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The effect of psychological treatment on repetitive negative thinking in youth depression and anxiety: a meta-analysis and meta-regression
- Imogen H. Bell, Wolfgang Marx, Katherine Nguyen, Sally Grace, John Gleeson, Mario Alvarez-Jimenez
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- Journal:
- Psychological Medicine / Volume 53 / Issue 1 / January 2023
- Published online by Cambridge University Press:
- 14 November 2022, pp. 6-16
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Background
Depression and anxiety are prevalent in youth populations and typically emerge during adolescence. Repetitive negative thinking (RNT) is a putative transdiagnostic mechanism with consistent associations with depression and anxiety. Targeting transdiagnostic processes like RNT for youth depression and anxiety may offer more targeted, personalised and effective treatment.
MethodsA meta-analysis was conducted to examine the effect of psychological treatments on RNT, depression and anxiety symptoms in young people with depression or anxiety, and a meta-regression to examine relationships between outcomes.
ResultsTwenty-eight randomised controlled trials examining 17 different psychological interventions were included. Effect sizes were small to moderate across all outcomes (Hedge's g depression = −0.47, CI −0.77 to −0.17; anxiety = −0.42, CI −0.65 to −0.20; RNT = −0.45, CI −0.67 to −0.23). RNT-focused and non-RNT focused approaches had comparable effects; however, those focusing on modifying the process of RNT had significantly larger effects on RNT than those focusing on modifying negative thought content. Meta-regression revealed a significant relationship between RNT and depression outcomes only across all intervention types and with both depression and anxiety for RNT focused interventions only.
ConclusionConsistent with findings in adults, this review provides evidence that reducing RNT with psychological treatment is associated with improvements in depression and anxiety in youth. Targeting RNT specifically may not lead to better outcomes compared to general approaches; however, focusing on modifying the process of RNT may be more effective than targeting content. Further research is needed to determine causal pathways.
Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach – CORRIGENDUM
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, JeanMichel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, HsiChung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil TekolaAyele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 221 / Issue 2 / August 2022
- Published online by Cambridge University Press:
- 04 May 2022, p. 494
- Print publication:
- August 2022
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Effects of Long-Term Deutetrabenazine Treatment in Patients with Tardive Dyskinesia and Underlying Psychiatric or Mood Disorders
- Robert A. Hauser, Hadas Barkay, Hubert H. Fernandez, Stewart A. Factor, Joohi Jimenez-Shahed, Nicholas Gross, Leslie Marinelli, Amanda Wilhelm, Mark Forrest Gordon, Juha-Matti Savola, Karen E. Anderson
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- Journal:
- CNS Spectrums / Volume 27 / Issue 2 / April 2022
- Published online by Cambridge University Press:
- 28 April 2022, pp. 245-246
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Introduction
Deutetrabenazine is FDA-approved for the treatment of tardive dyskinesia (TD) in adults. In two 12-week pivotal trials (ARM-TD/AIM-TD), deutetrabenazine significantly improved Abnormal Involuntary Movement Scale (AIMS) scores and was well-tolerated. This post hoc analysis examined the efficacy and safety of long-term deutetrabenazine treatment in TD patients with comorbid psychiatric illness, including schizophrenia/schizoaffective disorder and mood disorders (bipolar/depression/other).
MethodsPatients who completed ARM-TD or AIM-TD enrolled in the 3-year, open-label extension (OLE) study. Deutetrabenazine was titrated based on dyskinesia control and tolerability. Change from baseline in total motor AIMS score, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and adverse events (AEs) were analyzed in subgroups by comorbid psychiatric illness.
ResultsA total of 337 patients in the OLE study were included in the analysis: 205 patients with schizophrenia/schizoaffective disorder (mean age, 55 years; 50% male; 6.4 years since diagnosis; 92% taking DRA) and 131 patients with mood disorders (mean age, 60 years; 35% male; 4.6 years since diagnosis; 50% taking DRA). At week 145, mean ± SE dose was 40.4 ± 1.1 mg/day for schizophrenia/schizoaffective disorder (n = 88) and 38.5 ± 1.2 mg/day for mood disorders (n = 72). Mean ± SE change from baseline in AIMS score at week 145 was −6.3 ± 0.49 and −7.1 ± 0.58, 56% and 72% achieved PGIC treatment success, and 66% and 82% achieved CGIC treatment success in schizophrenia/schizoaffective disorder and mood disorder patients, respectively. Overall AE incidence (exposure-adjusted incidence rates [incidence/patient-years]) was low: any, 1.02 and 1.71; serious, 0.10 and 0.12; leading to discontinuation, 0.07 and 0.05).
