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1. The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorder

Author

Ashley L. Comes, Darina Czamara, Kristina Adorjan, Heike Anderson-Schmidt, Till F. M. Andlauer, Monika Budde, Katrin Gade, Maria Hake, Janos L. Kalman, Sergi Papiol, Daniela Reich-Erkelenz, Farah Klöhn-Saghatolislam, Sabrina K. Schaupp, Eva C. Schulte, Fanny Senner, Georg Juckel, Max Schmauß, Jörg Zimmermann, Jens Reimer, Eva Reininghaus, Ion-George Anghelescu, Carsten Konrad, Andreas Thiel, Christian Figge, Martin von Hagen, Manfred Koller, Detlef E. Dietrich, Sebastian Stierl, Harald Scherk, Stephanie H. Witt, Sugirthan Sivalingam, Franziska Degenhardt, Andreas J. Forstner, Marcella Rietschel, Markus M. Nöthen, Jens Wiltfang, Peter Falkai, Thomas G. Schulze, and Urs Heilbronner

Subjects
DNA methylation, Bipolar disorder, Stressful life events, Longitudinal, Epigenomics, Epigenetic aging, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495
Abstract

Abstract Background Stressful life events influence the course of affective disorders, however, the mechanisms by which they bring about phenotypic change are not entirely known. Methods We explored the role of DNA methylation in response to recent stressful life events in a cohort of bipolar patients from the longitudinal PsyCourse study (n = 96). Peripheral blood DNA methylomes were profiled at two time points for over 850,000 methylation sites. The association between impact ratings of stressful life events and DNA methylation was assessed, first by interrogating methylation sites in the vicinity of candidate genes previously implicated in the stress response and, second, by conducting an exploratory epigenome-wide association analysis. Third, the association between epigenetic aging and change in stress and symptom measures over time was investigated. Results Investigation of methylation signatures over time revealed just over half of the CpG sites tested had an absolute difference in methylation of at least 1% over a 1-year period. Although not a single CpG site withstood correction for multiple testing, methylation at one site (cg15212455) was suggestively associated with stressful life events (p

Published
2020
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3. The genetic relationship between educational attainment and cognitive performance in major psychiatric disorders

Author

Sebastian Stierl, Andreas Thiel, Fanny Senner, Volker Arolt, Ion-George Anghelescu, Manfred Koller, Eva C. Schulte, Markus M. Noethen, Janos L. Kalman, Daniela Reich-Erkelenz, Markus Jaeger, Here Folkerts, Urs Heilbronner, Bernhard T. Baune, Katrin Gade, Heike Anderson-Schmidt, Ashley L. Comes, Eva Z. Reininghaus, Kristina Adorjan, Georg Juckel, Maria Hake, Stephanie H. Witt, Harald Scherk, Farah Kloehn-Saghatolislam, Till F. M. Andlauer, Sabrina K. Schaupp, Jens Wiltfang, Franziska Degenhardt, Udo Dannlowski, Martin von Hagen, Max Schmauss, Monika Budde, Marcella Rietschel, Andreas J. Forstner, Moritz E. Wigand, Peter Falkai, Christian Figge, Thomas Becker, Carsten Konrad, Carsten Spitzer, Jens Reimer, Joerg Zimmermann, Sergi Papiol, Andreas J. Fallgatter, Detlef E. Dietrich, Vanessa Nieratschker, and Thomas G. Schulze

Subjects
0301 basic medicine, Male, Multifactorial Inheritance, Intelligence, Neuropsychological Tests, genetics [Mental Disorders], Cognition, 0302 clinical medicine, Memory span, Mental Disorders, physiology [Cognition], Genomics, Middle Aged, ddc, Psychiatry and Mental health, Memory, Short-Term, Schizophrenia, physiology [Memory, Short-Term], Educational Status, Female, Psychology, Adult, medicine.medical_specialty, Bipolar disorder, Fluid and crystallized intelligence, Verbal learning, physiology [Intelligence], Article, Learning and memory, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, medicine, Humans, Clinical genetics, Effects of sleep deprivation on cognitive performance, ddc:610, Psychiatry, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, medicine.disease, 030104 developmental biology, psychology [Mental Disorders], Endophenotype, 030217 neurology & neurosurgery
Abstract

