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Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants
- Sean R. McWhinney, Christoph Abé, Martin Alda, Francesco Benedetti, Erlend Bøen, Caterina del Mar Bonnin, Tiana Borgers, Katharina Brosch, Erick J. Canales-Rodríguez, Dara M. Cannon, Udo Dannlowski, Ana M. Diaz-Zuluaga, Lorielle M.F. Dietze, Torbjørn Elvsåshagen, Lisa T. Eyler, Janice M. Fullerton, Jose M. Goikolea, Janik Goltermann, Dominik Grotegerd, Bartholomeus C. M. Haarman, Tim Hahn, Fleur M. Howells, Martin Ingvar, Neda Jahanshad, Tilo T. J. Kircher, Axel Krug, Rayus T. Kuplicki, Mikael Landén, Hannah Lemke, Benny Liberg, Carlos Lopez-Jaramillo, Ulrik F. Malt, Fiona M. Martyn, Elena Mazza, Colm McDonald, Genevieve McPhilemy, Sandra Meier, Susanne Meinert, Tina Meller, Elisa M. T. Melloni, Philip B. Mitchell, Leila Nabulsi, Igor Nenadic, Nils Opel, Roel A. Ophoff, Bronwyn J. Overs, Julia-Katharina Pfarr, Julian A. Pineda-Zapata, Edith Pomarol-Clotet, Joaquim Raduà, Jonathan Repple, Maike Richter, Kai G. Ringwald, Gloria Roberts, Alex Ross, Raymond Salvador, Jonathan Savitz, Simon Schmitt, Peter R. Schofield, Kang Sim, Dan J. Stein, Frederike Stein, Henk S. Temmingh, Katharina Thiel, Sophia I. Thomopoulos, Neeltje E. M. van Haren, Cristian Vargas, Eduard Vieta, Annabel Vreeker, Lena Waltemate, Lakshmi N. Yatham, Christopher R. K. Ching, Ole A. Andreassen, Paul M. Thompson, Tomas Hajek, for the ENIGMA Bipolar Disorder Working Group
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- Journal:
- Psychological Medicine / Volume 53 / Issue 14 / October 2023
- Published online by Cambridge University Press:
- 27 February 2023, pp. 6743-6753
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Background:
Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.
Methods:We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.
Results:BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.
Conclusions:We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
Influence of birth cohort on age of onset cluster analysis in bipolar I disorder
- M. Bauer, T. Glenn, M. Alda, O.A. Andreassen, E. Angelopoulos, R. Ardau, C. Baethge, R. Bauer, F. Bellivier, R.H. Belmaker, M. Berk, T.D. Bjella, L. Bossini, Y. Bersudsky, E.Y.W. Cheung, J. Conell, M. Del Zompo, S. Dodd, B. Etain, A. Fagiolini, M.A. Frye, K.N. Fountoulakis, J. Garneau-Fournier, A. Gonzalez-Pinto, H. Harima, S. Hassel, C. Henry, A. Iacovides, E.T. Isometsä, F. Kapczinski, S. Kliwicki, B. König, R. Krogh, M. Kunz, B. Lafer, E.R. Larsen, U. Lewitzka, C. Lopez-Jaramillo, G. MacQueen, M. Manchia, W. Marsh, M. Martinez-Cengotitabengoa, I. Melle, S. Monteith, G. Morken, R. Munoz, F.G. Nery, C. O’Donovan, Y. Osher, A. Pfennig, D. Quiroz, R. Ramesar, N. Rasgon, A. Reif, P. Ritter, J.K. Rybakowski, K. Sagduyu, A.M. Scippa, E. Severus, C. Simhandl, D.J. Stein, S. Strejilevich, A. Hatim Sulaiman, K. Suominen, H. Tagata, Y. Tatebayashi, C. Torrent, E. Vieta, B. Viswanath, M.J. Wanchoo, M. Zetin, P.C. Whybrow
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- Journal:
- European Psychiatry / Volume 30 / Issue 1 / January 2015
- Published online by Cambridge University Press:
- 15 April 2020, pp. 99-105
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Purpose:
Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.
Methods:The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.
Results:There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups.
Conclusion:These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.