ConclusionLong-term deutetrabenazine treatment provided clinically meaningful improvements in TD-related movements, with a favorable safety profile, regardless of underlying comorbid psychiatric illness.
FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel
Long-Term Efficacy and Safety of Deutetrabenazine in Patients with Tardive Dyskinesia by Concomitant Dopamine-Receptor Antagonist Use
- Robert A. Hauser, Hadas Barkay, Hubert H. Fernandez, Stewart A. Factor, Joohi Jimenez-Shahed, Nicholas Gross, Leslie Marinelli, Amanda Wilhelm, Mark Forrest Gordon, Juha-Matti Savola, Karen E. Anderson
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- Journal:
- CNS Spectrums / Volume 27 / Issue 2 / April 2022
- Published online by Cambridge University Press:
- 28 April 2022, p. 246
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Introduction
Tardive dyskinesia (TD) is an involuntary movement disorder that can result from exposure to dopamine-receptor antagonists (DRAs). Deutetrabenazine demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores in the 12-week pivotal trials (ARM-TD/AIM-TD). This post hoc analysis assessed the long-term efficacy and safety of deutetrabenazine by baseline DRA use.
MethodsPatients who completed ARM-TD or AIM-TD enrolled in the 3-year, open-label extension (OLE) study, with deutetrabenazine dose titrated based on dyskinesia control and tolerability. Change from baseline in total motor AIMS score, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and adverse event (AE) rates were analyzed in subgroups by baseline DRA use.
ResultsOf 337 patients in the OLE study, 254 were taking DRAs at baseline (mean age, 56 years; 48% male; 6.0 years since diagnosis) and 83 were not (mean age, 60 years; 31% male; 4.9 years since diagnosis). Mean ± SE dose at week 145 was 39.9 ± 1.0 mg/day in patients taking DRAs (n = 108) and 38.5 ± 1.5 mg/day in patients not taking DRAs (n = 53). At week 145, mean ± SE change from baseline in AIMS score was −6.1 ± 0.43 and −7.5 ± 0.71; 64% and 62% achieved PGIC treatment success; and 69% and 81% achieved CGIC treatment success, respectively. Overall AE incidence was low (exposure-adjusted incidence rates [incidence/patient-years]: any, 1.08 and 1.97; serious, 0.10 and 0.12; leading to discontinuation, 0.06 and 0.05).
ConclusionThis analysis suggests that deutetrabenazine for long-term treatment of TD is beneficial, with a favorable safety profile, regardless of concomitant DRA use.
FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel
Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil Tekola-Ayele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 220 / Issue 4 / April 2022
- Published online by Cambridge University Press:
- 28 February 2022, pp. 219-228
- Print publication:
- April 2022
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Background
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
AimsTo use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
MethodThis study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
ResultsThe best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
ConclusionsUsing PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Negative symptoms in First-Episode Schizophrenia related to morphometric alterations in orbitofrontal and superior temporal cortex: the OPTiMiSE study
- Arsime Demjaha, Silvana Galderisi, Birthe Glenthøj, Celso Arango, Armida Mucci, Andrew Lawrence, Owen O'Daly, Matthew Kempton, Simone Ciufolini, Lone Baandrup, Bjørn H. Ebdrup, Roberto Rodriguez-Jimenez, Maria Diaz-Marsa, Covadonga Martinez Díaz-Caneja, Inge Winter van Rossum, Rene Kahn, Paola Dazzan, Philip McGuire
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- Journal:
- Psychological Medicine / Volume 53 / Issue 8 / June 2023
- Published online by Cambridge University Press:
- 24 February 2022, pp. 3471-3479
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Background
Negative symptoms are one of the most incapacitating features of Schizophrenia but their pathophysiology remains unclear. They have been linked to alterations in grey matter in several brain regions, but findings have been inconsistent. This may reflect the investigation of relatively small patient samples, and the confounding effects of chronic illness and exposure to antipsychotic medication. We sought to address these issues by investigating concurrently grey matter volumes (GMV) and cortical thickness (CTh) in a large sample of antipsychotic-naïve or minimally treated patients with First-Episode Schizophrenia (FES).
