contribution of Rare Copy Number Variants to Bipolar Disorder Risk Is Limited to Schizoaffective Cases
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Charney, Alexander W, Stahl, Eli A, Green, Elaine K, Chen, Chia-Yen, Moran, Jennifer L, Chambert, Kimberly, Belliveau, Richard A, Forty, Liz, Gordon-Smith, Katherine, Lee, Phil H, Bromet, Evelyn J, Buckley, Peter F, Escamilla, Michael A, Fanous, Ayman H, Fochtmann, Laura J, Lehrer, Douglas S, Malaspina, Dolores, Marder, Stephen R, Morley, Christopher P, Nicolini, Humberto, Perkins, Diana O, Rakofsky, Jeffrey J, Rapaport, Mark H, Medeiros, Helena, Sobell, Janet L, Backlund, Lena, Bergen, Sarah E, Juréus, Anders, Schalling, Martin, Lichtenstein, Paul, Knowles, James A, Burdick, Katherine E, Jones, Ian, Jones, Lisa A, Hultman, Christina M, Perlis, Roy, Purcell, Shaun M, McCarroll, Steven A, Pato, Carlos N, Pato, Michele T, Di Florio, Ariana, Craddock, Nick, Landén, Mikael, Smoller, Jordan W, Ruderfer, Douglas M, and Sklar, Pamela
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Genetics ,Serious Mental Illness ,Bipolar Disorder ,Mental Health ,Prevention ,Brain Disorders ,Schizophrenia ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Good Health and Well Being ,Case-Control Studies ,Cohort Studies ,DNA Copy Number Variations ,Gene Duplication ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Multifactorial Inheritance ,Psychotic Disorders ,Bipolar disorder ,Copy number variant ,Polygenic risk score ,Rare variant burden ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Biological sciences ,Biomedical and clinical sciences ,Psychology - Abstract
BackgroundGenetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood.MethodsRare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis.ResultsCNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p = .001), BD I (p = .0003), and BD II (p = .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p = .0007, PRS p = .004), and BD I without psychosis (CNV p = .0004, PRS p = 3.9 × 10-5). Within BD I, psychosis was associated with increased schizophrenia PRSs (p = .005) but not CNV burden.ConclusionsCNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.
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- 2019
25. History of Psychopharmacology
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Braslow, Joel T and Marder, Stephen R
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Biological Psychology ,Clinical and Health Psychology ,Psychology ,Applied and Developmental Psychology ,Mental Health ,Brain Disorders ,Mental health ,Good Health and Well Being ,History ,19th Century ,History ,20th Century ,History ,21st Century ,Humans ,Mental Health Services ,Psychiatry ,Psychopharmacology ,Psychotropic Drugs ,psychopharmacology ,history ,antipsychotics ,antidepressants ,mental illness ,treatment ,Clinical Psychology ,Applied and developmental psychology ,Biological psychology ,Clinical and health psychology - Abstract
We live in an age of psychopharmacology. One in six persons currently takes a psychotropic drug. These drugs have profoundly shaped our scientific and cultural understanding of psychiatric disease. By way of a historical review, we try to make sense of psychiatry's dependency on psychiatric drugs in the care of patients. Modern psychopharmacology began in 1950 with the synthesis of chlorpromazine. Over the course of the next 50 years, the psychiatric understanding and treatment of mental illness radically changed. Psychotropic drugs played a major part in these changes as state hospitals closed and psychotherapy gave way to drug prescriptions. Our review suggests that the success of psychopharmacology was not the consequence of increasingly more effective drugs for discrete psychiatric diseases. Instead, a complex mix of political economic realities, pharmaceutical marketing, basic science advances, and changes in the mental health-care system have led to our current infatuation with psychopharmacology.
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- 2019
26. Parsing components of auditory predictive coding in schizophrenia using a roving standard mismatch negativity paradigm.
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McCleery, Amanda, Mathalon, Daniel H, Wynn, Jonathan K, Roach, Brian J, Hellemann, Gerhard S, Marder, Stephen R, and Green, Michael F
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Humans ,Electroencephalography ,Mental Recall ,Attention ,Schizophrenia ,Schizophrenic Psychology ,Evoked Potentials ,Auditory ,Adolescent ,Adult ,Middle Aged ,Female ,Male ,Young Adult ,deviant negativity ,memory trace ,mismatch negativity ,prediction error signaling ,predictive coding ,psychotic disorders ,repetition negativity ,Brain Disorders ,Mental Health ,Clinical Research ,Neurosciences ,Public Health and Health Services ,Psychology ,Psychiatry - Abstract
BackgroundMismatch negativity (MMN) is an event-related potential (ERP) component reflecting auditory predictive coding. Repeated standard tones evoke increasing positivity ('repetition positivity'; RP), reflecting strengthening of the standard's memory trace and the prediction it will recur. Likewise, deviant tones preceded by more standard repetitions evoke greater negativity ('deviant negativity'; DN), reflecting stronger prediction error signaling. These memory trace effects are also evident in MMN difference wave. Here, we assess group differences and test-retest reliability of these indices in schizophrenia patients (SZ) and healthy controls (HC).MethodsElectroencephalography was recorded twice, 2 weeks apart, from 43 SZ and 30 HC, during a roving standard paradigm. We examined ERPs to the third, eighth, and 33rd standards (RP), immediately subsequent deviants (DN), and the corresponding MMN. Memory trace effects were assessed by comparing amplitudes associated with the three standard repetition trains.ResultsCompared with controls, SZ showed reduced MMNs and DNs, but normal RPs. Both groups showed memory trace effects for RP, MMN, and DN, with a trend for attenuated DNs in SZ. Intraclass correlations obtained via this paradigm indicated good-to-moderate reliabilities for overall MMN, DN and RP, but moderate to poor reliabilities for components associated with short, intermediate, and long standard trains, and poor reliability of their memory trace effects.ConclusionMMN deficits in SZ reflected attenuated prediction error signaling (DN), with relatively intact predictive code formation (RP) and memory trace effects. This roving standard MMN paradigm requires additional development/validation to obtain suitable levels of reliability for use in clinical trials.
