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3. Lithium induced hypercalcemia: an expert opinion and management algorithm

Author

Kovacs, Zoltan, Vestergaard, Peter, W. Licht, Rasmus, P. V. Straszek, Sune, Hansen, Anne Sofie, H. Young, Allan, Duffy, Anne, Müller-Oerlinghausen, Bruno, Seemueller, Florian, Sani, Gabriele, Rubakowski, Janusz, Priller, Josef, Vedel Kessing, Lars, Tondo, Leonardo, Alda, Martin, Manchia, Mirko, Grof, Paul, Ritter, Phillip, Hajek, Tomas, Lewitzka, Ute, Bergink, Veerle, Bauer, Michael, and Nielsen, René Ernst

Published
2022
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4. Remission in schizophrenia — What are we measuring? Comparing the consensus remission criteria to a CGI-based definition of remission and to remission in major depression

Author

Schennach, Rebecca, Obermeier, Michael, Spellmann, Ilja, Seemüller, Florian, Musil, Richard, Jäger, Markus, Schmauss, Max, Laux, Gerd, Pfeiffer, Herbert, Naber, Dieter, Schmidt, Lutz G., Gaebel, Wolfgang, Klosterkötter, Joachim, Heuser, Isabella, Bauer, Michael, Adli, Mazda, Zeiler, Joachim, Bender, Wolfram, Kronmüller, Klaus-Thomas, Ising, Marcus, Brieger, Peter, Maier, Wolfgang, Lemke, Matthias R., Rüther, Eckart, Klingberg, Stefan, Gastpar, Markus, Möller, Hans-Jürgen, and Riedel, Michael

Published
2019
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7. Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study

Author

Hou, Liping, Heilbronner, Urs, Degenhardt, Franziska, Adli, Mazda, Akiyama, Kazufumi, Akula, Nirmala, Ardau, Raffaella, Arias, Bárbara, Backlund, Lena, Banzato, Claudio E M, Benabarre, Antoni, Bengesser, Susanne, Bhattacharjee, Abesh Kumar, Biernacka, Joanna M, Birner, Armin, Brichant-Petitjean, Clara, Bui, Elise T, Cervantes, Pablo, Chen, Guo-Bo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Clark, Scott R, Colom, Francesc, Cousins, David A, Cruceanu, Cristiana, Czerski, Piotr M, Dantas, Clarissa R, Dayer, Alexandre, Étain, Bruno, Falkai, Peter, Forstner, Andreas J, Frisén, Louise, Fullerton, Janice M, Gard, Sébastien, Garnham, Julie S, Goes, Fernando S, Grof, Paul, Gruber, Oliver, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Lackner, Nina, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G, Jaramillo, Carlos A López, MacQueen, Glenda, Manchia, Mirko, Martinsson, Lina, Mattheisen, Manuel, McCarthy, Michael J, McElroy, Susan L, Mitjans, Marina, Mondimore, Francis M, Monteleone, Palmiero, Nievergelt, Caroline M, Nöthen, Markus M, Ösby, Urban, Ozaki, Norio, Perlis, Roy H, Pfennig, Andrea, Reich-Erkelenz, Daniela, Rouleau, Guy A, Schofield, Peter R, Schubert, K Oliver, Schweizer, Barbara W, Seemüller, Florian, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D, Shimoda, Kazutaka, Simhandl, Christian, Slaney, Claire M, Smoller, Jordan W, Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Tighe, Sarah K, Tortorella, Alfonso, Turecki, Gustavo, Volkert, Julia, Witt, Stephanie, Wright, Adam, Young, L Trevor, Zandi, Peter P, Potash, James B, DePaulo, J Raymond, Bauer, Michael, Reininghaus, Eva Z, Novák, Tomas, Aubry, Jean-Michel, Maj, Mario, Baune, Bernhard T, Mitchell, Philip B, Vieta, Eduard, Frye, Mark A, Rybakowski, Janusz K, Kuo, Po-Hsiu, Kato, Tadafumi, Grigoroiu-Serbanescu, Maria, Reif, Andreas, Del Zompo, Maria, Bellivier, Frank, Schalling, Martin, Wray, Naomi R, Kelsoe, John R, Alda, Martin, Rietschel, Marcella, McMahon, Francis J, and Schulze, Thomas G