MethodsT1-weighted structural MRI brain scans were acquired from 180 antipsychotic-naïve or minimally treated patients recruited as part of the OPTiMiSE study. The sample was stratified into subgroups with (N = 88) or without (N = 92) Prominent Negative Symptoms (PMN), based on PANSS ratings at presentation. Regional GMV and CTh in the two groups were compared using Voxel-Based Morphometry (VBM) and FreeSurfer (FS). Between-group differences were corrected for multiple comparisons via Family-Wise Error (FWE) and Monte Carlo z-field simulation respectively at p < 0.05 (2-tailed).
ResultsThe presence of PMN symptoms was associated with larger left inferior orbitofrontal volume (p = 0.03) and greater CTh in the left lateral orbitofrontal gyrus (p = 0.007), but reduced CTh in the left superior temporal gyrus (p = 0.009).
ConclusionsThe findings highlight the role of orbitofrontal and temporal cortices in the pathogenesis of negative symptoms of Schizophrenia. As they were evident in generally untreated FEP patients, the results are unlikely to be related to effects of previous treatment or illness chronicity.
Revisiting the four core functions (4Cs) of primary care: operational definitions and complexities
- Geronimo Jimenez, David Matchar, Gerald Choon Huat Koh, Shilpa Tyagi, Rianne M. J. J. van der Kleij, Niels H. Chavannes, Josip Car
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- Journal:
- Primary Health Care Research & Development / Volume 22 / 2021
- Published online by Cambridge University Press:
- 10 November 2021, e68
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Background:
The four primary care (PC) core functions (the ‘4Cs’, ie, first contact, comprehensiveness, coordination and continuity) are essential for good quality primary healthcare and their achievement leads to lower costs, less inequality and better population health. However, their broad definitions have led to variations in their assessment, in the innovations implemented to improve these functions and ultimately in their performance.
Objectives:To update and operationalise the 4Cs’ definitions by using a literature review and analysis of enhancement strategies, and to identify innovations that may lead to their enhancement.
Methods:Narrative, descriptive analysis of the 4Cs definitions, coming from PC international reports and organisations, to identify measurable features for each of these functions. Additionally, we performed an electronic search and analysis of enhancement strategies to improve these four Cs, to explore how the 4Cs inter-relate.
Results:Specific operational elements for first contact include modality of contact, and conditions for which PC should be approached; for comprehensiveness, scope of services and spectrum of population needs; for coordination, links between PC and higher levels of care and social/community-based services, and workforce managing transitions and for continuity, type, level and context of continuity. Several innovations like enrolment, digital health technologies and new or enhanced PC provider’s roles, simultaneously influenced two or more of the 4Cs.
Conclusion:Providing clear, well-defined operational elements for these 4Cs to measure their achievement and improve the way they function, and identifying the complex network of interactions among them, should contribute to the field in a way that supports efforts at practice innovation to optimise the processes and outcomes in PC.
Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Effect of Deutetrabenazine on Metabolic Parameters in the Treatment of Tardive Dyskinesia
- Joohi Jimenez-Shahed, Hadas Barkay, Karen E. Anderson, Hubert H. Fernandez, Stewart A. Factor, Robert A. Hauser, Maria Wieman, Mark Forrest Gordon, Juha-Matti Savola
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- Journal:
- CNS Spectrums / Volume 26 / Issue 2 / April 2021
- Published online by Cambridge University Press:
- 10 May 2021, pp. 159-160
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Background
Deutetrabenazine, a novel vesicular monoamine transporter 2 (VMAT2) inhibitor, is approved by the FDA for treatment of tardive dyskinesia (TD) in adults. Dopamine-receptor antagonists (DRAs) are associated with worsening of metabolic parameters, including weight gain, hyperlipidemia, and elevated blood glucose. This post hoc analysis assessed the short- and long-term effects of deutetrabenazine treatment on weight and metabolic parameters in individuals treated for TD.
MethodsTwo 12-week, randomized placebo-controlled trials (RCTs) of deutetrabenazine for patients with TD evaluated either fixed dosing (AIM-TD; 12, 24, or 36 mg) or dose titration (ARM-TD; max dose, 48 mg/day). Patients completing ARM-TD or AIM-TD were included in an open-label extension (OLE) study, in which all patients underwent response-driven titration of deutetrabenazine from 12 mg/day up to a maximum total dose of 48 mg/day. Weight, body mass index (BMI), serum glucose, serum total cholesterol, and serum triglycerides were evaluated at baseline and during treatment in the RCTs and in the OLE.