Cognitive deficits are a core feature of psychiatric disorders like schizophrenia and bipolar disorder. Evidence supports a genome-wide polygenic score (GPS) for educational attainment (GPSEDU) can be used to explain variability in cognitive performance. We aimed to identify different cognitive domains associated with GPSEDU in a transdiagnostic clinical cohort of chronic psychiatric patients with known cognitive deficits. Bipolar and schizophrenia patients from the PsyCourse cohort (N = 730; 43% female) were used. Likewise, we tested whether GPSs for schizophrenia (GPSSZ) and bipolar disorder (GPSBD) were associated with cognitive outcomes. GPSEDU explained 1.5% of variance in the backward verbal digit span, 1.9% in the number of correctly recalled words of the Verbal Learning and Memory Test, and 1.1% in crystallized intelligence. These effects were robust to the influences of treatment and diagnosis. No significant associations between GPSSZ or GPSBD with cognitive outcomes were found. Furthermore, these risk scores did not confound the effect of GPSEDU on cognitive outcomes. GPSEDU explains a small fraction of cognitive performance in adults with psychiatric disorders, specifically for domains related to linguistic learning and working memory. Investigating such a proxy-phenotype longitudinally, could give intriguing insight into the disease course, highlighting at what time genes play a more influential role on cognitive performance. Better understanding the origin of these deficits might help identify those patients at risk for lower levels of functioning and poor social outcomes. Polygenic estimates may in the future be part of predictive models for more personalized interventions.

Published
2019
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4. The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorder

Author

Eva Z. Reininghaus, Maria Hake, Sergi Papiol, Farah Klöhn-Saghatolislam, Fanny Senner, Peter Falkai, Ion-George Anghelescu, Detlef E. Dietrich, Marcella Rietschel, Jörg Zimmermann, Katrin Gade, Harald Scherk, Darina Czamara, Manfred Koller, Stephanie H. Witt, Kristina Adorjan, Eva C. Schulte, Ashley L. Comes, Monika Budde, Sugirthan Sivalingam, Sebastian Stierl, Markus M. Nöthen, Janos Kalman, Jens Reimer, Georg Juckel, Andreas Thiel, Martin von Hagen, Daniela Reich-Erkelenz, Sabrina K. Schaupp, Andreas J. Forstner, Thomas G. Schulze, Till F. M. Andlauer, Carsten Konrad, Max Schmauß, Christian Figge, Franziska Degenhardt, Heike Anderson-Schmidt, Jens Wiltfang, and Urs Heilbronner

Subjects
Epigenomics, Candidate gene, Stressful life events, Bipolar disorder, Bioinformatics, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, Medicine, ddc:610, Epigenetics, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, 030304 developmental biology, 0303 health sciences, DNA methylation, business.industry, Research, lcsh:QP351-495, Methylation, Epigenome, medicine.disease, Psychiatry and Mental health, lcsh:Neurophysiology and neuropsychology, Epigenetic aging, CpG site, Longitudinal, business, 030217 neurology & neurosurgery
Abstract

Background Stressful life events influence the course of affective disorders, however, the mechanisms by which they bring about phenotypic change are not entirely known. Methods We explored the role of DNA methylation in response to recent stressful life events in a cohort of bipolar patients from the longitudinal PsyCourse study (n = 96). Peripheral blood DNA methylomes were profiled at two time points for over 850,000 methylation sites. The association between impact ratings of stressful life events and DNA methylation was assessed, first by interrogating methylation sites in the vicinity of candidate genes previously implicated in the stress response and, second, by conducting an exploratory epigenome-wide association analysis. Third, the association between epigenetic aging and change in stress and symptom measures over time was investigated. Results Investigation of methylation signatures over time revealed just over half of the CpG sites tested had an absolute difference in methylation of at least 1% over a 1-year period. Although not a single CpG site withstood correction for multiple testing, methylation at one site (cg15212455) was suggestively associated with stressful life events (p −5). Epigenetic aging over a 1-year period was not associated with changes in stress or symptom measures. Conclusions To the best of our knowledge, our study is the first to investigate epigenome-wide methylation across time in bipolar patients and in relation to recent, non-traumatic stressful life events. Limited and inconclusive evidence warrants future longitudinal investigations in larger samples of well-characterized bipolar patients to give a complete picture regarding the role of DNA methylation in the course of bipolar disorder.