Genetic analysis of activity, brain and behavioral associations in extended families with heavy genetic loading for bipolar disorder
- Annabel Vreeker, Scott C. Fears, Susan K. Service, Lucia Pagani, Joseph S. Takahashi, Carmen Araya, Xinia Araya, Julio Bejarano, Maria C. Lopez, Gabriel Montoya, Claudia Patricia Montoya, Terri M. Teshiba, Javier Escobar, Rita M. Cantor, Carlos López-Jaramillo, Gabriel Macaya, Julio Molina, Victor I. Reus, Chiara Sabatti, Roel A. Ophoff, Nelson B. Freimer, Carrie E. Bearden
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- Journal:
- Psychological Medicine / Volume 51 / Issue 3 / February 2021
- Published online by Cambridge University Press:
- 09 December 2019, pp. 494-502
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Background
Disturbed sleep and activity are prominent features of bipolar disorder type I (BP-I). However, the relationship of sleep and activity characteristics to brain structure and behavior in euthymic BP-I patients and their non-BP-I relatives is unknown. Additionally, underlying genetic relationships between these traits have not been investigated.
MethodsRelationships between sleep and activity phenotypes, assessed using actigraphy, with structural neuroimaging (brain) and cognitive and temperament (behavior) phenotypes were investigated in 558 euthymic individuals from multi-generational pedigrees including at least one member with BP-I. Genetic correlations between actigraphy-brain and actigraphy-behavior associations were assessed, and bivariate linkage analysis was conducted for trait pairs with evidence of shared genetic influences.
ResultsMore physical activity and longer awake time were significantly associated with increased brain volumes and cortical thickness, better performance on neurocognitive measures of long-term memory and executive function, and less extreme scores on measures of temperament (impulsivity, cyclothymia). These associations did not differ between BP-I patients and their non-BP-I relatives. For nine activity-brain or activity-behavior pairs there was evidence for shared genetic influence (genetic correlations); of these pairs, a suggestive bivariate quantitative trait locus on chromosome 7 for wake duration and verbal working memory was identified.
ConclusionsOur findings indicate that increased physical activity and more adequate sleep are associated with increased brain size, better cognitive function and more stable temperament in BP-I patients and their non-BP-I relatives. Additionally, we found evidence for pleiotropy of several actigraphy-behavior and actigraphy-brain phenotypes, suggesting a shared genetic basis for these traits.
An overlapping pattern of cerebral cortical thinning is associated with both positive symptoms and aggression in schizophrenia via the ENIGMA consortium
- Ting Yat Wong, Joaquim Radua, Edith Pomarol-Clotet, Raymond Salvador, Anton Albajes-Eizagirre, Aleix Solanes, Erick J. Canales-Rodriguez, Amalia Guerrero-Pedraza, Salvador Sarro, Tilo Kircher, Igor Nenadic, Axel Krug, Dominik Grotegerd, Udo Dannlowski, Stefan Borgwardt, Anita Riecher-Rössler, Andre Schmidt, Christina Andreou, Christian G. Huber, Jessica Turner, Vince Calhoun, Wenhao Jiang, Sarah Clark, Esther Walton, Gianfranco Spalletta, Nerisa Banaj, Fabrizio Piras, Valentina Ciullo, Daniela Vecchio, Irina Lebedeva, Alexander S. Tomyshev, Vasily Kaleda, Tatyana Klushnik, Geraldo Busatto Filho, Marcus Vinicius Zanetti, Mauricio Henriques Serpa, Pedro Gomes Penteado Rosa, Ryota Hashimoto, Masaki Fukunaga, Anja Richter, Bernd Krämer, Oliver Gruber, Aristotle N. Voineskos, Erin W. Dickie, David Tomecek, Antonin Skoch, Filip Spaniel, Cyril Hoschl, Alessandro Bertolino, Aurora Bonvino, Annabella Di Giorgio, Laurena Holleran, Simone Ciufolini, Tiago Reis Marques, Paola Dazzan, Robin Murray, Jelle Lamsma, Wiepke Cahn, Neeltje van Haren, Ana M. Díaz-Zuluaga, Julián A. Pineda-Zapata, Cristian Vargas, Carlos López-Jaramillo, Theo G. M. van Erp, Ruben C. Gur, Thomas Nickl-Jockschat
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- Journal:
- Psychological Medicine / Volume 50 / Issue 12 / September 2020
- Published online by Cambridge University Press:
- 16 October 2019, pp. 2034-2045
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Background
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
MethodTo study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
ResultsThe result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
ConclusionThese findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.