Published
2016
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14. Genetics of emergent suicidality during antidepressive treatment—Data from a naturalistic study on a large sample of inpatients with a major depressive episode

Author

Musil, Richard, Zill, Peter, Seemüller, Florian, Bondy, Brigitta, Meyer, Sebastian, Spellmann, Ilja, Bender, Wolfram, Adli, Mazda, Heuser, Isabella, Fisher, Robert, Gaebel, Wolfgang, Maier, Wolfgang, Rietschel, Marcella, Rujescu, Dan, Schennach, Rebecca, Möller, Hans-Jürgen, and Riedel, Michael

Published
2013
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15. Lithium induced hypercalcemia:an expert opinion and management algorithm

Author

Kovacs, Zoltan, Vestergaard, Peter, W. Licht, Rasmus, P. V. Straszek, Sune, Hansen, Anne Sofie, H. Young, Allan, Duffy, Anne, Müller-Oerlinghausen, Bruno, Seemueller, Florian, Sani, Gabriele, Rubakowski, Janusz, Priller, Josef, Vedel Kessing, Lars, Tondo, Leonardo, Alda, Martin, Manchia, Mirko, Grof, Paul, Ritter, Phillip, Hajek, Tomas, Lewitzka, Ute, Bergink, Veerle, Bauer, Michael, Nielsen, René Ernst, Kovacs, Zoltan, Vestergaard, Peter, W. Licht, Rasmus, P. V. Straszek, Sune, Hansen, Anne Sofie, H. Young, Allan, Duffy, Anne, Müller-Oerlinghausen, Bruno, Seemueller, Florian, Sani, Gabriele, Rubakowski, Janusz, Priller, Josef, Vedel Kessing, Lars, Tondo, Leonardo, Alda, Martin, Manchia, Mirko, Grof, Paul, Ritter, Phillip, Hajek, Tomas, Lewitzka, Ute, Bergink, Veerle, Bauer, Michael, and Nielsen, René Ernst

Abstract

Background: Lithium is the gold standard prophylactic treatment for bipolar disorder. Most clinical practice guidelines recommend regular calcium assessments as part of monitoring lithium treatment, but easy-to-implement specific management strategies in the event of abnormal calcium levels are lacking. Methods: Based on a narrative review of the effects of lithium on calcium and parathyroid hormone (PTH) homeostasis and its clinical implications, experts developed a step-by-step algorithm to guide the initial management of emergent hypercalcemia during lithium treatment. Results: In the event of albumin-corrected plasma calcium levels above the upper limit, PTH and calcium levels should be measured after two weeks. Measurement of PTH and calcium levels should preferably be repeated after one month in case of normal or high PTH level, and after one week in case of low PTH level, independently of calcium levels. Calcium levels above 2.8 mmol/l may require a more acute approach. If PTH and calcium levels are normalized, repeated measurements are suggested after six months. In case of persistent PTH and calcium abnormalities, referral to an endocrinologist is suggested since further examination may be needed. Conclusions: Standardized consensus driven management may diminish the potential risk of clinicians avoiding the use of lithium because of uncertainties about managing side-effects and consequently hindering some patients from receiving an optimal treatment.

Published
2022

17. Response trajectories in “real-world” naturalistically treated schizophrenia patients

Author

Schennach, Rebecca, Meyer, Sebastian, Seemüller, Florian, Jäger, Markus, Schmauss, Max, Laux, Gerd, Pfeiffer, Herbert, Naber, Dieter, Schmidt, Lutz G., Gaebel, Wolfgang, Klosterkötter, Joachim, Heuser, Isabella, Maier, Wolfgang, Lemke, Matthias R., Rüther, Eckart, Klingberg, Stefan, Gastpar, Markus, Musil, Richard, Möller, Hans-Jürgen, and Riedel, Michael

Published
2012
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20. Influencing factors and predictors of early improvement in the acute treatment of schizophrenia and schizophrenia spectrum disorder

Author

Schennach-Wolff, Rebecca, Meyer, Sebastian, Seemüller, Florian, Jäger, Markus, Schmauss, Max, Laux, Gerd, Pfeiffer, Herbert, Naber, Dieter, Schmidt, Lutz G., Gaebel, Wolfgang, Klosterkötter, Joachim, Heuser, Isabella, Maier, Wolfgang, Lemke, Matthias R., Rüther, Eckart, Klingberg, Stefan, Gastpar, Markus, Möller, Hans-Jürgen, and Riedel, Michael