Published
2020
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5. A longitudinal approach to biological psychiatric research: The PsyCourse study

Author

Monika Budde, Janos Kalman, Harald Scherk, Martin von Hagen, Fabian U. Lang, Markus Jäger, Jens Wiltfang, Georg Juckel, Udo Dannlowski, Manfred Koller, Fanny Senner, Katrin Gade, Kristina Adorjan, Eva Z. Reininghaus, Eva C. Schulte, Ida Sybille Haußleiter, Anna Gryaznova, Andreas J. Fallgatter, Till F. M. Andlauer, Ion-George Anghelescu, Markus Reitt, Here Folkerts, Sybille Schulz, Urs Heilbronner, Jens Reimer, Marcella Rietschel, Max Schmauß, Christian Figge, Maria Hake, Sebastian Stierl, Andreas Thiel, Laura Flatau, Markus M. Nöthen, Stephanie H. Witt, Moritz E. Wigand, Detlef E. Dietrich, Heike Anderson-Schmidt, Ashley L. Comes, Carsten Spitzer, Thomas Becker, Volker Arolt, Daniela Reich-Erkelenz, Bernhard T. Baune, Kim Bartholdi, Milena Meyers, Thomas G. Schulze, Vanessa Nieratschker, Barbara Emons, Franziska Degenhardt, Peter Falkai, Carsten Konrad, Silke Quast, Sabrina K. Schaupp, Jörg Zimmermann, Sophia Stegmaier, Andreas J. Forstner, Sergi Papiol, and Farah Klöhn-Saghatolislam

Subjects
Male, Research design, Bipolar Disorder, diagnosis, psychology [Psychotic Disorders], diagnosis [Schizophrenia], 0302 clinical medicine, psychosis, Longitudinal Studies, Research Articles, psychology [Bipolar Disorder], Genetics (clinical), Psychopathology, Mental Disorders, Middle Aged, 3. Good health, Diagnostic and Statistical Manual of Mental Disorders, Psychiatry and Mental health, Phenotype, Research Design, Schizophrenia, diagnosis [Psychotic Disorders], Female, Schizophrenic Psychology, Research Article, Clinical psychology, Adult, Psychosis, medicine.medical_specialty, diagnosis [Mental Disorders], methods [Psychopathology], 03 medical and health sciences, Cellular and Molecular Neuroscience, RDoC, medicine, Humans, ddc:610, Bipolar disorder, diagnosis [Bipolar Disorder], Psychiatry, Kraepelinian dichotomy, Aged, affective disorder, medicine.disease, Mental health, 030227 psychiatry, Psychotic Disorders, psychology [Mental Disorders], polygenic risk score, 030217 neurology & neurosurgery
Abstract

In current diagnostic systems, schizophrenia and bipolar disorder are still conceptualized as distinct categorical entities. Recently, both clinical and genomic evidence have challenged this Kraepelinian dichotomy. There are only few longitudinal studies addressing potential overlaps between these conditions. Here, we present design and first results of the PsyCourse study (N = 891 individuals at baseline), an ongoing transdiagnostic study of the affective-to-psychotic continuum that combines longitudinal deep phenotyping and dimensional assessment of psychopathology with an extensive collection of biomaterial. To provide an initial characterization of the PsyCourse study sample, we compare two broad diagnostic groups defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) classification system, that is, predominantly affective (n = 367 individuals) versus predominantly psychotic disorders (n = 524 individuals). Depressive, manic, and psychotic symptoms as well as global functioning over time were contrasted using linear mixed models. Furthermore, we explored the effects of polygenic risk scores for schizophrenia on diagnostic group membership and addressed their effects on nonparticipation in follow-up visits. While phenotypic results confirmed expected differences in current psychotic symptoms and global functioning, both manic and depressive symptoms did not vary between both groups after correction for multiple testing. Polygenic risk scores for schizophrenia significantly explained part of the variability of diagnostic group. The PsyCourse study presents a unique resource to research the complex relationships of psychopathology and biology in severe mental disorders not confined to traditional diagnostic boundaries and is open for collaborations.

Published
2018
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6. Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