ResultsIn the RCTs, 282 and 133 patients received deutetrabenazine or placebo. At baseline, 77% of patients used DRAs. At Week 12, no meaningful changes in weight were observed, with mean (standard error) weight changes of 0.9–1.2 (0.3–0.5) and 0.2 (0.3) kg in the deutetrabenazine and placebo groups, respectively, and mean BMI changes of 0.3–0.5 (0.1–0.2) and 0.1 (0.1) kg/m2. 337 patients were included in the analysis of the OLE study. No meaningful changes were observed in weight (mean change: 0.4 [0.4] kg at Week 54, –0.5 [0.6] kg at Week 106, and –1.1 [0.6] kg at Week 145) or BMI (mean change: 0.1 [0.2] kg/m2 at Week 54, –0.2 [0.2] kg/m2 at Week 106, and –0.3 [0.2] kg/m2 at Week 145). Across the studies, no meaningful changes were observed in triglyceride, cholesterol, or glucose levels.
ConclusionDeutetrabenazine does not affect common metabolic parameters in patients with TD, even during long-term exposure.
FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel
Long-Term Deutetrabenazine Treatment Is Associated With Continued Improvement in Tardive Dyskinesia in the Completed 3-Year Open-Label Extension Study
- Robert A. Hauser, Hadas Barkay, Hubert H. Fernandez, Stewart A. Factor, Joohi Jimenez-Shahed, Nicholas Gross, Leslie Marinelli, Amanda Wilhelm, Mark Forrest Gordon, Juha-Matti Savola, Karen E. Anderson
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- Journal:
- CNS Spectrums / Volume 26 / Issue 2 / April 2021
- Published online by Cambridge University Press:
- 10 May 2021, p. 162
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Background
The 12-week ARM-TD and AIM-TD studies in tardive dyskinesia (TD) patients showed statistically significant improvements in TD symptoms with deutetrabenazine. The completed open-label extension (OLE) study (SD-809-C−20) evaluated long-term efficacy and safety of deutetrabenazine in TD.
MethodsPatients who completed ARM-TD or AIM-TD enrolled in the OLE study, with deutetrabenazine dose titrated based on dyskinesia control and tolerability. Change from baseline in Abnormal Involuntary Movement Scale (AIMS) score was assessed by local site raters. Treatment success was evaluated locally as patients being “much improved” or “very much improved” on Clinical Global Impression of Change (CGIC).
Results343 patients enrolled in the OLE study; 6 patients were excluded from analyses. At Week 54 (n=249; dose [mean±SE]: 38.7±0.66mg/day), mean change from baseline in AIMS score was –4.8±0.28; 66% of patients experienced treatment success. At Week 106 (n=194; dose: 39.3±0.75mg/day), mean change from baseline in AIMS score was –5.4±0.33; 65% of patients experienced treatment success. At Week 145 (n=160; dose: 39.4±0.83mg/day), mean change from baseline in AIMS score was –6.6±0.37; 73% of patients experienced treatment success. Treatment was generally well tolerated across 723 patient-years of exposure through Week 158, and exposure-adjusted incidence rates (incidence/patient-years) for akathisia/restlessness were 0.01, somnolence/sedation were 0.07, and symptoms which may represent parkinsonism or depression were 0.08 each.
ConclusionsPatients who received long-term treatment with deutetrabenazine achieved sustained improvement in AIMS scores. Findings from this open-label trial with response-driven dosing suggest the possibility of increasing benefit over time.
FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel
Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum
- L.-K. Pries, G. A. Dal Ferro, J. van Os, P. Delespaul, G. Kenis, B. D. Lin, J. J. Luykx, A. L. Richards, B. Akdede, T. Binbay, V. Altınyazar, B. Yalınçetin, G. Gümüş-Akay, B. Cihan, H. Soygür, H. Ulaş, E. Şahin Cankurtaran, S. Ulusoy Kaymak, M. M. Mihaljevic, S. Andric Petrovic, T. Mirjanic, M. Bernardo, G. Mezquida, S. Amoretti, J. Bobes, P. A. Saiz, M. Paz García-Portilla, J. Sanjuan, E. J. Aguilar, J. L. Santos, E. Jiménez-López, M. Arrojo, A. Carracedo, G. López, J. González-Peñas, M. Parellada, N. P. Maric, C. Atbaşoğlu, A. Ucok, K. Alptekin, M. Can Saka, Genetic Risk and Outcome of Psychosis (GROUP) investigators, C. Arango, M. O'Donovan, S. Tosato, B. P. F. Rutten, S. Guloksuz
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- Journal:
- Epidemiology and Psychiatric Sciences / Volume 29 / 2020
- Published online by Cambridge University Press:
- 17 November 2020, e182
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Aims
Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene–environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum.
MethodsThe sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components).