Published
2011
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21. Adressen

Author

Adorjan, Kristina, Allwang, Christine, Berlis, Ansgar, Dannecker, Christian, Dinkel, Andreas, Döscher, Johannes, Duraj, Edlira, Ebigbo, Alanna, Falkai, Peter, Fuchs, André, Geffken, Isabelle, Gensichen, Jochen, Gertzen, Marcus, Girrbach, Felix, Häckert, Jan, Hasan, Alkomiet, Hirschbeck, Anna, Hoffmann, Reinhard, Horns, Heidi, Ihringer, Regina, Kadmon, Martina, Khorikian-Ghazari, Naiiri, Kling, Elisabeth, Kunzmann, Tassilo, Laub, Christoph, Märkl, Bruno, Messmann, Helmut, Mueller, Arthur, Nagel, Ines, Naumann, Markus, Paul, Gregor, Pogarell, Oliver, Rabenstein, Andrea, Rahofer, Anna, Ratzka, Peter, Rémi, Jan, Röh, Astrid, Römmele, Christoph, Roos, Marco, Roser, David, Rotthoff, Thomas, Runge, Kimon, Rüther, Tobias, Sartorius, Alexander, Schneider, Christine, Seemüller, Florian, Seemüller, Güler, Siebdrath, Julian, Sonntag, Ulrich, Strube, Wolfgang, Stubbe, Hans Christian, van Elst, Ludger Tebartz, Trepel, Martin, Ventzke, Marc-Michael, von Bary, Christian, Waidhauser, Johanna, Weber, Kerstin, Weckermann, Dorothea, Welzel, Julia, Winkler, Deborah, Zellmer, Stephan, Zenk, Johannes, and Zilles-Wegner, David

Published
2024
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23. ¿Predice la mejoría precoz inducida por los antidepresivos la respuesta/remisión? Análisis de los datos de un estudio naturalista en una muestra a gran escala de pacientes hospitalizados con depresión mayor ,

Author

Henkel, Verena, Seemüller, Florian, Obermeier, Michael, Adli, Mazda, Bauer, Michael, Mundt, Christoph, Brieger, Peter, Laux, Gerhard, Bender, Wolfram, Heuser, Isabella, Zeiler, Joachim, Gaebel, Wolfgang, Mayr, Andreas, Möller, Hans-Jürgen, and Riedel, Michael

Published
2010
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25. Attitude towards adherence in patients with schizophrenia at discharge

Author

Schennach-Wolff, Rebecca, Jäger, Markus, Seemüller, Florian, Obermeier, Michael, Messer, Thomas, Laux, Gerd, Pfeiffer, Herbert, Naber, Dieter, Schmidt, Lutz G., Gaebel, Wolfgang, Klosterkötter, Joachim, Heuser, Isabella, Maier, Wolfgang, Lemke, Matthias R., Rüther, Eckart, Klingberg, Stefan, Gastpar, Markus, Möller, Hans-Jürgen, and Riedel, Michael

Published
2009
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29. Staging Kraepelin's life charts

Author

van der Markt, Afra, Klumpers, Ursula, Dols, Annemiek, Musil, Richard, Beekman, Aartjan, Seemueller, Florian, Kupka, Ralph, IOO, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, and Neurology

Published
2020

30. What happens with schizophrenia patients after their discharge from hospital? Results on outcome and treatment from a real-world 2-year follow-up trial

Author

Schennach, Rebecca, Riedel, Michael, Obermeier, Michael, Jaeger, Markus, Schmauss, Max, Laux, Gerd, Pfeiffer, Herbert, Naber, Dieter, Schmidt, Lutz G., Gaebel, Wolfgang, Klosterkoetter, Joachim, Heuser, Isabella, Maier, Wolfgang, Lemke, Matthias R., Ruether, Eckart, Klingberg, Stefan, Gastpar, Markus, Seemueller, Florian, Spellmann, Ilja, Musil, Richard, Moeller, Hans-Juergen, Schennach, Rebecca, Riedel, Michael, Obermeier, Michael, Jaeger, Markus, Schmauss, Max, Laux, Gerd, Pfeiffer, Herbert, Naber, Dieter, Schmidt, Lutz G., Gaebel, Wolfgang, Klosterkoetter, Joachim, Heuser, Isabella, Maier, Wolfgang, Lemke, Matthias R., Ruether, Eckart, Klingberg, Stefan, Gastpar, Markus, Seemueller, Florian, Spellmann, Ilja, Musil, Richard, and Moeller, Hans-Juergen