Author

Francis M. Mondimore, Farah Klohn-Sagatholislam, Jana Strohmaier, Jens Wiltfang, Jay Raymond DePaulo, Udo Dannlowski, Markus Jäger, Moritz E. Wigand, Ion Anghelescu, Michael Bauer, Louise Frisén, Ashley L. Comes, Carsten Spitzer, Claire Slaney, Janice M. Fullerton, Giovanni Severino, Janusz K. Rybakowski, Andreas J. Fallgatter, Maria Hake, Martin Alda, Peter R. Schofield, Susanne Bengesser, Nirmala Akula, Stefan Herms, Paul D. Shilling, Franziska Degenhardt, Mazda Adli, Armin Birner, Alexandre Dayer, Cristiana Cruceanu, Fanny Senner, Peter Falkai, Maria Del Zompo, Mark A. Frye, Christian Simhandl, Stéphane Jamain, Andrea Pfennig, Layla Kassem, Sébastien Gard, Heike Anderson-Schmidt, Marion Leboyer, Peter P. Zandi, Susan L. McElroy, Martin Schalling, Sebastian Stierl, Detlef E. Dietrich, Frank Bellivier, Palmiero Monteleone, Sybille Schulz, Caterina Chillotti, Volker Arolt, Michael McCarthy, Alfonso Tortorella, Andreas Thiel, Marcella Rietschel, Kristina Adorjan, Tatyana Shekhtman, Maria Grigoroiu-Serbanescu, Jean-Michel Aubry, Daniela Reich-Erkelenz, Laura Flatau, Markus Reitt, Harald Scherk, Here Folkerts, Julia Veeh, Joanna Hauser, Fernando S. Goes, Philip B. Mitchell, Gustavo Turecki, John R. Kelsoe, Thomas Stamm, Sophia Stegmaier, Georg Juckel, Markus M. Nöthen, Lina Martinsson, Bárbara Arias, Vanessa Nieratschker, Clara Brichant-Petitjean, Antonio Benabarre, Bernhard T. Baune, James B. Potash, Urs Heilbronner, Caroline M. Nievergelt, Raffaella Ardau, Mikael Landén, Pablo Cervantes, Pavla Stopkova, Adam Wright, Tomas Novak, Scott R. Clark, Manfred Koller, Gonzalo Laje, Katrin Gade, Andreas J. Forstner, Sarah Kittel-Schneider, Susan G. Leckband, Sebastian Kliwicki, Guy A. Rouleau, Kim Bartholdi, Martin von Hagen, Per Hoffmann, Eva C. Schulte, Alessio Squassina, Monika Budde, Thomas G. Schulze, Eduard Vieta, Liping Hou, Jörg Zimmermann, Barbara König, Stephan Ripke, Sarah K. Tighe, Jean-Pierre Kahn, Julie Garnham, Piotr M. Czerski, Janos Kalman, Anna Gryaznova, Francis J. McMahon, Mario Maj, Thomas Becker, Thomas Ethofer, Andreas Reif, Carsten Konrad, Mirko Manchia, Lena Backlund, Jens Reimer, Urban Ösby, Esther Jiménez, Abesh Kumar Bhattacharjee, Marina Mitjans, Sergi Papiol, Stephanie H. Witt, Sven Cichon, Bruno Etain, Till F. M. Andlauer, Joanna M. Biernacka, Max Schmauß, Christian Figge, Fabian U. Lang, N. Lackner, Eva Z. Reininghaus, Francesc Colom, Catharina Lavebratt, K Oliver Schubert, Kalman, Janos L, Papiol, Sergi, Forstner, Andreas J, Heilbronner, Ur, Degenhardt, Franziska, Strohmaier, Jana, Adli, Mazda, Adorjan, Kristina, Akula, Nirmala, Alda, Martin, Anderson-Schmidt, Heike, Andlauer, Till Fm, Anghelescu, Ion-George, Ardau, Raffaella, Arias, Bárbara, Arolt, Volker, Aubry, Jean-Michel, Backlund, Lena, Bartholdi, Kim, Bauer, Michael, Baune, Bernhard T, Becker, Thoma, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Bhattacharjee, Abesh Kumar, Biernacka, Joanna M, Birner, Armin, Brichant-Petitjean, Clara, Budde, Monika, Cervantes, Pablo, Chillotti, Caterina, Cichon, Sven, Clark, Scott R, Colom, Francesc, Comes, Ashley L, Cruceanu, Cristiana, Czerski, Piotr M, Dannlowski, Udo, Dayer, Alexandre, Del Zompo, Maria, Depaulo, Jay Raymond, Dietrich, Detlef E, Étain, Bruno, Ethofer, Thoma, Falkai, Peter, Fallgatter, Andrea, Figge, Christian, Flatau, Laura, Folkerts, Here, Frisen, Louise, Frye, Mark A, Fullerton, Janice M, Gade, Katrin, Gard, Sébastien, Garnham, Julie S, Goes, Fernando S, Grigoroiu-Serbanescu, Maria, Gryaznova, Anna, Hake, Maria, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Hou, Liping, Jäger, Marku, Jamain, Stephane, Jiménez, Esther, Juckel, Georg, Kahn, Jean-Pierre, Kassem, Layla, Kelsoe, John, Kittel-Schneider, Sarah, Kliwicki, Sebastian, Klohn-Sagatholislam, Farah, Koller, Manfred, König, Barbara, Konrad, Carsten, Lackner, Nina, Laje, Gonzalo, Landén, Mikael, Lang, Fabian U, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G, Maj, Mario, Manchia, Mirko, Martinsson, Lina, Mccarthy, Michael J, Mcelroy, Susan L, Mcmahon, Francis J, Mitchell, Philip B, Mitjans, Marina, Mondimore, Francis M, Monteleone, Palmiero, Nieratschker, Vanessa, Nievergelt, Caroline M, Novák, Toma, Ösby, Urban, Pfennig, Andrea, Potash, James B, Reich-Erkelenz, Daniela, Reif, Andrea, Reimer, Jen, Reininghaus, Eva, Reitt, Marku, Ripke, Stephan, Rouleau, Guy A, Rybakowski, Janusz K, Schalling, Martin, Scherk, Harald, Schmauß, Max, Schofield, Peter R, Schubert, K Oliver, Schulte, Eva C, Schulz, Sybille, Senner, Fanny, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D, Simhandl, Christian, Slaney, Claire M, Spitzer, Carsten, Squassina, Alessio, Stamm, Thoma, Stegmaier, Sophia, Stierl, Sebastian, Stopkova, Pavla, Thiel, Andrea, Tighe, Sarah K, Tortorella, Alfonso, Turecki, Gustavo, Vieta, Eduard, Veeh, Julia, von Hagen, Martin, Wigand, Moritz E, Wiltfang, Jen, Witt, Stephanie, Wright, Adam, Zandi, Peter P, Zimmermann, Jörg, Nöthen, Marku, Rietschel, Marcella, and Schulze, Thomas G