ResultsBoth genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene–environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions.
ConclusionsThe interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.
Genetic diversity and structure analysis of Vigna unguiculata L. (Walp.) landraces from southeastern Mexico using ISSR markers
- L. F. C. dos Santos, M. M. Ferrer, M. R. Ruenes-Morales, P. I. Montañez-Escalante, R. H. Andueza-Noh, J. Jiménez-Osornio
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- Journal:
- Plant Genetic Resources / Volume 18 / Issue 4 / August 2020
- Published online by Cambridge University Press:
- 04 November 2020, pp. 201-210
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Cowpea (Vigna unguiculata L. Walp.) is an important grain legume in tropical and subtropical regions. It requires low resource inputs and has a high nutritional value. Therefore, cowpea can play an important role in the development of agriculture. In southern Mexico, Mayan farmers have conserved and developed cowpea landraces for centuries. Nevertheless, information on their genetic diversity, conservation status and potential use is minimal. To generate information toward sustainable use, management and conservation of this species, we evaluated the genetic diversity and structure of 20 cowpea landraces from southeast Mexico using 10 inter-simple sequence repeat (ISSR) molecular markers. These ISSR markers generated 68 loci with a 67.7% polymorphism rate and average polymorphic information content of 0.36. The results of Bayesian assignation and the UPGMA analysis suggest the formation of two main groups defined by their genetic origin in southeast Mexico. High levels of genetic structure were found with a moderate level of genetic diversity distributed mainly between landraces. Low levels of intra-landrace variability were observed. Two landraces (P5 and P12) from Calakmul resulted in the high levels of genetic diversity. The selected markers were efficient at assessing genetic variability among Mexican cowpea landraces, providing valuable information that can be used in local conservation and participatory breeding programmes.
Parasomnias in patients with addictions—a systematic review
- Ulises Jiménez-Correa, Rafael Santana-Miranda, Andrés Barrera-Medina, Juan M. Martínez-Núñez, Hernán A. Marín-Agudelo, Adrián Poblano, Carlos H. Schenck, Irma Hernández-Berber
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- Journal:
- CNS Spectrums / Volume 27 / Issue 1 / February 2022
- Published online by Cambridge University Press:
- 23 October 2020, pp. 58-65
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Parasomnias are involuntary behaviors or subjective experiences during sleep. Our objective was to review existing information on the presence of parasomnias in patients with addictions or during treatment for addictions. Information about parasomnias related to rapid-eye-movement (REM) and non-REM sleep in patients with addictions, while using substances or in abstinence, was reviewed. A systematic search of published articles reporting parasomnias as a consequence of drug use or abuse was conducted in the PubMed and SciELO databases. The search for the studies was performed in three phases: (1) by title, (2) by abstract, and (3) by complete text. The search was performed independently by two researchers, who then compared their results from each screening phase. Seventeen articles were found. The consumption of alcohol was reported in association with arousal disorders, such as sexsomnia and sleep-related eating disorder; and REM sleep behavior disorder was reported during alcohol withdrawal. Cocaine abuse was associated with REM sleep behavior disorder with drug consumption dream content. Overall, we found that several types of parasomnias were very frequent in patients with addictions. To avoid accidents in bedroom, legal problems, and improve evolution and prognosis; must be mandatory to include security measures related to sleep period; avoid pharmacological therapy described as potential trigger factor; improve sleep hygiene; and give pharmacological and behavioral treatments for patients with these comorbid sleep disorders.
A SCRUM AGILE INTEGRATED DEVELOPMENT FRAMEWORK
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- H. Thiele, S. Weber, J. Reichwein, J. A. Bartolo, Y. Tchana, L. Jimenez, J. C. Borg
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- Journal:
- Proceedings of the Design Society: DESIGN Conference / Volume 1 / May 2020
- Published online by Cambridge University Press:
- 11 June 2020, pp. 747-756
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With design methodologies, as Integrated Product Development, industry is continuously looking to improve their product development processes. Staying ahead concurrence forces them to deliver new and more complex products in shorter time. When it comes to fast delivery and requirement changes, product development can be inspired by agile methods. Although the application is difficult, the idea to implement these methods for development of products other than software comes out. To ease its implementation, this paper proposes to use IPD as a framework for agile product development.