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- 2019
27. A dose-finding study of oxytocin using neurophysiological measures of social processing
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Wynn, Jonathan K, Green, Michael F, Hellemann, Gerhard, Reavis, Eric A, and Marder, Stephen R
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Biological Psychology ,Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Psychology ,Brain Disorders ,Schizophrenia ,Clinical Research ,Mental Health ,Clinical Trials and Supportive Activities ,Neurosciences ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Mental health ,Administration ,Intranasal ,Adult ,Brain ,Cross-Over Studies ,Double-Blind Method ,Electroencephalography ,Emotions ,Female ,Humans ,Male ,Middle Aged ,Oxytocin ,Photic Stimulation ,Recognition ,Psychology ,Social Behavior ,Social Perception ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Biological psychology - Abstract
Recent interest has focused on oxytocin (OT), a neurotransmitter that promotes social processing, to improve social functioning in people with schizophrenia. However, little information is available regarding the doses of OT that are effective for influencing social processing in the brain (i.e., target engagement). In this study, we conducted a double-blind, placebo-controlled, cross-over dose ranging study of OT. In total 47 patients with schizophrenia were randomly assigned to one of eight doses of OT (8, 12, 24, 36, 48, 60, 72, or 84 IU). Patients completed two social processing tasks: one electroencephalography (EEG) task, a biological motion Mu-suppression task (i.e., identifying the gender, emotion, or direction of walking of point-light animations of human movement); and one pupillometry task, pupil dilation in response to viewing affective faces. Participants completed these tasks twice, one week apart, and were randomly administered drug or placebo intranasally 30 min prior to each session. Mu-suppression, i.e., suppression of oscillations in the 8-12 Hz range over central electrodes in response to social stimuli, was significantly enhanced at doses of 36 and 48 IU in comparison to placebo, but not at other doses. Significant pupil dilation was observed in response to faces vs. non-face stimuli, though there were no drug effects at any dose. Results suggest that OT affects central measures of social information processing in patients with schizophrenia and is optimal at a mid-range dose (36-48 IU). These results provide dosing guidance for future studies of OT to be used to enhance social processing in people with schizophrenia.
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- 2019
28. N-Acetylcysteine effects on glutathione and glutamate in schizophrenia: A preliminary MRS study
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Yang, Yvonne S., Maddock, Richard J., Zhang, Huailin, Lee, Junghee, Hellemann, Gerhard, Marder, Stephen R., and Green, Michael F.
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- 2022
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29. Comparative risks of all-cause mortality for Veterans with schizophrenia with ongoing receipt of clozapine and other antipsychotic medications
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Katz, Ira R., Szymanski, Benjamin R., Marder, Stephen R., Shotwell, Abigail, Hein, Tyler C., McCarthy, John F., and Bowersox, Nicholas W.
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- 2022
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30. Mapping genomic loci implicates genes and synaptic biology in schizophrenia
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Trubetskoy, Vassily, Pardiñas, Antonio F., Qi, Ting, Panagiotaropoulou, Georgia, Awasthi, Swapnil, Bigdeli, Tim B., Bryois, Julien, Chen, Chia-Yen, Dennison, Charlotte A., Hall, Lynsey S., Lam, Max, Watanabe, Kyoko, Frei, Oleksandr, Ge, Tian, Harwood, Janet C., Koopmans, Frank, Magnusson, Sigurdur, Richards, Alexander L., Sidorenko, Julia, Wu, Yang, Zeng, Jian, Grove, Jakob, Kim, Minsoo, Li, Zhiqiang, Voloudakis, Georgios, Zhang, Wen, Adams, Mark, Agartz, Ingrid, Atkinson, Elizabeth G., Agerbo, Esben, Al Eissa, Mariam, Albus, Margot, Alexander, Madeline, Alizadeh, Behrooz Z., Alptekin, Köksal, Als, Thomas D., Amin, Farooq, Arolt, Volker, Arrojo, Manuel, Athanasiu, Lavinia, Azevedo, Maria Helena, Bacanu, Silviu A., Bass, Nicholas J., Begemann, Martin, Belliveau, Richard A., Bene, Judit, Benyamin, Beben, Bergen, Sarah E., Blasi, Giuseppe, Bobes, Julio, Bonassi, Stefano, Braun, Alice, Bressan, Rodrigo Affonseca, Bromet, Evelyn J., Bruggeman, Richard, Buckley, Peter F., Buckner, Randy L., Bybjerg-Grauholm, Jonas, Cahn, Wiepke, Cairns, Murray J., Calkins, Monica E., Carr, Vaughan J., Castle, David, Catts, Stanley V., Chambert, Kimberley D., Chan, Raymond C. K., Chaumette, Boris, Cheng, Wei, Cheung, Eric F. C., Chong, Siow Ann, Cohen, David, Consoli, Angèle, Cordeiro, Quirino, Costas, Javier, Curtis, Charles, Davidson, Michael, Davis, Kenneth L., de Haan, Lieuwe, Degenhardt, Franziska, DeLisi, Lynn E., Demontis, Ditte, Dickerson, Faith, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Duan, Jubao, Ducci, Giuseppe, Dudbridge, Frank, Eriksson, Johan G., Fañanás, Lourdes, Faraone, Stephen V., Fiorentino, Alessia, Forstner, Andreas, Frank, Josef, Freimer, Nelson B., Fromer, Menachem, Frustaci, Alessandra, Gadelha, Ary, Genovese, Giulio, Gershon, Elliot S., Giannitelli, Marianna, Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I., González Peñas, Javier, González-Pinto, Ana, Gopal, Srihari, Gratten, Jacob, Green, Michael F., Greenwood, Tiffany A., Guillin, Olivier, Gülöksüz, Sinan, Gur, Raquel E., Gur, Ruben