Subjects
Adult, Male, Oncology, Multifactorial Inheritance, medicine.medical_specialty, Schizophrenia/genetics, Disease onset, Adolescent, early onset, Late onset, ddc:616.89, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Bipolar disorder, Child, Research Articles, Biological Psychiatry, bipolar disorder, Trastorn bipolar, business.industry, Bipolar Disorder/genetics, age at onset, polygenic risk score, schizophrenia, Age Factors, Bipolar Disorder, Female, Middle Aged, Phenotype, Schizophrenia, Original Articles, medicine.disease, Genetic architecture, 030227 psychiatry, Psychiatry and Mental health, Institutional repository, Clinical research, Esquizofrènia, Original Article, business, 030217 neurology & neurosurgery
Abstract

OBJECTIVES: Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients. METHODS: A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models. RESULTS: BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment. CONCLUSIONS: The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype. peerReviewed

Published
2018
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7. Cover Image, Volume 180B, Number 2, March 2019

Author

Monika Budde, Heike Anderson‐Schmidt, Katrin Gade, Daniela Reich‐Erkelenz, Kristina Adorjan, Janos L. Kalman, Fanny Senner, Sergi Papiol, Till F. M. Andlauer, Ashley L. Comes, Eva C. Schulte, Farah Klöhn‐Saghatolislam, Anna Gryaznova, Maria Hake, Kim Bartholdi, Laura Flatau, Markus Reitt, Silke Quast, Sophia Stegmaier, Milena Meyers, Barbara Emons, Ida Sybille Haußleiter, Georg Juckel, Vanessa Nieratschker, Udo Dannlowski, Sabrina K. Schaupp, Max Schmauß, Jörg Zimmermann, Jens Reimer, Sybille Schulz, Jens Wiltfang, Eva Reininghaus, Ion‐George Anghelescu, Volker Arolt, Bernhard T. Baune, Carsten Konrad, Andreas Thiel, Andreas J. Fallgatter, Christian Figge, Martin von Hagen, Manfred Koller, Fabian U. Lang, Moritz E. Wigand, Thomas Becker, Markus Jäger, Detlef E. Dietrich, Sebastian Stierl, Harald Scherk, Carsten Spitzer, Here Folkerts, Stephanie H. Witt, Franziska Degenhardt, Andreas J. Forstner, Marcella Rietschel, Markus M. Nöthen, Peter Falkai, Thomas G. Schulze, and Urs Heilbronner

Subjects
Cellular and Molecular Neuroscience, Psychiatry and Mental health, Genetics (clinical)
Published
2019
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8. The influence of religious activity and polygenic schizophrenia risk on religious delusions in schizophrenia