151 Confirmed Safety of Deutet.rabenazine for Tardive Dyskinesia in a 3-Year Open-Label Extension Study
- Hubert H. Fernandez, Hadas Barkay, Robert A. Hauser, Stewart A. Factor, Joohi Jimenez-Shahed, Nicholas Gross, Leslie Marinelli, Mark Forrest Gordon, Juha-Matti Savola, Karen E. Anderson
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- Journal:
- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, pp. 296-297
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Background:
Deutetrabenazine (Austedo) is approved by the FDA for treatment of tardive dyskinesia (TD) in adults. In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The objective of this study was to evaluate the long-term safety and tolerability of deutetrabenazine in patients with TD at 3 years.
METHODS:Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12 mg/day, titrating up to a maximum total daily dose of 48 mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used for calculating AE frequencies. This analysis reports results up to Week 158.
RESULTS:A total of 343 patients were enrolled (111 received placebo and 232 received deutetrabenazine in the parent studies). At the time of this analysis, 183 patients were still receiving treatment; 259 completed 1 year, 172 completed 2 years, and 41 completed 3 years. There were 623 patient-years of exposure. More than 40% of patients reached the maximum dose. EAIRs of AEs were comparable to or lower than those observed in the ARM-TD and AIM-TD short-term randomized trials of deutetrabenazine vs. placebo. The frequency of SAEs (EAIR 0.10) was similar to that observed with short-term placebo (0.33) and short-term deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.06), dose reduction (0.10), and dose suspension (0.05) were uncommon.
CONCLUSION:These results support the safety outcomes observed in the ARM-TD and AIM-TD parent studies and the safety of deutetrabenazine for long-term use in patients with TD.
Funding Acknowledgements: This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel
134 Long-Term Deutetrabenazine Treatment Is Associated with Sustained Treatment Response in Tardive Dyskinesia: Results from an Open-Label Extension Study
- Robert A. Hauser, Hadas Barkay, Hubert H. Fernandez, Stewart A. Factor, Joohi Jimenez-Shahed, Nicholas Gross, Leslie Marinelli, Mark Forrest Gordon, Juha-Matti Savola, Karen E. Anderson
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- Journal:
- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, pp. 284-285
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Background:
In the 12-week ARM-TD and AIM-TD studies evaluating deutetrabenazine for the treatment of tardive dyskinesia (TD), the percentage of patients achieving ≥50% response was higher in the deutetrabenazine-treated group than in the placebo group. These studies also showed low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The current open-label study evaluated the long-term efficacy and safety of deutetrabenazine in patients with TD.
Methods:Patients with TD who completed ARM-TD or AIM-TD could enroll in this open-label, single-arm extension study, titrating up over 6 weeks to a maximum total daily dose of deutetrabenazine 48 mg/day on the basis of dyskinesia control and tolerability. The proportion of Abnormal Involuntary Movement Scale (AIMS; items 1-7) responders was assessed based on response rates for achieving ≥50% improvement from baseline in the open-label extension study. AlMS score was assessed by local site raters for this analysis.
Results:343 patients enrolled in the extension study. At Week 54 (n=249; total daily dose [mean ± standard error]: 38.6±0.66 mg), the mean percentage change from baseline in AIMS score was –40%; 48% of patients achieved a ≥50% response and 59% of those had already achieved a ≥50% response at Week 15. Further, 34% of those who had not achieved a ≥50% response at Week 15 achieved a ≥50% response at Week 54. At Week 106 (n=169; total daily dose: 39.6±0.77 mg), the mean percentage change from baseline in AIMS score was –45%; 55% of patients achieved a ≥50% response, 59% of those patients had already achieved a ≥50% response at Week 15, and 41% of those who had not achieved a ≥50% response at Week 15 but who reached Week 106 achieved a ≥50% response. At Week 132 (n=109; total daily dose: 39.7±0.97 mg), the mean percentage change from baseline in AIMS score was –61%; 55% of patients achieved a ≥50% response, 61% of those patients had already achieved a ≥50% response at Week 15, and 43% of those who had not achieved a ≥50% response at Week 15 but who reached Week 132 achieved a ≥50% response. Completer analysis suggests that long-term efficacy was not due to dose increases over time. Treatment with deutetrabenazine was generally well tolerated. There were 623 patient-years of exposure through Week 158, and exposure-adjusted incidence rates (incidence/patient-years) of adverse events of special interest were 0.01 for akathisia and restlessness, 0.07 for somnolence and sedation, 0.04 for parkinsonism, and 0.05 for depression.
Conclusions:Patients who received long-term treatment with deutetrabenazine achieved response rates that were indicative of clinically meaningful long-term benefit. Results from this open-label trial suggest the possibility of increasing benefit over time with individual dose titration of deutetrabenazine.