C., Gutiérrez, Blanca, Hahn, Eric, Hakonarson, Hakon, Haroutunian, Vahram, Hartmann, Annette M., Harvey, Carol, Hayward, Caroline, Henskens, Frans A., Herms, Stefan, Hoffmann, Per, Howrigan, Daniel P., Ikeda, Masashi, Iyegbe, Conrad, Joa, Inge, Julià, Antonio, Kähler, Anna K., Kam-Thong, Tony, Kamatani, Yoichiro, Karachanak-Yankova, Sena, Kebir, Oussama, Keller, Matthew C., Kelly, Brian J., Khrunin, Andrey, Kim, Sung-Wan, Klovins, Janis, Kondratiev, Nikolay, Konte, Bettina, Kraft, Julia, Kubo, Michiaki, Kučinskas, Vaidutis, Kučinskiene, Zita Ausrele, Kusumawardhani, Agung, Kuzelova-Ptackova, Hana, Landi, Stefano, Lazzeroni, Laura C., Lee, Phil H., Legge, Sophie E., Lehrer, Douglas S., Lencer, Rebecca, Lerer, Bernard, Li, Miaoxin, Lieberman, Jeffrey, Light, Gregory A., Limborska, Svetlana, Liu, Chih-Min, Lönnqvist, Jouko, Loughland, Carmel M., Lubinski, Jan, Luykx, Jurjen J., Lynham, Amy, Macek, Jr, Milan, Mackinnon, Andrew, Magnusson, Patrik K. E., Maher, Brion S., Maier, Wolfgang, Malaspina, Dolores, Mallet, Jacques, Marder, Stephen R., Marsal, Sara, Martin, Alicia R., Martorell, Lourdes, Mattheisen, Manuel, McCarley, Robert W., McDonald, Colm, McGrath, John J., Medeiros, Helena, Meier, Sandra, Melegh, Bela, Melle, Ingrid, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mitjans, Marina, Molden, Espen, Molina, Esther, Molto, María Dolores, Mondelli, Valeria, Moreno, Carmen, Morley, Christopher P., Muntané, Gerard, Murphy, Kieran C., Myin-Germeys, Inez, Nenadić, Igor, Nestadt, Gerald, Nikitina-Zake, Liene, Noto, Cristiano, Nuechterlein, Keith H., O’Brien, Niamh Louise, O’Neill, F. Anthony, Oh, Sang-Yun, Olincy, Ann, Ota, Vanessa Kiyomi, Pantelis, Christos, Papadimitriou, George N., Parellada, Mara, Paunio, Tiina, Pellegrino, Renata, Periyasamy, Sathish, Perkins, Diana O., Pfuhlmann, Bruno, Pietiläinen, Olli, Pimm, Jonathan, Porteous, David, Powell, John, Quattrone, Diego, Quested, Digby, Radant, Allen D., Rampino, Antonio, Rapaport, Mark H., Rautanen, Anna, Reichenberg, Abraham, Roe, Cheryl, Roffman, Joshua L., Roth, Julian, Rothermundt, Matthias, Rutten, Bart P. F., Saker-Delye, Safaa, Salomaa, Veikko, Sanjuan, Julio, Santoro, Marcos Leite, Savitz, Adam, Schall, Ulrich, Scott, Rodney J., Seidman, Larry J., Sharp, Sally Isabel, Shi, Jianxin, Siever, Larry J., Sigurdsson, Engilbert, Sim, Kang, Skarabis, Nora, Slominsky, Petr, So, Hon-Cheong, Sobell, Janet L., Söderman, Erik, Stain, Helen J., Steen, Nils Eiel, Steixner-Kumar, Agnes A., Stögmann, Elisabeth, Stone, William S., Straub, Richard E., Streit, Fabian, Strengman, Eric, Stroup, T. Scott, Subramaniam, Mythily, Sugar, Catherine A., Suvisaari, Jaana, Svrakic, Dragan M., Swerdlow, Neal R., Szatkiewicz, Jin P., Ta, Thi Minh Tam, Takahashi, Atsushi, Terao, Chikashi, Thibaut, Florence, Toncheva, Draga, Tooney, Paul A., Torretta, Silvia, Tosato, Sarah, Tura, Gian Battista, Turetsky, Bruce I., Üçok, Alp, Vaaler, Arne, van Amelsvoort, Therese, van Winkel, Ruud, Veijola, Juha, Waddington, John, Walter, Henrik, Waterreus, Anna, Webb, Bradley T., Weiser, Mark, Williams, Nigel M., Witt, Stephanie H., Wormley, Brandon K., Wu, Jing Qin, Xu, Zhida, Yolken, Robert, Zai, Clement C., Zhou, Wei, Zhu, Feng, Zimprich, Fritz, Atbaşoğlu, Eşref Cem, Ayub, Muhammad, Benner, Christian, Bertolino, Alessandro, Black, Donald W., Bray, Nicholas J., Breen, Gerome, Buccola, Nancy G., Byerley, William F., Chen, Wei J., Cloninger, C. Robert, Crespo-Facorro, Benedicto, Donohoe, Gary, Freedman, Robert, Galletly, Cherrie, Gandal, Michael J., Gennarelli, Massimo, Hougaard, David M., Hwu, Hai-Gwo, Jablensky, Assen V., McCarroll, Steven A., Moran, Jennifer L., Mors, Ole, Mortensen, Preben B., Müller-Myhsok, Bertram, Neil, Amanda L., Nordentoft, Merete, Pato, Michele T., Petryshen, Tracey L., Pirinen, Matti, Pulver, Ann E., Schulze, Thomas G., Silverman, Jeremy M., Smoller, Jordan W., Stahl, Eli A., Tsuang, Debby W., Vilella, Elisabet, Wang, Shi-Heng, Xu, Shuhua, Adolfsson, Rolf, Arango, Celso, Baune, Bernhard T., Belangero, Sintia Iole, Børglum, Anders D., Braff, David, Bramon, Elvira, Buxbaum, Joseph D., Campion, Dominique, Cervilla, Jorge A., Cichon, Sven, Collier, David A., Corvin, Aiden, Curtis, David, Forti, Marta Di, Domenici, Enrico, Ehrenreich, Hannelore, Escott-Price, Valentina, Esko, Tõnu, Fanous, Ayman H., Gareeva, Anna, Gawlik, Micha, Gejman, Pablo V., Gill, Michael, Glatt, Stephen J., Golimbet, Vera, Hong, Kyung Sue, Hultman, Christina M., Hyman, Steven E., Iwata, Nakao, Jönsson, Erik G., Kahn, René S., Kennedy, James L., Khusnutdinova, Elza, Kirov, George, Knowles, James A., Krebs, Marie-Odile, Laurent-Levinson, Claudine, Lee, Jimmy, Lencz, Todd, Levinson, Douglas F., Li, Qingqin S., Liu, Jianjun, Malhotra, Anil K., Malhotra, Dheeraj, McIntosh, Andrew, McQuillin, Andrew, Menezes, Paulo R., Morgan, Vera A., Morris, Derek W., Mowry, Bryan J., Murray, Robin M., Nimgaonkar, Vishwajit, Nöthen, Markus M., Ophoff, Roel A., Paciga, Sara A., Palotie, Aarno, Pato, Carlos N., Qin, Shengying, Rietschel, Marcella, Riley, Brien P., Rivera, Margarita, Rujescu, Dan, Saka, Meram C., Sanders, Alan R., Schwab, Sibylle G., Serretti, Alessandro, Sham, Pak C., Shi, Yongyong, St Clair, David, Stefánsson, Hreinn, Stefansson, Kari, Tsuang, Ming T., van Os, Jim, Vawter, Marquis P., Weinberger, Daniel R., Werge, Thomas, Wildenauer, Dieter B., Yu, Xin, Yue, Weihua, Holmans, Peter A., Pocklington, Andrew J., Roussos, Panos, Vassos, Evangelos, Verhage, Matthijs, Visscher, Peter M., Yang, Jian, Posthuma, Danielle, Andreassen, Ole A., Kendler, Kenneth S., Owen, Michael J., Wray, Naomi R., Daly, Mark J., Huang, Hailiang, Neale, Benjamin M., Sullivan, Patrick F., Ripke, Stephan, Walters, James T. R., and O’Donovan, Michael C.