Author

Till F. M. Andlauer, Fanny Senner, Ion-George Anghelescu, Markus M. Nöthen, Carsten Konrad, Max Schmauß, Christian Figge, Ashley L. Comes, Janos L. Kalman, Harald Scherk, Georg Juckel, Sebastian Stierl, Eva Z. Reininghaus, Urs Heilbronner, Kristina Adorjan, Andreas Thiel, Sergi Papiol, Laura Flatau, Anna Gryaznova, Markus Reitt, Marcella Rietschel, Monika Budde, Heike Anderson-Schmidt, Stephanie H. Witt, Martin von Hagen, Maria Hake, Thomas G. Schulze, Detlef E. Dietrich, Dörthe Malzahn, Katrin Gade, Manfred Koller, Jörg Zimmermann, Franziska Degenhardt, Peter Falkai, Here Folkerts, Jens Wiltfang, Carsten Spitzer, Thomas Becker, Daniela Reich-Erkelenz, and Jens Reimer

Subjects
Adult, Male, Religion and Psychology, Risk, Psychosis, physiopathology [Delusions], Multifactorial Inheritance, complications [Psychotic Disorders], Adolescent, etiology [Delusions], Schizoaffective disorder, genetics [Psychotic Disorders], Logistic regression, Delusions, 03 medical and health sciences, Young Adult, 0302 clinical medicine, physiopathology [Psychotic Disorders], Delusion, complications [Schizophrenia], medicine, Humans, In patient, genetics [Schizophrenia], ddc:610, Association (psychology), Biological Psychiatry, Aged, Aged, 80 and over, Middle Aged, medicine.disease, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Psychotic Disorders, Schizophrenia, genetics [Delusions], Marital status, Female, physiopathology [Schizophrenia], medicine.symptom, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract

Background Religious delusions are a common symptom in patients experiencing psychosis, with varying prevalence rates of religious delusions across cultures and societies. To enhance our knowledge of this distinct psychotic feature, we investigated the mutually-adjusted association of genetic and environmental factors with occurrence of religious delusions. Methods We studied 262 adult German patients with schizophrenia or schizoaffective disorder. Association with lifetime occurrence of religious delusions was tested by multiple logistic regression for the following putative predictors: self-reported degree of religious activity, DSM-IV diagnosis, sex, age, education level, marital status, presence of acute delusion at the time of interview and an individual polygenic schizophrenia-risk score (SZ-PRS, available in 239 subjects). Results Of the 262 patients, 101 (39%) had experienced religious delusions. The risk of experiencing religious delusions was significantly increased in patients with strong religious activity compared to patients without religious affiliation (OR = 3.6, p = 0.010). Low or moderate religious activity had no significant effect. The same analysis including the SZ-PRS confirmed the effect of high religious activity on occurrence of religious delusions (OR = 4.1, p = 0.008). Additionally, the risk of experiencing religious delusions increased with higher SZ-PRS (OR 1.4, p = 0.020, using pT = 0.05 for SZ-PRS calculation). None of the other variables were significantly associated with lifetime occurrence of religious delusions. Conclusions Our results suggest that strong religious activity and high SZ-PRS are independent risk factors for the occurrence of religious delusions in schizophrenia and schizoaffective disorder.

Published
2019
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9. A Longitudinal Approach to Biological Psychiatric Research: The PsyCourse Study

Author

Georg Juckel, Carsten Spitzer, Kim Bartholdi, Jörg Zimmermann, Heike Anderson-Schmidt, Andreas J. Fallgatter, Urs Heilbronner, Milena Meyers, Thomas G. Schulze, Detlef E. Dietrich, Peter Falkai, Markus M. Nöthen, Manfred Koller, Jens Wiltfang, Eva C. Schulte, Silke Quast, Markus Reitt, Carsten Konrad, Thomas Becker, Volker Arolt, Katrin Gade, Sergi Papiol, Farah Klöhn-Saghatolislam, Daniela Reich-Erkelenz, Stephanie H. Witt, Moritz E. Wigand, Monika Budde, Bernhard T. Baune, Sebastian Stierl, Andreas Thiel, Laura Flatau, Anna Gryaznova, Udo Dannlowski, Markus Jäger, Fabian U. Lang, Ashley L. Comes, Till F. M. Andlauer, Marcella Rietschel, Kristina Adorjan, Ida Sybille Haußleiter, Franziska Degenhardt, Max Schmauß, Janos Kalman, Christian Figge, Harald Scherk, Eva Z. Reininghaus, Jens Reimer, Martin von Hagen, Sophia Stegmaier, Here Folkerts, Andreas J. Forstner, Fanny Senner, Ion-George Anghelescu, Sybille Schulz, Vanessa Nieratschker, Barbara Emons, and Maria Hake

Subjects
psychiatry_mental_health_studies, medicine.medical_specialty, Psychosis, business.industry, medicine.disease, 030227 psychiatry, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Schizophrenia, mental disorders, medicine, Polygenic risk score, Psychiatry, business, 030217 neurology & neurosurgery, Depression (differential diagnoses)
Abstract