Abstract

Aim of the study was to examine the course of schizophrenia patients within 2 years after discharge. Within a multicenter study of the German Competence Network on Schizophrenia, patients suffering from a schizophrenia spectrum disorder were examined regarding their psychopathological improvement, tolerability, and the treatment regime applied during hospitalization and a 2-year follow-up period. Response, remission, the level of everyday functioning, and relapse were furthermore evaluated during the follow-up period using established definitions for these outcome domains. The psychopharmacological treatment was specifically evaluated in terms of a potential association with relapse. 149 patients were available for analysis, with 65% of the patients being in response, 52% in symptomatic remission, and 64% having a satisfiable everyday functioning 2 years after their discharge from hospital. Despite these favorable outcome rates, 63% of the patients suffered from a relapse within the 2-year follow-up period with 86% of these patients being rehospitalized. Discharge non-responder and non-remitter were twice as likely to relapse during follow-up. A significant decrease of side-effects was observed with negligible rates of extrapyramidal side-effects, sedation, and weight gain during follow-up. Patients receiving treatment with atypical antipsychotics were found to have the lowest risk to relapse (p < 0.0001). The results highlight the natural and unsteady course of schizophrenia in most patients underlining the need to develop more specific treatment strategies ensuring ongoing stability and preventing relapse.

Published
2020

34. Validity of remission and recovery criteria for schizophrenia and major depression: comparison of the results of two one-year follow-up naturalistic studies

Author

Spellmann, Ilja, Schennach, Rebecca, Seemueller, Florian, Meyer, Sebastian, Musil, Richard, Jaeger, Markus, Schmauss, Max, Laux, Gerd, Pfeiffer, Herbert, Naber, Dieter, Schmidt, Lutz G., Gaebel, Wolfgang, Klosterkoetter, Joachim, Heuser, Isabella, Bauer, Michael, Adli, Mazda, Zeiler, Joachim, Bender, Wolfram, Kronmueller, Klaus-Thomas, Ising, Marcus, Brieger, Peter, Maier, Wolfgang, Lemke, Matthias R., Ruether, Eckart, Klingberg, Stefan, Gastpar, Markus, Riedel, Michael, Moeller, Hans-Juergen, Spellmann, Ilja, Schennach, Rebecca, Seemueller, Florian, Meyer, Sebastian, Musil, Richard, Jaeger, Markus, Schmauss, Max, Laux, Gerd, Pfeiffer, Herbert, Naber, Dieter, Schmidt, Lutz G., Gaebel, Wolfgang, Klosterkoetter, Joachim, Heuser, Isabella, Bauer, Michael, Adli, Mazda, Zeiler, Joachim, Bender, Wolfram, Kronmueller, Klaus-Thomas, Ising, Marcus, Brieger, Peter, Maier, Wolfgang, Lemke, Matthias R., Ruether, Eckart, Klingberg, Stefan, Gastpar, Markus, Riedel, Michael, and Moeller, Hans-Juergen

Abstract

The objective of the present study was the application and comparison of common remission and recovery criteria between patients with the diagnosis of schizophrenia and major depressive disorder (MDD) under inclusion of other outcome parameters. Patients with schizophrenia and MDD who were treated as inpatients at the beginning of the study were examined within two naturalistic follow-up trials from admission to discharge of an inpatient treatment period and the one-year follow-up assessment. PANSS criteria of the Remission in Schizophrenia Working Group (RSWG) for schizophrenia and HAMD criteria of the ACNP Task Force in MDD for depressive patients as well as the Clinical Global Impression-Severity Scale (CGI-S) were applied as symptomatic outcome measures additionally to functional outcome parameters. Data of 153 schizophrenia patients and 231 patients with a MDD episode have been included in the analysis. More depressive than schizophrenia patients reached a threshold score of <= 3 on the CGI-S, indicating symptomatic remission at discharge and at the one-year follow-up. In contrast similar proportions of patients reaching symptomatic remission at discharge from inpatient treatment and at the one-year follow-up in the schizophrenia and in the MDD group were found when disease-related consensus criteria (RSWG vs. ACNP Task Force) were used. Functional remission and recovery rates were significantly lower in schizophrenia than in depressive patients at the one-year follow-up visit. Common outcome criteria for remission and recovery in schizophrenia and major depression were not directly comparable. However, our results indicated a significantly poorer outcome in schizophrenia than in depressive patients according to terms of remission and recovery.