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- 2022
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31. Examining racial differences in community integration between black and white homeless veterans
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Novacek, Derek M., Wynn, Jonathan K., Gabrielian, Sonya, Glynn, Shirley M., Hellemann, Gerhard, Horan, William P., Kern, Robert S., Lee, Junghee, Marder, Stephen R., Sugar, Catherine, and Green, Michael F.
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- 2022
- Full Text
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32. Understanding the Association Between Negative Symptoms and Performance on Effort-Based Decision-Making Tasks: The Importance of Defeatist Performance Beliefs.
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Reddy, L Felice, Horan, William P, Barch, Deanna M, Buchanan, Robert W, Gold, James M, Marder, Stephen R, Wynn, Jonathan K, Young, Jared, and Green, Michael F
- Subjects
Behavioral and Social Science ,Brain Disorders ,Schizophrenia ,Clinical Research ,Mental Health ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Adult ,Attitude ,Decision Making ,Female ,Humans ,Male ,Middle Aged ,Motivation ,Psychomotor Performance ,Volition ,motivation ,avolition ,deck choice effort task ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
Effort-based decision-making paradigms are increasingly utilized to gain insight into the nature of motivation deficits. Research has shown associations between effort-based decision making and experiential negative symptoms; however, the associations are not consistent. The current study had two primary goals. First, we aimed to replicate previous findings of a deficit in effort-based decision making among individuals with schizophrenia on a test of cognitive effort. Second, in a large sample combined from the current and a previous study, we sought to examine the association between negative symptoms and effort by including the related construct of defeatist beliefs. The results replicated previous findings of impaired cognitive effort-based decision making in schizophrenia. Defeatist beliefs significantly moderated the association between negative symptoms and effort-based decision making such that there was a strong association between high negative symptoms and deficits in effort-based decision making, but only among participants with high levels of defeatist beliefs. Thus, our findings suggest the relationship between negative symptoms and effort performance may be understood by taking into account the role of defeatist beliefs, and finding that might explain discrepancies in previous studies.
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- 2018
33. Bifactor Modeling of the Positive and Negative Syndrome Scale: Generalized Psychosis Spans Schizoaffective, Bipolar, and Schizophrenia Diagnoses.
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Anderson, Ariana E, Marder, Stephen, Reise, Steven P, Savitz, Adam, Salvadore, Giacomo, Fu, Dong Jing, Li, Qingqin, Turkoz, Ibrahim, Han, Carol, and Bilder, Robert M
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Humans ,Severity of Illness Index ,Factor Analysis ,Statistical ,Models ,Statistical ,Bipolar Disorder ,Psychotic Disorders ,Schizophrenia ,Psychiatric Status Rating Scales ,Adult ,Middle Aged ,Female ,Male ,Serious Mental Illness ,Brain Disorders ,Behavioral and Social Science ,Mental Health ,2.3 Psychological ,social and economic factors ,Aetiology ,Mental health ,Good Health and Well Being ,PANSS ,bifactor model ,schizophrenia ,schizoaffective ,bipolar disorder ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
Objective:Common genetic variation spans schizophrenia, schizoaffective and bipolar disorders, but historically, these syndromes have been distinguished categorically. A symptom dimension shared across these syndromes, if such a general factor exists, might provide a clearer target for understanding and treating mental illnesses that share core biological bases. Method:We tested the hypothesis that a bifactor model of the Positive and Negative Syndrome Scale (PANSS), containing 1 general factor and 5 specific factors (positive, negative, disorganized, excited, anxiety), explains the cross-diagnostic structure of symptoms better than the traditional 5-factor model, and examined the extent to which a general factor reflects the overall severity of symptoms spanning diagnoses in 5094 total patients with a diagnosis of schizophrenia, schizoaffective, and bipolar disorder. Results:The bifactor model provided superior fit across diagnoses, and was closer to the "true" model, compared to the traditional 5-factor model (Vuong test; P < .001). The general factor included high loadings on 28 of the 30 PANSS items, omitting symptoms associated with the excitement and anxiety/depression domains. The general factor had highest total loadings on symptoms that are often associated with the positive and disorganization syndromes, but there were also substantial loadings on the negative syndrome thus leading to the interpretation of this factor as reflecting generalized psychosis. Conclusions:A bifactor model derived from the PANSS can provide a stronger framework for measuring cross-diagnostic psychopathology than a 5-factor model, and includes a generalized psychosis dimension shared at least across schizophrenia, schizoaffective, and bipolar disorder.
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- 2018
34. Disparity between General Symptom Relief and Remission Criteria in the Positive and Negative Syndrome Scale (PANSS): A Post-treatment Bifactor Item Response Theory Model.