In current diagnostic systems, schizophrenia and bipolar disorder are still conceptualized as distinct categorical entities. Recently, both clinical and genetic evidence have challenged this Kraepelinian dichotomy. There are only few longitudinal studies addressing the potential overlaps between these conditions. Here, we present design and first results of the PsyCourse study, an ongoing transdiagnostic study of the affective-to-psychotic continuum that combines longitudinal deep phenotyping and dimensional assessment of psychopathology with an extensive collection of biomaterial. Within the DSM-IV framework, we compare two broad diagnostic groups: one consisting of predominantly affective and one of predominantly psychotic disorders. Depressive, manic, and psychotic symptoms as well as global functioning over time were analyzed. Furthermore, we explore the effects of polygenic risk scores for schizophrenia on diagnostic group membership and address their effects on non-participation in follow-up visits. While phenotypic results show differences in both current psychotic and manic symptoms, depressive symptoms did not vary between both groups. Polygenic risk scores for schizophrenia significantly explained part of the variability of the diagnostic group. Furthermore, there was a trend that a higher polygenic loading for schizophrenia was associated with attrition. Because of its unique properties, the PsyCourse study presents a prime resource for the interrogation of complex genotype-phenotype relationships.

Published
2017
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10. HDAC1 links early life stress to schizophrenia-like phenotypes

Author

Eva Benito, Antje Zitzelsberger, Carsten Spitzer, Susanne Burkhardt, Andrea Schmitt, Detlef E. Dietrich, Sanaz Bahari-Javan, Alexander Dityatev, Judith Stöckel, Christian Figge, Hristo Varbanov, Heike Anderson-Schmidt, Rashi Halder, Andre Fischer, Manfred Koller, Ivana Delalle, Urs Heilbronner, Here Folkerts, Joan Costa, Katrin Gade, Harald Scherk, Peter Falkai, Sara Y. Nussbeck, Ion Anghelescu, Martin von Hagen, Juan F. Medina, Farahnaz Sananbenesi, Carsten Konrad, Monika Budde, Roman M. Stilling, Thomas G. Schulze, Sybille Schulz, Jörg Zimmermann, Sebastian Stierl, Lalit Kaurani, and Andreas Thiel

Subjects
0301 basic medicine, Male, etiology [Schizophrenia], Hippocampus, genetics [Stress, Psychological], Histone Deacetylase 1, Disease, enzymology [Schizophrenia], Biochemistry, biophysics & molecular biology [F05] [Life sciences], Corrections, Mice, 0302 clinical medicine, genetics [Schizophrenia], Prefrontal cortex, Biochimie, biophysique & biologie moléculaire [F05] [Sciences du vivant], HDAC1 protein, human, Multidisciplinary, Middle Aged, Phenotype, 3. Good health, PNAS Plus, Schizophrenia, DNA methylation, embryonic structures, Female, ddc:500, genetics [Histone Deacetylase 1], Adult, medicine.medical_specialty, blood [Histone Deacetylase 1], animal structures, Prefrontal Cortex, Mice, Transgenic, Biology, metabolism [RNA, Messenger], 03 medical and health sciences, genetics [RNA, Messenger], Young Adult, Hdac1 protein, mouse, enzymology [Hippocampus], complications [Stress, Psychological], Internal medicine, mental disorders, medicine, Genetic predisposition, Animals, Humans, RNA, Messenger, enzymology [Prefrontal Cortex], Aged, metabolism [Histone Deacetylase 1], DNA Methylation, enzymology [Stress, Psychological], medicine.disease, HDAC1, Mice, Mutant Strains, Mice, Inbred C57BL, Histone Deacetylase Inhibitors, enzymes and coenzymes (carbohydrates), 030104 developmental biology, Endocrinology, Neuroscience, Stress, Psychological, 030217 neurology & neurosurgery, pharmacology [Histone Deacetylase Inhibitors]
Abstract

Schizophrenia is a devastating disease that arises on the background of genetic predisposition and environmental risk factors, such as early life stress (ELS). In this study, we show that ELS-induced schizophrenia-like phenotypes in mice correlate with a widespread increase of histone-deacetylase 1 (Hdac1) expression that is linked to altered DNA methylation. Hdac1 overexpression in neurons of the medial prefrontal cortex, but not in the dorsal or ventral hippocampus, mimics schizophrenia-like phenotypes induced by ELS. Systemic administration of an HDAC inhibitor rescues the detrimental effects of ELS when applied after the manifestation of disease phenotypes. In addition to the hippocampus and prefrontal cortex, mice subjected to ELS exhibit increased Hdac1 expression in blood. Moreover, Hdac1 levels are increased in blood samples from patients with schizophrenia who had encountered ELS, compared with patients without ELS experience. Our data suggest that HDAC1 inhibition should be considered as a therapeutic approach to treat schizophrenia.