Published
2017

35. Add-on Antidepressants in the Naturalistic Treatment of - Schizophrenia Spectrum Disorder - When, Who, and How?

Author

Schennach, Rebecca, Obermeier, Michael, Seemueller, Florian, Jaeger, Markus, Schmauss, Max, Laux, Gerd, Pfeiffer, Herbert, Naber, Dieter, Schmidt, Lutz G., Gaebel, Wolfgang, Klosterkoeter, Joachim, Heuser, Isabella, Maier, Wolfgang, Lemke, Matthias R., Ruether, Eckart, Klingberg, Stefan, Gastpar, Markus, Spellmann, Ilja, Musil, Richard, Moeller, Hans-Jurgen, Riedel, Michael, Schennach, Rebecca, Obermeier, Michael, Seemueller, Florian, Jaeger, Markus, Schmauss, Max, Laux, Gerd, Pfeiffer, Herbert, Naber, Dieter, Schmidt, Lutz G., Gaebel, Wolfgang, Klosterkoeter, Joachim, Heuser, Isabella, Maier, Wolfgang, Lemke, Matthias R., Ruether, Eckart, Klingberg, Stefan, Gastpar, Markus, Spellmann, Ilja, Musil, Richard, Moeller, Hans-Jurgen, and Riedel, Michael

Abstract

Introduction The aim of this study was to evaluate antidepressant add-on treatment within the acute treatment of schizophrenia spectrum disorder patients. Methods Antidepressant add-on was evaluated in 365 patients within a naturalistic multicenter study. Patients with/without antidepressant add-on were compared regarding clinical and treatment-related variables, response and remission, and remission of depressive and negative symptoms. The efficacy of antidepressant add-on treatment was furthermore analyzed applying marginal structure models. Results Twenty-three percent of the patients received antidepressant add-on for a mean duration of 50.28 (33.42) days. Patients with the diagnosis of a schizoaffective disorder, multiple illness episodes, and a longer duration of their illness as well as those with significantly fewer baseline positive symptoms, more negative and depressive symptoms, more side effects, and less subjective well-being were augmented with antidepressants. At discharge no significant effect of antidepressant add-on treatment was observed in terms of a 25 % improvement (p = 0.2623), a 50 % improvement (p = 0.3946), remission (p = 0.0552), or remission of depressive (p = 0.6336) and negative symptoms (p = 0.8756). Also, when analyzing marginal structure models considering the diagnostic subgroups, no significant effect was found. Discussion Add-on with antidepressants is common. A final recommendation in terms of this strategy's efficacy cannot be given.

Published
2017

36. Challenging the understanding of significant improvement and outcome in schizophrenia - the concept of reliable and clinically significant change methods

Author

Schennach, Rebecca, Moeller, Hans-Juergen, Obermeier, Michael, Seemueller, Florian, Jaeger, Markus, Schmauss, Max, Laux, Gerd, Pfeiffer, Herbert, Naber, Dieter, Schmidt, Lutz G., Gaebel, Wolfgang, Klosterkoetter, Joachim, Heuser, Isabella, Maier, Wolfgang, Lemke, Matthias R., Ruether, Eckart, Klingberg, Stefan, Gastpar, Markus, Musil, Richard, Spellmann, Ilja, Riedel, Michael, Schennach, Rebecca, Moeller, Hans-Juergen, Obermeier, Michael, Seemueller, Florian, Jaeger, Markus, Schmauss, Max, Laux, Gerd, Pfeiffer, Herbert, Naber, Dieter, Schmidt, Lutz G., Gaebel, Wolfgang, Klosterkoetter, Joachim, Heuser, Isabella, Maier, Wolfgang, Lemke, Matthias R., Ruether, Eckart, Klingberg, Stefan, Gastpar, Markus, Musil, Richard, Spellmann, Ilja, and Riedel, Michael

