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Genetic analysis of activity, brain and behavioral associations in extended families with heavy genetic loading for bipolar disorder

Published online by Cambridge University Press:  09 December 2019

Annabel Vreeker
Affiliation:
Department of Genetics, UMC Utrecht, Utrecht University, Utrecht, The Netherlands Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA
Scott C. Fears
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA
Susan K. Service
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA
Lucia Pagani
Affiliation:
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA Dobeco Spa a Socia Unico, Milano, Italy
Joseph S. Takahashi
Affiliation:
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA
Carmen Araya
Affiliation:
Cell and Molecular Biology Research Center, Universidad de Costa Rica, San José, Costa Rica
Xinia Araya
Affiliation:
Cell and Molecular Biology Research Center, Universidad de Costa Rica, San José, Costa Rica
Julio Bejarano
Affiliation:
Cell and Molecular Biology Research Center, Universidad de Costa Rica, San José, Costa Rica
Maria C. Lopez
Affiliation:
Departamento de Psiquiatría Facultad de Medicina, Grupo de Investigación en Psiquiatría (Research Group in Psychiatry; GIPSI), Universidad de Antioquia, Medellín, Colombia
Gabriel Montoya
Affiliation:
Departamento de Psiquiatría Facultad de Medicina, Grupo de Investigación en Psiquiatría (Research Group in Psychiatry; GIPSI), Universidad de Antioquia, Medellín, Colombia
Claudia Patricia Montoya
Affiliation:
Departamento de Psiquiatría Facultad de Medicina, Grupo de Investigación en Psiquiatría (Research Group in Psychiatry; GIPSI), Universidad de Antioquia, Medellín, Colombia
Terri M. Teshiba
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA
Javier Escobar
Affiliation:
Department of Psychiatry and Family Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
Rita M. Cantor
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA
Carlos López-Jaramillo
Affiliation:
Departamento de Psiquiatría Facultad de Medicina, Grupo de Investigación en Psiquiatría (Research Group in Psychiatry; GIPSI), Universidad de Antioquia, Medellín, Colombia Mood Disorders Program, Hospital Universitario San Vicente Fundacion, Medellín, Colombia
Gabriel Macaya
Affiliation:
Cell and Molecular Biology Research Center, Universidad de Costa Rica, San José, Costa Rica
Julio Molina
Affiliation:
BioCiencias Lab, Guatemala City, Guatemala
Victor I. Reus
Affiliation:
Department of Psychiatry, University of California, San Francisco, CA, USA
Chiara Sabatti
Affiliation:
Department of Health Research and Policy, Division of Biostatistics, Stanford University, Stanford, CA, USA
Roel A. Ophoff
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University California Los Angeles, Los Angeles, CA, USA
Nelson B. Freimer
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University California Los Angeles, Los Angeles, CA, USA
Carrie E. Bearden
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University California Los Angeles, Los Angeles, CA, USA Department of Psychology, University California Los Angeles, Los Angeles, CA, USA
Corresponding
E-mail address:

Abstract

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.

Methods

Relationships 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.

Results

More 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.

Conclusions

Our 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.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2019

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