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Anderson, Ariana E, Reise, Steven P, Marder, Stephen R, Mansolf, Maxwell, Han, Carol, and Bilder, Robert M
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Biological Psychology ,Biomedical and Clinical Sciences ,Psychology ,Brain Disorders ,Mental Health ,Clinical Research ,Mental health ,PANSS ,Schizophrenia ,item response theory ,remission ,symptom relief - Abstract
Objective: Total scale scores derived by summing ratings from the 30-item PANSS are commonly used in clinical trial research to measure overall symptom severity, and percentage reductions in the total scores are sometimes used to document the efficacy of treatment. Acknowledging that some patients may have substantial changes in PANSS total scores but still be sufficiently symptomatic to warrant diagnosis, ratings on a subset of 8 items, referred to here as the "Remission set," are sometimes used to determine if patients' symptoms no longer satisfy diagnostic criteria. An unanswered question remains: is the goal of treatment better conceptualized as reduction in overall symptom severity, or reduction in symptoms below the threshold for diagnosis? We evaluated the psychometric properties of PANSS total scores, to assess whether having low symptom severity post-treatment is equivalent to attaining Remission. Design: We applied a bifactor item response theory (IRT) model to post-treatment PANSS ratings of 3,647 subjects diagnosed with schizophrenia assessed at the termination of 11 clinical trials. The bifactor model specified one general dimension to reflect overall symptom severity, and five domain-specific dimensions. We assessed how PANSS item discrimination and information parameters varied across the range of overall symptom severity (θ), with a special focus on low levels of symptoms (i.e., θ
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- 2017
35. Disparity between General Symptom Relief and Remission Criteria in the Positive and Negative Syndrome Scale (PANSS): A Post-treatment Bifactor Item Response Theory Model.
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Mansolf, Maxwell, Han, Carol, Reise, Steven, Bilder, Robert, Marder, Stephen, and Anderson, Ariana
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PANSS ,Schizophrenia ,item response theory ,remission ,symptom relief - Abstract
Objective: Total scale scores derived by summing ratings from the 30-item PANSS are commonly used in clinical trial research to measure overall symptom severity, and percentage reductions in the total scores are sometimes used to document the efficacy of treatment. Acknowledging that some patients may have substantial changes in PANSS total scores but still be sufficiently symptomatic to warrant diagnosis, ratings on a subset of 8 items, referred to here as the Remission set, are sometimes used to determine if patients symptoms no longer satisfy diagnostic criteria. An unanswered question remains: is the goal of treatment better conceptualized as reduction in overall symptom severity, or reduction in symptoms below the threshold for diagnosis? We evaluated the psychometric properties of PANSS total scores, to assess whether having low symptom severity post-treatment is equivalent to attaining Remission. Design: We applied a bifactor item response theory (IRT) model to post-treatment PANSS ratings of 3,647 subjects diagnosed with schizophrenia assessed at the termination of 11 clinical trials. The bifactor model specified one general dimension to reflect overall symptom severity, and five domain-specific dimensions. We assessed how PANSS item discrimination and information parameters varied across the range of overall symptom severity (θ), with a special focus on low levels of symptoms (i.e., θ
- Published
- 2017
36. Risperidone versus olanzapine among patients with schizophrenia participating in supported employment: Eighteen-month outcomes
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Noordsy, Douglas L, Glynn, Shirley M, Sugar, Catherine A, O'Keefe, Christopher D, and Marder, Stephen R
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Biological Psychology ,Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Psychology ,Clinical Trials and Supportive Activities ,Mental Health ,Clinical Research ,Brain Disorders ,Schizophrenia ,Serious Mental Illness ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Mental health ,Adult ,Antipsychotic Agents ,Benzodiazepines ,Double-Blind Method ,Employment ,Supported ,Female ,Humans ,Male ,Middle Aged ,Olanzapine ,Outcome Assessment ,Health Care ,Risperidone ,Weight Gain ,Antipsychotic medication ,Supported employment ,BMI ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences ,Clinical and health psychology - Abstract
This study compares the efficacy and tolerability of olanzapine versus risperidone among patients with schizophrenia who are established in outpatient psychiatric care and entering supported employment. A multicenter, randomized, double-blind trial was conducted among 107 outpatients with schizophrenia, who were cross-titrated to flexible dose risperidone or olanzapine over 2 weeks. Clinical endpoints included time to hospitalization and persistence on assigned medication. Weight, laboratory tests, psychopathology, neurologic side effects, social adjustment and role functioning were assessed at 3-6 month intervals. Data were analyzed first by randomized treatment, and then reassessed controlling for prior medication treatment. The proportion of patients on assigned medication at 18 months was 30.9% for risperidone and 37.3% for olanzapine. Mean doses were 6.4 ± 3.2 mg daily for risperidone, and 17.0 ± 5.0 mg daily for olanzapine. The groups did not differ significantly in time to medication discontinuation, first hospitalization or first employment. There were few differences in psychopathology, laboratory, or neurological assessments between groups at 18 months. Patients randomized to olanzapine gained modestly more weight. Controlling for pre-randomization medication suggested improvement in some aspects of psychopathology from switching medications; however, switching from olanzapine to risperidone was associated with more hospitalizations. Risperidone and olanzapine have similar efficacy and tolerability in patients with schizophrenia who are participating in supported employment. Randomization to olanzapine was associated with more weight gain, but randomization from olanzapine to risperidone appeared to be associated with a greater likelihood of hospitalization. Careful monitoring of metabolic effects and participation in supported employment may have contributed to minimal weight gain and metabolic effects.
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- 2017
37. Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments (SMART-CAT) in first-episode schizophrenia patients: Rationale and trial design
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Li, Xuan, Guo, Xiaoyun, Fan, Xiaoduo, Feng, Tienan, Wang, Chuanyue, Yao, Zhijian, Xu, Xiufeng, Chen, Zhiyu, Wang, Huiling, Xie, Shoufu, He, Jiangjiang, Zhuo, Kaiming, Xiang, Qiong, Cen, Haixin, Wang, Jinhong, Smith, Robert C., Jin, Hua, Keshavan, Matcheri S., Marder, Stephen R., Davis, John M., Jiang, Kaida, Xu, Yifeng, and Liu, Dengtang
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- 2021
- Full Text
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38. The current conceptualization of negative symptoms in schizophrenia
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Marder, Stephen R and Galderisi, Silvana
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Mental Health ,Schizophrenia ,Serious Mental Illness ,Brain Disorders ,Mental health ,Negative symptoms ,schizophrenia ,blunted affect ,alogia ,anhedonia ,asociality ,avolition ,expression factor ,experiential factor ,assessment instruments ,objective measures ,treatment ,Clinical Sciences ,Psychiatry - Abstract
Negative symptoms have long been conceptualized as a core aspect of schizophrenia. They play a key role in the functional outcome of the disorder, and their management represents a significant unmet need. Improvements in definition, characterization, assessment instruments and experimental models are needed in order to foster research aimed at developing effective interventions. A consensus has recently been reached on the following aspects: a) five constructs should be considered as negative symptoms, i.e. blunted affect, alogia, anhedonia, asociality and avolition; b) for each construct, symptoms due to identifiable factors, such as medication effects, psychotic symptoms or depression, should be distinguished from those regarded as primary; c) the five constructs cluster in two factors, one including blunted affect and alogia and the other consisting of anhedonia, avolition and asociality. In this paper, for each construct, we report the current definition; highlight differences among the main assessment instruments; illustrate quantitative measures, if available, and their relationship with the evaluations based on rating scales; and describe correlates as well as experimental models. We conclude that: a) the assessment of the negative symptom dimension has recently improved, but even current expert consensus-based instruments diverge on several aspects; b) the use of objective measures might contribute to overcome uncertainties about the reliability of rating scales, but these measures require further investigation and validation; c) the boundaries with other illness components, in particular neurocognition and social cognition, are not well defined; and d) without further reducing the heterogeneity within the negative symptom dimension, attempts to develop successful interventions are likely to lead to great efforts paid back by small rewards.