Abstract

Significant changes of schizophrenia patients during inpatient treatment were evalutaed and compared to established outcome criteria. The concept of reliable and clinically significant change methods was applied to three hundred and ninety-six patients suffering from a schizophrenia spectrum disorder. First, information on whether or not the change of the patient's condition is sufficient in order to declare that it is beyond a measurement error or random effect (= reliable change) was evaluated and in a second step it was observed if the reliable change was clinically meaningful (= clinically significant change). Different Positive and Negative Syndrome Scale for Schizophrenia (PANSS) thresholds were applied to define the clinically significant change (40, 45 and 50 points). These changes were then compared to established outcome criteria such as response and remission. Seventy-nine of the 396 patients (20%) showed a reliable improvement of symptoms, whereas 70% improved without achieving a reliable change of their condition. Of the 79 patients achieving a reliable change during treatment 8-15% concurrently showed a clinically significant change depending on the respective PANSS threshold. In contrast, 56% of the patients achieved response and 60% were in remission at discharge when applying established outcome criteria. Our results showed that a rather small number of schizophrenia patients were found to reliably change during inpatient treatment, with even less patients achieving a clinically significant change. The concept of reliable and clinically significant changes revealed to be a lot more stringent than today's established outcome criteria and should be critically evaluated regarding its use in schizophrenia patients. Copyright (c) 2015 John Wiley & Sons, Ltd. Significant changes of schizophrenia patients during inpatient treatment were evalutaed and compared to established outcome criteria. The concept of reliable and clinically significant change methods

Published
2016

38. Akathisia and Suicidal Ideation in First-Episode Schizophrenia

Author

Seemueller, Florian, Schennach, Rebecca, Mayr, Andreas, Musil, Richard, Jaeger, Markus, Maier, Wolfgang, Klingenberg, Stefan, Heuser, Isabella, Klosterkoetter, Joachim, Gastpar, Markus, Schmitt, Andrea, Schloesser, Ralf, Schneider, Frank, Ohmann, Christian, Lewitzka, Ute, Gaebel, Wolfgang, Moeller, Hans-Juergen, Riedel, Michael, Seemueller, Florian, Schennach, Rebecca, Mayr, Andreas, Musil, Richard, Jaeger, Markus, Maier, Wolfgang, Klingenberg, Stefan, Heuser, Isabella, Klosterkoetter, Joachim, Gastpar, Markus, Schmitt, Andrea, Schloesser, Ralf, Schneider, Frank, Ohmann, Christian, Lewitzka, Ute, Gaebel, Wolfgang, Moeller, Hans-Juergen, and Riedel, Michael

Abstract

Patients with first-episode schizophrenia (FES) are known to be notably sensitive for developing extrapyramidal adverse effects, but the relation of akathisia and suicidal ideation has rarely been studied. The current report is an ongoing analysis of an 8-week double-blind randomized controlled multicenter trial in 289 FES, comparing risperidone and haloperidol. Assessments were conducted weekly and included the Hillside Akathisia Scale and 21-item Hamilton Depression Rating Scale ratings. Suicidal ideation was significantly associated with clinician observed akathisia, depressed mood, younger age, and use of propranolol. The allocated treatment, anxiety, and nervousness had no influence. The present findings suggest a promoting effect of akathisia on suicidal ideation can not be ruled out in patients with FES.

Published
2012

39. Does Clinical Judgment of Baseline Severity and Changes in Psychopathology Depend on the Patient Population? Results of a CGI and PANSS Linking Analysis in a Naturalistic Study

Author

Schennach-Wolff, Rebecca, Obermeier, Michael, Seemueller, Florian, Jaeger, Markus, Schmauss, Max, Laux, Gerd, Pfeiffer, Herbert, Naber, Dieter, Schmidt, Lutz G., Gaebel, Wolfgang, Klosterkoetter, Joachim, Heuser, Isabella, Maier, Wolfgang, Lemke, Matthias R., Ruether, Eckart, Klingberg, Stefan, Gastpar, Markus, Engel, Rolf R., Moeller, Hans-Juergen, Riedel, Michael, Schennach-Wolff, Rebecca, Obermeier, Michael, Seemueller, Florian, Jaeger, Markus, Schmauss, Max, Laux, Gerd, Pfeiffer, Herbert, Naber, Dieter, Schmidt, Lutz G., Gaebel, Wolfgang, Klosterkoetter, Joachim, Heuser, Isabella, Maier, Wolfgang, Lemke, Matthias R., Ruether, Eckart, Klingberg, Stefan, Gastpar, Markus, Engel, Rolf R., Moeller, Hans-Juergen, and Riedel, Michael