Funding Acknowledgements:This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.
P-929 - Relationship Between Personality and Physical Activity Among First-year Medical Residents From Hospital Universitario 12 de Octubre de Madrid
- N. Mesa Rodas, H. Fernández Garcimartin, J.C. Vázquez Caubet, E.J. Verdura Vizcaíno, A.T. Bagney Lifante, R. Rodríguez Jiménez
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- European Psychiatry / Volume 27 / Issue S1 / 2012
- Published online by Cambridge University Press:
- 15 April 2020, p. 1
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Introduction
Several studies have stated the possitive effects of physical exercise over mental health, mainly in clinical samples. However, the results of these experimental estudies might not be generalized to general population. Some authors propose that physical activity could be not really promoting a psychological benefit but, instead, be a consequence of some personal or circumstantial features that would be acting as confusion factors. Personality, as it involves a steady pattern of behaviors, is theorized to arise as one of these factors.
ObjectiveOur objective was to assess the relationship between personality features and voluntary physical activity in a medical resident sample from Hospital 12 de Octubre (Madrid).
HypothesisHigh levels of voluntary physical activity will be associated to high scores on extraversion and conscientiousness dimensions after assessing personality.
MethodsThe project has been conducted as a transversal descriptive study. Sample: 80 first-year medical residents, ages 23 to 40, and no story of mental disorder, nor chronic disabilities. Main variables: voluntary physical activity measured through International Physical Activity Questionary (IPAQ) and personality features assessed through Revised NEO Personality Inventory (NEO PI-R) as proposed from the 5 factors model (neuroticism, extraversion, openess, agreeableness and conscientiouness).
Statistical analysisFrequency measures have been used to describe qualitative variables. Arithmetic mean and standard deviation were used to describe quantitative variables. Pearson's correlation was used in order to study the relationship between scores on physical activity and personality factors.
ResultsWe present preliminary results from first stage of the study, as well implications are discused.
Childhood trauma in suicide attempters: Case-control study
- L. Jimenez-Trevino, L. Gonzalez-Blanco, M.P. Garcia-Portilla, H. Blasco Fontecilla, J. Lopez Castroman, P. Courtet, V. Carli, M. Sarchiapone, E. Baca-Garcia, P. Saiz Martinez, J. Bobes Garcia
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- Journal:
- European Psychiatry / Volume 33 / Issue S1 / March 2016
- Published online by Cambridge University Press:
- 23 March 2020, p. S111
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Introduction
An expanding body of research suggests that childhood trauma and adverse experiences can lead to a variety of negative health outcomes, including substance abuse, depressive disorders, and attempted suicide among adolescents and adults. Alcoholism, depressed affect, and illicit drug use, which are strongly associated with such experiences, appear to partially mediate this relationship as observed in population studies.
ObjectivesWe have tested the association between early trauma and suicide attempts in a sample of suicide attempters from the Eureca International Project and a matched healthy control sample.
MethodsWe have studied the prevalence of childhood stressful events compared with healthy controls in a multicentre sample of 791 suicide attempters (SA) and 630 healthy controls (C), we have measured childhood parental neglect, physical abuse, sexual abuse, and emotional abuse, using the Childhood Trauma Questionnaire (CTQ). Chi2 tests were performed using SPSS v15.0.
ResultsA significant increase in prevalence of childhood trauma was found in the suicide attempters sample for all types of trauma: childhood physical abuse: 25.3% (SA) vs. 11.1% (C) (Chi2 test: 120,108 P = 0.000); childhood sexual abuse: 18.2% (SA) vs. 2.4% (C) (Chi2 test: 88,212 P = 0.000); parental neglect 25.3% (SA) vs. 1.1% (C) (Chi2 test: 164,910 P = 0.000); childhood emotional abuse: 34.9% (SA) vs. 5.6% (C) (Chi2 test: 176,546 P = 0.000).
Suicide attempters were increasingly overrepresented compared with controls if experiencing more than 1 trauma: represented 77% of the sample who suffered 1 type of childhood trauma vs. more than 90% of the sample with 2 or more types of trauma.
ConclusionsA powerful graded relationship exists between adverse childhood experiences and risk of attempted suicide.
Disclosure of interestThe authors have not supplied their declaration of competing interest.