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- 2017
39. Task-related fMRI responses to a nicotinic acetylcholine receptor partial agonist in schizophrenia: A randomized trial
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Barch, Deanna M, Marder, Stephen R, Harms, Michael P, Jarskog, L Fredrik, Buchanan, Robert W, Cronenwett, Will, Chen, Li-Shiun, Weiss, Markus, Maguire, Ralph P, Pezous, Nicole, Feuerbach, Dominik, Lopez-Lopez, Cristina, Johns, Donald R, Behrje, Rhett B, and Gomez-Mancilla, Baltazar
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Clinical Research ,Neurosciences ,Clinical Trials and Supportive Activities ,Schizophrenia ,Mental Health ,Brain Disorders ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Mental health ,Neurological ,Adolescent ,Adult ,Azabicyclo Compounds ,Brain ,Cross-Over Studies ,Dose-Response Relationship ,Drug ,Double-Blind Method ,Female ,Humans ,Image Processing ,Computer-Assisted ,Magnetic Resonance Imaging ,Male ,Memory Disorders ,Memory ,Episodic ,Memory ,Short-Term ,Middle Aged ,Nicotinic Agonists ,Oxygen ,Psychiatric Status Rating Scales ,Pyridines ,Receptors ,Nicotinic ,Young Adult ,AQW051 ,Clinical trial ,Functional magnetic resonance imaging ,Nicotinic acetylcholine receptor ,Medical and Health Sciences ,Clinical Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Biochemistry and cell biology ,Clinical sciences - Abstract
IntroductionAQW051, an α7-nicotinic acetylcholine receptor partial agonist, enhanced cognitive function in rodent models of learning and memory. This study evaluated brain activation during performance of a working memory task (WMT) and an episodic memory task (EMT), and the effect of AQW051 on task-related brain activation and performance in subjects with schizophrenia.MethodsThis was a double-blind, randomized, placebo-controlled, multicenter, 2-period cross-over trial (NCT00825539) in participants with chronic, stable schizophrenia. Participants, stratified according to smoking status, were randomized (1:1:1:1:1:1) to 1 of 6 sequence groups that determined the study drug dose (AQW051 7.5mg, 50mg or 100mg) and order of administration versus placebo. The primary outcome was brain activation in a priori target regions of interest (ROIs) during performance of the WMT and EMT, measured using functional magnetic resonance imaging. The effect of AQW051 on task-related (EMT and WMT) brain activation and performance was also assessed, as were safety and tolerability.ResultsOverall, 60 of 68 enrolled participants completed the study (AQW051 then placebo: 7.5mg n=9; 50mg n=11; 100mg n=10. Placebo then AQW051: 7.5mg n=10; 50mg n=11; 100mg n=9). Significant task-related brain activation (5% significance level) was observed with placebo. During the WMT, a medium effect size was observed in the inferior prefrontal cortex with AQW051 100mg versus placebo (0.431; p=0.105). During the EMT encoding phase, a large effect size was observed in the anterior hippocampus (0.795; p=0.007) and a medium effect size in the posterior hippocampus (0.476; p=0.079) with AQW051 7.5mg. No other medium/large effect sizes were observed with any dose on either task. Effects on brain activation were generally not associated with changes in cognitive performance. AQW051 was well tolerated with an acceptable safety profile.ConclusionsOverall, no consistent effects of AQW051 on brain regions involved in the performance of a WMT or EMT were observed; however, this study presents a model for evaluating potential response to pharmacological interventions for cognitive impairment in schizophrenia.
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- 2016
40. Rethinking the risks and benefits of long-term maintenance in schizophrenia
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Zito, Michael F. and Marder, Stephen R.
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- 2020
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41. Sustained Treatment Response and Global Improvements With Long-term Valbenazine in Patients With Tardive Dyskinesia.
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Correll, Christoph U., Citrome, Leslie, Singer, Carlos, Lindenmayer, Jean-Pierre, Zinger, Celia, Liang, Grace, Dunayevich, Eduardo, and Marder, Stephen R.
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- 2024
- Full Text
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42. The characteristics of cognitive neuroscience tests in a schizophrenia cognition clinical trial: Psychometric properties and correlations with standard measures
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Kraus, Michael S., Gold, James M., Barch, Deanna M., Walker, Trina M., Chun, Charlotte A., Buchanan, Robert W., Csernansky, John G., Goff, Donald C., Green, Michael F., Jarskog, L. Fredrik, Javitt, Daniel C., Kimhy, David, Lieberman, Jeffrey A., McEvoy, Joseph P., Mesholam-Gately, Raquelle I., Seidman, Larry J., Ball, M. Patricia, Kern, Robert S., McMahon, Robert P., Robinson, James, Marder, Stephen R., and Keefe, Richard S.E.