Abstract

Background: Linking of the Clinical Global Impression (CGI) Scale and the Positive and Negative Syndrome Scale (PANSS) was performed within a naturalistic sample. Furthermore, these linking results were compared with those derived from randomized controlled trials to examine if the baseline severity might influence the linking results. Methods: Biweekly PANSS and CGI ratings were performed from admission to discharge in 398 schizophrenia patients treated within a naturalistic study. Equipercentile linking was performed using the statistical program, R 2.8.1. To evaluate how the naturalistic study design would influence linkage results, a so-called study sample was computed with patients of the naturalistic study fulfilling common inclusion criteria of randomized controlled trials (n = 199). Patients not fulfilling these criteria (less ill sample) and those fulfilling the criteria (study sample) were compared using confidence intervals. Results: We found a considerable difference between the linking of the CGI severity score and the PANSS total score comparing the less ill sample and the study sample. Being considered mildly ill'' at admission in the less ill sample corresponded to a PANSS total score of 47 points and to a PANSS total score of 67 points in the study sample. Considering the linking of the CGI improvement score and PANSS changes, similar results were found for CGI improvement ratings ranging from very much improved'' to minimally improved.'' Conclusions: Despite considerable differences, a 50% PANSS reduction was found to correspond to a clinical rating of much improved, which seems to be a suitable definition for response in clinical drug trials.

Published
2010

40. Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder

Author

Reinbold, Céline S., Forstner, Andreas J., Hecker, Julian, Fullerton, Janice M., Hoffmann, Per, Hou, Liping, Heilbronner, Urs, Degenhardt, Franziska, Adli, Mazda, Akiyama, Kazufumi, Akula, Nirmala, Ardau, Raffaella, Arias, Bárbara, Backlund, Lena, Benabarre, Antonio, Bengesser, Susanne, Bhattacharjee, Abesh K., Biernacka, Joanna M., Birner, Armin, Marie-Claire, Cynthia, Cervantes, Pablo, Chen, Guo-Bo, Chen, Hsi-Chung, Chillotti, Caterina, Clark, Scott R., Colom, Francesc, Cousins, David A., Cruceanu, Cristiana, Czerski, Piotr M., Dayer, Alexandre, Étain, Bruno, Falkai, Peter, Frisén, Louise, Gard, Sébastien, Garnham, Julie S., Goes, Fernando S., Grof, Paul, Gruber, Oliver, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Jamain, Stéphane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Lackner, Nina, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G., López Jaramillo, Carlos A., MacQueen, Glenda, Manchia, Mirko, Martinsson, Lina, Mattheisen, Manuel, McCarthy, Michael J., McElroy, Susan L., Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Nievergelt, Caroline M., Ösby, Urban, Ozaki, Norio, Perlis, Roy H., Pfennig, Andrea, Reich-Erkelenz, Daniela, Rouleau, Guy A., Schofield, Peter R., Schubert, K. Oliver, Schweizer, Barbara W., Seemüller, Florian, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D., Shimoda, Kazutaka, Simhandl, Christian, Slaney, Claire M., Smoller, Jordan W., Squassina, Alessio, Stamm, Thomas J., Stopkova, Pavla, Tighe, Sarah K., Tortorella, Alfonso, Turecki, Gustavo, Volkert, Julia, Witt, Stephanie H., Wright, Adam J., Young, L. Trevor, Zandi, Peter P., Potash, James B., DePaulo, J. Raymond, Bauer, Michael, Reininghaus, Eva, Novák, Tomáš, Aubry, Jean-Michel, Maj, Mario, Baune, Bernhard T., Mitchell, Philip B., Vieta, Eduard, Frye, Mark A., Rybakowski, Janusz K., Kuo, Po-Hsiu, Kato, Tadafumi, Grigoroiu-Serbanescu, Maria, Reif, Andreas, Del Zompo, Maria, Bellivier, Frank, Schalling, Martin, Wray, Naomi R., Kelsoe, John R., Alda, Martin, McMahon, Francis J., Schulze, Thomas G., Rietschel, Marcella, Nöthen, Markus M., and Cichon, Sven

Subjects
bipolar disorder, lithium response, microRNA, common variants, genome-wide association study
Abstract

Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable. Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen). Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD-associated miRNAs. However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene-based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted.