Published
2017
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12. The 'DGPPN-Cohort': A national collaboration initiative by the German Association for Psychiatry and Psychotherapy (DGPPN) for establishing a large-scale cohort of psychiatric patients

Author

Otto Rienhoff, Roswitha Bianco, Detlef E. Dietrich, Dominikus Bönsch, Frank Schneider, Tilo Kircher, Heike Anderson-Schmidt, Henrik Walter, Matthias Riemenschneider, Jürgen Zielasek, Anke Jahn-Brodmann, Eva Z. Reininghaus, Markus Reitt, Matthias Quade, Judith Stöckel, Daniel Feldhaus, Georg Juckel, Wolfgang P. Kaschka, Antje Zitzelsberger, Axel Krug, Peter Falkai, Andrea Pfennig, Karoline Buckow, Mahsa Lee, Jessica Baumgärtner, Cosima Bitter, Joachim Becker, Ulrich Hegerl, Verena Gullatz, Thomas Wobrock, Tilman Hensch, Markus Leweke, Andreas Heinz, Markus Jäger, Andreas J. Fallgatter, Michael Franz, Stephanie H. Witt, Marlenna Pieper, Andreas Meyer-Lindenberg, Moritz Mühlbacher, Michael Bauer, Jacqueline Ohle, Klaus Lieb, Harald Scherk, Christian Figge, Jürgen Deckert, Alexandra Schosser, Dan Rujescu, Martin Bührig, Martin von Hagen, Jens Schwanke, Linda Gusky, Thomas G. Schulze, Ion Anghelescu, Marcella Rietschel, Sybille G. Schwab, Barbara Nierste, K. Helbing, Sebastian Stierl, Christoph Hiemke, Andreas Thiel, Matthias J. Müller, Rebecca Schennach, Manfred Koller, Johannes Kornhuber, Björn H. Schott, Sara Y. Demiroglu, Vanessa Nieratschker, Patrik Roser, Daniela Reich-Erkelenz, Oliver Gruber, Susanne Stübner, Hans Peter Volz, Wolfgang Gaebel, Lothar Adler, Uta Engelhardt, Hans J. Grabe, Bernd Reininghaus, Mechthild Mammes, Marina Krause, Thomas Becker, Carsten Spitzer, Andreas Reif, Max Schmauss, Monika Budde, Wolfgang Maier, Here Folkerts, Katrin Gade, Jörg Zimmermann, Chadiga Aly, Franz Kandulski, Michael Dümpelmann, Urs Heilbronner, Daniela Skrowny, Carsten Konrad, Farmacologie en Toxicologie, and RS: CARIM School for Cardiovascular Diseases

Subjects
Male, medicine.medical_specialty, Psychotherapist, Bipolar disorder, German, Cohort Studies, Germany, Epidemiology, medicine, Major depression, Humans, Pharmacology (medical), Cooperative Behavior, Association (psychology), Psychiatry, Biological Psychiatry, Societies, Medical, Biobank, business.industry, Mental Disorders, General Medicine, medicine.disease, language.human_language, Data sharing, Psychotherapy, Psychiatry and Mental health, Scale (social sciences), Cohort, language, Schizophrenia, Female, business, Anxiety disorders
Abstract

The German Association for Psychiatry and Psychotherapy (DGPPN) has committed itself to establish a prospective national cohort of patients with major psychiatric disorders, the so-called DGPPN-Cohort. This project will enable the scientific exploitation of high-quality data and biomaterial from psychiatric patients for research. It will be set up using harmonised data sets and procedures for sample generation and guided by transparent rules for data access and data sharing regarding the central research database. While the main focus lies on biological research, it will be open to all kinds of scientific investigations, including epidemiological, clinical or health-service research.

Published
2012

13. [The reformation of psychiatry was only a modernization]

Author

Sebastian, Stierl and Manfred, Bauer

Subjects
Hospitals, Psychiatric, Health Services Needs and Demand, National Health Programs, Psychiatric Department, Hospital, Hospitals, General, Health Facility Closure, Hospital Bed Capacity, Germany, Health Care Reform, Ambulatory Care, Humans, Community Psychiatry, Delivery of Health Care, Forecasting
Published
2007

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