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- 2020
- Full Text
- View/download PDF
43. Phase 2 Trial of an Alpha-7 Nicotinic Receptor Agonist (TC-5619) in Negative and Cognitive Symptoms of Schizophrenia
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Walling, David, Marder, Stephen R, Kane, John, Fleischhacker, W Wolfgang, Keefe, Richard SE, Hosford, David A, Dvergsten, Chris, Segreti, Anthony C, Beaver, Jessica S, Toler, Steven M, Jett, John E, and Dunbar, Geoffrey C
- Subjects
Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Brain Disorders ,Neurosciences ,Clinical Research ,Clinical Trials and Supportive Activities ,Schizophrenia ,Mental Health ,Behavioral and Social Science ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Mental health ,Adult ,Benzofurans ,Female ,Humans ,Male ,Middle Aged ,Nicotinic Agonists ,Outcome Assessment ,Health Care ,Quinuclidines ,Severity of Illness Index ,Young Adult ,alpha7 Nicotinic Acetylcholine Receptor ,schizophrenia ,negative symptoms ,cognition ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences - Abstract
ObjectivesThis trial was conducted to test the effects of an alpha7 nicotinic receptor full agonist, TC-5619, on negative and cognitive symptoms in subjects with schizophrenia.MethodsIn 64 sites in the United States, Russia, Ukraine, Hungary, Romania, and Serbia, 477 outpatients (18-65 years; male 62%; 55% tobacco users) with schizophrenia, treated with a new-generation antipsychotic, were randomized to 24 weeks of placebo (n = 235), TC-5619, 5mg (n = 121), or TC-5619, 50 mg (n = 121), administered orally once daily. The primary efficacy measure was the Scale for the Assessment of Negative Symptoms (SANS) composite score. Key secondary measures were the Cogstate Schizophrenia Battery (CSB) composite score and the University of California San Diego Performance-Based Skills Assessment-Brief Version (UPSA-B) total score. Secondary measures included: Positive and Negative Syndrome Scale in Schizophrenia (PANSS) total and subscale scores, SANS domain scores, CSB item scores, Clinical Global Impression-Global Improvement (CGI-I) score, CGI-Severity (CGI-S) score, and Subject Global Impression-Cognition (SGI-Cog) total score.ResultsSANS score showed no statistical benefit for TC-5619 vs placebo at week 24 (5 mg, 2-tailed P = .159; 50 mg, P = .689). Likewise, no scores of CSB, UPSA-B, PANSS, CGI-I, CGI-S, or SGI-Cog favored TC-5619 (P > .05). Sporadic statistical benefit favoring TC-5619 in some of these outcome measures were observed in tobacco users, but these benefits did not show concordance by dose, country, gender, or other relevant measures. TC-5619 was generally well tolerated.ConclusionThese results do not support a benefit of TC-5619 for negative or cognitive symptoms in schizophrenia.
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- 2016
44. Report on ISCTM Consensus Meeting on Clinical Assessment of Response to Treatment of Cognitive Impairment in Schizophrenia
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Keefe, Richard SE, Haig, George M, Marder, Stephen R, Harvey, Philip D, Dunayevich, Eduardo, Medalia, Alice, Davidson, Michael, Lombardo, Ilise, Bowie, Christopher R, Buchanan, Robert W, Bugarski-Kirola, Dragana, Carpenter, William T, Csernansky, John T, Dago, Pedro L, Durand, Dante M, Frese, Frederick J, Goff, Donald C, Gold, James M, Hooker, Christine I, Kopelowicz, Alex, Loebel, Antony, McGurk, Susan R, Opler, Lewis A, Pinkham, Amy E, and Stern, Robert G
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Neurosciences ,Behavioral and Social Science ,Rehabilitation ,Clinical Research ,Comparative Effectiveness Research ,Brain Disorders ,Management of diseases and conditions ,7.3 Management and decision making ,Mental health ,Antipsychotic Agents ,Cognition Disorders ,Humans ,Neuropsychological Tests ,Nootropic Agents ,Patient Selection ,Psychiatric Rehabilitation ,Schizophrenia ,Schizophrenic Psychology ,Severity of Illness Index ,cognitive assessment ,neuropsychology ,treatment ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences - Abstract
If treatments for cognitive impairment are to be utilized successfully, clinicians must be able to determine whether they are effective and which patients should receive them. In order to develop consensus on these issues, the International Society for CNS Clinical Trials and Methodology (ISCTM) held a meeting of experts on March 20, 2014, in Washington, DC. Consensus was reached on several important issues. Cognitive impairment and functional disability were viewed as equally important treatment targets. The group supported the notion that sufficient data are not available to exclude patients from available treatments on the basis of age, severity of cognitive impairment, severity of positive symptoms, or the potential to benefit functionally from treatment. The group reached consensus that cognitive remediation is likely to provide substantial benefits in combination with procognitive medications, although a substantial minority believed that medications can be administered without nonpharmacological therapy. There was little consensus on the best methods for assessing cognitive change in clinical practice. Some participants supported the view that performance-based measures are essential for measurement of cognitive change; others pointed to their cost and time requirements as evidence of impracticality. Interview-based measures of cognitive and functional change were viewed as more practical, but lacking validity without informant involvement or frequent contact from clinicians. The lack of consensus on assessment methods was viewed as attributable to differences in experience and education among key stakeholders and significant gaps in available empirical data. Research on the reliability, validity, sensitivity, and practicality of competing methods will facilitate consensus.
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- 2016
45. Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 1—Psychometric Characteristics of 5 Paradigms
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Reddy, L Felice, Horan, William P, Barch, Deanna M, Buchanan, Robert W, Dunayevich, Eduardo, Gold, James M, Lyons, Naomi, Marder, Stephen R, Treadway, Michael T, Wynn, Jonathan K, Young, Jared W, and Green, Michael F
- Subjects
Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Brain Disorders ,Mind and Body ,Schizophrenia ,Clinical Research ,Neurosciences ,Mental Health ,Clinical Trials and Supportive Activities ,Mental health ,Adult ,Clinical Trials as Topic ,Decision Making ,Female ,Humans ,Male ,Middle Aged ,Motivation ,Neuropsychological Tests ,Psychometrics ,Psychomotor Performance ,Reproducibility of Results ,Reward ,schizophrenia ,effort ,motivation ,psychometric ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences - Abstract
Impairments in willingness to exert effort contribute to the motivational deficits characteristic of the negative symptoms of schizophrenia. The current study evaluated the psychometric properties of 5 new or adapted paradigms to determine their suitability for use in clinical trials of schizophrenia. This study included 94 clinically stable participants with schizophrenia and 40 healthy controls. The effort-based decision-making battery was administered twice to the schizophrenia group (baseline, 4-week retest) and once to the control group. The 5 paradigms included 1 that assesses cognitive effort, 1 perceptual effort, and 3 that assess physical effort. Each paradigm was evaluated on (1) patient vs healthy control group differences, (2) test-retest reliability, (3) utility as a repeated measure (ie, practice effects), and (4) tolerability. The 5 paradigms showed varying psychometric strengths and weaknesses. The Effort Expenditure for Rewards Task showed the best reliability and utility as a repeated measure, while the Grip Effort Task had significant patient-control group differences, and superior tolerability and administration duration. The other paradigms showed weaker psychometric characteristics in their current forms. These findings highlight challenges in adapting effort and motivation paradigms for use in clinical trials.