Published
2018
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41. Corrigendum to “Pleckstrin homology domain containing 6 protein (PLEKHA6) polymorphisms are associated with psychopathology and response to treatment in schizophrenic patients” [Prog Neuro-Psychopharmacol Biol Psychiatry 51 (2014) 190–195]

Author

Spellmann, Ilja, Rujescu, Dan, Musil, Richard, Meyer, Sebastian, Giegling, Ina, Genius, Just, Zill, Peter, Dehning, Sandra, Cerovecki, Anja, Seemüller, Florian, Schennach, Rebecca, Hartmann, Annette M., Martin, Schäfer, Norbert, Müller, Möller, Hans-Jürgen, and Riedel, Michael

Published
2015
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44. Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report

Author

Manchia, Mirko, Adli, Mazda, Akula, Nirmala, Ardau, Raffaella, Aubry, Jean-Michel, Backlund, Lena, Banzato, Claudio EM., Baune, Bernhard T., Bellivier, Frank, Bengesser, Susanne, Biernacka, Joanna M., Brichant-Petitjean, Clara, Bui, Elise, Calkin, Cynthia V., Cheng, Andrew Tai Ann, Chillotti, Caterina, Cichon, Sven, Clark, Scott, Czerski, Piotr M., Dantas, Clarissa, Zompo, Maria Del, DePaulo, J. Raymond, Detera-Wadleigh, Sevilla D., Etain, Bruno, Falkai, Peter, Frisén, Louise, Frye, Mark A., Fullerton, Jan, Gard, Sébastien, Garnham, Julie, Goes, Fernando S., Grof, Paul, Gruber, Oliver, Hashimoto, Ryota, Hauser, Joanna, Heilbronner, Urs, Hoban, Rebecca, Hou, Liping, Jamain, Stéphane, Kahn, Jean-Pierre, Kassem, Layla, Kato, Tadafumi, Kelsoe, John R., Kittel-Schneider, Sarah, Kliwicki, Sebastian, Kuo, Po-Hsiu, Kusumi, Ichiro, Laje, Gonzalo, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G., López Jaramillo, Carlos A., Maj, Mario, Malafosse, Alain, Martinsson, Lina, Masui, Takuya, Mitchell, Philip B., Mondimore, Frank, Monteleone, Palmiero, Nallet, Audrey, Neuner, Maria, Novák, Tomás, O’Donovan, Claire, Ösby, Urban, Ozaki, Norio, Perlis, Roy H., Pfennig, Andrea, Potash, James B., Reich-Erkelenz, Daniela, Reif, Andreas, Reininghaus, Eva, Richardson, Sara, Rouleau, Guy A., Rybakowski, Janusz K., Schalling, Martin, Schofield, Peter R., Schubert, Oliver K., Schweizer, Barbara, Seemüller, Florian, Grigoroiu-Serbanescu, Maria, Severino, Giovanni, Seymour, Lisa R., Slaney, Claire, Smoller, Jordan W., Squassina, Alessio, Stamm, Thomas, Steele, Jo, Stopkova, Pavla, Tighe, Sarah K., Tortorella, Alfonso, Turecki, Gustavo, Wray, Naomi R., Wright, Adam, Zandi, Peter P., Zilles, David, Bauer, Michael, Rietschel, Marcella, McMahon, Francis J., Schulze, Thomas G., and Alda, Martin

Subjects
Biology, Computational Biology, Genomics, Pharmacogenomics, Genetics, Genome-Wide Association Studies, Genomic Medicine, Medicine, Drugs and Devices, Behavioral Pharmacology, Neuropharmacology, Pharmacogenetics, Psychopharmacology, Epidemiology, Pharmacoepidemiology, Mental Health, Psychiatry, Mood Disorders, Psychology, Psychometrics, Therapies
Abstract

Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the “Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder” scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (κ)] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (κ = 0.66 and κ = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.

Published
2013
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