Prenatal restraint stress impairs recognition memory in adult male and female offspring
- Clarissa A. Moura, Matheus C. Oliveira, Layse F. Costa, Pamella R. F. Tiago, Victor A. D. Holanda, Ramon H. Lima, Fernanda C. Cagni, Bruno Lobão-Soares, Franscico Bolaños-Jiménez, Elaine C. Gavioli
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- Acta Neuropsychiatrica / Volume 32 / Issue 3 / June 2020
- Published online by Cambridge University Press:
- 29 January 2020, pp. 122-127
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Objective:
Accumulating evidence from preclinical and clinical studies indicates that prenatal exposure to stress impairs the development of the offspring brain and facilitates the emergence of mental illness. This study aims to describe the impact of prenatal restraint stress on cognition and exploration to an unfamiliar environment at adulthood in an outbred strain of mice.
Methods:Late pregnant mice were exposed to restraint stress and adult offspring (60 days of age) behaviours were assessed in the object recognition task and open field test.
Findings:Prenatal stress (PNS) impaired new object recognition in male and female mice. Importantly, the learning deficits in female PNS mice were linked to their estrous cycle. Actually, PNS females in metestrus/diestrus but not in proestrus/estrus phases displayed recognition deficits compared to controls. Concerning locomotion in an unfamiliar environment, male but not female PNS mice displayed significant increase, but showed no differences in the distance travelled within the centre zone of the arena.
Conclusion:Present findings support the view that maternal restraint-stress during late pregnancy impairs recognition memory in both male and female offspring, and in females, this cognitive deficit is dependent on the estrous cycle phase. Ultimately, these data reinforce that PNS is an aetiological component of psychiatric disorders associated with memory deficits.
34 Long-Term Deutetrabenazine Treatment Response in Tardive Dyskinesia by Concomitant Dopamine-Receptor Antagonists and Baseline Comorbidities
- Karen E. Anderson, David Stamler, Mat D. Davis, Robert A. Hauser, L. Fredrik Jarskog, Joohi Jimenez-Shahed, Rajeev Kumar, Stanislaw Ochudlo, Joseph McEvoy, Hubert H. Fernandez
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- Journal:
- CNS Spectrums / Volume 24 / Issue 1 / February 2019
- Published online by Cambridge University Press:
- 12 March 2019, p. 193
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Background
Tardive dyskinesia (TD) results from exposure to dopamine-receptor antagonists (DRAs), such as typical and atypical antipsychotics. Clinicians commonly manage TD by reducing the dose of or stopping the causative agent; however, this may cause psychiatric relapse and worsen quality of life. In the 12-week ARM-TD and AIM-TD trials, deutetrabenazine demonstrated statistically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores versus placebo and was generally well tolerated, regardless of baseline DRA use or comorbidities.
Study ObjectiveTo evaluate the impact of underlying disease and current DRA use on efficacy and safety of long-term therapy of deutetrabenazine in patients with TD.
MethodPatients with TD who completed ARM-TD or AIM-TD were eligible to enter this open-label, single-arm, long-term extension after completing the 1-week washout period and final evaluation in the blinded portion of the trial. Change in AIMS scores from baseline to Week 54 and patients “Much Improved” or “Very Much Improved” (treatment success) on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC) at Week 54 were analyzed by baseline psychiatric illness type, including mood disorders (bipolar disorder/depression/other) or psychotic disorders (schizophrenia/schizoaffective disorder), and presence or absence of current DRA use.
ResultsAt Week 54, meaningful improvements from baseline in mean (standard error) AIMS scores were observed for patients with baseline mood disorders (–5.2[0.93]) and psychotic disorders (–5.0[0.63]), and in patients currently using DRAs (–4.6[0.54]) or not using DRAs (–6.4[1.27]). Most patients with mood disorders (73%) and psychotic disorders (71%) were “Much Improved” or “Very Much Improved” on CGIC at Week 54, similar to patients currently using (71%) or not using (74%) DRAs. The majority of patients with mood disorders (62%) and psychotic disorders (57%), as well as patients currently using (58%) or not using (63%) DRAs, were also “Much Improved” or “Very Much Improved” on PGIC at Week 54. Prior treatment in ARM-TD and AIM-TD did not impact the long-term treatment response. Underlying psychiatric disorder and concomitant DRA use did not impact the occurrence of adverse events (AEs). The frequencies of dose reductions, dose suspensions, and withdrawals due to AEs were low, regardless of baseline psychiatric comorbidities and DRAuse.
ConclusionsLong-term deutetrabenazine treatment demonstrated meaningful improvements in abnormal movements in TD patients, which were recognized by clinicians and patients, regardless of underlying psychiatric illness or DRAuse.
Presented at: American Psychiatric Association Annual Meeting; May 5–9, 2018, New York, New York, USA
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.