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- 2015
46. Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia : A Randomized Clinical Trial
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Subotnik, Kenneth L, Casaus, Laurie R, Ventura, Joseph, Luo, John S, Hellemann, Gerhard S, Gretchen-Doorly, Denise, Marder, Stephen, and Nuechterlein, Keith H
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Schizophrenia ,Behavioral and Social Science ,Prevention ,Clinical Trials and Supportive Activities ,Clinical Research ,Serious Mental Illness ,Mental Health ,Brain Disorders ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Mental health ,Administration ,Oral ,Antipsychotic Agents ,Cognitive Behavioral Therapy ,Combined Modality Therapy ,Delayed-Action Preparations ,Early Medical Intervention ,Female ,Health Behavior ,Humans ,Male ,Medication Adherence ,Risperidone ,Secondary Prevention ,Treatment Outcome ,Young Adult ,Other Medical and Health Sciences ,Psychology ,Cognitive Sciences - Abstract
ImportanceLong-acting, injectable, second-generation antipsychotic medication has tremendous potential to bring clinical stability to persons with schizophrenia. However, long-acting medications are rarely used following a first episode of schizophrenia.ObjectiveTo compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia.Design, setting, and participantsA randomized clinical trial performed at a university-based research clinic, between 2005 and 2012. Eighty-six patients with recent onset of schizophrenia were randomized to receive long-acting injectable risperidone or oral risperidone. Half of each group was simultaneously randomized to receive cognitive remediation to improve cognitive functioning or healthy-behaviors training to improve lifestyle habits and well-being. An intent-to-treat analysis was performed between October 4, 2012, and November 12, 2014.InterventionsA 12-month trial comparing the long-acting injectable vs oral risperidone and cognitive remediation vs healthy-behaviors training.Main outcomes and measuresPsychotic relapse and control of breakthrough psychotic symptoms.ResultsOf the 86 patients randomized, 3 refused treatment in the long-acting injectable risperidone group. The psychotic exacerbation and/or relapse rate was lower for the long-acting risperidone group compared with the oral group (5% vs 33%; χ21 = 11.1; P
- Published
- 2015
47. Evaluating visual neuroplasticity with EEG in schizophrenia outpatients
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Wynn, Jonathan K., Roach, Brian J., McCleery, Amanda, Marder, Stephen R., Mathalon, Daniel H., and Green, Michael F.
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- 2019
- Full Text
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48. Herpes simplex virus 1 infection and valacyclovir treatment in schizophrenia: Results from the VISTA study
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Breier, Alan, Buchanan, Robert W., D'Souza, Deepak, Nuechterlein, Keith, Marder, Stephen, Dunn, Walter, Preskorn, Sheldon, Macaluso, Matthew, Wurfel, Brent, Maguire, Gerald, Kakar, Rishi, Highum, Diane, Hoffmeyer, Debra, Coskinas, Evagelos, Litman, Robert, Vohs, Jenifer L., Radnovich, Alexander, Francis, Michael M., Metzler, Emmalee, Visco, Andrew, Mehdiyoun, Nicole, Yang, Ziyi, Zhang, Ying, Yolken, Robert H., and Dickerson, Faith B.
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- 2019
- Full Text
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49. Efficacy of cariprazine across symptom domains in patients with acute exacerbation of schizophrenia: Pooled analyses from 3 phase II/III studies
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Marder, Stephen, Fleischhacker, W. Wolfgang, Earley, Willie, Lu, Kaifeng, Zhong, Yan, Németh, György, Laszlovszky, István, Szalai, Erzsébet, and Durgam, Suresh
- Published
- 2019
- Full Text
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50. The Reliability and Validity of the MATRICS Functional Assessment Battery
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Velligan, Dawn I, Fredrick, Megan, Mintz, Jim, Li, Xueying, Rubin, Maureen, Dube, Sanjay, Deshpande, Smita N, Trivedi, Jitendra K, Gautam, Shiv, Avasthi, Ajit, Kern, Robert S, and Marder, Stephen R
- Subjects
Clinical Research ,Mental Health ,Brain Disorders ,Schizophrenia ,Mental health ,Adult ,Clinical Trials as Topic ,Female ,Humans ,Male ,Outcome Assessment ,Health Care ,Psychiatric Status Rating Scales ,Psychometrics ,Reproducibility of Results ,schizophrenia ,co-primary measures ,intermediate measures ,international clinical trials ,functional capacity measures ,cognitive impairments ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
ObjectivesThe Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative was designed to encourage the development of cognitive enhancing agents for schizophrenia. For a medication to receive this indication, regulatory agencies require evidence of improvement in both cognition and functional outcome. Functional capacity measures typically used in clinical trials as intermediate measures of functional outcome must be adapted to fit different cultural contexts for use internationally. We examined the psychometric properties of the MATRICS Functional Assessment Battery (MFAB), comprised of 2 subtests from the UCSD Performance-based Skills Assessment (UPSA) and one from the Test of Adaptive Behavior in Schizophrenia (TABS) that were rated by experts in a previous study to be the most appropriate functional capacity assessments across different cultural contexts.MethodFour sites in India administered the MFAB, a brief version of the UPSA, the MATRICS Cognitive Consensus Battery, measures of symptomatology, and a measure of global functional outcome to 141 individuals with schizophrenia at a baseline assessment and at 4 weeks later.ResultsTest-retest reliability based on the intraclass correlation coefficient was significantly better for the UCSD Performance-Based Skills Assessment-Brief (UPSA-B). Pearson correlation coefficients over time were not significantly different for the 2 measures. Only the MFAB was significantly correlated with functional outcome as measured by the Specific Levels of Functioning Scale.ConclusionsThe psychometric properties of the MFAB and UPSA-B were similar. The MATRICS scientific board chose to translate the MFAB into multiple languages for potential use in studies of novel medications seeking an indication for improving cognition in schizophrenia.
- Published
- 2014
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